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May 2002 (Vol. 40, Issue 3)

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PrefaceWomen's imaging: an oncologic focusby Liberman L, Hricak Hpages xi-xiiFull Text | PDF (46 KB)Screening mammography: proven benefit, continued controversyby Lee CHpages 395-407Full Text | PDF (138 KB)Breast imaging reporting and data system (BI-RADS)by Liberman L, Menell JHpages 409-430Full Text | PDF (757 KB)Ultrasound for breast cancer screening and stagingby Gordon PBpages 431-441Full Text | PDF (278 KB)Breast cancer imaging with MRIby Morris EApages 443-466Full Text | PDF (912 KB)New modalities in breast imaging: digital mammography, positron emission tomography, and sestamibi scintimammographyby Leung JWTpages 467-482Full Text | PDF (425 KB)Percutaneous image-guided core breast biopsyby Liberman Lpages 483-500Full Text | PDF (526 KB)Breast imaging and the conservative treatment of breast cancerby Dershaw D Dpages 501-516Full Text | PDF (971 KB)Breast imaging: a breast surgeon's perspectiveby Van Zee KJpages 517-520Full Text | PDF (59 KB)What do we expect from imaging?by Barakat RR, Hricak Hpages 521-526Full Text | PDF (74 KB)

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Radiologic Clinics of North America

Postmenopausal bleeding: value of imagingby Reinhold C, Khalili Ipages 527-562Full Text | PDF (2137 KB)Imaging of cancer of the endometriumby Ascher SM, Reinhold Cpages 563-576Full Text | PDF (636 KB)Imaging of cancer of the cervixby Scheidler J, Heuck AFpages 577-590Full Text | PDF (719 KB)Detection and characterization of adnexal massesby Funt SA, Hann LEpages 591-608Full Text | PDF (866 KB)Staging ovarian cancer: role of imagingby Coakley FVpages 609-636Full Text | PDF (1664 KB)Imaging of the vagina and vulvaby Chang SDpages 637-658Full Text | PDF (1601 KB)Postsurgical pelvis: treatment follow-upby Sugimura K, Okizuka Hpages 659-680Full Text | PDF (1227 KB)Indexpages 681-687PDF (55 KB)View Selected Abstracts Display:

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Preface

Women’s imaging: an oncologic focus

Laura Liberman, MD Hedvig Hricak, MD, PhD

Guest Editors

Advances in imaging technology have expanded

the radiologist’s role in detection, diagnosis, staging,

and follow-up of women with cancer. The American

Cancer Society estimates that there will be 647,400

new cases of cancer in women in the United States in

2002, of which over half will be cancers of the breast

or genital organs. Breast cancer will be diagnosed in

257,800 women (invasive in 203,500 and in situ in

54,300); an additional 81,400 women will be diag-

nosed with gynecologic malignancies. This issue of

the Radiologic Clinics of North America focuses on

the role of modern imaging techniques in treating

women with breast and gynecologic cancers.

Controversies remain regarding many aspects of

breast imaging. Does screening mammography reduce

breast cancer mortality? How useful is the stand-

ardized language used to describe mammograms?

Can other modalities such as ultrasound or MR

imaging supplement mammography in breast cancer

screening and staging? What is the role of digital

imaging and other new technologies? Articles

addressing these issues should be of value to radiol-

ogists and clinicians who refer women for screening

or diagnostic examinations of the breast.

The diagnosis and treatment of breast cancer

are often minimally invasive, with percutaneous

biopsy for diagnosis and breast conserving therapy.

How does one select the appropriate percutaneous

biopsy method, and which lesions warrant excision

after percutaneous biopsy? How does one track the

patient after breast conservation, to assess adequacy

of excision and diagnose recurrent disease? Analysis

of these issues should be of use to practitioners. Close

coordination is necessary between the radiologist and

clinicians caring for the patient, as illustrated in the

article on the role of breast imaging from the per-

spective of a dedicated breast surgeon.

The articles on imaging gynecologic cancers brief

the reader on what clinicians expect to learn from

imaging and provide insight into the imaging findings

and staging of these neoplasms. Interpretation of

imaging studies of the pelvis after surgery, a complex

subject, is addressed in a separate article. An array of

cross-sectional imaging modalities is now available;

information regarding the appropriate use of ultra-

sound, CT, and MR imaging should provide guidance

for the reader.

Cancer is the leading cause of death in American

women age 40 to 79. The American Cancer Society

estimates that there will be 267,300 deaths in women

due to cancer in the United States in 2002, of which

approximately one-fourth will be due to breast or

gynecologic cancers. They project 39,600 deaths

from breast cancer and 26,200 from gynecologic

cancers. We hope that this issue of the Radiologic

Clinics provides information that will be valuable to

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (02 )00016 -7

Radiol Clin N Am 40 (2002) xi–xii

colleagues in all specialties who share the goal of

improving the outcome and quality of life for women

with breast and gynecologic cancers. We are grateful

to our contributors for their scholarly work, and to

Barton Dudlick and the WB Saunders staff for their

invaluable support.

Laura Liberman, MD

Hedvig Hricak, MD, PhD

Department of Radiology

Memorial Sloan-Kettering Cancer Center

1275 York Avenue

New York, NY 10021, USA

Preface / Radiol Clin N Am 40 (2002) xi–xiixii

Screening mammography: proven benefit,

continued controversy

Carol H. Lee, MD

Department of Diagnostic Radiology, Yale University School of Medicine, PO Box 208042, New Haven, CT 06520, USA

Breast cancer is the most frequently diagnosed

malignancy among American women, accounting

for 32% of all cancers in this population [1]. It is the

second leading cause of cancer death (after lung can-

cer) among women of all ages and the leading cause of

cancer death among women aged 40 to 59 years [1].

Mammography has been shown to be efficacious in

detecting breast cancer before it becomes clinically

evident [2], and screening of asymptomatic women

has become widespread as a means of achieving early

detection. Routine screening with mammography

is now generally accepted as a valuable tool for de-

creasing mortality from breast cancer.

The use of screening mammography has not been

without controversy, however. Although the role of

screening mammography in reducing breast cancer

mortality is widely accepted, continuing areas of con-

troversy include lack of consensus as to the age at

which regular screening should start, the age at which

screening should stop, the appropriate interval be-

tween screenings, and the value of screening young

women at high risk. In addition, much attention

has been paid recently to the so-called risks of

screening mammography, which include observer var-

iability in interpretation and false-negative and false-

positive readings.

Proven benefit of screening mammography

Evidence for the benefit of screening mammog-

raphy in reducing mortality from breast cancer largely

derives from several large randomized controlled

trials (RCTs) conducted in North America and

Europe beginning in the 1960s and involving a

combined total of nearly 500,000 women [3–7].

These studies varied greatly in terms of study design.

Most enrolled women as young as age 40, whereas

others used 45 or 50 years as the lower age limit.

Some performed two-view mammograms and others

a single view. The screening interval varied from 12

to 33 months, and the number of rounds of screening

ranged from 2 to 6. Some included clinical breast

examination in the screening process. Despite the

varying research designs, meta-analysis of the results

from these studies has shown a statistically signifi-

cant reduction in mortality from breast cancer on the

order of 25% to 30% among screened groups com-

pared with controls after 5 to 7 years [8]. The results

of the RCTs are summarized in Table 1. Based on the

results of these trials, routine mammography has

become established as a valuable screening tool for

breast cancer detection.

In addition to decreasing mortality from breast

cancer, the use of screening mammography has been

shown to result in the diagnosis of smaller and more

node-negative tumors [9,10]. In a recent update of the

experience of the Swedish two-county screening trial,

Tabar et al [11] reported that 50% of screen-detected

cancers were in the good prognostic category (gen-

erally stage 0 or 1, depending on histologic type)

as opposed to 19% in the clinically detected group.

For the woman whose cancer is detected by mam-

mography before it becomes palpable, this translates

into less aggressive therapy options—lumpectomy

followed by radiation therapy rather than mas-

tectomy and decreased need for systemic chemo-

therapy [9].

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00015 -X

E-mail address: leec@biomed.med.yale.edu (C.H. Lee).

Radiol Clin N Am 40 (2002) 395–407

Continued controversy

Does screening mammography decrease breast

cancer mortality?

Although screening mammography has been

widely accepted as a useful tool for decreasing breast

cancer mortality, recently published works by Danish

researchers Gotzsche and Olsen have served to revive

the debate over its efficacy. In the first of these

reports, published in Lancet in January 2000 [13],

the authors reviewed the eight existing randomized

controlled trials of screening mammography and

concluded that six of the eight should be discounted

due to seriously flawed methodology. Because the

remaining two trials that were judged to be acceptable

in terms of methodology did not show a mortality

reduction among screened women, the authors con-

cluded that screening for breast cancer with mam-

mography is not justified. In their second report,

published in October 2001, Gotzsche and Olsen

confirmed their earlier conclusions [14]. In addition,

they stated that all-cause mortality among the

screened women was no different from that of the

control group, suggesting that although there may

have been fewer deaths from breast cancer in the

screened group, lives were not saved overall. They

reiterated their belief that screening with mammog-

raphy is unjustified.

In their critique, Gotzsche and Olsen cited differ-

ences in the ages of women in the screened and

control groups as being indicative of serious flaws in

randomization. These age differences ranged from

one to five months; however, the age distribution of

the women enrolled in the two studies that were

accepted as being adequately randomized (Canadian

and Malmo), was not known. Additionally, Gotzsche

and Olsen chose to ignore the fact that randomization

in the Canadian study resulted in more women with

advanced, palpable cancers in the screened group

than in the control group.

Finally, as breast cancer accounts for approxi-

mately 5% of mortality among women, a reduction

in mortality resulting from screening would not nec-

essarily affect all-cause mortality rates without sub-

stantially larger cohorts of subjects. The Danish

researchers conceded that the size of the studied

population was not sufficient to make conclusions

concerning the effect of screening mammography on

all-cause mortality [14]. In addition, the screening

trials were not designed to evaluate all-cause mortality

and were not controlled for important factors such as

smoking history, blood pressure, or cholesterol level.

No study ever performed has been entirely flaw-

less. To discount studies because of small differences

in age between study and control groups seems

unjustified. In addition, it appears that the Danish

authors chose to concentrate on certain discrepancies

in some studies and to ignore those in others. Despite

the opinion of Gotzsche and Olsen, the National

Cancer Institute in early 2002 reiterated their recom-

mendation that women of average risk for breast

cancer begin screening with mammography at age

40 [15]. Also in early 2002, the United States

Table 1

Summary of randomized controlled trials of screening mammography

Study [reference]

Ages at

entry (y) Modalities used Interval (mo)

Relative risk (95%

confidence interval)

Hip [3] 40–64 2-view MMG, CBE 12 0.77 (0.61–0.97)

Malmo [4] 45–69 2-view MMG 18–24 0.81 (0.62–1.07)

Kopparberg [4] 40–74 1-view MMG 24 younger than 50 0.68 (0.52–0.89)

33 younger than 50

or older

Ostergotland [4] 40–74 1-view MMG 24 months < 50 0.82 (0.64–1.05)

33 months � 50

Edinburgh [5] 45–64 2-view MMG initially, then

1-view MMG Annual CBE

24 0.84 (0.63–1.12)

CNBSS1 [6] 40–49 2-view MMG, CBE 12 1.36 (0.74–2.21)

CNBSS2 [7] 50–59 2-view MMG, CBE 12 1.02 (0.78–1.33)

Stockholm [4] 40–64 1-view MMG 28 0.80 (0.53–1.22)

Gothenburg [95] 40–59 2-view MMG initially, then

1-view MMG

18 0.86 (0.54–1.37)

All studies — — 0.74 (0.66–0.83)

MMG = mammogram; CBE = clinical breast examination; CBNSS = Canadian National Breast Screening Study.

C.H. Lee / Radiol Clin N Am 40 (2002) 395–407396

Preventive Services Task Force, a respected panel of

experts who issue guidelines for preventive health

measures based on review of available evidence,

reviewed the same studies as the Danish researchers

and actually lowered their recommendation for when

regular screening with mammography should start

from age 50 to age 40 [16].

What should be remembered in the controversy

surrounding the efficacy of screening mammography

is that mortality from breast cancer in the United

States has been decreasing steadily in recent years

[17,18]. Although some of this decrease may be

related to improvements in treatment, it is difficult

to believe that some of the decrease is not related to

earlier detection. Mammography remains the single

most valuable tool for achieving early detection of

breast cancer.

At what age should screening begin?

A continued point of controversy surrounding

screening mammography centers on the age at which

regular screening should begin. The debate over this

point has been heated and sometimes acrimonious on

both sides. The controversy stems from the finding of

the RCTs that mortality reduction for women in their

40s was less than that of women aged 50 and older

and that the benefits, if any, did not reach statistical

significance after 7 to 9 years of follow-up [8].

Possible explanations as to why screening may

not be as effective for younger women include the

fact that breast density is generally greater in younger

women and breast cancer may be obscured by over-

lying dense tissue [19]. Therefore, the sensitivity of

mammography may not be as high as in older women

with less dense breasts. In addition, tumor biology

may be a factor because tumors in younger women

tend to be faster growing [20]. Therefore, early

detection may not lead to decreased mortality because

these tumors may already have spread by the time

they are found by mammography.

Another argument against routine screening of

women in their 40s relates to cost. Because the

incidence of breast cancer is lower in younger women,

a greater number must be screened to detect one

cancer. One study of cost-effectiveness by Salzmann

et al [21] reported that the incremental cost-effective-

ness of screening women aged 40 to 49 years was

nearly five times that of screening women aged 50 to

69 years ($105,000 per year of life saved compared to

$21,400). However, Rosenquist and Lindfors [22]

used a Markov model to compare the relative cost-

effectiveness of four different age-related screening

strategies. They found that screening women aged 40

to 79 years at differing intervals would result in

marginal cost per year of life saved of $18,800 for

the most expensive strategy (annually from age 40) to

$16,100 for the least expensive (annually for 40 to

49 years, biennially from 50 to 79 years). These costs

are well within the range of cost generally accepted as

reasonable for life-saving interventions [23].

Evidence in favor of using mammography to

screen women in their 40s include the fact that

mammography has been shown to be efficacious in

detecting small, early-stage tumors in this age group

[24,25]. In addition, several series have reported no

statistically significant difference in size, stage, or

lymph node status among invasive cancers detected

by screening mammography in women aged 40 to 49

compared to women aged 50 to 64 years [10,26–29],

suggesting that screening in the younger age group

should be as efficacious as that observed in older

women. Finally, the proportion of screening detected

cancers that are ductal carcinoma in situ (DCIS) in

women 40 to 49 years of age is significantly higher

than it is in older women [30,31]. DCIS has been

reported to account for 37% to 47% of all screen-

detected cancers among women aged 40 to 49 com-

pared with 21% to 37% in women older than 50

[26,31,32].

The increased detection of DCIS has been cited as

an advantage and a disadvantage to screening of

younger women [30,31]. DCIS is primarily detected

through mammography. With the increased use of

screening, the incidence of DCIS has risen to account

for nearly 15% of all breast cancers, up from 3% to

4% in the 1970s and early 1980s [32]. What is

controversial about DCIS is how often it progresses

in the absence of treatment to become invasive

cancer. Several autopsy series in which women died

of causes other that breast cancer have reportedly

shown an incidence of occult DCIS between 0.2%

and 14%, which is higher than the incidence of breast

cancer diagnosed in the general population [33–36].

This has been cited as evidence that DCIS may not

progress to invasive disease [30]. Studies of women

in whom breast biopsy specimens were initially

interpreted as benign but later were classified as

DCIS and who were not treated further have shown

subsequent development of invasive disease in 20%

to 60% after prolonged follow-up [37–40].

Because it is impossible to determine which cases

of DCIS will progress to become invasive if untreated

and which will not, nearly all cases of DCIS are

treated aggressively with lumpectomy, usually com-

bined with radiation, or with mastectomy. It has been

argued that many women, particularly younger

women in whom DCIS is more likely to be diagnosed,

C.H. Lee / Radiol Clin N Am 40 (2002) 395–407 397

undergo treatment that may be unnecessary. This

argument ignores the fact that occult DCIS uncovered

at autopsy may be a different disease from that

detectable mammographically. Similarly, the women

in whom DCIS was treated by biopsy alone had small,

low-grade tumors that were initially considered

benign. None had the comedo form of DCIS. The

solution to possible overtreatment of some patients

with DCIS is the development of ways to distinguish

those cases that will progress to invasive disease from

those that will not rather than to stop diagnosing DCIS

by avoidance of screening mammography.

Finally, in the most recent meta-analyses of the

RCTs specifically concerning the 40- to 49-year-old

age group, statistically significant reductions in breast

cancer mortality were found [40,41]. In one of these

analyses, an 18% reduction in mortality was found

after an average of 12.7 years of follow-up [40]. In the

second, a 16% mortality reduction was observed after

10 to 14 years of follow-up [41]. Despite these results,

controversy remains. Summaries of guidelines for

screening mammography of various medical organi-

zations in the United States are presented in Table 2,

and national policy concerning screening mammogra-

phy of several foreign countries is outlined in Table 3.

When should screening stop?

Although there has been much debate about when

regular screening mammography should start, rel-

atively little attention has been paid to when it should

end. Only 2 of 8 large RCTs examining screening

efficacy included women older than 69, and the

number of women 70 and older included in these

trials is insufficient to make meaningful conclusions

as to the value of mammographic screening in this age

group. Despite the lack of information, and perhaps

because of it, most guidelines for mammographic

screening issued by professional societies in the

United States do not specify an age limit after which

screening should cease (Table 4). The recommended

upper age limit for screening in several foreign coun-

tries ranges from 59 to 74 years [45] (see Table 3).

The incidence of breast cancer in the United States

increases until approximately age 80 and plateaus

thereafter [46]. Nearly half of all cases of breast

cancer diagnosed annually occur in women aged 65

and older [47]. It has been shown that the sensitivity

and positive predictive value of mammography in

diagnosing breast cancer increases with increasing

age [24,32,48]; therefore, mammography would be

expected to be of benefit to older women. In a recently

reported retrospective cohort study of more than

690,000 women aged 66 to 79 years, the incidence

of metastatic breast cancer was reduced by 43% in the

Table 2

Current screening mammography guidelines of professional organizations in the United States

Organization

Age at which screening

should begin (y) Upper age limit Interval

American Cancer Society [42] 40 None Yearly

American College of Obstetricians

and Gynecologists [43]

40 None Every 1–2 y,

ages 40–49

Yearly starting

at age 50

American College of Radiology [44] 40 None Yearly

National Cancer Institute [15] 40 None Every 1–2 y

United States Preventive Services Task Force [16] 50 None Every 1–2 y

Based on women at average risk for breast cancer.

Table 3

Screening mammography guidelines in foreign countries

Country

Lower age

limit (y)

Upper age

limit (y) Interval

Australia 40 69 Every 2 y

Denmark 50 69 Every 2 y

Finland 50 59 Every 2 y

France 50 65–69 Every 2–3 y

Hungary 50 64 Yearly

Israel 50 74 Every 2 y

Italy 50 69 Every 2 y

Japan 30 None Yearly

The Netherlands 50 69 Every 2 y

Sweden 40–50a 64–74a Every 18 mos

for ages 40–49,

Every 2 y for 50

and older

United Kingdom 50 64 Every 3 y

Adapted from Shapiro S, Coleman EA, Broeders M, et al.

Breast cancer screening program in 22 countries: current

policies, administration and guidelines. Int J Epidemiol

1998;27:735–742; with permission.a Recommended ages for screening decided by each

county.

C.H. Lee / Radiol Clin N Am 40 (2002) 395–407398

screened versus the non-screened population [47].

Although actual mortality from breast cancer could

not be gauged from this study, metastatic breast

cancer seems a reasonable surrogate for mortality,

and this study confirms the effectiveness of screening

in the older age group. At what point the potential

benefit of screening of the elderly is outweighed by

the disadvantages of cost and the inconvenience and

morbidity associated with additional testing generated

by an abnormal screening examination is still a matter

of debate [49–51].

In a cost-effectiveness analysis of screening

women aged 70 to 79 years, three screening strategies

were compared [52]. In these strategies, the fact that

breast cancer risk is lower in older women with low

bone mineral density (BMD) was taken into account

[53]. In the first strategy, all women aged 65 to 69

years underwent biennial screening. In the second,

biennial screening was performed from ages 65 to 69;

BMD was then measured, and continued biennial

screening was performed only for women whose

BMD was in the top three quartiles. In the third

strategy, all women were screened biennially from

ages 65 to 79. It was assumed that screening would

reduce breast cancer mortality by 27%. It was found

that continuing to screen only those women with

BMD in the top three quartiles beyond age 69 would

prevent 9.4 deaths and gain 2.1 days of life expect-

ancy at a cost of $66,773 per year of life saved.

Compared to stopping at age 69, continuing to screen

all women to age 79 years would prevent an addi-

tional 1.4 deaths and add 7.2 hours of life expectancy

at an incremental cost of $117,689 per year of life

saved. It must be kept in mind that the numbers of

added life expectancy are averaged over the entire

study population—most of whom will not have breast

cancer. Therefore, the benefit in terms of increased

longevity to the individual woman with cancer could

be substantial. The investigators of this study con-

cluded that women’s preferences of a small gain in

life expectancy, balanced with the potential harms of

screening, should be taken into account in the

decision to screen for breast cancer.

The preceding analysis presumes the same life

expectancy for all women of the same age. Women

in average health aged 70 to 74 years can expect to

live an additional 13.4 years [46]. Life expectancy for

women aged 75 to 79 in average health is approx-

imately 10 years; it is nearly 8 years for women aged

80 to 84 and 6.6 years for women aged 85 and older

[46]; however, women of these ages who have health

problems might have a substantially shorter life

expectancy. In one study of 3-year survival among

women aged 40 to 84 with breast cancer, it was shown

that women with three or more of seven identified

comorbid conditions (myocardial infarction, other

types of heart disease, diabetes, other types of cancer,

and respiratory, gallbladder, or liver disease) were 20

times more likely to die of causes other than breast

cancer regardless of the breast cancer stage [54].

The health status of women older than 70 is

variable, and some women of that age and older

may have many years of longevity. Conversely, it

has been shown from the RCTs that it takes approx-

imately 5 years for the benefit of mortality reduction

from screening to become evident [52], and if comor-

bid conditions make survival for that length of time

unlikely, screening mammography may not be a wise

choice. Therefore, universal upper age limits for

screening mammography may not be justified. In

deciding who should be screened, it seems reasonable

to take into account a woman’s life expectancy based

on age and co-morbid conditions and an individual

woman’s preference regarding the potential benefit of

diagnosing an occult breast cancer versus the dis-

advantage of additional testing that screening mam-

mography may generate.

What is the optimal screening interval?

As can be seen from the various screening rec-

ommendations, there is no consensus on the optimum

interval between screenings, particularly for women

younger than 50. Lengthening the time between

screening results in more interval cancers, that is,

those detected between screenings. It has been shown

that cancers in younger women tend to grow more

Table 4

Summary of randomized controlled trial results for women

aged 40 to 49 years

Study

Ages

included in

analysis (y)

Years of

follow-up

Relative risk

(95% confidence

interval)

HIP 40–49 18 0.77 (0.53–1.11)

Edinburgh 45–49 12.6 0.81 (0.54–1.20)

Kopparberg 40–49 15.2 0.67 (0.37–1.22)

Ostergotland 40–49 14.2 1.02 (0.59–1.77)

Malmo 45–49 12.7 0.64 (0.45–0.89)

Stockholm 40–49 11.4 1.01 (0.51–2.02)

Gothenberg 39–49 12 0.56 (0.32–0.98)

CNBSS1 40–49 10.5 1.14 (0.83–1.56)

All studies — — 0.82 (0.71–0.95)

CNBSS = Canadian National Breast Screening Study.

Adapted from Hendrick RE, Smith RA, Rutledge JH, et al.

Benefits of screening mammography in women aged 40–49:

a new meta-analysis of randomized controlled trials. Monogr

Natl Cancer Inst 1997;22:87–92; with permission.

C.H. Lee / Radiol Clin N Am 40 (2002) 395–407 399

rapidly than cancers in older women [20]. Therefore,

it is postulated that the screening interval in the RCTs,

which was generally 18 to 24 months, was too long to

allow early detection of faster growing tumors,

thereby decreasing the realized benefit from screen-

ing in the 40-to 49-year age group [55,56].

It has also been shown that interval cancers are

more likely to be of higher nuclear grade and, in

women in their 40s, less likely to be small and node-

negative than screen-detected cancers [56]. Finally, in

a study of the sensitivity of first screening mammog-

raphy as a function of age and breast density, Kerli-

kowski et al [32] reported that the sensitivity of

screening mammography decreased from 83% to

71% when the interval from a previously normal

mammogram increased from 13 to 25 months. Sur-

prisingly, in their series, breast density in women aged

40 to 49 years did not significantly affect sensitivity of

screening mammography. In a study of screening

mammography in women aged 65 and older, it was

found that annual screening diagnosed tumors that

were significantly smaller and of lower stage than did

biennial screening [57]. These data argue for a shorter

(ie, 12-month) rather than longer screening intervals,

particularly for younger women.

Screening of high-risk women younger than 40

For young women who are at high risk for breast

cancer because of a history of breast cancer or a

biopsy-proven diagnosis of lobular carcinoma in situ,

annual mammography begins after the diagnosis is

made. Controversy remains regarding screening

guidelines for other young women at increased risk

for breast cancer, including those with a significant

family history of breast cancer, those who have

mutations for the BRCA-1 or BRCA-2 gene, and

women with a history of Hodgkin’s disease treated

with radiation.

Women who have a first-degree relative with

breast cancer are at approximately twice the risk of

women who do not [58]. This risk increases with

the number of first-degree relatives affected and

with decreasing age at diagnosis in the relative

[58]. For carriers of the BRCA-1 mutation, the risk

for breast cancer has been reported to be approxi-

mately 3% by age 30, 19% by age 40, 50% by age

50, 54% by age 60, and 85% by age 70 [59].

The risk for women with the BRCA-2 gene is similar

[60]. Unfortunately, no data on the efficacy of

screening these high-risk women with mammo-

graphy exist. Because there is such a high risk at

a relatively young age, however, many experts re-

commend that regular screening with breast self-

examination, clinical breast examination, and annual

mammography begin at an early age [61–64].

A survey was performed of 16 clinics run by the

European Familial Breast Cancer Collaborative

Group in 9 European countries (Denmark, Finland,

France, Germany, Italy, The Netherlands, Norway,

Sweden, and the United Kingdom) to determine

recommended surveillance protocols for women at

high risk [65]. Fourteen of the 16 recommended that

surveillance be performed for women with a lifetime

risk for breast cancer that was more than double that

of the general population. All 16 centers recom-

mended that for women at high risk, regular mam-

mography be performed, but the age at which

screening with mammography should begin varied

from 25 to 35 years. In six centers, the recommenda-

tion was for screening to start 5 years before the

earliest age of breast cancer diagnosis in the family.

There was similar disagreement among the centers

as to the recommended interval for screening (1 or

2 years). In the United States in 1997, a consensus

statement concerning recommendations for surveil-

lance of women with BRCA-1 and BRCA-2 mutations

was issued by a task force convened by the Cancer

Genetics Studies Consortium [61]. They recom-

mended annual mammography screening of this

population beginning at age 25 to 35 years. They

cautioned, however, that this recommendation was

based on expert opinion only and that the risks and

benefits of annual mammography in women younger

than 50 has not been proved. Those who disagreed

with this consensus recommendation cited the pos-

sibility of increased radiation risk in women with the

BRCA-1 and BRCA-2 mutations because of impaired

DNA repair capabilities [66,67].

In Canada and the United Kingdom, studies on

screening mammography in high-risk women under

the age of 50 report success in detecting early cancers

[62]. However, the reported numbers are small, and

the women studied were generally in their 40s. Larger

studies and those including younger women at high

risk will be needed before definitive data are available

on the efficacy of screening mammography in

decreasing mortality in these women. Until then,

expert opinion, without the benefit of supporting

data, recommends screening women who have a

significant family history for breast cancer and

screening those with mutations for the BRCA-1 and

BRCA-2 genes beginning at age 25 to 35, or 5 to 10

years younger than the earliest age of diagnosis of an

affected relative, but not before age 25 [62].

In addition to women with a genetic predisposi-

tion for breast cancer, it has been shown that women

C.H. Lee / Radiol Clin N Am 40 (2002) 395–407400

previously treated for Hodgkin’s disease with mantle

radiation are at a significantly increased risk for

breast cancer after a latency period [68–71]. Because

Hodgkin’s disease occurs in children, adolescents,

and young adults, the age of onset of breast cancer

in this group of women can be quite young. The risk

for subsequent development of breast cancer appears

to be highest among women who were treated

between age 10 and age 30 years [68]. In one report,

the relative risk for women treated before the age of

15 was 136 times that of the general population [70].

Other series have reported a relative risk of 2 to 75

times that of the general population [68–71]. The risk

for breast cancer in women older than 30 at the time

of treatment of Hodgkin’s disease does not appear to

be significantly increased [68,70]. The latency period

before breast cancer is diagnosed in women treated

with mantle radiation has been reported to be between

4 and 34 years, with a median of approximately 15 to

18 years [68].

Mammography has been shown to be successful

in detecting breast cancer in women previously

treated for Hodgkin’s disease, despite the young age

of many of these women [71,72]. In one series

reported by Tardivon et al [71], the average age at

diagnosis among 23 women was 40 years (range, 23

to 70 years). In a series of 27 women reported by

Dershaw et al [72], the average age was 47 years.

Both these reported means are significantly younger

than the mean age for breast cancer occurrence in the

general population, which is 57 years [72]. In addi-

tion, 55% of the women in the series by Dershaw et al

[72] were younger than 45 years, and 31% were

younger than 40 years. The mean latency period for

both studies was 18 years, with ranges in the two

studies between 15 months and 35 years. Both studies

reported that mammography had a sensitivity of 90%

for depicting malignancy (52 of 58 cancers, com-

bined). Of the total of 58 cancers in the two studies,

18 (31%) were not palpable and were detected only

by mammography. The cancers occurred most com-

monly in the upper outer quadrant of the breast and

were equally divided in laterality.

Although these studies demonstrate that mam-

mography is indeed useful for detecting breast cancer

in women previously irradiated for Hodgkin’s dis-

ease, no data support the efficacy of screening young

women in this population. However, based on the

data of incidence and latency of breast cancer in

these women, it has been recommended that these

women undergo careful surveillance for the devel-

opment of breast cancer, including annual screening

mammography beginning 8 to 10 years after the

radiation exposure.

Accuracy of screening mammography

The overall accuracy of mammographic inter-

pretation, in terms of sensitivity and specificity, has

been another area of controversy surrounding the

issue of screening mammography. False-negative

and false-positive interpretations have been called

risks of screening mammography and have been cited

as reasons against routine screening of various pop-

ulations of women [73–75].

Observer variability

Observer variability in mammographic interpreta-

tion has generated controversy in recent years. Several

studies have reported variability that is sometimes

‘‘substantial’’ among radiologists’ interpretation of

screening mammograms [76–80]. All the studies

were enriched with more abnormal cases than would

be found in a normal screening population, and in all

but one, only two views of each breast were supplied

without previous films for comparison. In all but one

of the studies, the participating radiologists were

asked to make recommendations and final assess-

ments based only on the two views in each case.

In the study by Elmore et al [79], 10 radiologists of

varying levels of experience and numbers of mammo-

grams interpreted yearly in their practices were asked

to read 150 selected cases. The radiologists were asked

to make management recommendations and to give a

diagnostic interpretation for each case. The choices for

management recommendation included routine mam-

mography in 1 year, another mammogram within

6 months, or immediate follow-up, which could con-

sist of additional mammographic views, ultrasound, or

biopsy. The choices for diagnostic interpretation were

normal, abnormal – probably benign, abnormal –

indeterminate, and abnormal–suggestive of cancer.

The management recommendations and diagnostic

interpretations were not linked so a radiologist could

potentially choose a recommendation of biopsy but

indicate an interpretation of abnormal –probably

benign if he or she thought the likelihood of a positive

result was low. The agreement among the 10 radiol-

ogists was found to be moderate (k values of 0.47

for diagnostic interpretation and 0.49 for biopsy

recommendation). Sensitivity for cancer cases

(defined as a recommendation of immediate work-

up) ranged from 74% to 96%. Elmore et al [79]

concluded that ‘‘radiologists can differ, sometimes

substantially, in their mammographic interpretations

and recommendations for management’’ (p. 1478).

This study, however, and the others that are

similar to it have several flaws in study design.

C.H. Lee / Radiol Clin N Am 40 (2002) 395–407 401

Among the major criticisms is the fact that asking

radiologists to reach a diagnostic impression for

findings based on only the two standard views of

the breast does not reflect actual clinical practice. In

addition, the methods used for data analysis in the

study by Elmore et al [79] and others tended to

exaggerate the amount of variability actually ob-

served. For example, in the report by Elmore et al

[79], substantial diagnostic disagreement occurred in

only 2% of pair-wise comparisons. In addition, in a

study reported by Kerlikowske et al [80], an assess-

ment of ‘‘suspicious abnormality’’ was considered to

be in disagreement with an assessment of ‘‘highly

suggestive of malignancy’’. In actual practice, how-

ever, both these assessments would likely lead to a

similar outcome for the patient, which would be

biopsy. In the study by Berg et al [77], which is the

only evaluation of observer variability in which

work-up views and previous films were supplied,

the k statistic for agreement in final assessment was

poor at 0.38. However, the five participating radiol-

ogists recommended further evaluation or biopsy for

between 21 and 22 of the 23 cancer cases in the

series, suggesting that they did not miss the cancers

even though their final assessments disagreed.

The discrepancy between the artificial testing

situation of the reported studies on observer variabil-

ity and performance in actual clinical practice was

confirmed by a study reported by Rutter and Taplin

[81]. They found that there was moderate correlation

in radiologists’ tendency to call an examination

positive in both the testing and the clinical setting

but that test performance did not correlate with actual

clinical accuracy. They cautioned against extrapol-

ating the results from one setting to the other.

In the field of diagnostic radiology, the interpreta-

tion of mammograms is particularly challenging

because there is no standard anatomy of the breast,

there is wide variability in what constitutes a normal

examination and the overlap between the appearance

of benign and malignant lesions is large. Clearly,

there is variability in the interpretation of mammo-

grams among radiologists; however, it has been

demonstrated that screening mammography reduces

breast cancer mortality despite this variability. Per-

haps the take-home message from the studies of

observer variability in mammography should be that

individual radiologists who interpret mammograms

should track their results, as is now recommended

within the mandates of the Mammography Quality

Standards Act, and strive to improve performance

with the help of this feedback. It should be empha-

sized, however, particularly to the lay public, that

despite observer variability in interpretation, screen-

ing mammography has been demonstrated to reduce

mortality from breast cancer.

False-negative interpretations

False-negative interpretations have been cited as a

risk of screening mammography because they might

give ‘‘false reassurance’’ to women. It is argued that

if a woman with undiagnosed breast cancer has

screening examination results falsely interpreted as

normal, she may not seek attention for symptoms that

subsequently develop, possibly delaying diagnosis

[75,82]. It has also been stated that if a woman

knows she is scheduled to have a screening examina-

tion in the future, she may not seek immediate

attention for a symptom and may wait instead for

the mammogram to be performed, again potentially

delaying diagnosis [82]. Although these scenarios are

certainly possible, it has not been established how

often they occur or to what extent they contribute to

the efficacy of screening mammography in decreas-

ing breast cancer mortality.

In a meta-analysis of the published RCTs and

large case-control studies of screening mammography

reported by Mushlin et al [83] in 1998, the sensitivity

ranged from 83% to 95%. These investigators found

the reported sensitivity in these studies to be approx-

imately 10 percentage points lower in women

younger than 50 years of age and suggest that this

decreased sensitivity may partially explain the de-

creased effectiveness of screening in these younger

women. On the other hand, a review of more than

183,000 screening mammograms performed in New

Mexico found no statistically significant difference in

screening sensitivity among women aged 40 to 49

years compared with those 50 and older [29].

False-negative interpretations are caused by a

variety of reasons. Mammograms may be truly nega-

tive despite the presence of breast cancer because the

malignancy may be obscured by overlying dense

parenchyma or because a noncalcified tumor may

not form a visible mass or distortion, as is sometimes

seen with invasive lobular carcinoma [23]. False-

negatives may also result from poor mammographic

technique, causing the malignancy to be undetectable

[19]. Breast cancer may be overlooked by the inter-

preting radiologist or mistakenly classified as benign

[19]. Finally, false-negative mammograms can occur

because rapidly growing cancers may be below the

detection threshold at the time of the mammogram

but may grow to become palpable before the next

screening examination is performed [55]. Some of

these reasons are potentially avoidable or correctable.

Strict attention to maintaining optimum mammo-

C.H. Lee / Radiol Clin N Am 40 (2002) 395–407402

graphic technique, double reading, computer-aided

detection, participation in continuing education in

mammographic interpretation, optimizing mam-

mographic technique, and decreasing the interval

between screening examinations may all serve to de-

crease the false-negative rate [19,55,84–88]. Some

level of false-negative interpretation, however, is

unavoidable and is inherent in the nature of x-ray

mammography. Despite the fact that mammography

has a less than perfect sensitivity for the detection of

breast cancer, it has been shown to reduce mortality

from this disease, and to call the possibility of a false-

negative interpretation a ‘‘risk’’ of the procedure

seems unwarranted.

False-positive interpretations

Because screening mammography is just that, a

screening tool to separate women with normal exam-

ination results from all others, screening will gen-

erate the need for additional evaluation in women

with inconclusive, indeterminate, or suspicious find-

ings on the screening examination. These women

will be recalled for additional testing, such as extra

mammographic views, ultrasound, or biopsy. When

recalled examinations do not lead to a diagnosis of

cancer, they have been termed ‘‘false positives’’ by

most of the reports. The issue of false-positive

interpretations is another source of controversy con-

cerning screening mammography that has received

much attention recently.

The recall rate associated with screening mam-

mography varies among reports. In a recent meta-

analysis of the large RCTs and case-controlled studies

of screening efficacy, most of which were performed

in Europe, recall rates varied between 1% and 6.5%

[83]. Review of several community-based practices in

the United States revealed recall rates that varied

between 3% and 57% with a mean of 11% overall

[85]. Other reports from community and academic

practices in the US report recall rates of approxi-

mately 6% to 8% [87,89–91]. Most of these recalls

do not result in a diagnosis of breast cancer and can

therefore be termed false-positive.

Elmore et al [92], in a retrospective study of

nearly 10,000 screening mammograms performed

on 2400 women, estimated the cumulative 10-year

risk of a false-positive mammogram to be 49.1% and

the number undergoing benign biopsy because of a

mammographic abnormality to be 18.6% [92]. These

figures were extrapolated to yield a 10-year estimated

risk. In actuality, the average number of mam-

mograms performed per patient in their study was

four. The authors cited the increased cost, anxiety,

and possible morbidity associated with these false-

positive readings.

In a follow-up to this study by Christiansen et al

[73] using the same cohort of women, factors con-

tributing to the risk of a false-positive screening

mammogram were described. The risk increased with

number of breast biopsies, family history of breast

cancer, estrogen use, time between screenings, lack of

comparison mammograms, and tendency of the inter-

preting radiologist to call mammogram results abnor-

mal. Many of these factors are also associated with an

increased risk for true-positive examination results.

Risk for false-positive mammogram results decreased

with increasing age. The estimated 10-year cumulat-

ive risk ranged from 5% for those women at lowest

risk for a false-positive reading to 100% with highest-

risk variables. Both this report and that of Elmore

et al [92] cite psychological distress as a problem

associated with false-positive mammographic inter-

pretations. However, a review of several studies

evaluating the psychological impact of abnormal

screening mammogram results in women without

breast cancer reported that the most common con-

sequence was anxiety, which can be considered a

normal reaction to the situation [93]. Although the

adverse psychological consequences of a false-pos-

itive screening mammogram have been emphasized

by some, other studies have reported that this anxiety

is short-lived and does not prevent women from

returning for future screening mammograms [94–

98]. Most significantly, a survey of attitudes regard-

ing false-positive results conducted among 479

American women showed that 99% were aware that

false-positives occurred and that 63% thought 500

false-positives to save one life would be acceptable

and 37% thought that 10,000 false-positives per life

saved was an acceptable number [99]. Therefore, it

seems the perception of false-positive interpretations

as a serious risk associated with screening mammog-

raphy is greater for some health professionals than for

the general public.

The report by Elmore et al [92] that by Christian-

sen et al [73] call for efforts to decrease the false-

positive rate of screening mammography. Although

certainly a desirable goal, neither addresses the issue

of trade-off between sensitivity for detecting breast

cancer and recall rate. Indeed, the study on observer

variability by Elmore et al [79] showed that the

radiologist with the highest sensitivity for calling

cancer cases abnormal also had the highest false-

positive rate. Elmore et al [92] call for ways to reduce

false-positive interpretations to decrease the associ-

ated psychological and economic costs. They propose

immediate work-up of abnormal screening examina-

C.H. Lee / Radiol Clin N Am 40 (2002) 395–407 403

tions to decrease anxiety. However, this practice,

while beneficial, is impractical in many clinical set-

tings because of equipment and personnel constraints

and could lead to increased cost associated with

screening mammography [100].

Christiansen et al [73] suggest that an equation

could be developed to predict a woman’s risk for a

false-positive mammogram. This could be used, they

state, along with predictive models for the same

woman’s risk for breast cancer, such as the Gail

model [101], and the woman can then decide whether

to undergo screening. This proposal ignores the fact,

however, that the woman would be comparing her

risk of a recall that might involve nothing more than

having a few additional mammographic views or

ultrasound against the risk of having breast cancer

and the possible benefit of early detection.

The other proposal by Elmore et al [92] that

women be educated about their chances of having

abnormal screening results and the small likelihood

that such a recall will result in a diagnosis of ma-

lignancy, seems the best solution to the perceived

problem of false-positive screening mammograms,

especially given the fact that it appears that many

women would tolerate many more false-positives to

detect one breast cancer than it currently takes.

False-positive mammographic interpretations

occur despite efforts to eliminate them. Perhaps the

best way of dealing with false-positive results is to try

to minimize them by having prior mammograms

available for comparison at the time of interpretation,

by emphasizing to patients that recalls are a possibil-

ity and that most do not lead to a diagnosis of breast

cancer, and by performing the needed evaluation in

recalled women in a timely fashion.

Summary

Screening mammography, despite its limitations,

remains the best means for diagnosing breast cancer in

asymptomatic women. Regarding the continuing con-

troversies concerning the age at which screening

should start, evidence supports beginning regular

screening at age 40 in women at average risk [12,

24,26,40,41]. Similarly, evidence suggests that the

screening interval should be yearly, especially in

younger women [43,55]. Rather than an arbitrary

age at which screening should stop, the decision on

screening elderly women should be made on an

individual basis, taking into account level of health

and life expectancy. More work needs to be done on

determining the optimum screening strategies for

high-risk women. As to the interpretation of screening

mammography, a certain level of observer variability

and of false-negative and false-positive readings are

inherent in the process. These should be kept to a

minimum through efforts by the interpreting radiolo-

gist to improve performance through auditing of

individual results and continuing education. The

impact of double reading and computer-aided detec-

tion in the interpretation of screening mammograms

warrants further evaluation in terms of efficacy and

cost-effectiveness.

Despite these continuing controversies, mortality

from breast cancer in the United States has been

decreasing steadily for the past 25 years [17]. The

magnitude of the decrease has been reported to range

from 8% to 25% [18,102]. Although some of this

decrease may be attributable to improvements in the

treatment of breast cancer, early detection through

screening mammography has undoubtedly played a

role in this mortality reduction. The controversies that

surround the issue of screening should not detract

from the fact that screening mammography has

proved to save lives.

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C.H. Lee / Radiol Clin N Am 40 (2002) 395–407 407

Breast imaging reporting and data system (BI-RADS)

Laura Liberman, MD*, Jennifer H. Menell, MD

Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA

The Breast Imaging Reporting and Data System

(BI-RADS) lexicon was developed by the American

College of Radiology (ACR) to standardize mammo-

graphic reporting [1–3]. The lexicon includes terms

for describing breast parenchymal patterns, features of

masses and calcifications, associated findings, and

final assessment categories. Potential benefits of the

lexicon include increased clarity in reporting, im-

proved communication, and facilitation of research,

particularly across different institutions. This article

reviews the terms defined in the BI-RADS lexicon for

mammography, describes strengths and limitations of

the lexicon, and discusses the preliminary work relat-

ing to the development of standardized lexicons for

breast sonography and breast MRI.

BI-RADS lexicon for mammography

The BI-RADS lexicon describes four classes of

breast parenchymal density: class 1, almost entirely

fat; class 2, scattered fibroglandular densities; class 3,

heterogeneously dense; and class 4, dense (Fig. 1). A

mass is defined as a space-occupying lesion seen in

two different projections; if a potential mass is seen in

only a single projection, it should be called a density

until its three-dimensionality is confirmed. Mass

margins are described as circumscribed, microlobu-

lated (undulate in short cycles), obscured (hidden by

superimposed adjacent tissue), indistinct (poor def-

inition not caused by superimposed tissue, raising the

possibility of infiltration of the lesion into adjacent

tissue), and spiculated (lines radiate from the mar-

gins) (Fig. 2). Mass shape can be described as round,

oval, lobular, or irregular. Architectural distortion is

shape with radiating spicules but no definite mass

visible (Fig. 3). Mass density can be described as

high, equal, low, or fat containing.

The lexicon also defines special cases, including:

intramammary lymph node (typically reniform or

with radiolucent notch because of fat in the hilum,

most often seen in the upper outer quadrant) (Fig. 4);

solitary dilated duct (usually of minor significance

unless it represents an interval change from prior

mammograms); asymmetric breast tissue (judged rel-

ative to the corresponding area in the contralateral

breast, usually a normal variant, but may be important

when it corresponds to a palpable asymmetry); focal

asymmetric density (a density that cannot be accu-

rately described using the other shapes, could repre-

sent an island of fibroglandular tissue, but may

warrant additional evaluation)

The lexicon defines specific terms to describe the

shapes (morphology) of calcifications and the pat-

terns in which they are arrayed in the breast pa-

renchyma (distribution). Morphologic descriptors are

typically benign, intermediate concern, and higher

probability of malignancy. Typically benign calcifi-

cations include skin, vascular, coarse or popcorn-

like, large rod-like, round (or punctate if smaller

than 0.5 mm), lucent-centered, eggshell or rim, milk

of calcium, suture, and dystrophic (Fig. 5). Inter-

mediate concern calcifications are amorphous or

indistinct; these calcifications are often round or

‘‘flake’’ shaped and are sufficiently small or hazy

that a more specific morphologic classification can-

not be determined. Calcifications with a higher

probability of malignancy include pleomorphic or

heterogeneous calcifications (formerly called granu-

lar) and fine linear or fine, linear, branching (cast-

ing) calcifications (Fig. 6). The distribution of

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00017 -3

* Corresponding author.

E-mail address: libermal@mskcc.org (L. Liberman).

Radiol Clin N Am 40 (2002) 409–430

calcifications has been described as grouped or clus-

tered (multiple calcifications in less than 2 mL tissue),

linear, segmental (suggesting deposits in a duct), re-

gional (large volume not necessarily conforming to a

duct distribution), diffuse/scattered (random distri-

bution), or multiple.

In addition, the lexicon defines associated find-

ings, used with masses or calcifications or alone when

no other abnormality is present, including skin or

nipple retraction, skin or trabecular thickening, skin

lesion, axillary adenopathy, or architectural distortion.

The lexicon suggests that the location of the lesion be

Fig. 1. Breast parenchymal density as seen on mediolateral oblique view mammograms. (A) Fatty (ACR class 1); (B) Mildly

dense (ACR class 2); (C) Moderately dense (ACR class 3); (D) Dense (ACR class 4).

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430410

expressed by indicating the side (left, right, or both),

the location (according to the face of the clock and

subareolar, central, or axillary tail, if appropriate) and

the depth of the lesion (anterior, middle, or posterior).

Perhaps most important, the lexicon defines

assessment categories to describe the radiologist’s

level of suspicion regarding the mammographic find-

ing (Table 1). As of April 1999, it has been required

by law that all mammography reports in the United

States contain a BI-RADS assessment category, with

its description in layman’s terms. Note that although

there are six assessment categories, there are only

four possible outcomes: additional imaging studies

(category 0), routine annual mammography (category

1 or 2), 6-month follow-up (category 3), and biopsy

(category 4 or 5).

Potential usefulness of the lexicon

Final assessment categories

Final assessment categories of the BI-RADS lex-

icon are useful predictors of malignancy. In three

published series, the frequency of carcinoma was

significantly higher for BI-RADS category 5 (highly

Fig. 2. Mass margin characteristics as defined by the BI-RADS lexicon. (A) Circumscribed mass, shown to be a simple cyst at

sonography. (B) Partially obscured mass; sonography showed as simple cyst. (C) Microlobulated mass corresponding to palpable

lump denoted by radiopaque skin marker; biopsy showed infiltrating ductal carcinoma and ductal carcinoma in situ (DCIS). (D)

Spiculated mass; biopsy showed infiltrating ductal carcinoma and DCIS.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 411

suggestive of malignancy) than for category 4 (sus-

picious), ranging from 81% to 97% for category 5

versus 23% to 34% for BI-RADS category 4 (Table 2)

[4–6]. Liberman et al [5] found a significantly higher

frequency of carcinoma among category 5 than among

category 4 lesions for all mammographic findings and

all interpreting radiologists.

Except for some guidelines regarding calcification

morphology, the lexicon does not explicitly state

which mammographic features should be included

in the different final assessment categories. Analysis

of the descriptive terms of the lexicon, however,

allows some recommendations to be made. In an

analysis of 492 lesions that had needle localization

and surgical biopsy, Liberman et al [5] found that the

features with highest positive predictive value for

masses were spiculated borders and irregular shape

(Table 3). For calcifications, they were linear mor-

phology and segmental or linear distribution (Table 4).

On the basis of this finding, they recommended that

these findings warrant a designation of category 5.

Further study is needed to better define the mammo-

graphic patterns with the highest positive predictive

value and those that have the highest likelihood of

representing benign disease.

BI-RADS category 3: probably benign

A potential advantage of the lexicon is precise

definition of lesions that are probably benign, allow-

ing women with probably benign lesions the option

of mammographic surveillance rather than biopsy.

Few studies have addressed the frequency of a BI-

RADS category 3 (probably benign) designation.

Caplan et al [7] reported that 7.7% of 372,760

mammograms performed as part of the National

Breast and Cervical Cancer Detection Program were

classified as category 3. They found the probability of

receiving a category 3 classification was higher in

women who were young, symptomatic, or had abnor-

mal findings on clinical breast examinations. They

also reported that the percentage of mammograms

classified as category 3 by state or tribal organization

ranged from 1.4% to 14.0%, suggesting variability

among radiologists in using this BI-RADS code for

probably benign lesions.

Fig. 3. Spiculated architectural distortion at mammography (straight arrow), corresponding to a vaguely palpable thickening

denoted by radiopaque skin marker. Biopsy yielded infiltrating lobular carcinoma. There was an adjacent lobulated mass with

coarse calcification (curved arrow), stable from prior years and consistent with a benign fibroadenoma.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430412

Although one series in the surgical literature noted

that almost half the lesions referred for biopsy were in

category 3 (probably benign) [4], published studies in

the radiology literature indicate that approximately

70% of lesions referred for biopsy are in category 4

and that approximately 20% are in category 5, with

only a small number of category 3 lesions referred for

biopsy [5,6]. Several studies published before and

after introduction of the BI-RADS lexicon support

the use of short-term follow-up mammography for

probably benign lesions.

Sickles [8] prospectively evaluated the value of

short-term follow-up mammography in 3184 pa-

tients with baseline mammographic lesions classified

as probably benign in a study published before the

BI-RADS lexicon. Lesions were only classified as

probably benign after careful evaluation, including

magnification images. All probably benign lesions

were evaluated with a short-term follow-up mammo-

graphy protocol that included imaging the ipsilateral

breast 6 months after the initial mammogram, and

then both breasts 12, 24, and 36 months after the

initial mammogram, to document stability.

Of the 3184 probably benign lesions included in

the study, cancer was subsequently discovered in 17

(0.5%) [8]. Fifteen of the 17 cancers were diagnosed

by means of interval change at follow-up mammog-

raphy before they were palpable; all 17 were stage 0

or stage I at the time of diagnosis (one positive axillary

lymph node was present in two patients; one had

a circumscribed solid nodule and one had an asym-

metric area of fibroglandular tissue). Cancer was

discovered in 1 of 1234 (0.1%) clusters of round or

punctate calcifications, 12 of 589 (2%) solitary solid

circumscribed masses, 2 of 448 (0.4%) focal asym-

metric densities, 1 of 522 (0.2%) scattered or ran-

domly clustered calcifications, and 1 of 253 (0.4%)

multiple solid circumscribed nodules.

Sickles [9] has also addressed the question of

whether patient age or lesion size should prompt

immediate biopsy of nonpalpable, circumscribed,

solid nodules. Of 1403 cases included in this study,

cancer was found in 19 (1.4%). Only small differ-

ences in the frequency of cancer were found for

various patient age and lesion size subgroups. Even

in the group of women aged 50 and older, the

frequency of cancer was 1 of 560 (1.7%). These

data suggest that lesion size and patient age should

not deter from recommending short-interval follow-

up mammography for nonpalpable circumscribed

solid masses.

A second large-scale prospective study evaluating

the use of short-term follow-up for probably benign

lesions was published before the BI-RADS lexicon

Fig. 4. A benign intramammary lymph node (BI-RADS category 2). Note the notch corresponding to the fatty hilum.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 413

by Varas et al [10]. Probably benign lesions in this

study included single or multiple circumscribed

masses, multiple rounded, clustered, or scattered cal-

cifications within less than one quadrant of the breast,

and abnormal parenchymal opacities (areas of lo-

calized dense tissue, without definable margins or

architectural distortion, identified on two views).

Carcinoma was found in 9 of 535 (1.7%) probably

benign lesions, including 4 of 289 (1.4%) solitary

circumscribed masses, 4 of 104 (3.8%) lesions evident

as microcalcifications, and 1 of 54 (1.9%) abnormal

parenchymal opacities. Of the nine carcinomas iden-

tified, two were ductal carcinoma in situ (DCIS) and

seven were invasive carcinomas (including one DCIS

with microinvasion); two had positive axillary nodes.

These data also support the use of short-term follow-

up as an alternative to biopsy for probably benign

(BI-RADS category 3) lesions.

If short-term follow-up is selected, interval pro-

gression (increase in size of a mass or increase in

number of calcifications) at follow-up should prompt

a biopsy. In Sickles’ [8] study, carcinoma was iden-

tified in 15 of 131 (11%) biopsies performed for

mammographic progression; in the study of Varas

et al [10], 9 of 16 (56%) lesions that demonstrated

mammographic progression were found to represent

carcinoma. In both studies, no carcinomas were

identified in probably benign lesions that remained

Fig. 5. Typically benign calicifications. (A) Variety of benign calcifications: peripherally calcified oil cysts of fat necrosis, large

rod-like calcifications of secretory disease, and vascular calcifications. (B) Milk of calcium. Note the layering or ‘‘teacup’’

appearance of this 90� lateral magnification view (arrows). (C) Popcorn calcification typical of fibroadenoma. (D) Eggshell

calcifications associated with architectural distortion in area of postoperative fat necrosis.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430414

stable on follow-up mammography. Careful attention

to the follow-up protocol should allow us to detect

carcinoma at an early stage while minimizing the

number of benign biopsies.

In an update of data from the University of

California at San Francisco, Sickles [11] noted that

the frequency of cancer among probably benign

lesions was 0.7% (33 of 4533), with the likelihood

of malignancy 23 of 1692 (1.4%) for solid circum-

scribed masses, 3 of 502 (0.6%) for focal asymmetric

densities, 5 of 1338 (0.4%) for localized microcalci-

fications, 1 of 329 (0.3%) for multiple circumscribed

masses, 1 of 619 (0.2%) for generalized microcalcifi-

cations, and 0 (0%) for other miscellaneous findings.

With further update to 7484 probably benign lesions,

Sickles [11] reported carcinoma in 36 (0.5%). Of these

36 cancers found at periodic mammographic surveil-

lance, 6 (16.7%) were identified at the 6-month

follow-up mammogram, 2 (5.6%) by palpation bet-

ween 6 months and 1 year, 17 (47.2%) at the 1-year

mammogram, 2 (5.6%) by palpation between year 1

and year 2, 7 (19.4%) at the 2-year follow-up mammo-

gram, and 2 (5.6%) at the 3-year follow-up mammo-

gram. Thirty-five (97%) of these 36 cancers were

smaller than 2 cm at diagnosis, and 34 (94.4%) were

node-negative at the time of diagnosis; two each had

one positive node; none had distant metastases.

The potential benefits of short-term follow-up

mammography for probably benign lesions were

recently restated by Sickles [11]. He noted that 95%

Fig. 6. Calcifications with higher probability of malignancy. (A) Calcifications with linear morphology and linear distribution

(arrows). Biopsy yielded ductal carcinoma in situ (DCIS) with calcification. (B) Pleomorphic calcifications in segmental dis-

tribution. Biopsy yielded infiltrating ductal carcinoma and with calcifications present in DCIS. (C) Two clusters of pleomorphic

calcifications (arrows). Both yielded DCIS with calcifications at biopsy, and the patient was treated with mastectomy.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 415

of patients complied with at least half of the recom-

mended examinations in the follow-up protocol, and

50% completed the entire protocol. He also noted that

only approximately 2% of women chose biopsy rather

than follow-up. Compared to percutaneous core

biopsy, follow-up lowers the cost by a factor of 8,

with savings of $1040 per probably benign lesion; it is

also associated with lower patient stress. Although

existing data support that probably benign lesions can

be identified and safely managed with short-term

follow-up mammography, the management of BI-

RADS category 3 lesions continues to be debated [12].

Breast parenchymal density

Literature before the BI-RADS lexicon defined

different breast density parenchymal patterns and

evaluated the frequency of carcinoma among women

with different breast densities [13–15]. Analysis of

the impact of breast density on breast cancer incidence

are complicated by the inverse relationship between

age and breast parenchymal density and by the lower

sensitivity of mammography in women with dense

breasts. The BI-RADS lexicon potentially allows

standardization of reporting of breast parenchymal

density, facilitating further research in this area.

Dense breast tissue interferes with interpretation

of mammograms. Mandelson et al [16] evaluated

breast density as a predictor of mammographic detec-

tion. Mammographic sensitivity was 80% among

women with predominantly fatty breasts (ACR class

1) but 30% in women with extremely dense breasts

(ACR class 4). The odds ratio for interval cancer

among women with extremely dense breasts was 6.14

(95% confidence interval [CI], 1.95–19.4), compared

with women with extremely fatty breasts, after adjust-

ment for age at index mammogram, menopausal

status, use of hormone replacement therapy, and body

mass index. When only those interval cancer cases

confirmed by retrospective review of index mammo-

grams were considered, the odds ratio rose to 9.47

(95% CI, 2.78–32.3).

Although it remains controversial, it has been

suggested that mammographic density may be an

independent risk factor for development of breast

cancer. Satija et al [17] reviewed results of 82,391

screening mammograms among 36,495 women aged

40 to 80 with no history of breast cancer. They

found that ACR class 1 and 2 breasts, at age 40,

were associated with a relative risk of 0.39 with

respect to the general population at the same age,

whereas at age 80 the relative risk was 0.61. The

relative risk for ACR class 3 was 0.72 at age 40

Table 1

Assessment categories of the BI-RADS lexicon

Stage Result

0 Assessment incomplete. Need

additional imaging evaluation.

1 Negative. Routine mammogram

in 1 year recommended.

2 Benign finding. Routine mammogram

in 1 year recommended.

3 Probably benign finding. Short-interval

follow-up suggested.

4 Suspicious. Biopsy should

be considered.

5 Highly suggestive of malignancy.

Appropriate action should be taken.

Data from American College of Radiology. Breast Imaging

Reporting and Data System (BI-RADS). Reston, VA: College

of Radiology; 1995; with permission.

Table 2

Final assessment categories: number of lesions referred for biopsy and positive predictive value

BI-RADS category

Investigator 3 4 5

No. lesions referred for biopsy

Liberman [5] 8/492 (2) 355/492 (72) 129/492 (26)

Orel [6] 141/1312 (11) 936/1312 (71) 170/1312 (13)

Lacquement [4] 322/688 (47) 234/688 (34) 106/688 (15)

PPV

Liberman [5] 0/8 (0) 120/355 (34) 105/129 (81)

Orel [6] 3/141 (2) 279/936 (30) 165/170 (97)

Lacquement [4] 9/322 (3) 54/234 (23) 97/106 (92)

Numbers in parentheses are percentages.

PPV = positive predictive value, which is equal to the number of cancers divided by total number of lesions that underwent

biopsy in that category.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430416

and 1.13 at age 80. ACR class 4 was divided into

two groups with respect to risk, with the relative

risk for the densest pattern as high as 2.49 times

the risk of the patterns in the general population.

Additional study is necessary to further evaluate the

impact of breast density on mammographic inter-

pretation and breast cancer incidence and to assess

the use of computer-aided diagnostic techniques

in quantifying parenchymal density and its associ-

ated risk.

Computer-aided diagnosis

It has been suggested that computer-aided diag-

nostic techniques may assist in mammographic

interpretation, for lesion detection and for classifica-

tion. In particular, some investigators have proposed

the use of an artificial neural network (ANN), a

form of artificial intelligence that can be trained to

‘‘learn’’ essential information from a data set, may

improve the positive predictive value (PPV) of

Table 3

Frequency of carcinoma versus combinations of features: mass shape and margins

Mass shape

Mass margins Irregulara Round Lobulated Oval Distortion Total

Spiculatedb 45/54 (83) 6/6 (100) — 1/1 (100) 4/8 (50) 56/69 (81)

Indistinct 20/35 (57) 5/14 (36) 3/9 (33) 1/8 (13) — 29/66 (44)

Obscured — 2/3 (67) 1/3 (33) 0/3 (0) — 3/9 (33)

Microlobulated — 0/2 (0) 1/2 (50) 0/2 (0) — 1/6 (17)

Circumscribed 1/1 (100) 0/6 (0) 1/4 (25) 0/11 (0) — 2/22 (9)

Total 66/90 (73) 13/31 (42) 6/18 (33) 2/25 (8) 4/8 (50) 91/172 (53)

Data refer to lesions that were subject to surgical biopsy. Numbers in parentheses are percentages. Dash (—) indicates there were

no lesions with the specified combination of features.

Reprinted from Liberman L, Abramson AF, Squires FB, Glassman J, Morris EA, Dershaw DP. The Breast Imaging Reporting

and Data System: positive predictive value of mammographic features and final assessment categories. AJR Am J Roentgenol

1998;171:35–40; with permission.a Frequency of carcinoma was significantly higher for spiculated margins than for all other margin characteristics (56/69 =

81% versus 35/103 = 34%, P < 0.001, relative risk 2.4 [95% confidence intervals 1.8–3.2]).b Frequency of carcinoma was significantly higher for irregular shape than for all other shapes (66/90 = 73% versus 25/82 =

30%, P < 0.001, relative risk 2.4 [95% confidence intervals 1.7–3.4]).

Table 4

Frequency of carcinoma versus combination of features: calcification distribution and morphology

Calcification morphology

Calcification distribution Lineara Pleomorphic Amorphous Punctate Coarse Total

Segmentalb 10/10 (100) 7/12 (58) 0/1 (0) — — 17/23 (74)

Linearb 6/8 (75) 7/9 (78) — 0/2 (0) — 13/19 (68)

Multiple 1/1 (100) 4/6 (67) 0/2 (0) — — 5/9 (56)

Regional 0/1 (0) 4/9 (44) 2/3 (67) — — 6/13 (46)

Clustered 9/12 (75) 76/204c (37) 7/29 (24) 1/9 (11) 0/1 (0) 93/255 (36)

Diffuse — 0/1 (0) — — — 0/1 (0)

Total 26/32 (81) 98/241 (41) 9/35 (26) 1/11 (9) 0/1 (0) 134/320 (42)

Data refer to lesions that were subject to surgical biopsy. Numbers in parentheses are percentages. Dash (—) indicates there were

no lesions with the specified combination of features.

Reprinted from Liberman L, Abramson AF, Squires FB, Glassman J, Morris EA, Dershaw DD. The Breast Imaging Reporting

and Data System: positive predictive value of mammographic features and final assessment categories. AJR Am J Roentgenol

1998;171:35–40; with permission.a Frequency of carcinoma was significantly higher for linear morphology than for all other morphologies (26/32 = 81%

versus 108/288 = 38%, P< 0.001, relative risk 2.2 [95% confidence intervals 1.8–2.8]).b Frequency of carcinoma was significantly higher for segmental or linear distribution than for all other distributions

(30/42 = 71% versus 104/278 = 37%, P < 0.001, relative risk 1.9 [95% confidence intervals 1.5–2.4]).c Of 320 calcification lesions that underwent surgical biopsy in this study, 204 (64%) were described as clusters of

pleomorphic calcifications.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 417

biopsy recommendations. Previous work in this area

was limited by lack of standardization of terminology,

diminishing the potential applicability of a common

artificial neural network to multiple institutions. By

providing standardized terminology, the BI-RADS

lexicon may facilitate progress in computer-aided

diagnostic techniques.

Baker et al [18] constructed an artificial neural

network based on the BI-RADS lexicon. Eighteen

inputs to the network included 10 BI-RADS lesion

descriptors and eight input values from the patient’s

medical history. The network was trained and tested

on 206 cases, of which 73 were malignant. They

found that at a specified output threshold, the ANN

would have improved the PPVof biopsy from 35% to

61%, with a relative sensitivity of 100%. At a fixed

sensitivity of 95%, the specificity of the ANN (62%)

was significantly higher than that of the radiologists

(30%) (P < 0.01). These data suggest that the BI-

RADS lexicon provides a standardized language

between mammographers and an ANN that can

improve the PPV of breast biopsy.

In a subsequent study, Baker et al [19] studied the

performance and interobserver and intraobserver vari-

ability of an artificial neural network for predicting

breast biopsy outcome. Five radiologists used the

BI-RADS terminology to describe 60 mammograph-

ically detected lesions, including 23 cancers. Interob-

server and intraobserver variability were evaluated

with the k statistic. They found that the ANN main-

tained 100% sensitivity while improving the PPV of

biopsy from 38% (23 of 60) to between 58% (23 of

40) and 66% (23 of 35; P< 0.001). Interobserver

variability for interpretation of the lesions was sig-

nificantly reduced by the ANN (P < 0.001); there was

no statistically significant effect on nearly perfect

intraobserver reproducibility. The authors concluded

that use of an ANN with radiologists’ descriptions of

abnormal findings might improve the interpretation

of mammographic abnormalities.

Limitations of the lexicon

Interobserver and intraobserver variability

The issue of variability in mammographic inter-

pretation has been a subject of intense scrutiny.

Elmore et al [20] published a study in which 10

radiologists reviewed 150 mammograms, including

27 in women with breast cancer. Immediate work-up

was recommended for 74% to 96% of women with

cancer and 11% to 65% of women without cancer.

Beam et al [21] reported results of 108 radiologists

who reviewed screening mammograms from 79

women, 45 of whom had cancer. Screening sensitiv-

ities ranged from 47% to 100%, and specificity

ranged from 36% to 99%. The wide variation noted

in these studies may be multifactorial, likely reflect-

ing differences in detection, intervention threshold,

and inclusion of subtle cases [22,23]. Reduction of

interobserver and intraobserver variability is a poten-

tial benefit of the BI-RADS lexicon.

Observer variability in the use of the BI-RADS

lexicon was first evaluated by Baker et al [24]. In that

study, 60 mammograms were evaluated independ-

ently by five radiologists; one radiologist read each

case twice. Readers were asked to select a single term

from the BI-RADS lexicon for a variety of lesion

descriptors. Interobserver and intraobserver variabil-

ity was assessed by means of the k statistic, with k �0.2 indicating slight agreement; k = 0.21–0.4, fair

agreement; k = 0.41–0.6, moderate agreement; k =

0.61–0.8, substantial agreement; and k = 0.81–1.0,

almost perfect agreement. Baker et al [24] noted

substantial agreement between readers for choosing

terms to describe masses and calcifications and sim-

ilar intraobserver agreement (Table 5). Considerable

interobserver and intraobserver variabilities were

noted for associated findings and special cases. Use

of terms to describe calcifications did not always

conform to BI-RADS–defined levels of suspicion.

Variability in mammographic interpretation has

also been assessed by Kerlikowske et al in a study

of 2616 mammograms, including 267 (10.2%) with

cancer, with agreement assessed using the k statistic

(Table 5). They found moderate agreement between

the two radiologist readers in reporting the presence of

a finding when cancer was present (k = 0.54) and

substantial agreement when cancer was not present

(k = 0.62). Agreement was moderate in assigning one

of the five assessment categories but was significantly

lower when cancer was present relative to when

cancer was not present (k = 0.46 vs 0.56; P = 0.02).

Agreement for reporting the presence of a finding and

mammographic assessment was 2-fold more likely for

examinations with less dense breasts. Intraobserver

agreement in final assessment (86%, k = 0.73) was

higher than interobserver agreement (78%, k = 0.58).

Berg et al [26] analyzed interobserver and intra-

observer variability in use of BI-RADS terminology.

Five experienced mammographers used the lexicon to

describe and assess 103 screening mammograms, of

which 30 (29%) showed cancer, and a subset of 86

diagnostic mammograms, including 23 (27%) that

showed cancer. A subset of 13 mammograms was

reviewed by each radiologist 2 months later. Agree-

ment, as measured by the k statistic, showed a wide

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430418

range (Table 5). Lesion management was highly

variable: when assessments were grouped as to

whether the lesion needed immediate evaluation

(BI-RADS 0, 4, or 5) versus follow-up (BI-RADS

1, 2, and 3), five observers agreed on management for

only 47 (55%) of 86 lesions. Intraobserver agreement

on management was seen in 47 (85%) of 55 inter-

pretations. The authors noted that in spite of the

variability, the performance of the radiologists was

outstanding, with recommendations for additional

evaluation or biopsy in 90% to 97% of cancers on

screening and 91% to 96% on diagnostic evaluation.

The impact of training in BI-RADS on reader

agreement in feature analysis was evaluated by Berg

et al [27]. They developed a test set of mammograms

with 54 proven lesions (28 masses and 26 calcification

lesions), of which 19 (35.2%) were malignant.

Twenty-seven physicians reviewed the mammograms

before and after a 1-day training session in BI-RADS.

Readers were asked to describe mass borders, cal-

cification morphology, and calcification distribution,

and agreement with expert consensus was assessed

using the k statistic. For mass borders, mean k was

0.42 before training and 0.47 afterward; for micro-

calcification morphology, mean k was 0.40 before

training and 0.46 afterward; for microcalcification

distribution, mean k was 0.32 before training and

0.42 afterward. They concluded that after 1-day train-

ing in BI-RADS, agreement with expert consensus

improved, but only moderate agreement on feature

analysis was achieved.

These studies indicate that even in the presence of

a standardized lexicon, variability in mammographic

reporting persists. Although variability is inherent in

the practice of medicine (as in all endeavors in life),

some of the observed variability may reflect weakness

in the lexicon itself, deficiencies in radiologist train-

ing, and differences in performance level among the

different physicians. The studies identified some spe-

cific areas that may need clarification, such as ‘‘punc-

tate’’ calcifications, associated findings, and special

cases. A larger illustrated lexicon, currently under

development, may be useful. The BI-RADS lexicon

remains a work in progress and may be modified on

the basis of user input and continued research.

Communication with referring clinicians

The level of understanding of BI-RADS final

assessment categories by referring clinicians was

recently evaluated by Vitiello et al [28]. Of 86

Table 5

Inter- and intraobserver variability in use of the BI-RADS lexicon

Investigator

Baker [24] Kerlikowske [25] Berg [26]

Feature Inter Intra Inter Intra Inter Intra

Calcifications

Distribution 0.77 0.80 0.46 — 0.47 —

Number 0.77 0.84 — — — —

Description 0.50 0.57 0.33 — 0.36 —

Masses

Margin 0.63 0.66 0.58 — 0.40 —

Shape 0.65 0.72 0.40 — 0.28 —

Density 0.62 0.63 0.23 — 0.40 —

Other findings

Associated 0.32 � 0.02 — — — —

Special cases 0.16 0.38 — — 0.38–1.0 —

Location of primary finding — — 0.69 — — —

Finding/no finding — — 0.66 0.79 — —

Primary finding — — 0.56 0.71 0.75 —

Breast density — — 0.59 0.72 0.43 —

Assessment category — — 0.58 0.73 0.37 0.6 (0.35–1.0)

Recommendation — — 0.59 0.59 — —

Data reflect the k statistic, with < 0.2 indicating slight agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement;

0.61–0.80, substantial agreement; and 0.81–1.0, almost perfect agreement.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 419

clinicians who responded to a survey, 46% were not

aware that radiologists were required to report mam-

mograms using BI-RADS terminology, 64% had no

information or education regarding BI-RADS, and

only 35% were comfortable with reports using BI-

RADS. For patients with a BI-RADS category 3 (pro-

bably benign) reading, 93% of clinicians followed the

radiologist’s recommendation for short-term radio-

logic follow-up; in addition, 62% of clinicians sent

BI-RADS 3 patients for further work-up, including

physical examination in their offices, surgical consul-

tation, or both. These results indicate that many re-

ferring clinicians have little knowledge of BI-RADS

and are not comfortable with it. If the goal of improv-

ing communication is to be achieved, further edu-

cation is needed.

Toward a lexicon for breast sonography

Lesion characterization

The classic teaching has been that breast sono-

graphy can provide excellent differentiation of cystic

(Fig. 7) from solid (Fig. 8) masses but that it is of

limited usefulness in distinguishing benign from

malignant solid masses in the breast. Data from

Stavros et al [29] challenge this paradigm.

Stavros et al [29] published results of 750 sono-

graphically solid breast nodules that were prospec-

tively classified as benign, indeterminate, or malignant

(Fig. 9). They defined specific features they con-

sidered malignant (Table 6) and other specific

features they considered benign (Table 7). If a sin-

gle malignant feature was present, the nodule was

excluded from the benign classification. If one of

the three combinations of benign characteristics was

found (Table 7), the lesion was classified as benign.

If no malignant features were found and none of

the combinations of benign characteristics was

present, the lesion was classified as indeterminate.

In 1 of 5 groups, mammograms were also classified

as negative, probably benign, indeterminate, prob-

ably malignant, and malignant, a classification that

preceded the BI-RADS lexicon. All lesions under-

went biopsy.

Of the 750 nodules, 625 (83%) were benign and

125 (17%) were malignant. The sonographic clas-

sification had a sensitivity of 98.4% (123 of 125),

specificity of 67.8% (424 of 625), positive predictive

value of 38.0% (123 of 324), negative predictive

value of 99.5% (424 of 426), and accuracy of

Fig. 7. Sonography of a simple cyst. Characteristics of a simply cyst include a thin wall, no internal echoes, round/oval shape,

and posterior acoustic enhancement.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430420

72.9% (547 of 750). Of particular interest is the

negative predictive value of 99.5%. This indicates

that of lesions classified as benign by sonographic

criteria, only 0.5% were cancer; note that this is

identical to the frequency of cancer among probably

benign (BI-RADS category 3) lesions in the study by

Sickles [8]. These data suggest that ultrasound may

help identify lesions that have an overwhelmingly

high likelihood of benignity and can be safely eval-

uated with short-term follow-up imaging.

The study of Stavros et al [29] also indicates that

sonography can increase the radiologist’s level of

suspicion for lesions that prove to be cancer. Among

125 cancers, 64 (51.2%) were classified as benign

(n = 20) or indeterminate (n = 44) by mammography

but malignant by sonography. Among 44 palpable

cancers, 32 (72.3%) were classified as benign (n = 16)

or indeterminate (n = 16) by mammography but

malignant by sonography.

Berg et al [30] correlated sonographic features

with risk of malignancy in 588 lesions that under-

went biopsy in the Radiologic Diagnostic Oncology

Group V study, of which 116 (20%) were malig-

nant. The shape feature most predictive of malig-

nancy was irregular, with PPV of 65% for irregular,

13% for lobular, 12% for round, and 8% for oval

masses. The posterior attenuation feature most pre-

dictive of malignancy was shadowing, present in

half the malignant lesions; PPV was 32% for

shadowing, 15% for no posterior characteristics,

and 8% for posterior acoustic enhancement. Malig-

nancy was present in 34% of lesions that had

heterogeneous echotexture without cysts, 14% of

homogeneous lesions, and 13% of heterogeneous

lesions with cysts. Echogenicity did not discrim-

inate between benign and malignant lesions, with

PPV of 21%, 18%, and 9% for hypoechoic, hyper-

echoic, and isoechoic lesions, respectively. These

data lend further support to the role of sonography

in lesion characterization and help provide a scient-

ific basis for the development of a BI-RADS

lexicon for ultrasound.

Lexicon development

The ACR has developed an initial draft of a

breast ultrasound lexicon [31], supported by the

Office on Women’s Health, Department of Health

Fig. 8. Biopsy-proven fibroadenoma at sonography. Note the circumscribed borders, oval shape that is wider than it is tall, and

echogenic capsule. Minimal posterior acoustic shadowing is present.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 421

and Human Services. The initial draft includes

descriptors for mass shape (oval, round, or irregular),

echopattern (anechoic, hyperechoic, complex, or

hypoechoic), and posterior acoustic features (none,

enhancement, shadowing, or combined). Mass ori-

entation is described as parallel (oriented along skin

line, ‘‘wider than tall’’) or not parallel (axis not

oriented along skin line, or ‘‘taller than wide’’). Mass

margins are circumscribed (with no rim, thin rim, or

thick rim) or irregular (indistinct, angular, micro-

lobulated, or spiculated).

Effect on surrounding tissue is also noted, in-

cluding effect on ducts or Cooper ligaments, edema,

architectural distortion, skin thickening or retraction,

and unclear plane with pectoral muscle. Also included

are descriptors for associated calcifications (none,

Fig. 9. Sonographic findings in breast cancers. (A) Sonography shows a spiculated, irregular, hypoechoic mass that is taller than

wide and has posterior acoustic shadowing. Biopsy showed infiltrating ductal carcinoma and ductal carcinoma in situ (DCIS).

(B) Sonography shows lobulated, hypoechoic solid mass with ductal extension. Posterior acoustic enhancement (a feature more

common in benign lesions) is observed. Biopsy showed infiltrating ductal carcinoma and DCIS.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430422

macrocalcifications, microcalcifications in mass, mi-

crocalcifications outside of mass), special cases (mass

in or on skin, foreign body, intramammary lymph

nodes, or axillary lymph nodes), vascularity (cannot

assess, none, same as normal tissue, decreased, or

increased), and final assessment categories.

Mendelson et al [31] suggest that descriptors

should be based on multiple views of masses

obtained in orthogonal imaging planes and that the

location of the abnormality be described using a

quadrant, clock-face location, or labeled diagram of

the breast, ideally including distance from the nip-

ple. Development of a sonographic lexicon is made

more complex by additional variables in sonogra-

phy, including the high level of operator depend-

ence, technical differences dependent on equipment,

and availability of real-time assessment. Further

work is needed to validate the lexicon terminology

and to assess the positive and negative predictive

values of the different descriptors.

Breast sonography: observer variability in lesion

description and assessment

Baker et al [32] evaluated 60 consecutive sono-

graphic studies of solid breast lesions. Static sono-

graphic images of each solid breast lesion were

acquired and reviewed by five radiologists experi-

enced in breast imaging, and radiologists described

mass shape, margin, echogenicity, presence of a pseu-

docapsule, acoustic transmission, and echotexture

according to terms defined by Stavros et al [29]. In-

terobserver and intraobserver variability were assessed

using the k statistic (Table 8).

In that study, Baker et al [32] reported moderate

interobserver agreement and substantial intraob-

server agreement for most categories (Table 8). In-

terobserver agreement ranged from lowest for

determining the presence of an echogenic capsule

to highest for mass shape; intraobserver agreement

was lowest for mass echotexture and highest for

Table 6

Malignant sonographic characteristics versus malignant histologic findings

Characteristics Sensitivity Specificity PPV NPV Accuracy OR

Spiculation 36.0 99.4 91.8 88.6 88.8 5.5

Taller than wide 41.6 98.1 81.2 89.4 88.7 4.9

Angular margins 83.2 92.0 67.5 96.5 90.5 4.0

Shadowing 48.8 94.7 64.9 90.2 87.1 3.9

Branch pattern 29.6 96.6 64.0 87.3 85.5 3.8

Hypoechogenicity 68.8 90.1 60.1 93.6 87.2 3.6

Calcifications 27.2 96.3 59.6 86.9 84.8 3.6

Duct extension 24.8 95.2 50.8 86.4 79.3 3.0

Microlobulation 75.2 83.8 48.2 94.4 82.4 2.9

Numbers reflect percentages.

PPV = positive predictive value; NPV = negative predictive value; OR = odds ratio.

Adapted from Stavros AT, Thickman D, Rapp CL, Dennis MA, Parker SH, Sisney GA. Solid breast nodules: use of sonography

to distinguish between benign and malignant lesions. Radiology 1995;196:123–34; with permission.

Table 7

Benign sonographic characteristics versus benign histologic findings

Characteristic Sensitivity Specificity PPV NPV Accuracy OR

Hyperechogenicity 100.0 7.4 17.8 100.0 22.8 0.00

Two or three lobulations 99.2 19.4 19.7 99.2 32.7 0.05

Ellipsoid 97.6 51.2 28.6 99.1 59.2 0.05

Thin capsule 95.2 76.0 44.2 98.8 79.2 0.07

Numbers reflect percentages.

PPV= positive predictive value; NPV= negative predictive value; OR= odds ratio.

Classification of a solid nodule as benign required lack of malignant characteristics, plus hyperechogenicity or a thin echogenic

capsule plus ellipsoid shape, or a thin echogenic capsule plus two or three gentle lobulations.

Adapted from Stavros AT, Thickman D, Rapp CL, Dennis MA, Parker SH, Sisney GA. Solid breast nodules: use of sonography

to distinguish between benign and malignant lesions. Radiology 1995;196:123–34; with permission.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 423

mass shape. Variability in descriptions contributed

to interobserver and intraobserver inconsistency in

assessing the likelihood of malignancy. It is likely

the interobserver variability would be even higher

if real-time imaging were incorporated into the

analysis. Additional work will be necessary to

evaluate the interobserver and intraobserver vari-

ability in the finalized version of the ACR breast

ultrasound lexicon.

Toward a lexicon for breast MRI

Lexicon development

Magnetic resonance imaging of the breast has

high sensitivity in the detection of breast cancer,

reported as up to 100% in some series, but has

lower specificity, ranging from 37% to 97% [33].

Parenchymal breast MRI is also an expensive exa-

Table 8

Inter- and intraobserver variability in evaluation of sonography of solid breast masses

Interobserver Reproducibility Intraobserver Reproducibility

Echogenic pseudocapsule 0.09 Slight 0.63 Substantial

Echogenicity 0.40 Fair 0.69 Substantial

Margin 0.43 Moderate 0.62 Substantial

Echotexture 0.44 Moderate 0.24 Fair

Acoustic transmission 0.55 Moderate 0.63 Substantial

Shape 0.80 Substantial 0.79 Substantial

Final assessment 0.51 Moderate 0.66 Substantial

Data reflect the k statistic, with < 0.2 indicating slight agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement;

0.61–0.80, substantial agreement; and 0.81–1.0, almost perfect agreement.

Adapted from Baker JA, Kornguth PJ, Soo MS, Walsh R, Mengoni P. Sonography of solid breast lesions: observer variability of

lesion description and assessment. AJR Am J Roentgenol 1999;172:1621–5; with permission.

Fig. 10. MRI of fibroadenoma. Sagittal, T1-weighted, contrast-enhanced image shows a lobulated enhancing mass with non-

enhancing internal septations.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430424

mination that requires the injection of intravenous

contrast material. Published work supports the use-

fulness of MRI in specific scenarios, such as

identification of occult carcinoma, problem-solving,

local staging of breast cancer (including skin or

pectoral muscle involvement), and (potentially) high-

risk screening [33,34]. Progress in breast MRI has

been limited by lack of standardization in image

acquisition and image interpretation, with some

methods focusing on morphology (spatial res-

olution) and others stressing kinetics (tempo-

ral resolution).

Fig. 11. MRI patterns of breast cancers in sagittal, T1-weighted, contrast-enhanced images. (A) Spiculated, irregular enhanced

mass in superior breast; biopsy yielded infiltrating ductal carcinoma and ductal carcinoma in situ (DCIS). Note suboptimal fat

suppression inferiorly. (B) Lobulated mass with heterogeneous and rim enhancement; histologic analysis yielded infiltrating

ductal carcinoma and DCIS. (C) Extensive linear and segmental clumped enhancement; biopsy yielded DCIS.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 425

In 1997, Nunes et al [35] analyzed the diagnostic

accuracy of specific architectural (morphologic) fea-

tures identified during breast MRI in 93 women.

Architectural features that were highly predictive of

benign disease included smooth or lobulated borders

(97% to 100%), the absence of mass enhancement

(100%), and enhancement that was less than the

enhancement of surrounding fibroglandular tissue

(93% to 100%). Nonenhancing internal septations,

present in 9 of 14 (64%) fibroadenomas in a sub-

sequent study, were specific for the diagnosis of fib-

roadenoma and correlated with collagenous bands at

histologic analysis (Fig. 10). Architectural features

that were highly predictive of carcinoma included

spiculated borders (76–88%) and peripheral rim

enhancement in the presence of central lesion

enhancement (79–92%) (Fig. 11).

In 1999, Kuhl et al [36] assessed the relevance of

signal-intensity time-course analysis (kinetics) for the

differential diagnosis of enhancing lesions in breast

MRI in a study of 266 breast lesions, of which 101

(40.0%) were malignant. They classified enhance-

ment curves as type 1, steady; type 2, plateau; or

type 3, washout (Fig. 12). A washout pattern was sig-

nificantly more frequently observed in cancers than

in benign lesions (Table 9). The diagnostic indices

for time signal intensity curves were sensitivity, 91%;

specificity, 83%; and diagnostic accuracy, 86%. There

was almost perfect interobserver agreement in categor-

izing the shape of the time signal intensity curve, with

k = 0.85. The shape of the time signal intensity curve

was a more useful predictor of malignancy than the

rate of enhancement (Table 9).

Supported by the Office of Women’s Health and

the ACR, The International Working Group on Breast

MRI Imaging is developing a lexicon of terms for

breast MRI reporting, the first version of which was

published in 1999 [37]. Schnall and Ikeda [37] sug-

gested that MRI reports include descriptions of clin-

ical abnormalities, previous biopsies, hormonal status,

Fig. 12. Schematic drawing of time-signal intensity curve types. Type 1 (persistent or steady) corresponds to a straight (1a) or

curved (1b) line; enhancement continues over the entire dynamic study. Type II is a plateau curve with a sharp bend after the

initial upstroke. Type III is a washout time course. SIc = signal intensity after contrast enhancement; SI = signal intensity before

contrast injection. (Data from Kuhl CK, Mielcareck P, Klaschik S, et al. Dynamic breast MR imaging: are signal intensity time

course data useful for differential diagnosis of enhancing lesions? Radiology 1999;211:101–110; with permission.)

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430426

and comparison with prior studies. Technical factors

should be stated, including the location of markers and

significance, magnet field strength, use of a dedicated

breast coil, contrast media, pulse sequence, anatomy

(including slice thickness and scan orientation and

plane), and post-processing techniques. Findings

described should include mention of artifacts that

affect interpretation, breast composition, implants,

and presence or absence of abnormal enhancement,

with specific descriptors defined for focal enhance-

ment, kinetics, summary impression, and recommen-

dations. Descriptive terms for breast MRI were

elegantly illustrated by Morris [38].

Although limited data validate the assignment of

final assessment categories based on MRI findings,

guidelines were suggested by Kuhl et al [39] in an

investigation of breast MRI for high-risk screening.

In that study, BI-RADS category 1 was assigned to

lesions without any contrast material enhancement.

BI-RADS category 2 was assigned to lesions in

which enhancement was detected but was classified

as benign (focal masses with well-circumscribed

morphology, internal septations but otherwise homo-

geneous enhancement, steady time-signal intensity

course, and centrifugal progression of enhancement;

or non-mass-related gradual enhancement). BI-RADS

category 3 was assigned to lesions compatible with

‘‘unidentified bright objects’’ or UBOs (spontaneous,

hormone-induced enhancement) and in lesions with

presumably benign masses that lacked some of the

BI-RADS category 2 features.

BI-RADS category 4 was assigned to lesions with

a washout time course, irrespective or morphology, or

lesions with suspicious morphology, irrespective of

Table 9

Breast MRI: time signal intensity curves as predictors of

malignancy

Cancers

(n = 101)

Benign lesions

(n = 165)

Time signal intensity curve

Type I (steady) 8.9 83.0

Type II (plateau) 33.6 11.5

Type III (washout) 57.4 5.5

Enhancement rate

Slow 9.0 36.9

Intermediate 25.7 28.5

Fast 65.3 34.5

Numbers reflect the proportion of cancers or benign lesions

that had the kinetic features shown. Enhancement rate was

defined as the signal intensity increase on the first

postcontrast image, with slow being an increase less than

or equal to 60%, intermediate being an increase of more than

60% and less than or equal to 80%, and fast being an

increase of more than 80%.

Adapted from Kuhl CK, Mielcareck P, Klaschik S, et al.

Dynamic breast MR imaging: are signal intensity time

course data useful for differential diagnosis of enhancing

lesions? Radiology 1999;211:101–110; with permission.

Descriptive terms for breast MRI

Focus/foci

Mass marginSmoothIrregularSpiculated

Mass shapeOvalRoundLobulatedIrregular

Mass enhancementHomogeneousHeterogeneousRimDark internal septationsEnhancing internal septationsCentral enhancement

Non-mass enhancementLinear (smooth, irregular, or clumped)SegmentalRegionalMultiple regionsDiffuse

Non-mass enhancement descriptors for allother types

HomogeneousHeterogeneousStippled/punctateClumpedSeptal/dendritic

Symmetric versus asymmetric for bi-lateral studies

Adapted from Morris EA. Illustratedbreast MR lexicon. In: Miller WT, BertWA, editors. Seminars in roentgenology.Breast imaging. Vol. 36. Philadelphia: WBSaunders; 2001. p. 238–49; with per-mission.

L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430 427

kinetics. Morphology was suspect if there was spicu-

lated or irregular lesion configuration, heterogeneous

internal architecture (particularly rim enhancement),

and asymmetric segmental or linear enhancement (see

Fig. 11). BI-RADS category 5 was attributed to

lesions in which morphologic and architectural fea-

tures were suggestive of malignancy. Further work is

needed to validate this approach.

Potential usefulness of the breast MRI lexicon

Preliminary work supports the usefulness of a BI-

RADS lexicon for MRI-detected lesions. Kim et al

[40] described the magnetic resonance appearance of

72 focally enhancing infiltrating breast carcinomas.

They reported that mass margins were spiculated in

34 (47%), indistinct in 22 (31%), circumscribed in 15

(21%), and obscured in 1 (1%). Mass shape was

irregular in 41 (57%), lobular in 16 (22%), round in

10 (14%), and oval in 5 (7%). Enhancement pattern

was heterogeneous in 43 (60%), homogeneous in 15

(21%), and rim in 14 (19%). BI-RADS final impres-

sion was 3 in 3 (4%), 4 in 26 (36%), and 5 in 43

(60%). There was moderate interobserver agreement

for mass margins (k = 0.46), mass shape (k = 0.41),

and enhancement pattern (k = 0.56).

Siegmann et al [41] reviewed MRI and histologic

findings in 70 exclusively MRI-detected lesions that

were prospectively classified as BI-RADS analogous

class 3 (probably benign), class 4 (suspicious), or

class 5 (highly suggestive of malignancy). The

frequency of carcinoma was 0% (0 of 4) for class

3, 23.7% (14 of 59) for class 4, and 85.7% (6 of 7)

for class 5, comparable to the frequency of carcino-

ma for analogous classes in studies of the BI-RADS

lexicon for mammography [42–44]. Few details are

given regarding criteria for assigning different final

assessment categories; this should be clarified in

future work.

Precise definition of terms facilitates studies into

PPV of specific MRI features. Morakkabati et al [45]

reported a pattern of segmental or ductal enhance-

ment in 19 (3.8%) of 500 consecutive patients who

underwent dynamic breast MRI. Segmental enhance-

ment occurred in 14 of 19 patients, 10 of whom had

DCIS and 4 of whom had fibrocystic change. Ductal

enhancement was seen in 5 of 19 patients, 1 of

whom had DCIS and 4 of whom had benign findings

(1 papilloma and 3 fibrocystic change). The PPV of

segmental or ductal enhancement was 58% (11 of

19), and the specificity of this criterion was 98% (481

of 489). The authors concluded that ductal or seg-

mental enhancement was an infrequent finding on

breast MRI but that it had high PPV for malignancy.

The breast MRI lexicon is a work in evolution.

Standardization of technique would help in the devel-

opment of the breast MRI lexicon. Further research

into the positive and negative predictive values of

specific MRI features will be of great value in the

complex business of interpreting breast MR images

and would allow more women to benefit from the use

of breast MRI in the detection and local staging of

breast cancer.

Summary and future directions

The BI-RADS lexicon was created to standardize

mammographic reporting, thereby enabling better

communication, improving clarity in reporting, and

facilitating research. The lexicon has enabled studies

that have better defined the positive predictive value

of specific mammographic features and has contrib-

uted to progress in computer-aided diagnosis. In spite

of the lexicon’s goal of standardization, considerable

interobserver and intraobserver variability in mammo-

graphic interpretation persists. Further work is neces-

sary to refine the lexicon, to assess training techniques

for lexicon use, and to further develop and validate

lexicons for breast sonography, breast MRI, and other

new imaging modalities as they become available.

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L. Liberman, J.H. Menell / Radiol Clin N Am 40 (2002) 409–430430

Ultrasound for breast cancer screening and staging

Paula B. Gordon, MD, FRCPC

Department of Radiology, University of British Columbia, 505-750 West Broadway Vancouver,

British Columbia, Canada V5Z 1H4

Ultrasound (US) is well accepted as the most

useful adjunct to mammography for the diagnosis

of breast abnormalities. US is most often used to

assess palpable masses and nonpalpable masses that

have been detected during screening mammography

[1–5]. Mammographic sensitivity for detection of

a mass is excellent when the mass is surrounded

partially or entirely by fat; however, mammo-

graphic sensitivity is impaired for noncalcified

masses in radiographically dense breast tissue and

for masses at locations in the breast that may not

be included because of the limitations of mammo-

graphic positioning. In these settings, US may

demonstrate malignancies and other masses that

are not visible mammographically. It is not surpris-

ing, then, that US can also detect cancers that are

both mammographically occult and too small to

be palpable.

Efforts to replace screening mammography with

US in the 1970s were prompted by the concern

raised by Bailar [6], who suggested that the use of

ionizing radiation in mammography could be car-

cinogenic. Automated prone and supine US units

were developed, and most operated at low frequen-

cies. Early studies found few, if any, cancers with

US that were not palpable or mammographically

visible, and US screening was also shown to have a

high false-positive rate [7–10]. Later, higher fre-

quency probes for hand-held real-time US became

available. These transducers were usually small

field-of-view instruments that were light and easy

to hold. These small footprint probes are adequate

for problem-solving examinations; the transducer

can be placed directly on a palpable abnormality

or can be used to scan a region in which a mass has

been seen at mammography. Whole-breast scanning

with these probes is more time consuming, labor

intensive, and operator dependent than with auto-

mated devices.

In North America, breast ultrasound is most often

a targeted examination, limited to the area of concern

based on palpation or mammography. On the other

hand, survey (whole-breast) real-time scanning has

been more prevalent in Europe.

With higher frequency transducers, ultrasound’s

usefulness for breast diagnosis slowly increased.

Initially, US was used to demonstrate palpable

masses that were not visible on mammograms

because of surrounding dense tissue and to assess

nonpalpable masses detected at screening mammog-

raphy. In these settings it was used mainly to confirm

the presence of a discrete mass and to distinguish

cysts from solid masses. US has become the primary

imaging modality for younger women and pregnant

or lactating patients, and it is important for guiding

interventional procedures [4]. More recently, sono-

graphic features have been described to contribute in

the differentiation of benign, indeterminate, and

malignant masses [11]. However, because of its

inability to demonstrate microcalcifications, sonogra-

phy cannot replace mammography for the purpose of

mass screening.

With US, unexpected findings are extremely com-

mon. This is particularly true for cysts. If a patient is

referred for ultrasound because of a palpable or

mammographic finding that ultimately proves to be

a cyst on sonography, it is highly likely that other

cysts that are neither palpable nor visible on the

mammogram will be detected during the course of

the US examination. Cysts are common and are

frequently encountered regardless of the indication

for referral.

The same is true for incidental solid masses. Most

solid-appearing masses that are detected unexpect-

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00014 -8

Radiol Clin N Am 40 (2002) 431–441

edly during breast US are benign. Most are fibroade-

nomas, some are complex or inspissated cysts with

internal echoes, and a small but significant percentage

are malignancies. These incidentalomas [12] should

not be ignored.

Staging

It is not surprising to find incidental cancer(s)

when performing US in a patient with a known

malignancy elsewhere in the ipsilateral breast, espe-

P.B. Gordon / Radiol Clin N Am 40 (2002) 431–441432

cially when the tissue is mammographically dense.

Indeed, this represents useful staging information for

treatment planning because the diagnosis of multi-

focal cancer is usually a contraindication to con-

servative surgery. When there is no opportunity to

detect these otherwise occult cancers preoperatively,

patients are categorized as understaged and may

eventually have postoperative ‘‘recurrences’’ or

‘‘metachronous new primaries.’’ This is consistent

with pathologic data that showed unsuspected addi-

tional foci of malignancy in mastectomy specimens

from 30% to 63% of women who had been thought to

have unifocal breast cancer [13,14].

However, the true benefit derived from more

accurate staging using US and other modalities such

as MRI is unknown, and whether cancers detected in

this way are of biologic significance is also unknown.

The theoretical benefit of detecting and treating them

may be decreased mortality or decreased rate of

recurrence. Survival has been shown to be equal

when wide excision combined with radiation is

compared with mastectomy, so it is possible that

many undiagnosed multifocal cancers are adequately

treated by postlumpectomy radiation. Reducing the

rate of recurrence is potentially important for patients

preferring breast conservation because recurrent

tumors must be treated with mastectomy. Though

breast reconstruction is an option after mastectomy,

it is more likely to be successful in a breast that has

not been irradiated [15]. In addition, early recurrences

(within the first 5 years) have a worse prognosis than

later occurrences [16], and the National Surgical

Adjuvant Bowel Project suggested that 86% of early

local recurrences were actually overlooked residual

Fig. 1. This 48-year-old woman was known to have multiple bilateral breast cysts and had required cyst aspirations from time to

time. She presented because of two new palpable masses, one in each breast. Craniocaudal (A) and mediolateral oblique (B)

mammograms showed dense breast tissue, Breast Imaging Reporting and Data System 4, and multiple, bilateral, round, and oval

circumscribed masses consistent with cysts. Radio-opaque markers on the skin indicate the locations of the palpable lumps. US

showed that the palpable masses were cysts, and there were cysts elsewhere throughout each breast. No solid mass was seen on

either side. Because neither was particularly tender, she declined aspiration. Three months later she returned for aspiration

because of acutely tender masses. These were cystic on US and were easily aspirated, two on the right and three on the left. A

deliberate survey scan was not planned because bilateral whole-breast sonography had been performed so recently. Nevertheless,

during imaging to localize one of the tender cysts on the right for aspiration, a subtle solid mass (C), measuring 1.1 � 1.2 � 1.4

cm, was noted incidentally. It had almost the same echogenicity as the adjacent normal tissue. US-guided FNAB was performed,

and it was interpreted as suspicious. Subsequent large-core needle biopsy and surgical excision confirmed grade II/III invasive

lobular carcinoma.

P.B. Gordon / Radiol Clin N Am 40 (2002) 431–441 433

cancer [17]. Thus, more accurate staging before

surgery could prompt mastectomy earlier for these

patients, allowing more successful reconstruction and

possibly improving prognosis.

Berg and Gilbreath [18] used whole-breast US to

evaluate the ipsilateral breast preoperatively in

women with known cancer or in whom there was a

high suspicion of cancer. They found 9 of 64 (14%)

cancers with US only. These included invasive and in

situ ductal carcinomas and invasive lobular carcino-

mas. This led to a change in the planned management

for seven patients, including four women with mam-

mographically occult disease whose cancer was

depicted by US and 3 of 20 (15%) women with

mammographically unifocal disease in whom US

revealed multifocal disease requiring wider excision.

Kolb et al [19] used bilateral whole-breast sono-

graphy (BWBS) to evaluate 150 consecutive women

with dense tissue who were known to have cancer.

They found 16 additional cancers in 10 women, 13

ipsilateral and 3 contralateral. These findings altered

the planned management for 8 (80%) of these 10

patients, constituting 5% of the 150 women in the

study. Palpability and size of the index tumor were

associated with a greater likelihood of detecting

additional cancers with BWBS.

Moon et al [20] performed BWBS in 201 patients

known to have breast cancer. Only 52% of these were

thought to have dense breast tissue. Thirty-six cancers

were seen only on US, 28 in the ipsilateral breast and

8 in the contralateral breast. These included invasive

and in situ ductal carcinoma and invasive lobular

carcinoma. Surprisingly, three of the cancers seen

only with US were in mammographically fatty

breasts, but the authors did not indicate the Breast

Imaging Reporting and Data System (BI-RADS)

density category or whether the location of the cancer

was in a dense area in an otherwise fatty breast. Their

findings altered planned management in 32 women

originally thought to have unifocal disease.

Screening

US may depict cancers that are mammographi-

cally occult and nonpalpable during imaging of a

patient whose index lesion is ultimately shown to be

benign (Fig. 1). There is some disagreement among

experts as to how the unexpected finding of an

‘‘incidental’’ solid mass during US should be

handled. Some laboratories [12] have a policy that

only the index area is to be scanned. This is simple

enough for palpable masses. For mammographic

findings, the matter is more problematic. Because of

the inexact task of triangulation, a preliminary search

with US to find the index lesion is usually required.

In the process of searching, other masses may

unavoidably be seen; however, if our goal as breast

imagers is to diagnose cancers as early as possible,

this kind of discovery is potentially lifesaving. Some

of the cancers detected in this manner are the interval

cancers that would be diagnosed clinically before the

next scheduled screening mammogram.

In the 1980s and early 1990s, there were sporadic

reports in the literature [7,8,21–26] of cancers de-

tected incidentally during US (Table 1). Some inves-

tigators performed survey scans whenever a patient

had been referred for a particular indication. Others

undertook ultrasound for no indication other than

mammographically dense breasts. Not all incidental

cancers were detected during intentional survey scan-

ning; some were found even when the intention was to

target the examination to a particular quadrant [27].

Gordon et al [28], in a 1993 study on the use of

US-guided fine-needle aspiration biopsy (FNAB)

of solid breast masses, reported their experience of

finding 15 of 225 breast cancers that were detected

only with US. In 1995, these authors [29] updated

their experience. They retrospectively reviewed

whole-breast US performed on the ipsilateral breast

in 12,706 women referred because of palpable or

mammographically detected masses and found incid-

ental solid masses in 1575 (12%). Of these, 279

underwent FNAB; 44 masses were cancerous, and

Table 1

Cancers detected only on ultrasound

Study

No.

patients

No.

cancers

No. US

only

No. US only

cancers/no.

patients (%)

Gordon [28] 7,322 213 15 0.2

Egan [23] 2,530 107 3 0.1

Egan [8] 786 31 1 0.1

Bassett [7] 1,212 45 1 0.1

Dempsey [21] NS 381 3 NS

Vilaro [26] 73 10 2 2.7

Croll [22] NS 173 8 NS

Rothchild [25] 796 1 1 0.1

Giuseppetti [24] 11,254 57 10 0.1

Parker [27] NS 34 2 NS

Gordon [29] 12,706 NS 44 0.3

Kolb [19] 3,626 NA 11 0.3

Buchberger [31] 6,113 NA 23 0.3

Kaplan [33] 1,350 NA 6 0.4

US = ultrasound; NS = not stated, NA = not applicable

(represents a study of US screening).

Adapted from Gordon PB, Goldenberg SL. Malignant breast

masses detected only by ultrasound: a retrospective review.

Cancer 1995;76:626–30; with permission.

P.B. Gordon / Radiol Clin N Am 40 (2002) 431–441434

the median size was 1 cm (range, 0.4–2.5 cm). Thus,

cancer was identified in 44 of 279 (16%) lesions by

FNAB, in 44 of 1575 (3%) incidental solid masses,

and during 44 of 12,706 (0.3%) sonographic exami-

nations. The 44 nonpalpable, mammographically

occult cancers were found in 30 women. In 15 women,

the index lesion that led to the US examination was

malignant (ie, unsuspected multifocal disease, essen-

tially a staging finding); in 15 women, the index lesion

proved to be benign (a serendipitous finding, in effect

the result of ‘‘screening’’ the remainder of the breast).

Stavros et al [11] did not set out to perform

screening US, but, in the process of their study, they

encountered 44 incidental solid masses, 11 (25%) of

which proved to be cancers. Five of these were

second foci in women with other ipsilateral malig-

nancy, and six were unsuspected primaries that were

neither palpable nor visible mammographically. Of

11,220 consecutive patients referred for screening

mammography, Kolb et al [30] offered sonographic

screening of 3626 asymptomatic women whose

mammogram findings were negative but who had

mammographically dense breast tissue. They iden-

tified 215 solid masses in the 3626 patients. Biopsy

was performed on 123 solid masses (ie, in 57% of the

215 solid masses identified, or in 3% of the patients

who had screening sonography) using FNAB in 111

patients and surgical biopsy in 12 patients. Cancer

was identified in 11 lesions, as follows: 11 of 123

(9%) solid lesions for which biopsy samples were

taken, 11 of 215 (5%) solid masses, and 11 of 3626

(0.3%) sonographic examinations.

The 11 US-only cancers identified by Kolb et al

[30] were similar in size and stage to the mammog-

raphically detected cancers and smaller and lower in

stage than the palpable cancers in their referred

symptomatic patients. In women with dense breasts,

use of screening US as a supplement to mammog-

raphy resulted in increased cancer detection by 17%

(from 63 to 74 tumors), and the number of tumors

detected only with imaging increased by 37% (from

30 to 41 tumors). The frequency of detecting cancer

by screening US was 0.6% (6 of 1043) in high-risk

women versus 0.2% (5 of 2583) in average-risk

women (P = 0.09).

Buchberger et al [31] scanned 6113 asymptomatic

patients with mammographically negative, but dense

breasts, and detected 23 malignancies in 21 women

(0.31%). They compared these lesions to those in

687 patients who were referred because of palpable

or mammographically detected masses. The mean

size of the US-only cancers was not significantly

different than the mean size of the invasive cancers

found by mammography.

Levy et al [32] retrospectively reviewed 110

consecutive cases of breast cancer that had been

assessed with mammography and BWBS. Twenty-

four (21.8%) breast cancers were seen only with US.

This resulted in a 28.2% enhancement of the detec-

tion of nonpalpable invasive cancer. Their criteria for

performing BWBS were moderately dense breast and

either high-risk profile, mammogram categorized as

BI-RADS 0, 4, or 5, or abnormal findings on physical

examination. Hence, this was a combined screening–

staging population.

Kaplan [33] studied 1350 women using BWBS

who had negative findings on clinical breast exami-

nations and negative mammograms with BI-RADS

density of 3 or 4. This was a pure screening popu-

lation. One hundred seventy-seven patients had sono-

graphic findings, but most were not thought to require

intervention. Fifty-one biopsies were recommended

in 50 patients (3.7%). Six cancers were diagnosed,

indicating that cancers were detected by US only in 6

of 1350 (0.4%) women in the study.

Barriers to clinical acceptance

There remains understandable reluctance to

embrace BWBS for its potential value as a screening

tool [12,34]. This can be attributed to several reasons.

Lack of proof of benefit

Screening mammography has been subjected to

intense scrutiny during the last four decades. The true

independent contribution of US to breast cancer

screening cannot be determined other than by the

performance of a randomized, blinded, controlled

trial using death as the endpoint [35]. It is unlikely

that a clinical trial of sufficient magnitude could be

performed to assess the potential benefits of US

screening and to allow subgroup analysis. A large

cohort would be required because the incidence of

US-only cancers is low. ‘‘Contamination’’ would

prove challenging unless the study was population

based. One of the many lessons learned from the

Canadian National Breast Screening Study [36] is

that women who volunteer for a trial and are assigned

to the control group frequently seek the examination

evaluated outside the trial setting. This occurred in

26% of the women aged 40 to 49 years in that study

[36], and it can dramatically affect the difference in

mortality between the two groups. Furthermore, well-

informed women offered US because of known

mammographic parenchymal density, who may be

at higher cancer risk, might be even less likely than

P.B. Gordon / Radiol Clin N Am 40 (2002) 431–441 435

average-risk women to comply with their assignment

to a control group. The use of ‘‘surrogate endpoints’’

is an indirect measurement of benefit, but it is less

robust than the proof of decreased mortality, and it

has been rejected in the context of mammographic

screening because of lead-time bias and length bias

sampling [37]. Allowing for expected contamination

would require an even larger cohort.

Nature of the examination

The lack of global images in breast US and the

operator dependence of the procedure have contrib-

uted to its mystique among non-sonologist physi-

cians. Whether an abnormality is detected at US is

completely dependent on the perception and skill of

the person performing the procedure. If a mass is

subtle and at the limit of perceptibility on US but is

not noticed at the time of the examination, it cannot

be detected afterward by reviewing hard copy images

except, perhaps, on videotape. Having representative

normal images is not proof that a mass was not

present. This is a limitation of ultrasound in general.

(eg, the same situation occurs with malignancies in

other organs in which it is possible to obtain normal

images from a plane different than the one where the

mass is visible). In this regard, US is more akin to

clinical examinations than to other radiographic stud-

ies. If a patient detects a breast lump 1 month after

her physician has performed a clinical breast exam-

ination with negative results, no one can state with

certainty whether that mass became palpable during

that month or whether it was detectable but missed on

the initial physical examination. We can acknowledge

the limitations of US without abandoning it. Even

more standardized examinations such as mammogra-

phy have a component that is operator dependent; the

quality of the study depends to a large extent on the

skill of the technologist in positioning. These poten-

tial challenges could be minimized to a great extent

by having physicians, rather than technologists, per-

form screening US examinations, as has been sug-

gested by Mendelson [38], but this requirement could

possibly act as a further deterrent because of the cost.

Indeed, it may be that the current impending shortage

of specialized breast radiologists would limit the

availability for this relatively labor-intensive task.

Difficulty with reproducibility inherent in

US techniques

Difficulty with reproducibility potentially limits

the ability to accurately monitor the ‘‘US-only’’

masses that are thought to be probably benign and

suitable for surveillance with follow-up examina-

tions. A certain amount of intraobserver, interob-

server, or both variability is to be expected. Having

the previous images available at the time of the

examination is critical. In addition to the location

indicated in the text of the report (ideally including

location on the clock face and distance from the

nipple in centimeters), the sonographer can then use

the appearance of the mass on the images, the mass

depth relative to the skin, and especially the pattern of

the surrounding normal tissues as a guide. In many

patients the adjacent subcutaneous fat and Cooper

ligaments and the distance from the skin and pectoral

muscle can act as landmarks to ensure that the same

mass is being examined and compared.

Small footprint probes are suboptimal for

survey scans

Commercially available, wider field-of-view

transducers minimize scan time, allowing a thorough

examination without omitting any tissue. Whole-

breast imaging can take as little as 2 to 3 minutes

when the breast is normal [29,30], though Buch-

berger et al [31] reported 10 to 15 minutes per patient,

Kaplan [33] reported 10 minutes, and Berg and

Gilbreath [18] reported 15 minutes on average (range,

10 to 45 minutes). More time is required to measure

and record masses, when they are encountered. These

time requirements are considerably greater than the

time spent, on average, reading a screening mammo-

gram. If the use of US as a second-level screening test

is to be implemented, automated scanners with higher

frequency transducers would ideally be developed.

Potential false-positives and subjective or

nonstandard thresholds for intervention

From a public health perspective, false-positive

findings and subjective or nonstandard intervention

thresholds are regarded as a harm to patients. How-

ever, all screening modalities with acceptable sen-

sitivity, including mammography, will result in the

detection of abnormalities that are not cancer. The

extent of false-positivity of US must be addressed

because the technique will not be practical if it is

unacceptably high. Stavros [11] and others [39,40]

have defined sonographic characteristics that allow

classification of masses, even when mammographic

criteria cannot be applied if masses are not mammo-

graphically visible. These could minimize the need for

percutaneous biopsy and allow surveillance for most.

Of the 424 of 750 masses that Stavros [11] predicted

would be benign based on US criteria, only 2 were

P.B. Gordon / Radiol Clin N Am 40 (2002) 431–441436

malignant. This 99.5% negative predictive value does

not significantly differ from the 98% negative pre-

dictive value possible for ‘‘probably benign masses’’

based on mammographic criteria [41,42], which is the

accepted standard of care.

In the studies conducted as screening examina-

tions, Kolb [30] performed 30 FNABs on complex

cysts and FNAB (n = 111) or surgical biopsy (n = 12)

in 123 of the 215 solid masses, leading to the

diagnosis of 11 cancers. Buchberger et al [31] per-

formed biopsies on all solid nodules: percutaneous

14-gauge core biopsies on 196 lesions and 24 surgical

biopsies after US-guided wire localization, leading to

the diagnosis of 23 cancers. Gordon and Golden-

berg’s [29] study was retrospective, and their patient

population comprised mixed screening and staging.

They did not indicate separate biopsy rates for masses

seen in these two groups of patients, but they did

perform FNAB on 279 of the 1575 solid masses seen

only on US, leading to the diagnosis of 30 cancers.

Hence, biopsy of a solid mass was performed on the

basis of US findings in 2% to 4% of examinations in

these studies, and the frequency of carcinoma among

US-only solid lesions for which biopsy samples were

taken was 7% to 11%.

Additional masses found in women known to

have breast cancer have a higher probability of

malignancy, regardless of their appearances, so a

lower threshold for recommending biopsy is appro-

priate in US performed for staging. Berg and Gil-

breath [18] performed US-guided, 14-gauge core

biopsy on all discrete solid lesions identified on US

of the ipsilateral breast in women with known breast

cancer or with high suspicion of breast cancer.

Ultimately, as with mammography, few masses

detected in this manner required surgical excision

because even those requiring tissue diagnosis because

of indeterminate imaging characteristics can be accu-

rately diagnosed with percutaneous biopsy [28].

Among 13 US-only lesions detected in the series of

Berg and Gilbreath [18], five (38%) were malignant.

In spite of the limitations described above, it

behooves us to continue searching for a second-level

screening test for breast cancer. Clinical breast exami-

nations and mammography are the gold standards,

but they are far from ideal. Delay in the diagnosis of

breast cancer is now the most frequent reason for

medical malpractice litigation in the United States.

For the sake of the women who are not optimally

served by screening mammography alone, to improve

our ability to find breast cancers as early as possible

and to live up to the public’s high expectations, we

must continue investigating new technologies. Feig

[43] has shown that even if women complied with

annual screening mammography, the calculated mor-

tality reduction would be only approximately 50%.

Other modalities for supplementary screening

and staging

It is hoped that full-field digital mammography,

with its higher contrast resolution, will mature into a

screening tool that misses fewer cancers than film-

screen mammography. So far this has not proved to

be the case. In a recent study in which 4945 full-field

digital mammography examinations were performed

in women 40 years and older presenting for screen-

ing, Lewin et al [44] found no difference in the cancer

detection rate when this procedure was compared

with film-screen mammography.

MRI for high-risk screening and preoperative

staging is under investigation, and it appears to be

sensitive but not specific. A significant limitation is

the inability to take biopsy samples easily of abnor-

malities found on MRI but not visible on mammog-

raphy or US. Biopsy-guidance devices are not

standard equipment on MRI units yet, though proto-

types are in development. Even when needle biopsy

or wire localization can be guided, some lesions are

seen only after contrast enhancement. With closed

magnets it is cumbersome to remove the patient from

the magnet to advance the needle or wire. Further-

more, by the time the patient is replaced in the

magnet, the contrast may wash out and the lesion

may no longer be visible. Additionally, the require-

ment of contrast for visualization of the lesion pre-

cludes the confirmation of adequate excision by the

use of specimen evaluation because the excised tissue

cannot be perfused ex vivo. It is interesting that US,

though not yet embraced for secondary screening or

even preoperative staging, has been recommended as

a ‘‘second-look’’ procedure for intervention when a

lesion is detected by MRI. Panizza et al [45], using

US in this manner, were able to find 11 masses,

including five cancers that had been found on MRI.

MRI demonstrates high sensitivity for breast can-

cer detection. Currently, however, its high cost,

variable specificity [46–50], and difficulties with

MRI-guided intervention may make it impractical

for widespread use as a supplementary screen for

high-risk women. Some of the same issues related to

breast MRI apply to positron-emission tomography

(PET). US appears to be less sensitive than MRI, but

it is lower in cost, more widely available, and readily

used to guide biopsies.

Technetium 99m sestamibi has been shown to be

74% sensitive and 89% specific for tumors larger

P.B. Gordon / Radiol Clin N Am 40 (2002) 431–441 437

than 1 cm, but it is considerably less sensitive (48%)

for smaller tumors [51]. The imperfect specificity is

also problematic: the technique is only quantitative,

and lesions cannot be evaluated for characterization.

Furthermore, there is now way to localize a lesion if it

is seen only scintigraphically.

When incidental masses are found during US

and are not palpable or visible on mammography

P.B. Gordon / Radiol Clin N Am 40 (2002) 431–441438

(even in retrospect), the recommendations regarding

tissue sampling versus short-interval follow-up must

be made on the basis of only the sonographic

appearance of the mass [11]. Clearly there will be

a degree of overlap between the appearances of

benign and malignant lesions. The decision to

biopsy or to recommend follow-up should be made

after discussion of both options with the patient,

considering the US impression, the patient’s age,

and clinical risk factors. Aside from the other

criteria used for US assessment, the fact that a

given mass is a US-only finding is, by definition,

considerably favorable. Tissue sampling should be

advised if a mass is at all worrisome based on its

appearance [11] or if there are significant clinical

risk factors. In staging US in a patient with known

cancer, the threshold for recommending a biopsy

should be lower than the one used in the screening

setting. The patient may prefer tissue diagnosis

rather than surveillance for her own peace of mind,

even if it is not advised.

Summary

The question then arises whether and for whom

BWBS should be recommended. As yet there are no

scientific criteria on which to base an answer, and

the examination should not be considered the stand-

ard of care until its benefits can be established

prospectively. We know that mass screening mam-

mography will detect occult cancers in two to seven

of every 1000 women screened, depending on

patient age and whether the screens are prevalence

or incidence examinations. Should we expect a

similar yield for survey US? Kopans [35] com-

mented that Kolb’s [30] cancer detection rate was

lower than would be expected from a mammo-

graphic prevalence screen. This was not a reasonable

comparison. These women all had negative findings

on screening mammography and would normally be

told to have repeat screening mammography 1 year

later. Kolb’s [30] cancer detection rate using US was

comparable to a mammographic incidence screen, so

the cancer diagnoses of these fortunate women were

advanced by 1 year.

To maximize the yield, it is obvious that US has

little to offer over mammography in women with

fatty breasts because mammography is less likely to

be falsely negative. The group of patients in whom

incidental cancers would be expected to be found

more commonly are those with dense breasts who

also are at higher-than-average risk either because

of a previous personal history of breast cancer

(Fig. 2) or a significant family history. Because it

would be impractical to consider BWBS for all

women with radiographically dense breasts, it

would be useful to know what its potential yield

would be in the relatively smaller group of high-

risk patients.

Annual mammography remains the standard of

care for breast cancer screening. However, in our

practice in Vancouver, I suggest that high-risk

women undergo mammography and US annually,

recognizing that this goes beyond the standard of

care. Instead of having both examinations simulta-

neously, I recommend that they alternate the two

modalities at 6-month intervals. Theoretically, this

could increase lead-time in the detection of occult

cancers. The usefulness of this approach remains to

be determined.

BWBS for staging in women known to have

breast cancer has tremendous promise and should

be considered for any breast cancer patient with dense

breast tissue in whom the finding of additional

unsuspected foci would change the planned manage-

ment. The cost of implementation would be sub-

stantial but considerably less than staging MRI. A

large-scale study comparing these two modalities is

needed, including assessment of the impact of iden-

tifying additional mammographically occult lesions

on breast cancer mortality.

Fig. 2. This 43-year-old woman had a history of left breast cancer treated by segmental resection, radiation, and chemotherapy

and a recent right breast fine wire-guided biopsy for calcifications that proved to be benign. She presented because of tender

thickening in the region of the scar on her left breast.

Craniocaudal (A) and mediolateral oblique (B) mammograms showed postoperative changes bilaterally, including surgical clips

and fat necrosis on the left and architectural distortion and probable fat necrosis on the right. The breast tissue was moderately

dense, BI-RADS 3. The right mediolateral oblique view was overexposed but was technically acceptable when viewed with a

bright light. There were no suspicious findings on either side.

US was performed on the left breast because of the clinical signs, but findings were negative. The right breast was scanned as a

deliberate screening examination. A small solid mass (C) measuring 1.1 � 0.6 � 0.7 cm was seen in the right upper, outer

quadrant. US-guided FNAB was performed, and cytology was suspicious for malignancy. Surgical histology showed grade II/III

invasive ductal carcinoma with associated ductal carcinoma in situ.

P.B. Gordon / Radiol Clin N Am 40 (2002) 431–441 439

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Breast cancer imaging with MRI

Elizabeth A. Morris, MD*

Weill Medical College, Cornell University, 525 East 68th Street, New York, NY 10021, USA

Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

The use of breast MRI for cancer detection has the

potential to change our current algorithms in the

detection and treatment of breast cancer. By being

able to detect cancer that is occult on conventional

imaging methods, such as mammography and sonog-

raphy, MRI can provide valuable information about

breast cancer that was up to this point unimaginable.

The robustness of this technique has generated con-

siderable enthusiasm, although this enthusiasm is

somewhat tempered by the fact that many unan-

swered questions remain regarding the integration

of MRI into clinical practice.

Many studies [1–6] suggest that breast MRI is best

used for situations where there is a high prior proba-

bility of cancer. For example, in the preoperative

evaluation of the patient with a known cancer, the

ability of MRI to detect multifocal and multicentric

disease that was previously unsuspected (Fig. 1) facili-

tates accurate staging [4–9]. Incidental contralateral

carcinomas have also been detected (Figs. 2, 3) [7,8].

Another indication that is promising, although not yet

established, is the use of MRI for high-risk screening

(Fig. 4), which is further discussed.

This article addresses current and evolving trends

in breast MRI for cancer detection. Terminology used

when describing lesions is reviewed, and examples

are presented. Emphasis is placed on image analysis

and potential pitfalls in image acquisition and inter-

pretation. Suggestions on how to perform optimal

studies are made, and clinical situations where MRI is

valuable in the work-up of breast lesions is discussed.

MRI for cancer detection

Breast MRI for cancer detection relies almost

exclusively on the fact that tumors generate neovascu-

larity to support their growth. The administration of an

intravenous contrast agent such as gadolinium-diethy-

lenetriamine penta-acetic acid (Gd-DTPA) allows

lesions to be well visualized, particularly if fat-sup-

pressed, T1-weighted images are used. Malignant

angiogenesis results in leaky capillaries and arterio-

venous shunts that allow the contrast agent to leave the

lesion rapidly, resulting in the wash-out time intensity

curves that can be seen with most but not all malig-

nancies. Detection of invasive breast carcinoma is

extremely reliable on MRI, with sensitivity approach-

ing 100%. False negatives have been reported with

well differentiated, invasive ductal carcinomas and

invasive lobular carcinoma [10]. Although the sensi-

tivity is high for invasive carcinoma, the same may

not be true for ductal carcinoma in situ (DCIS), for

which the sensitivity has been reported as low as 40%

[11–13], possibly secondary to more variable angio-

genesis in these lesions. Although more work needs to

be performed in the MR assessment of in situ disease,

the use of MRI to exclude preinvasive carcinoma is

imprudent with current technology. With these limi-

tations, breast MRI is best used as an adjunct test to

conventional imaging, complementing but not replac-

ing mammography and sonography. Mammographi-

cally suspicious findings, such as areas of distortion,

spiculation, or calcification, warrant appropriate

biopsy, regardless of a negative MR examination [14].

False positives may pose a problem in interpreta-

tion and are listed in Table 1, accounting for the lower

specificity that is reported with breast MRI. Reliance

on morphologic features may help reduce false-pos-

itive findings in some cases. If classic morphologic

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00005 -7

* Department of Radiology, Memorial Sloan-Kettering

Cancer Center, 1275 York Avenue Northwest, New York,

NY 10021.

E-mail address: morrise@mskcc.org (E.A. Morris).

Radiol Clin N Am 40 (2002) 443–466

signs are seen, such as non-enhancing bands in a

fibroadenoma (Fig. 5) or the reniform shape of a lymph

node (Fig. 6), the interpreter can be confident that the

lesion is benign. If classic benign lesion morphology is

not seen, time-intensity curves can be helpful in

deciding whether to biopsy a lesion (Fig. 7). If the

time-intensity curve does not exhibit wash-out (a

characteristic of malignant lesions), careful watchful

waiting may be an option over biopsy, although this

approach has yet to be validated clinically. A proposed

algorithm for image analysis is presented in Table 2.

Image acquisition

Proposed minimal requirements

Minimal technical requirements have been pro-

posed by the International Working Group for Breast

Fig. 2. A 58-year-old woman presented with a suspicious

mass at 6 o’clock in the right breast that was percutaneously

biopsied under ultrasound guidance yielding infiltrating

ductal carcinoma. (A) At the time of the ultrasound exam-

ination, there was a questionable second satellite lesion that

was confirmed on MRI (arrow). A single focus of infiltrating

ductal carcinomameasuring 1.9 cmwas found surgically with

abundant surrounding ductal carcinoma in situ (DCIS).

Margins were negative. (B) Contralateral screening MRI

depicts clumped of enhancement (arrow) that proved to be

incidental contralateral DCIS after MRI guided localization.

Fig. 1. A 45-year-old woman presented with new nipple

retraction and vague architectural distortion at 12 o’clock in

an extremely dense breast on mammography. Directed

ultrasound demonstrated multiple simple cysts but no solid

mass. (A) MRI depicts multiple heterogeneously enhancing

irregular masses in one quadrant compatible with multifocal

carcinoma. (B) MRI guided-needle localization with three

wires (arrowheads) brackets the region for attempt at con-

servation. Pathology yielded mixed lobular and ductal

carcinoma with positive margins for which the patient

underwent mastectomy. Note that the masses are not visible

on this delayed image because the masses have washed out

and the background parenchyma has slowly enhanced over

time. This and all subsequent images are post-Gd-DTPA

(0.1 mMol/kg) sagittal, fat-suppressed three-dimensional

FSPGR, T1-weighted images TR 17/TE 2.4, flip angle 35�,slice thickness � 2 mm, no gap, matrix 256 � 192.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466444

MRI [15] with the aim of detecting small lesions by

assessing lesion morphology and enhancement kinet-

ics. A dedicated breast coil must be used, preferably

one with localization or biopsy capability for MRI-

only detected lesions. So far in the literature, only

1.5-T systems have been validated; these systems

provide a high signal-to-noise ratio and allow fat

suppression to be performed. To detect lesions and

analyze morphology, high spatial resolution is rec-

ommended—1 mm in all planes. High temporal

resolution is recommended to facilitate enhancement

kinetic data gathering; each sequence should be

performed in less than 2 minutes. New imaging

sequences that are in development may allow both

high spatial and temporal resolution so that neither

one need be sacrificed [16,17]. To detect small

lesions and to decrease volume averaging, slice thick-

ness should be approximately 2 mm with no gap.

Fat suppression

The suppression of signal from fat is important for

increasing conspicuity of contrast-enhanced breast

lesions relative to the breast background tissue that

can contain variable amounts of high-signal fat. One

can suppress signal from fat by performing a fat

suppression technique or subtracting the precontrast

image from the postcontrast image. For diagnostic

purposes, if subtraction is the only method used,

misregistration from patient movement between the

pre- and the postcontrast images may result, possibly

rendering the examination uninterpretable. For this

reason, chemical-selective fat suppression is often

preferred and can be performed without excessively

increasing the imaging time. Fat suppression by

selectively identifying and suppressing the fat peak

can be performed manually or automatically. To

optimize fat suppression in the breasts, fat suppression

should be performed manually because the relative

water and fat content in women is highly variable. In

fatty breasts, the auto-pre-scan may erroneously iden-

tify the fat peak as water when setting the frequency,

resulting in incomplete fat suppression. Generally, this

problem is solved if manual prescan is used.

Memorial Sloan-Kettering Cancer Center protocol

At Memorial Sloan-Kettering Cancer Center, an

immobilization/biopsy coil from MRI Devices (Wau-

kesha, WI) is used to perform breast MRI on a 1.5-T

GE Signa (Milwaukee, WI) magnet. This system

allows for compression for diagnostic imaging and

interventional procedures. Sagittal fat-suppressed

T2-weighted images are initially obtained to assess

for cystic changes in the breast, manifested as high-

signal intensity. Then the entire breast is imaged

using a fat-suppressed, three-dimensional FSPGR

T1-weighted sequence. After Gd-DTPA administra-

tion (0.1mMol/kg), the same sequence is then repeated

three times immediately following one another. Slice

thickness is 2 to 3 mm without gap, depending on

breast thickness in compression; TR 17.1; TE 2.4;

flip angle 35�; bandwidth 31.25; matrix 256 � 192;

1 NEX; frequency in the AP direction. Image acquisi-

tion takes approximately 90 to 120 seconds. Com-

pression of the breast allows for a smaller volume of

breast tissue to be imaged, which can translate into

Fig. 3. A 50-year old-woman presented with vague thicken-

ing in the 12 o’clock axis of the right breast that was identified

on ultrasound and biopsied yielding infiltrating lobular carci-

noma. MRI was performed for to assess multicentricity and

bilaterality given the histology. (A) The index lesion is iden-

tified as a spiculated heterogeneously enhancing mass. (B) In

the contralateral breast, an unsuspected mass was identified

(arrow) that was not seen on ultrasound examination. MRI-

guided localization of the contralateral region was performed,

and pathology yielded infiltrating lobular carcinoma.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 445

shorter imaging time. Subtraction imaging is per-

formed in addition to fat suppression to evaluate

possible enhancement of high signal areas on the

TI-weighted images. Images are read out on a GE

picture archiving and communication system (PACS),

which is ideal for comparing prior studies and for

windowing-appropriately. Prior mammograms and

breast ultrasound examinations are available. If a

time-intensity curve needs to be generated, a work-

station is available. It is helpful to train an MRI

technologist to perform time-intensity curves so that

the radiologist’s workflow is not interrupted.

For performing diagnostic MR examinations, an

MRI technologist, who can be trained in positioning

of the breast within the breast coil, is essential. As

with mammography, image quality depends on opti-

mal positioning. The breast should be pulled away

from the chest wall by the MRI technologist as much

as possible and placed in the center of the coil to

image the entire breast and reduce artifacts. If a

compression plate is used for immobilization, this

can be adjusted so that the medial breast tissue and

axillary tail are not excluded. It is helpful for the MRI

technologist to have a calm and reassuring manner to

facilitate patient cooperation. For interventional pro-

cedures, it is helpful to include the mammography

technologist who is trained in interventional breast

procedures in addition to the MRI technologist who is

trained in image acquisition.

Fig. 4. Screen-detected cancer. A high-risk 50-year-old woman who had undergone contralateral mastectomy was on

chemoprevention and studied yearly with breast MRI. Screening MR examination depicts an interval heterogeneously enhancing

irregular mass (arrow) in the axillary tail. A directed ultrasound of this region yielded a subtle solid mass that underwent

ultrasound-guided core biopsy. Pathology yielded infiltrating ductal carcinoma, histologically different from the contralateral

carcinoma. Nodal status was negative.

Table 1

False positive on breast MRI

Fibroadenoma

Lobular carcinoma in situ

Ductal atypia

Fibrocystic changes

Proliferative changes

Papilloma

Sclerosing adenosis

Duct hyperplasia

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466446

At Memorial Sloan-Kettering Cancer Center, de-

tailed clinical and physical examination information

is required on the MRI requisition. A breast imager

protocols the examination in advance. When the

patient arrives, a nurse performs an intake question-

naire that gathers information on surgical history,

family history, last menstrual period, hormone

replacement treatment, and date and place of last

Fig. 5. A 44-year-old woman with a history of fibrocystic disease. Lobulated homogeneously enhancing mass with dark non-

enhancing internal septations is characteristic of a fibroadenoma, and, if seen, a benign diagnosis can be made.

Fig. 6. Lymph nodes (arrows). (A) Reniform homogeneous enhancement. (B) Note that a vessel can be seen entering the lymph

node hilum, a helpful sign that the lesion may represent a lymph node.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 447

mammogram and ultrasound, if not brought with the

patient or not performed at our institution. The nurse

draws on a preprinted diagram any scars, areas of

discoloration, or lumps and then marks the breast

with vitamin E capsules over any areas of palpable

abnormality and sites of prior surgery. The patient’s

prior films are available at the time of interpretation

so that correlation with the mammogram and sono-

gram can be made.

Image analysis

Breast MRI lexicon

Breast MRI analysis relies on both the morphol-

ogy and kinetics of the lesion. The American College

of Radiology (ACR) is supporting a group of interna-

tional experts to develop a lexicon to standardize

terminology and reporting [18–20]. The ACR breast

Fig. 7. Time intensity curves. Type I curve is continuous enhancement. Type II curve reaches a plateau. Type III curve washes out

where there is a decrease in signal intensity after peak enhancement.

Table 2

Suggested algorithm for image interpretation

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466448

MRI lexicon is a work in progress and is modeled on

the BI-RADSTM lexicon [21] for morphology and

also incorporating the dynamic enhancement proper-

ties of the lesion. Although the lexicon is still in

evolution, several descriptions are presented in this

paper so that readers can acquaint themselves with

pertinent terminology (Table 3).

When reporting findings, the International Work-

ing Group on Breast MRI recommends that a clinical

statement and a description of the technique used be

included in the report. Lesions should be described

using standardized terminology from the developing

breast MRI lexicon, and a final assessment recom-

mendation should be made so that the referring

clinician understands the next appropriate step in

the work-up of the lesion.

Morphology

When analyzing an enhancing lesion on MRI,

the first distinction is to decide if the finding is a

focus, mass, or nonmass (Table 3). Further descrip-

tion of the lesion will depend on this distinction. It

is often difficult to define what is a focus or a mass.

A focus is defined as a tiny spot of enhancement

that is a dot and does not occupy space (Fig. 8).

Most of the tiny foci of enhancement are a few

millimeters in size and appear round and smooth.

Some examples of small areas of enhancement that

are not smoothly marginated and are slightly larger

than true ‘‘foci’’ are shown in Fig. 9. These exam-

ples represent DCIS at surgery following MR-

guided needle localization. When innumerable foci

are present, the breast has a characteristically benign

‘‘stippled’’ appearance (Fig. 10).

What should one do with foci of enhancement?

If the lesion meets the criteria of a focus and is not a

space-occupying mass, then one may elect to do

nothing, although long-term follow-up studies have

not documented this approach, and these studies

need to be performed. If at all concerned when

interpreting an examination, short-term follow-up

may be warranted, although this has yet to be

proven as cost effective and efficacious. Follow-up

may be an option in a premenopausal patient or a

postmenopausal patient on hormones in whom there

is suspicion that the foci are hormone related.

Studies have shown that small areas of enhance-

ment, when present in patients with a known pri-

mary breast carcinoma [22], are more likely to

represent malignancy, but further study is necessary

to address this issue.

Investigators have analyzed architectural features

of MR-detected masses and nonmass lesions, result-

ing in the development of interpretation models

[23,24]. These studies have shown that smooth

(Fig. 11) or lobulated borders (Fig. 5) have a high

negative predictive value for carcinoma (95% and

90%, respectively). Spiculated (Fig. 12) and irregular

(Fig. 13) margins have high positive predictive value

for malignancy (91% and 81%, respectively). Rim

enhancement (Fig. 14) has an 86% predictive value

for malignancy [24]. To demonstrate that these

descriptors may co-exist, a carcinoma is shown with

lobulated shape, a benign finding, and rim enhance-

ment, a malignant finding (Fig. 15). This illustrates

that the most suspicious feature, in this case rim

enhancement, is the most pertinent morphologic

finding directing further work-up.

Nonmass enhancement, such as ductal enhance-

ment, has a positive predictive value of malignancy

of 85% [24] (Fig. 16). Clumped enhancement can be

arranged within a single ductal system, generating a

segmental enhancement pattern on MRI (Fig. 17);

when seen, this is suspicious for DCIS (Fig. 18).

Table 3

Preliminary ACR breast MRI lexicon (work in progress)a

Focus/foci

Mass enhancement Non-mass enhancement

Linear

Segmental

Regional

Diffuse

Margins Descriptors linear

Smooth Smooth

Irregular Irregular

Spiculated Clumped

Shape

Oval

Descriptors segmental/

regional/diffuse

Round Homogeneous

Lobulated Heterogeneous

Irregular Clumped

Septal/dendritic

Enhancement pattern

Homogeneous

Heterogeneous

Rim

Non-enhancing septations

Enhancing septations

Central enhancement

a Members of the lexicon working group: Debra Ikeda,

MD; Nola Hylton, PhD; Mitchell Schnall, MD, PhD; Steven

Harms, MD; Jeffrey Weinreb, MD; Werner Kaiser, MD,

PhD; Mary Hochman, MD; Karen Kinkel, MD; Christiane

Kuhl, MD, PhD; John Lewin, MD; Elizabeth Morris, MD;

Petra Wiehweg, MD, PhD; Hadassa Degani, PhD, Stanley

Smazal, MD.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 449

Regional enhancement (Fig. 19) can be seen with

both benign and malignant disease and has a negative

predictive value of 53% [24]. A unique descriptor

that is used in the case of inflammatory carcinoma

with diffuse enhancement is reticular (Fig. 20), where

there is no underlying mass and the enhancement

pattern appears lace-like.

Kinetics

Enhancement kinetic analysis evaluates what hap-

pens to the intravenous contrast within a lesion over a

period of time. Signal intensity (SI) increase follow-

ing contrast administration (SIpost) is measured rela-

tive to precontrast level (SIpre):

½ðSIpost�SIpreÞ� � 100%

When plotted, time/signal intensity curves are gen-

erated and can provide further information about the

vascular properties of a lesion. They generally require

at least several time points, with the first being at time

zero when there is no contrast within the lesion. To

generate these time points, the breast must be scanned

and rescanned many times following intravenous con-

trast bolus injection. The more time points desired in a

certain time frame, the faster the acquisition. Just what

Fig. 8. Foci of enhancement (arrows) in two patients with dense breasts on mammography.

Fig. 9. Suspicious areas of enhancement that are not foci. (A) Spiculated solitary tiny area of enhancement (arrow) in a woman

with a strong family history proved to represent DCIS at surgery following MR-guided needle localization. (B) Two small areas

of spiculated enhancement (arrows) also proved to represent DCIS in a 59-year-old woman with documented infiltrating ductal

carcinoma in a separate quadrant.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466450

constitutes an adequate time/signal curve is a matter

of debate. Most imagers agree that each dynamic

scan should be less than 2 minutes; however, the

faster the dynamic scan, the less the resolution.

Therefore, a compromise must be reached.

There are three general types of time-intensity

curves (Fig. 7) [25]. Type I is continuous progressive

enhancement over time, indicating that contrast accu-

mulates within the lesion, typically seen with benign

findings. Type III is a washout curve, indicating that

after the lesion takes up contrast, the contrast

promptly washes out, presumably by leaky capillaries

and shunts found in malignant lesions. Type II is a

plateau curve that is a combination of a Type I and a

Type III curve and can be seen with both benign and

malignant lesions.

Pitfalls in analysis

Clip artifact

Clips in the breast can cause difficulties in inter-

pretation. Clips used in surgery are generally made of

titanium and cause susceptibility artifact that presents

as a signal void with adjacent linear high signal that

Fig. 10. Examples of benign stippled enhancement in three pre-menopausal women. Note the low signal cyst (arrow) in panel A.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 451

should not be misinterpreted as residual or recurrent

disease at the lumpectomy site (Fig. 21). Surgical clips

that are placed at the time of lumpectomy will produce

more artifact than a clip placed at the time of stereo-

Fig. 11. Round homogeneously enhancing masses (arrows) with smooth borders. (A) Fibroadenoma at biopsy. (B) Fat

necrosis at biopsy

Fig. 12. Spiculated heterogeneously enhancing mass corresponding to infiltrating ductal carcinoma.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466452

tactic biopsy because they are larger and usually more

numerous. The detection of recurrence when the

patient is months to years out from surgery will there-

fore be limited in a patient with a large number of clips

in the lumpectomy bed. Detection of residual disease

following surgery, however, is not as compromised

(Fig. 22) because a seroma is generally present in the

immediate postoperative period. Although seroma

cavities are variable in size, they are fluid filled,

generally allowing detection of residual disease along

the margin of the seroma cavity. Similarly, with stereo-

tactically placed clips, it is possible to detect small

amounts of residual disease adjacent to the biopsy site

because the amount of artifact is almost negligible.

Fat suppression

Inhomogeneous fat suppression (Fig. 23) can se-

verely compromise image quality and generally results

in a scan that is uninterpretable. Technologists should

perform manual fat suppression, if possible. In our

practice, if all efforts fall short of adequate fat sup-

pression, the patient will be brought back on another

day to repeat the examination at no extra charge. Inter-

preting a study that is technically suboptimal leads to

interpretation errors and possibly to legal redress.

Window levels

When interpreting breast MR examinations, appro-

priate windowing is essential for accurate morphologic

analysis. Fig. 24 shows how appropriate windowing

may change the diagnosis from a potentially suspi-

cious lesion to an obviously benign fibroadenoma.

When reading images on a monitor, such as PACS,

manipulation of the contrast and brightness levels is

feasible and allows the radiologist greater freedom to

window appropriately. When reading hard-copy film,

where the brightness and contrast levels are set, there is

less freedom, although one should not hesitate to

interpret from the MR monitor or work station.

Misregistration

We have found it very helpful to perform sub-

traction imaging because it can be difficult to deter-

Fig. 13. Irregular heterogeneously enhancing mass in a 41-year-old woman. Pathology yielded infiltrating ductal carcinoma.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 453

mine whether high-signal masses on the precontrast,

T1-weighted images enhance the postcontrast T1-

weighted images. Because the masses appear bright

on both the pre-and postcontrast images, subtle

enhancement may be missed. It should be realized

that when performing subtraction, a small degree of

movement of the patient translates into signal mis-

registration (Fig. 25). A non-enhancing lesion may

erroneously appear to show enhancement because

the high signals on the pre- and postcontrast images

do not get subtracted as the patient changes posi-

tion between the two acquisitions. If one relies

solely on subtraction for image interpretation,

image quality is not as reliable, and lesions may

be missed as well as over-read. For this reason, fat-

suppressed images may be preferred for lesion

analysis, and subtraction images may be used for

supplemental information.

Delayed imaging time

If image acquisition is delayed more than 2minutes

(Fig. 26) or if the image sequence itself takes more

than 2 minutes, there may be a problem with diffuse

parenchymal enhancement obscuring an underlying

lesion. If the scan is delayed for more than 2 minutes

after giving the contrast bolus, the diagnostic quality

of the examination is questionable. In our practice, if a

mishap occurs after contrast injection and we are

Fig. 14. Irregular rim-enhancing mass proved to represent infiltrating ductal carcinoma. Note the adjacent satellite lesion (arrow).

Fig. 15. Lobulated rim-enhancing infiltrating ductal carci-

noma in a 46-year-old woman who underwent MRI to assess

if breast conservation was feasible.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466454

unable to image quickly in the first several minutes,

the patient returns for a repeat scan on a subsequent

day to ensure that a high-diagnostic-quality test

is performed.

Unilateral examinations

In general, those centers using high-resolution

techniques have confined their practices to unilateral

Fig. 16. (A) Incidental linear irregular enhancement (arrow)

in a 50-year-old woman with a prior history of infiltrating

lobular carcinoma 5 years ago in the right breast. Note artifact

from clips (arrowheads) in the superior breast at the prior

lumpectomy site. Pathology yielded ductal carcinoma in situ

(DCIS). The MRI was performed for a palpable abnormality

in the contralateral left breast that also proved to represent

DCIS. The patient opted for bilateral mastectomy. (B) Linear

irregular enhancement in a ductal distribution in a 48-year-old

woman with a history of bilateral lumpectomies. Mammog-

raphy was negative. Subsequent MR localization demon-

strated DCIS.

Fig. 17. (A) A 66-year-old woman with bloody nipple

discharge, negative mammogram, and an unsuccessful

attempt at ductography. Linear irregular enhancement in a

segmental distribution (arrows) was found on MRI, which

was localized under MRI guidance and corresponded to

ductal carcinoma in situ (DCIS), detected only on MRI. At

mastectomy, no invasive carcinoma was identified. (B)

Clumped linear and nonlinear enhancement representing

DCIS in a 47-year-old woman with palpable fullness in the

lower breast for which MRI was performed. Mammog-

raphy and ultrasonography were negative. On multiple

sagittal sections (not shown) the entire lower breast

contained suspicious clumped enhancement.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 455

examinations, and those using high-temporal techni-

ques have performed bilateral examinations. Per-

forming a bilateral examination allows contralateral

cancers to be detected and comparison with the

contralateral breast tissue and patterns of enhance-

ment. Investigators have found that incidental con-

tralateral cancers in patients undergoing breast MRI

are detected [7,8]. Additionally, enhancement in dif-

fuse carcinoma can be difficult to differentiate from

diffuse parenchymal enhancement if there is no

dominant mass and if the tumor diffusely infiltrates

the breast. Having the contralateral breast to compare

with may prevent an erroneous benign interpretation

in diffuse carcinoma (Fig. 27). Time-intensity en-

hancement curves are also invaluable in the assess-

ment of diffuse enhancement.

Performing a bilateral examination with the cur-

rent available imaging sequences poses a unique set

of problems. Images of both breasts may be acquired

simultaneously with a large field of view; however,

Fig. 18. Paget disease. A 45-year-old woman presented with

Paget disease of the nipple. The breast was fatty, and

mammography was negative. MRI depicts clumped linear

enhancement in a segmental distribution (arrows) that proved

to represent extensive ductal carcinoma in situ, resulting

in mastectomy.

Fig. 19. Regional enhancement (arrows). (A) Regional

heterogeneous enhancement in a patient with locally

advanced breast carcinoma. (B) Regional homogeneous

enhancement in a patient with fibrocystic changes.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466456

spatial resolution is usually sacrificed with this

method. Because we have performed high spatial

resolution examinations to detect small lesions, imag-

ing is alternated between each breast following con-

trast administration. Although not ideal, it has

allowed us to maintain spatial resolution with mini-

mal sacrifice to temporal resolution. The breast of

interest is always the first postcontrast acquisition.

Research into new MR sequences that allow both

high spatial as well as temporal resolution is needed

for bilateral imaging and is currently underway

[16,17].

Patient selection

Difficult histologies

Selection criteria for breast MRI include preop-

erative staging, particularly in difficult histologies

(infiltrating lobular carcinoma and tumors with ex-

tensive intraductal component), where tumor size

assessment is difficult. Infiltrating lobular carcinoma

is notoriously difficult to detect on mammography,

and MRI has been shown to better assess the extent

of disease compared with mammography [26,27].

MRI can demonstrate unsuspected DCIS, which can

be helpful when assessing extent of disease in

preoperative staging. Extensive intraductal compo-

nent (EIC) is present when > 25% of the tumor is

DCIS. EIC is associated with residual carcinoma

and positive margins after lumpectomy, and there is

some evidence that the presence of extensive intra-

ductal component may indicate an increased risk of

local recurrence.

Fig. 20. Diffuse enhancement in a reticular pattern in a

woman with clinically apparent inflammatory breast carci-

noma. Note enhancement of the thickened skin indicating

the inflammatory component.

Fig. 22. A 69-year-old woman who presented for a second

opinion following conservation therapy yielding infiltrat-

ing ductal carcinoma with positive margins. MRI depicts

residual infiltrating ductal carcinoma seen as a heteroge-

neously enhancing lobulated mass (long arrow) adjacent to

the postlumpectomy seroma cavity (short arrows). Note the

adjacent high signal cyst (open arrow) that did not

demonstrate enhancement. Elsewhere in the breast another

suspicious mass (not shown) was identified that was

biopsied percutaneously, and the patient ultimately under-

went mastectomy.

Fig. 21. Clip artifact. Note artifact (arrows) where high

signal is adjacent to low signal that should not be

interpreted as enhancement. Subtraction imaging can aid

in this differentiation.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 457

Staging

Breast MRI can give helpful information for stag-

ing tumor size, multicentricity, chest wall, or pecto-

ralis muscle invasion. MR defines the anatomic extent

of disease more accurately than mammography, par-

ticularly in tumors with difficult histologies, such as

those discussed above.

Several investigators have shown that MRI is able

to detect additional foci of disease (Fig. 28) in up to

one third of patients [4,5], possibly resulting in a

treatment change [7]. MRI can provide valuable

information for preoperative planning in the single-

stage resection of breast cancer [9].

Chest wall involvement is an important considera-

tion for the surgeon before surgical planning. Mam-

Fig. 23. Inhomogeneous fat suppression. (A) Focal (arrow); (B) diffuse.

Fig. 24. Suboptimal windowing. (A) High contrast and high brightness obscures evaluation of the internal architecture of

the lesions. (B) Lower contrast and brightness show non-enhancing internal septations in both lesions, confirming that

these are fibroadenomas.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466458

mography does not image the ribs, intercostal

muscles, and serratus anterior muscle that comprise

the chest wall. Tumor involvement of the chest wall

changes the patient’s stage to IIIB, indicating that the

patient may benefit from neo-adjuvant chemotherapy

before surgery (Fig. 29). Tumor involvement of the

pectoralis muscle does not alter staging, and surgery

can usually proceed; however, knowledge that the

muscle is involved may alter the surgeon’s plan. For

example, if the full thickness of the pectoralis major

muscle is involved with tumor, the surgeon may be

more inclined to perform a radical instead of a

modified radical mastectomy [28].

Controversies about MR staging include the pos-

sibility that MRI may identify cancer that is currently

adequately treated with adjuvant chemotherapy and

Fig. 25. Misregistration artifact caused by patient motion between the precontrast and postcontrast images. (A) precontrast image

demonstrates high signal in a duct in the retroareolar location, possibly representing proteinaceous debris or hemorrhage.

(B) Postcontrast image shows the same high signal. It is not clear if enhancement has occurred. (C) Subtraction image documents

no significant enhancement. The interpreter should not misinterpret the thin high signal (arrows), which is caused by mis-

registration as enhancement.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 459

radiation therapy, especially DCIS. If that is true, then

what size lesion can we safely ignore on MRI? These

questions lead to a broader question: Is MRI too

sensitive in detecting cancer in general? For our

current treatment algorithms, this may be the case in

certain situations. MRI may detect subclinical disease

that may never have been clinically relevant. On the

other hand, MRI does detect additional disease that

would clearly not be treated with adjuvant therapy.

The challenge is in knowing what is significant and

what is not so that the patient is counseled on

appropriate therapy options. Trials that involve radi-

ologists, radiation oncologists, and surgeons are

needed to answer these perplexing questions.

Fig. 26. Importance of early imaging. Image acquisition should occur within the (A) first 2 minutes after contrast administration.

If delayed, early enhancement and rapid washout in malignancy may be missed, and the background enhancement may obscure

any significant lesion as seen on this 6 minutes postcontrast image (B).

Fig. 27. Bilateral examination. (A) A 50-year-old woman with diffuse enhancement throughout the breast but no focal mass. This

image may be mistaken for diffuse parenchymal enhancement without the benefit of comparison with the contralateral breast.

(B) The contralateral breast demonstrates no enhancement, therefore suggesting that the diffuse enhancement is suspicious.

Subsequent biopsy demonstrated diffuse infiltrating ductal carcinoma.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466460

With our current treatment protocols it is imper-

ative to verify all suspicious breast MRI lesions as

cancer before submitting the patient to a mastectomy.

If preoperative histologic verification of additional

lesions is not performed, there is the potential to deny

breast conservation to women who would have oth-

erwise been candidates.

Neo-adjuvant chemotherapy response

MRI can assess response to neo-adjuvant chemo-

therapy for locally advanced breast cancer. A com-

plete pathologic response (elimination of tumor)

following neo-adjuvant therapy is strongly predictive

of excellent long-term survival. Minimal response

(Fig. 30) suggests a poor long-term survival regard-

less of postoperative therapy. MRI may be able to

predict earlier than is now possible which patients are

responding to neo-adjuvant chemotherapy because the

mammogram and physical examination may be com-

promised because of fibrosis. Investigators [29,30]

are assessing if residual tumor measurements corre-

late with the pathologic residual disease following

neo-adjuvant chemotherapy. Patterns of response are

Fig. 28. A 46-year-old woman with a strong family history and dense breasts underwent screening ultrasound, which demonstrated

a solitary solid mass. MRI was performed for assessment of disease extent. (A) Multiple irregular heterogeneously enhancing

masses proved to represent sites of mammographically occult carcinoma. (B) Another mass in the ipsilateral breast proved to

represent additional areas of infiltrating ductal carcinoma. (C) Incidental contralateral ductal carcinoma in situ was also found.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 461

being evaluated in the hope that these findings may

predict recurrence and survival [31].

Assessment of residual disease

For patients who have undergone lumpectomy

and have positive margins and no evidence of resid-

ual disease on mammography, MRI can be helpful in

the assessment of residual tumor load (Fig. 31).

Postoperative mammography detects residual calcifi-

cations [32], although it is limited for the evaluation

of residual mass. MRI detects residual masses and

determines whether the patient would be best served

with re-excision or whether the patient warrants

mastectomy. Before mastectomy, it is important to

verify other suspicious sites seen only on MRI. In one

study [33], MRI detected residual disease in 23/33

(70%) and alone identified multifocal or multicentric

disease in 9/33 (27%).

Tumor recurrence at the lumpectomy site

Tumor recurrence after conservation occurs at a

rate of 1% to 2% per year. Recurrence at the lumpec-

tomy site occurs earlier than elsewhere in the breast.

Evaluation of the lumpectomy site is limited because

of postoperative scarring, and physical examination

may have greater sensitivity than mammography in

the detection of recurrence. Mammography detects

25% to 45% of recurrences and is more likely to

detect noninvasive recurrences with calcifications

than invasive recurrences without calcifications,

although histology of most recurrences is invasive

[34]. All recurrences in one study [35] with nodular

enhancement in all cases of invasive carcinoma

(Fig. 32), and linear enhancement was observed in

the cases of DCIS recurrence. The majority of scars

showed no enhancement [36].

When to image for potential recurrence is problem-

atic because scar tissue can enhance for years follow-

ing surgery. Recurrence peaks in the first few years

following surgery, and the most likely site of recur-

rence is the lumpectomy site; therefore, the usefulness

of the information obtained from a costly MRI study

needs to be weighed against that obtained from a

potentially less expensive needle biopsy of the area.

Occult primary breast cancer

Patients presenting with axillary metastases sus-

picious for primary breast cancer and a negative

physical examination and negative mammogram are

Fig. 29. A 53-year-old woman presents with a 5-cm palpable mass that was seen mammographically. MRI was performed for

extent of disease assessment because it was not clear if the patient was a candidate for conservation therapy. (A) MRI depicts the

dominant mass (arrow), pectoralis muscle invasion (curved arrow), and chest wall invasion (open arrow) where the tumor

extends into the intercostal muscles. It was decided to give the patient neoadjuvant therapy before surgery. (B) Follow-up MRI

shows that the patient did not respond to chemotherapy as the mass has increased in size. There is now tumor involving the skin,

compatible with inflammatory cancer.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466462

Fig. 31. A 45-year-old woman who presented with thickening and a negative mammogram showing extremely dense breasts.

Biopsy done revealed ductal carcinoma in situ with multiple positive margins. MRI, performed 2 weeks after surgery and depicts

a seroma (small arrows) with abundant surrounding clumped enhancement in a segmental distribution (large arrows) involving

an entire quadrant from the pectoralis muscle to the nipple. Re-excision yielded positive margins. Because the patient refused

mastectomy, a third excision was performed that obtained negative margins.

Fig. 30. Response to neo-adjuvant chemotherapy for stage III breast cancer. (A) Multiple irregular and spiculated masses are seen

in the upper breast in this 57-year-old woman with biopsy-proven infiltrating lobular carcinoma who presented with a palpable

mass but with a mammogram that demonstrated diffuse increase in density in the upper outer quadrant. MRI was performed for

assessment of disease extent. Findings on MRI confirmed the presence of a 9-cm mass. (B) Following three cycles of

chemotherapy, there is no appreciable response.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466 463

ideal candidates for MRI because of the high

sensitivity of MRI for invasive carcinoma [37]. In

patients with this presentation, MRI has been able to

detect cancer in 90% to 100% of cases if a tumor is

indeed present [38,39]. The tumors are generally

small in size (< 2 cm) and may evade detection by

conventional imaging.

The ability to detect a site of malignancy in this

rare presentation of breast cancer is important ther-

apeutically. Patients traditionally undergo mastec-

tomy because the primary site is unknown. Whole-

breast radiation can be given, although it is generally

not recommended because, although the survival rate

is equal to that for mastectomy, the recurrence rate is

up to 23% higher [40]. The results of MRI can have a

significant impact on patient management. In one

study, the results of the MR examination changed

therapy in approximately one half of cases, usually

allowing conservation in lieu of mastectomy [41].

High-risk screening

A potential future use of breast MRI is high-risk

screening for patients who are premenopausal with

dense breasts. Because mammography has a false-

negative rate of up to 15% and is perhaps more

limited in this population, there has been exploration

into alternative screening methods. Of the available

methods, MRI holds the most promise, mostly

because the high-resolution capabilities and the

potential to detect preinvasive DCIS. The use of

breast MRI in this population is experimental at the

time of this writing. The data to determine the

appropriateness of MR for screening high-risk

patients are presently being acquired in several

ongoing studies in the United States and elsewhere,

and the use of MR for screening is currently unjus-

tified outside a study protocol. Furthermore, no

information exists for screening ‘‘dense, difficult to

examine’’ breasts in patients for whom there is no

significant family or personal history of breast cancer.

Screening by MRI in this population where the

incidence of breast cancer is low would likely result

in too many false-positive interpretations to justify

its use.

BRCA 1 or 2 carriers are a group of high-risk

patients who have an up to 85% risk of developing

breast cancer over their lifetime. The onset of

inherited breast cancer is earlier than sporadic cases,

and the prevalence of bilaterality is higher. One study

[42] showed that MRI was able to detect, mammo-

graphically and sonographically occult breast cancers

in a group of patients who were known or suspected

carriers of either the BRCA 1 or 2 gene. Nine cancers

were detected in a group of 192 women; three of

these cancers were detected on MRI only, indicating a

frequency of ‘‘MRI-only’’ cancers of 2%. All were

pT1 and node negative. Although these results are

Fig. 32. Evaluation of recurrence at the lumpectomy site following breast conservation 3 years prior in a 34-year-old woman.

(A) MR examination following lumpectomy depicts a linear enhancing scar (arrow) between two clips (arrowheads) visualized

as signal void. Recurrence at the lumpectomy site is demonstrated in another patient. (B) A different 36-year-old woman

underwent lumpectomy 1 year ago and had a screening ultrasound that found a small mass adjacent to the lumpectomy site. MR

examination confirmed the recurrence as a rim-enhancing mass (arrow). Mammography was unremarkable in both patients.

E.A. Morris / Radiol Clin N Am 40 (2002) 443–466464

encouraging, applying this technology to the high-

risk population at large is not advocated at this time.

Larger studies need to be performed to validate these

data. If validated, a definition of what constitutes

‘‘high-risk’’ is needed. Ultimately, MRI needs to be

shown not to result in too many false-positive inter-

pretations and needs to be cost-effective, important

criteria for a screening test.

Summary

Breast MRI is an emerging technology that may

revolutionize our management of women with known

or suspected breast cancer. MRI examinations should

be interpreted with an awareness of the pitfalls and

artifacts that can affect on image evaluation. Develop-

ment of an MRI lexicon will assist by providing

standardized terminology that may improve our under-

standing of the positive predictive value of different

MRI features. To date, breast MRI has proven most

useful in patients with proven breast cancer to assess

for multifocal/multicentric disease, chest wall involve-

ment, chemotherapy response, or tumor recurrence or

to identify the primary site in patients with occult

breast cancer. Further work is necessary to assess the

utility of breast MRI in other settings, such as screen-

ing of women at high risk for breast cancer.

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E.A. Morris / Radiol Clin N Am 40 (2002) 443–466466

New modalities in breast imaging: digital mammography,

positron emission tomography, and

sestamibi scintimammography

Jessica W.T. Leung, MD

Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School,

75 Francis Street, Boston, MA 02115, USA

With an incidence of more than 180,000 cases per

year, breast cancer is the second leading cause of

cancer deaths among women in the United States.

The wi-despread implementation of screening mam-

mography has resulted in earlier detection of breast

cancer, reducing both the morbidity and mortality of

the disease. Several large-scale controlled trials have

shown that screening mammography is efficacious

and can reduce breast cancer mortality by 18% to

30% [1,2].

Conventional screening mammography consists

of screen-film images. Screen-film mammography

(SFM) fails to detect 10% to 20% of palpable breast

cancers, particularly in the dense breast where there is

insufficient contrast difference between normal and

cancerous tissues [3,4]. Furthermore, the positive

predictive value of SFM for cancer is less than 50%

(range of 5% to 40%) [5,6], so more than half of the

biopsies performed result in benign diagnoses. Even

if a biopsy is not performed, excessive recall imaging

decreases the cost-effectiveness of screening mam-

mography and increases patient anxiety.

This article is devoted to three new modalities in

breast cancer screening. It focuses on digital mam-

mography (DM), which has received much attention

and interest within both the radiology community and

the general public. This chapter also examines the

roles of positron emission tomography (PET) and

sestamibi scintimammography in breast cancer

screening and breast imaging.

Digital mammography

Broadly speaking, DM encompasses two distinct

technologies. One use of the term refers to the

digitization (by means of optical scanners and

computers) of screen-film mammograms. Whereas

this technique allows for computerized processing

and storage, the original image must be obtained

initially using analog screen-film techniques. Hence,

the digitized image remains limited by the quality

of the original analog mammogram. True DM refers

to the use of dedicated equipment for obtaining the

initial image in the digital form, using detector and

display systems that are distinct from those of

SFM. This latter meaning of DM is the subject of

this chapter.

Functional components

In SFM, the emulsion film serves multiple func-

tions: image acquisition mechanism, display unit, and

storage device. In DM, these tasks are performed by

separate components, enabling the optimal perform-

ance of each component. This decoupling is the key

underlying the technical success of DM.

Image acquisition

In SFM, x-ray photons cause light emission from

a phosphor screen, which then imprints a latent image

upon the film emulsion. Photographic processing

produces a permanent film image that is the final

mammogram. In DM, x-ray photons strike the digital

detector, and the photons are absorbed by a phosphor

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00004 -5

E-mail address: jleung@partners.org (J.W.T. Leung).

Radiol Clin N Am 40 (2002) 467–482

material. The absorbed energy is then converted into

an electronic (rather than a light) signal. The signal is

received, processed, and stored as a matrix (repre-

senting the image) in a computer. The spatial reso-

lution of DM (9–10 line-pairs per mm) is comparable

to that of SFM (9–12 line-pairs per mm).

As the image acquisition device, the digital detec-

tor offers several advantages over emulsion film. The

electronic output signal of the digital detector is

linearly proportional to the transmitted x-ray inten-

sity, in contrast to the sigmoidal Hurter and Driffield

curve found in emulsion film. Thus, DM has a wide

dynamic range (1000:1 compared with 40:1 of SFM)

[7]. This wide dynamic range translates into higher

contrast resolution, particularly in the dense breast.

Furthermore, read-out of the digital detector is

extremely rapid, occurring in an average of 0.3

second. Noise is reduced because there is no signifi-

cant quantum mottle effect and no granular artifact

from film emulsion [7,8]. Because of efficient photon

absorption by the digital detector, the radiation dose

(depending on the system) may be less than that in

SFM [9]. Certain systems (eg, Fischer) use the slot-

scanning technique, which eliminates the use of the

grid and further reduces radiation dose [7].

Image processing

Rather than a single, unalterable, permanent

mammographic image, DM allows for postacquisi-

tion image processing. This unique aspect of DM

promises to be a significant advantage over SFM be-

cause it provides diagnostic information without ex-

posing the patient to additional radiation or the

discomfort of compression.

Basic processing tools include the ability to

change the brightness and contrast of an image (i.e.,

to ‘‘window’’ and ‘‘level’’) and to enlarge either the

entire breast or focal areas within the breast (Fig. 1).

Different parts of the breast may be viewed at differ-

ent brightness and contrast settings, enabling detailed

analysis of both the fatty and dense components.

Problems associated with under- or overexposure

may thus be overcome, avoiding the need for repeat

exposures. It remains to be tested clinically whether

digital enlargement can replace direct radiographic

magnification. Initial studies have shown that digital

enlargement is of diagnostic benefit [10]. A recent

study using quality control phantoms found that DM

(with abilities to zoom image, invert gray scale, and

alter contrast) performed better for low-contrast

objects, but analog magnified views performed better

for fine, faint filaments [11]. Additionally, various

sophisticated postacquisition image enhancement

techniques are under development, including tissue

equalization (Fig. 1), image inversion, edge enhance-

ment, noise suppression, and unsharp masking [12].

Image display

There are two methods of displaying DM: (1)

cathode-ray tube monitor (ie, soft copy) and (2) laser-

print film (ie, hard copy). Each method has advan-

tages and disadvantages. Commercial laser printers

generate digital mammograms of high spatial reso-

lutions (up to 4.8 � 6.4 K matrix size) and max-

imum optical densities close to those of screen-film

mammograms (3.5 to 4.0 for DM, compared with

slightly over 4.0 for SFM) [13]. In contrast to

emulsion films, digital films generated by laser print-

ers are not subject to processor artifacts or the day-to-

day variability of film processors. Because the film

medium is familiar to radiologists, the current light-

box film-viewing conditions can be continued easily,

using a ‘‘hot light’’ and magnifying glass to enhance

interpretation; however, hard-copy films are associ-

ated with higher costs. In addition to the costs of the

film and digital printer, costs are incurred in terms of

manpower and space in printing and storing films.

Furthermore, only one version of the image can be

displayed at one time, when several processed ver-

sions may be helpful for interpretation.

Because most of the benefits afforded by DM can

be used fully and efficiently only through monitor

display, soft-copy viewing is preferable.

With soft-copy display, multiple processed ver-

sions can be viewed simultaneously. Advanced appli-

cations, such as computer-aided image analysis and

telemammography, can be more readily applied.

Without the need to generate film, soft-copy display

is rapid. It also enables the incorporation of DM into

an efficient ‘‘filmless’’ picture archival and commu-

Fig. 1. Application of image processing techniques to enhance detection of cancer and assess extent of disease. (A) Preprocessed

digital mammogram showing a spiculated mass with adjacent pleomorphic calcifications in the mid-portion of the right breast on

the MLO view. (B) Postprocessed digital image after application of tissue equalization. This technique alters the digital values of

pixels at the periphery so that the absolute intensities of the image are more equivalent throughout the image. The overall contrast

of the image is then increased, enhancing lesion conspicuity without losing information at the periphery. (C) Magnification of the

postprocessed digital image shows the spiculated margin and the adjacent pleomorphic calcifications. Histologic analysis showed

invasive ductal carcinoma and ductal carcinoma-in-situ. (Courtesy of John M. Lewin, MD, University of Colorado, Denver, CO.)

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482468

nications system (PACS). On the other hand, costly

high-resolution monitors (4 � 5 K pixel) are required

for proper viewing. The soft-copy display worksta-

tion is also less efficient than the current lightbox

film-viewing conditions when comparing multiple

studies [7,13].

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482 469

Image storage and retrieval

Digital storage allows for rapid, reliable, and

convenient access to a large amount of data. When

considering the manpower and space needed for

storage and retrieval of screen-film mammograms,

the computerized storage and retrieval of digital

mammograms may prove to be cost-effective. Fur-

thermore, the problem of ‘‘lost films’’ would be

eliminated, thus improving clinical care.

A sizable amount of computer memory is required

to store the large amount of data associated with

digital mammograms. To depict subtle findings, dig-

ital mammograms require high spatial resolution (50

mm or less per pixel) and wide quantization resolution

(4096 gray shades or higher). Thus, the file size for a

single digital mammogram is large, containing appro-

ximately 40 to 60 Mbytes of data [14].

Fortunately, technical advancements in storage

media are paralleling the development of DM. A

variety of inexpensive storage media is now avail-

able. A jukebox is one such storage device, contain-

ing approximately 1000 magnetic tapes or optical

disks. The typical jukebox can store information for

50,000 digital mammograms, and several jukeboxes

may be chained together as a functional unit to further

increase storage capacity.

Compression techniques are used to increase

hardware storage capacity. Automatic segmentation

and extraction algorithms separate the actual breast

region from the large proportion of pixels that contain

no diagnostic information, thus reducing image file

size for efficient storage [15]. Also, DM enables the

use of PACS, which in turn reduces the need for

storage space and facilitates retrieval.

Digital mammography systems

At this time, there are five major full-field digital

mammographic systems in the United States: (1)

Fischer Imaging SenoScan (Fischer Imaging, Denver,

CO), (2) Fuji Medical Systems Computed Radiogra-

phy for Mammography (Fuji Medical Systems USA,

Stamford, CT), (3) General Electric (GE) Senographe

2000D (GE Medical Systems, Milwaukee, WI), (4)

Siemens Digital Mammography System (Siemens

Medical Systems, Iselin, NJ), and (5) Trex Digital

Mammography (Trex Medical, Danbury, CT). The

systems differ from each other in their underlying

technology [13].

The specific features of each model are beyond

the scope of this chapter. The types of digital detec-

tor, spatial resolution, and contrast resolution are lis-

ted in Table 1. Decreasing the pixel size results in

higher spatial resolution. Increasing the number of

bits per pixel results in higher contrast resolution. The

Fuji system differs from the other systems in that it

uses the conventional mammographic exposure

equipment and standard screen-film Bucky trays.

The image is captured on a special imaging plate

(rather than on emulsion film) where electronic char-

ges are stored in ‘‘traps’’ within the photostimulable

phosphor plate.

The GE Senographe 2000D became the first DM

machine to receive approval by the Food and Drug

Administration (FDA) in January 2000 [16]. Since

that time, it has received FDA approval for ‘‘soft-

copy’’ interpretations. FDA approval for the Fischer

system is expected in the near future.

Advanced adjunctive applications

DM makes possible certain advanced adjunctive

applications. Although most of these applications are

investigational at this time, they have the potential of

enhancing everyday mammography practices. The

three major applications of DM are (1) computer-

aided detection and diagnosis, (2) telemammography,

and (3) new-modality imaging.

Computer-aided detection and diagnosis

Computer-aided detection (CAD) is aimed toward

reducing the false-negative rate of screening mam-

Table 1

Technical specifications of digital mammography equipment

Manufacturer Digital detector Spatial resolution Contrast resolution

Fischer Charge-coupled device 54 mm per pixel (standard resolution) 12 bits per pixel

27 mm per pixel (high resolution)

Fuji Computed radiography 100 mm per pixel 10 bits per pixel

GE Flat panel 100 mm per pixel 14 bits per pixel

Siemens Charge-coupled device 48 mm per pixel (standard resolution) 12 bits per pixel

24 mm per pixel (high resolution)

Trex Charge-coupled device 41 mm per pixel 14 bits per pixel

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482470

mography by marking the perceived ‘‘abnormal’’

areas and directing the interpreting radiologist to re-

review these areas [17]. Image analysis algorithms

are used to search for suspicious findings. The areas

that lie above some probability threshold are relayed

to the radiologist. Typically, the radiologist would

interpret the mammograms in the standard fashion,

followed by re-examination of the areas indicated by

the CAD device. CAD is not designed to replace the

radiologist. Rather, it is intended to aid the radiologist

in avoiding the ‘‘misses’’ associated with inattention

or fatigue when viewing a large number of mammo-

graphic studies.

Several groups using prototype machines have

shown improved radiologist performance when CAD

is applied to digitized screen-film mammograms [18–

20], and Congress recently approved $15 incremental

Medicare reimbursement for the use of CAD in screen-

ing mammograms. At this time, CAD is best for de-

tecting clustered calcifications and spiculated masses

and is less good for poorly defined masses and asym-

metric densities.

ImageChecker M1000 is the only FDA-approved

CAD device (R2 Technology, Los Altos, CA) cur-

rently. In June 1998, it received FDA approval for

screen-film mammograms that are subsequently digi-

tized but not yet for direct digital mammograms.

Another CAD device, Mammex TR (Scanis, Inc,

Foster City, CA), is currently under consideration

for FDA approval. GE Medical Systems has licensed

the R2 software for exclusive use in its FDA-

approved digital units. Fischer and Trex are similarly

working with other CAD companies, and Fuji is

currently testing its own CAD product [13].

A blinded, retrospective study of 427 cancers

found a false-negative rate of 21% in screening

mammography and concluded that CAD (using Im-

ageChecker M1000) could have potentially reduced

this rate by 77% without increasing the recall rate

[21]. In a separate study using a similar cohort, CAD

retrospectively marked 88 of 115 cancers that were

not identified by the interpreting radiologist [22]. The

only prospective data available at this time was pre-

sented at the 2000 meeting of the Radiologic Society

of North America. In this study, CAD was prospec-

tively applied to 12,860 screening mammograms,

and CAD increased the cancer detection rate by

20% (from 41 cancers to 49 cancers) [23]. This was

achieved with only a slight increase in recall rate from

6.5% to 7.7%.

The recent data suggest that CAD is a promising

technique. It would be most beneficial in small rural

practices where there are few radiologists and where

the radiologist is less subspecialized. Nevertheless,

its cost-effectiveness remains to be tested. It also

needs to be compared with second reading by

another radiologist and by the same radiologist at a

different sitting.

Computer-aided diagnosis goes beyond detection

in that the computer employs algorithms to classify

breast lesions as benign or malignant [24]. It aims to

reduce not only the false-negative but also the false-

positive rate of screening mammography, thereby

reducing the number of biopsies performed of benign

lesions. The classification schemes used in computer-

aided diagnosis require greater spatial resolution than

do the detection schemes in computer-aided detection

[25]. Artificial intelligence techniques are used,

including discriminant analysis methods, expert rule-

based systems, and artificial neural networks [26]. At

this time, there is no commercially available com-

puter-aided diagnosis device, and computer-aided

diagnosis has not been shown to improve the diag-

nostic accuracy of an experienced mammographer.

Telemammography

Telemammography refers to the rapid transmis-

sion of high-quality mammographic images in dig-

ital format from one site to another. As breast

imaging becomes more subspecialized, telemam-

mography offers the potential of expert interpreta-

tions and consultation, much of which can be

performed under near real-time circumstances. Tele-

mammography can be used to enhance the perform-

ance of mobile mammography units by eliminating

the need to transport films and by allowing the off-

site radiologist to monitor image quality and direct

the technologist in obtaining additional views. It

also plays a potentially important role in the daily

clinical work of a multi-site practice and in multi-

site conferencing.

Because mammography requires very high reso-

lution, the technical aspects of telemammography are

particularly challenging. For the large amount of data

to be transmitted in a reasonable amount of time,

special compression techniques are used. Automatic

extraction techniques are being developed so that

image file sizes can be reduced to contain only

information from the breast region for efficient trans-

mission [15]. Patient privacy during data transmission

must be protected vigilantly. Furthermore, convenient

mechanisms for image retrieval, image viewing, and

remote consultation are needed.

At the University of California, San Francisco,

Sickles and colleagues are conducting two ongoing

studies on the technical feasibility and clinical ef-

fectiveness of two specific aspects of telemammogra-

phy: (1) telemanagement—comparing the diagnostic

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482 471

accuracy of an expert breast imager at a remote site

with that of the on-site general radiologist, and (2)

teleconsultation—measuring the additional clinical

utility of real-time consultation with an off-site expert

breast imager [27]. Preliminary data indicate that tele-

mammography is time efficient: 300 seconds are

required for conventional screen-film mammograms

to be displayed on-site, compared with 120 seconds for

digital mammograms to be viewed at a remote location

across the city of San Francisco (E.A. Sickles, personal

communication, 2001).

New-modality imaging

Digital imaging allows multiple images to be

shifted electronically, combined into three-dimen-

sional views, and subtracted from one another. Areas

of active research include tomosynthesis, stereomam-

mography, dual-energy subtraction mammography,

and contrast-medium mammography. Tomosynthesis

refers to the acquisition of low-dose mammographic

images as the radiation source moves in an arc above

the stationary breast and digital detector in a ‘‘step-

and-expose’’ fashion [28]. The planes above and

below the lesion are blurred to increase the conspi-

cuity of the lesion, similar to the use of conventional

tomography, but without the associated time and

radiation exposure.

In stereomammography, two images are obtained

at slightly different angles, usually 2 to 5 degrees

apart. They are then fused together on soft-copy

display, allowing the reader to perceive the relative

depths of structures within the image. This technique

may be useful in reducing obscuration by super-

imposed structures.

Dual-energy subtraction mammography refers to

the acquisition of two images in which the effective

energy of the detected radiation differs [29]. The

lower-exposure image is typically obtained at 20 to

30 kVp, and the higher-exposure image at 40 to 80

kVp. Alternatively, dual-energy subtraction mam-

mography may be performed by means of a single

exposure using two stacked detectors, with one detec-

tor preferentially absorbing the low-energy photons

and the other detector absorbing the high-energy

photons. This technique may be used to remove

undesirable masking contrast while preserving the

contrast of the relevant structures, such as calcifica-

tions within a dense breast [7].

Contrast-enhancement mammography is based on

the theory that new and abnormal vessels (ie, an-

giogenesis) occur in breast cancers. Two images of

the same view are obtained before and after the

administration of intravenous contrast. DM enables

subtraction of the non-enhanced image from the

contrast-enhanced image, similar to the performance

of contrast-enhanced MRI. The spatial resolution in

DM is higher than that in MRI, potentially detecting

very small cancers. This tool may also be useful in

assessing extent of disease, particularly in patients

with dense breasts or an infiltrative process such as

invasive lobular carcinoma [13].

Clinical trials

To date, there have been two major clinical trials

funded by nonindustrial sources. The International

Digital Mammography Development Group Digital

Mammography Pilot Study consists of 210 women

from the diagnostic population who were imaged in

eight centers using the Fischer, GE, and Trex digital

mammographic units. This pilot study is the basis of a

larger clinical trial in which 1075 women from the

diagnostic cohort will be enrolled at six centers [13].

The Colorado/Massachusetts Full-Field Digital Mam-

mography Screening Trial is the first and only pub-

lished study comparing the performance of DM and

SFM in the screening population. It aims to enroll

15,000 asymptomatic patients from a screening pop-

ulation at two sites (University of Colorado and

University of Massachusetts), using only a single

system (GE Senographe 2000 D).

Initial results from the Colorado/Massachusetts

Full-Field Digital Mammography Screening Trial

were published in March 2001. Lewin et al [30]

prospectively imaged 3890 asymptomatic women,

each of whom underwent both SFM and DM, for a

total of 4945 paired (SFM and DM) mammographic

exams. The study was designed to minimize both

entry and verification bias. Because the patients

originated from the screening population, entry into

the study was not predicated on having an abnormal

screen-film mammogram. Because recall exams and

biopsy recommendations were based on findings at

either SFM or DM, preferential verification of SFM

(versus DM) findings did not occur.

In this study, DM was equal to SFM in cancer

detection (60% for DM and 63% for SFM). DM had

a statistically significant lower recall rate (11.5%)

than SFM (13.8%). This improvement in recall rate

may have been related to the ability to manipulate

images on soft-copy display. The positive predictive

value of mammographic screening was similar

between the two studies: 3.7% for DM and 3.2%

for SFM. The positive biopsy yield was higher for

DM (30%) than for SFM (19%), but this difference

was not statistically significant. Interestingly, most

(19/31) cancers were identified on one modality only

(Figs. 2, 3). In other words, cancer detection was

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482472

increased when DM was performed in addition to,

but not in place of, SFM. SFM detected 4.5 cancers

per 1000 women. This rate increased to 6.3 cancers

per 1000 women when DM was performed in addi-

tion to SFM. The primary cause of discordance

between DM and SFM appeared to be visibility

differences, most commonly caused by fortuitous

positioning [31], and not related to technical differ-

ences underlying the two modalities. Because the

number of cancers in a screening population is

inherently small, a large study cohort is required

for statistically significant results. Thus, the Colo-

rado/Massachusetts Full-Field Digital Mammography

Screening Trial is continuing with patient accrual,

and a third site has been added.

In a recent study of interpretation differences

between DM and SFM, Venta et al [32] found only

a 4% difference in interpretation that affected manage-

ment. The most common cause of interpretation

variation was difference in management approach

Fig. 2. Invasive ductal carcinoma prospectively identified on digital mammogram only. (A) Digital mammogram showing

spiculated mass in the midposterior right breast. (B) Magnified view of the digital mammogram showing the spiculated margin to

greater detail. (C) Corresponding screen-film mammogram shows a poorly defined density in the same location that was not

identified prospectively (perhaps due to a slight projection difference). (D) On the magnified view of the screen-film

mammogram, the density remains difficult to visualize. (Courtesy of John M. Lewin, MD, University of Colorado, Denver, CO.)

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482 473

between radiologists, rather than in lesion visibility.

These results differ from those of Lewin et al [31]. The

study of Venta et al [32] consisted of a diagnostic

cohort, and a third view was allowed in addition to the

two standard screening views.

On July 16, 2001, the American College of Radi-

ology Imaging Network began a $27 million, multi-

institutional, prospective screening trial [13]. This

Digital Mammographic Imaging Screening Trial will

consist of 49,500 women from the screening popula-

tion in 19 centers and will test equipment from four

manufacturers (Fischer, Fuji, GE, Trex). The primary

objective is to determine the diagnostic accuracy of

DM versus SFM for breast cancer screening. Secon-

dary goals are tomeasure the cost-effectiveness of both

technologies and to examine the effect on quality of

life from the expected reduction of false-positive

mammograms resulting from DM.

Cost-effectiveness

Currently, the major limitation of DM is its high

cost. The GE Senographe 2000D DM equipment

costs approximately $500,000, compared with the

$50,000 to $70,000 cost of the SFM unit. Additional

costs include laser printers and display monitors,

retraining of radiologists and technologists, and re-

design of imaging facilities. Because of the higher

costs, the Health Care Financing Administration has

approved reimbursement for DM that is 150% of the

reimbursement for film-screen mammography.

The issue of cost-effectiveness must be investi-

gated [33]. Some proponents contend that DM may

prove to be cost-effective in the long term. Using a

mathematical model, Hiatt et al [34] estimated that it

would take 3.1 years for a radiology practice to

break even after converting to DM and that the

United States would save $103 million per year in

going filmless. The numbers used in this study were

only estimates, however, based on discussions with

hospital personnel and industry representatives.

Others suggest that the high costs of DM may be

prohibitive, even with the reduction in costs in

converting to a filmless system [13]. The potential

savings in terms of increased cancer detection and

reduction in patient morbidity and mortality are

additional parameters that are difficult to quantitate.

Positron emission tomography

Positron emission tomography imaging is based

upon the energy released when a positron encounters

an electron. Two 511-keV photons are released at 180

degrees apart, and the PET camera captures the

coincidental lines of energy produced. These lines

Fig. 3. Invasive ductal carcinoma prospectively identified on screen-film mammogram only. (A) Screen-film mammogram of the

right breast shows architectural distortion, representing the cancer. Although this finding was subtle, it was identified

prospectively. (B) Even in retrospect, the abnormality was not identifiable in the corresponding digital mammogram. (Courtesy

of John M. Lewin, MD, University of Colorado, Denver, CO.)

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482474

are reconstructed into tomographic images, similar to

CT reconstructions. The most commonly used and

the only FDA-approved radiopharmaceutical in PET

imaging of the breast is 2-[18F]-fluoro-2-deoxy-D-

glucose (FDG). FDG is transported into the cell

through the glucose transporter, where it is then

phosphorylated by hexokinase into FDG-6-phos-

phate. The phosphorylated compound does not

become metabolized significantly and remains trap-

ped in the cell. Rapidly dividing neoplastic cells

display higher metabolism of glucose than the sur-

rounding non-neoplastic cells and, hence, preferential

uptake of FDG [35,36] (Figs. 4, 5). Inflammation or

infection may also result in increased FDG uptake,

resulting in false-positive interpretations [37,38].

Diagnostic accuracy

Investigators have used both the qualitative and

quantitative information provided by PET in detecting

breast cancers and distinguishing malignant from

benign disease. Reported sensitivities range from

80% to 96% and specificities from 83% to 100%

[38–45]. Because of limitations in spatial resolution,

the sensitivity of PET depends largely on lesion size.

PET does not reliably detect lesions less than 1 cm in

diameter [39,41,44–47]. It is also limited in identify-

ing ductal carcinoma in situ [41] and slowly growing

cancers such as tubular carcinoma. One recent report

suggested that PET is less sensitive in detecting inva-

sive lobular carcinoma than the ductal counterpart [48].

Clinical applications

Positron emission tomography imaging is not suit-

able for breast cancer screening because both the

scanners and radiopharmaceuticals are expensive, its

availability is limited, and its spatial resolution pre-

cludes confident detection of lesions less than 1 cm.

Whereas PET may potentially detect multiple tumor

foci [44], MRI offers greater spatial resolution and

clinical utility in presurgical planning [49]. Similarly,

MRI remains the imaging modality of choice in

patients with axillary nodal metastases of unknown

primary malignancy [50], although PET has been

examined as a diagnostic tool in this clinical setting

[45,51]. On the other hand, PET imaging shows

promise in identifying regional nodal and distant

metastases in patients with known primary breast

cancer and in monitoring treatment response.

Regional nodal metastases

Axillary nodal status is an important prognostic

indicator in breast cancer patients [52]. Surgical

nodal dissection is associated with significant costs

and potential morbidity, including lymphedema and

infection. PET has been investigated as a noninva-

sive means of detecting axillary nodal metastases

(Figs. 4, 5). Wahl et al [53] noted that FDG uptake in

metastatic nodes is more than that in normal nodes.

In a prospective study of 124 patients with

recently diagnosed breast cancer, Utech et al. [54]

correctly identified all 44 cases of positive axillary

nodes using PET, resulting in 100% sensitivity.

Specificity in this study was 75%. In other smaller

studies, the sensitivities ranged from 50% to 100%

[55–57]. PET has been found to be more accurate

than clinical examination. In one study, the sensitivity

and specificity were 90% and 97%, respectively,

compared with 57% and 90% for clinical examination

[56]. Primary lesion size influenced the sensitivity

and specificity of PET for axillary nodal metastasis.

Avril et al. [58] reported that the sensitivity was 94%

when primary tumor size was > 2 cm but dropped to

33% when primary tumor size was < 2 cm.

Positron emission tomography alone cannot be

used to obviate surgical nodal dissection, although it

may allow for selection of women likely to benefit

from the procedure. Given its large field-of-view,

PET may also be used to evaluate more remote nodal

groups, such as internal mammary or supraclavicular

nodes [59] (Fig. 5).

Distant metastases

Early studies have shown that PET can be used

to detect unsuspected distant metastases that are

not identified by conventional imaging modalities

[38,47] (Fig. 5). In a study of axillary metastases

detection, Avril et al [41] found that additional infor-

mation regarding unsuspected distant metastases was

provided by axillary PET imaging in 29% of patients,

impacting clinical management. Moon et al. [60], in a

study of 57 patients, reported the following numbers

for PET in staging recurrent or metastatic disease:

sensitivity 93%, specificity 79%, positive predictive

value 82%, and negative predictive value 92%.

Treatment monitoring

Both clinical examination and mammography can

be limited in monitoring treatment response because

of the difficulty in distinguishing fibrosis from resid-

ual tumor [61,62]. As a functional imaging modality,

PET offers information on early tumor response to

medical treatment (Fig. 5). This information can be

used to minimize drug toxicity, the costs of ineffective

treatment, and delay in initiation of more effective

treatment. Studies have demonstrated the usefulness

of PET in detecting early response to both chemo-

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482 475

Fig. 4. PET imaging of an invasive ductal carcinomawith bilobed morphology, correlating with the mammographic and ultrasound

findings. (A) A 2-cm bilobed mass was identified in the left upper breast on the MLO view, corresponding to a palpable lump. (B)

Sonography demonstrated a hypoechoic solid mass with similar morphology. (C) Coronal whole-body PET projection view shows

a corresponding bilobed focus of increased uptake (closed arrow) and a focus of increased uptake in left axilla (open arrow). Four of

23 axillary nodes were found to be positive for metastases at surgery. (D) Selected sagittal PET image shows the bilobed breast mass

(closed arrow) and the axillary nodal pathology (open arrow). (E) Selected axial PET image also depicts the morphology of this

bilobed cancer (arrow). (Courtesy of Annick D. Van den Abbeele, MD, Dana-Farber Cancer Institute, Boston, MA.)

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482476

therapy and hormonal therapy. In clinical studies, both

qualitative and quantitative FDG uptake parallels tu-

mor response [46,63]. Bassa et al [64] applied PET

imaging in monitoring 16 patients receiving neoadju-

vant chemotherapy. They found that PET was better

than mammography or ultrasound in initial tumor

detection and more sensitive early in the course of ef-

fective therapy, but less sensitive for detection of resi-

dual tumor measuring less than 1 cm.

Of particular interest is the observation that early

PET findings appear to predict long-term outcome.

Smith et al [65], in a study of 30 patients with >3 cm

cancers, found that PET imaging after a single pulse

of chemotherapy was predictive of complete patho-

logic response with sensitivity of 90% and speci-

ficity of 74%. Schelling et al [66] found similar

results in a study of 22 patients. After the first course

of chemotherapy, patients responding to treatment

were identified with sensitivity of 100% and specifi-

city of 85%.

Sestamibi scintimammography

99mTc-sestamibi is currently the only FDA-

approved scintigraphic agent for breast imaging

[67] (Fig. 6). It is a cationic lipophilic compound

that is transferred across the cell membrane into the

cytoplasm and mitochondria and retained because of

electrical potentials across membranes [68]. Selective

uptake by cancer cells depends on cellular perfusion,

mitochondrial uptake, and transmembrane electro-

negativitiy [67]. Tumor histology correlates with

degree of 99mTc-sestamibi uptake [69]. Slow-growing

tumors and those of low cellularity often do not

demonstrate significant tracer uptake, potentially

resulting in false-negative interpretations. Benign

causes of focal uptake include infection, inflamma-

tion, and benign tumors such as papillomas or fibroa-

denomas [70]. Hyperproliferative fibrocystic breast

disease is the most common benign cause of diffuse

uptake [70].

Diagnostic accuracy

Since the 1994 large-series report by Khalkhali

et al. [71] on the use of 99mTc-sestamibi in breast im-

aging, many studies investigating the diagnostic accu-

racy of this method have been published. These studies

were reviewed by Taillefer in 1999 [70]. In summary,

20 studies published between 1994 and 1998 exam-

ined 2009 patients collectively. There were 2.3 pal-

pable lesions for every 1 nonpalpable lesion. The

overall sensitivity was 85%, specificity 89%, positive

predictive value 89%, negative predictive value 84%,

and accuracy 86%. Since the review, several additional

studies have been published, the results of which are

summarized in Table 2. The scintigraphic detection of

palpable cancers is significantly greater than that of

nonpalpable cancers. For example, a European three-

center trial consisting of 420 patients reported sensi-

tivities of 98% and 62% for palpable and nonpalpable

lesions, respectively [72]. Detection of lesions less

than 1 cm was limited in nearly all studies.

Clinical applications

Sestamibi scintimammography is not currently

used as a screening tool because of its high cost,

relatively low sensitivity, insufficiently high negative

Fig. 4. (continued )

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482 477

predictive value, and limited ability to detect lesions

less than 1 cm. There is no published report eval-

uating its use in breast cancer screening [73]. Inves-

tigators have examined the utility of sestamibi

scintimammography as an adjunct to conventional

imaging modalities in obviating benign biopsies and

in detecting axillary nodal metastases and monitor-

ing treatment.

Several studies have shown that sestamibi scinti-

mammography is more specific than mammography,

ultrasound, or MRI, particularly for the palpable mass

[74–78]. However, the negative predictive value re-

mains insufficiently high to replace biopsy. In particu-

lar, it is unlikely that sestamibi scintimammography

can assume the role of percutaneous large-core needle

biopsy, which is of high accuracy and low morbidity.

Sestamibi scintimammography can also detect

axillary nodal metastases in patients with primary

breast cancer (Fig. 6). Taillefer reviewed reports

published between 1994 and 1998 on its diagnostic

performance [70]. In a total of 350 patients, the

cumulative sensitivity of the test was 77%, specificity

89%, positive predictive value 86%, and negative

predictive value 84%. In a separate report of 31

patients, the sensitivity of sestamibi scintimammog-

raphy was 75%, specificity 82%, positive predictive

value 88%, and negative predictive value 64% [79].

In a recent report of 38 patients, both the sensitivity

Fig. 5. Coronal whole-body positron emission tomography (PET) projection views demonstrating the utility of PET in

monitoring patient response to treatment and in assessing metastatic disease. (A) Pretreatment image demonstrates multiple areas

of nodular uptake in the right breast centrally representing the primary cancer. Additionally, increased uptake is identified in the

right axilla, the supraclavicular regions bilaterally, and the right internal mammary chain, representing nodal metastases. Bony

metastases are identified as foci of increased uptake in T9, L3, L4, and the left acetabulum. (B) After chemotherapy and stem-cell

transplantation, there is significant interval resolution of disease in right breast, with minimal residual uptake. The abnormal foci

of uptake in the lymph nodes and bones have resolved. Note the normal distribution of radioactivity within the heart, kidneys,

and bladder. (Courtesy of Annick D. Van den Abbeele, MD, Dana-Farber Cancer Institute, Boston, MA.)

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482478

and specificity of MIBI-SPECT for axillary nodal

metastases were poor [57], likely reflecting the small

size ( < 1 cm) of the primary lesions and the lack of

prone imaging in the study. No correlation has been

found between the number of nodes demonstrating

scintigraphic uptake and the number of positive

nodes at pathologic examination [80]. Overall, the

negative predictive value is not sufficiently high for

sestamibi scintimammography to replace surgical

nodal dissection.

Similar to PET, sestamibi scintimammography is a

functional imaging test and may be used to monitor

tumor response to treatment. Maini et al [81] studied

20 patients with locally advanced breast carcinoma

who underwent sestamibi scintimammography before

and after three cycles of neoadjuvant chemotherapy.

The test showed sensitivity of 65% for the presence

of tumor and specificity of 100% for the absence of

tumor. These results were superior to clinical exami-

nation alone. Scintimammography performed the

same as mammography in patients without response

but better than mammography in patients with pos-

itive response.

Summary

Digital mammography, PET, and sestamibi scinti-

mammography are three new modalities in breast

imaging. DM has advantages over film-screen mam-

mography in image storage, retrieval, and processing

and may lower the recall rate. Computer-aided detec-

tion may increase the sensitivity of mammographic

screening without a substantial reduction in specific-

ity. Whereas PET and sestambi scintimammography

are not useful in breast cancer screening, PET may

play a role in detecting nodal metastases and mon-

itoring treatment response, and sestamibi scintimam-

mography in selected cases may serve as an adjunct

to conventional imaging. The cost-effectiveness of

these new modalities remains to be evaluated, but all

Fig. 6. Sestamibi scintimammogram (left and right lateral projections) acquired on a standard gamma camera system in planar

format. Foci of increased uptake are identified in the left mid-breast (corresponding to a 3-cm palpable mass) and in the left

axilla. Surgery revealed stage 3 invasive ductal carcinoma, with 4 of 12 axillary nodes positive for metastases. (Courtesy of Iraj

Khalkhali, MD, Harbor-UCLA Medical Center, Torrance, CA.)

Table 2

Diagnostic accuracy of sestamibi scintimammography

Study/year

(reference)

Patients

(n)

Sensitivity

(%)

Specificity

(%)

PPV

(%)

NPV

(%)

Taillerfer/

1998 [70]

2009 85 89 89 84

Flanagan/

1998 [82]

79 81 81 61 92

Cwikla/

1998 [83]

70 89 52 84 67

Prats/

1999 [84]

90 85 79 74 88

Buscombe/

2001 [85]

353 89 71 79 84

Abbreviations: PPV, positive predictive value; NPV, neg-

ative predictive value.

J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482 479

have the potential to significantly advance the diag-

nosis and management of women with breast cancer.

Acknowledgments

The author is indebted to Drs. John M. Lewin

(University of Colorado, Denver, CO) and Annick D.

Van den Abbeele (Dana-Farber Cancer Institute,

Boston, MA) for contributing their expertise and

clinical images to this article. The author also thanks

Dr. Alan S.L. Yu (Brigham and Women’s Hospital,

Boston, MA) for his critical reading during manu-

script preparation.

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J.W.T. Leung / Radiol Clin N Am 40 (2002) 467–482482

Percutaneous image-guided core breast biopsy

Laura Liberman, MD

Breast Imaging Section, Department of Radiology, Memorial Sloan-Kettering Cancer Center,

1275 York Avenue, New York, NY 10021, USA

Percutaneous image-guided biopsy is increasingly

an alternative to surgical biopsy for the histologic

assessment of breast lesions [1,2]. Guidance for

percutaneous biopsy is usually provided by stereo-

taxis or ultrasound; recently, there has been prelimi-

nary experience with percutaneous core biopsy under

the guidance of magnetic resonance imaging. Tissue

acquisition for percutaneous biopsy is usually accom-

plished with automated core needles (Fig. 1) or

directional vacuum-assisted biopsy probes (Fig. 2).

This article reviews advantages, limitations, contro-

versies, and future directions of percutaneous image-

guided core breast biopsy.

Guidance

Stereotaxis

Stereotactic biopsy is based on the principle that

the precise location of a lesion in three dimensions

can be determined based on its apparent change in

position on two angled (stereotactic) images. In early

validation studies, concordance between results of

stereotactic 14-gauge automated core biopsy and

surgical biopsy was 87% to 96%; the best results

were achieved by obtaining multiple specimens using

a long excursion gun with the patient prone on a

dedicated table (Table 1) [3–9].

Stereotactic biopsy can be performed with the

patient prone or upright. Advantages of the prone

table include more working room and decreased

likelihood of patient motion and vasovagal reaction;

the table also provides a psychological barrier

between the patient and the procedure. The main

disadvantages of the prone table are expense and

space. Use of recumbent positioning may improve

results with the upright method [10]. Digital imaging

may improve outcome by decreasing procedure time

[11]. Stereotactic guidance can be used for all types

of mammographic lesions (masses and calcifications)

but is most often used for calcifications.

Ultrasound

Ultrasound-guided 14-gauge automated core biop-

sy was first described by Parker et al in 1993 [7]. In

that study, one hundred eighty-one lesions had ultra-

sound-guided core biopsy with a 14-gauge automated

needle. Among 49 lesions with surgical correlation,

there was 100% concordance between results of ultra-

sound-guided 14-gauge automated core biopsy and

surgery; among 132 lesions yielding benign results,

no carcinomas were identified at 12- to 36-month

follow-up. Since that time, other investigators have

also demonstrated that ultrasound-guided 14-gauge

automated core biopsy is fast, safe, accurate, and cost-

saving [12–16]. Ultrasound-guided biopsy can also be

performed with an 11-gauge vacuum-assisted biopsy

device [17–19].

Advantages of ultrasound as a guidance modality

for percutaneous breast biopsy include lack of ioniz-

ing radiation, use of nondedicated equipment, acces-

sibility of all areas of the breast and axilla, real-time

visualization of the needle, multi-directional sam-

pling, and low cost [7,12,14,16]. The main disadvan-

tage of ultrasound guidance is that the lesion must be

sonographically evident to undergo ultrasound-

guided biopsy. Thus, ultrasound-guided core biopsy

may not be feasible for calcifications or for the small

subset of solid masses that are sonographically inap-

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00011 -2

E-mail address: libermal@mskcc.org (L. Liberman).

Radiol Clin N Am 40 (2002) 483–500

parent. For lesions amenable to either stereotactic or

ultrasound-guided biopsy, ultrasound-guided biopsy

may be preferable in terms of patient comfort and

radiation exposure, procedure time, and cost (Fig. 3).

MR imaging

MR imaging can demonstrate breast cancers that

are not detected by mammography, sonography, or

physical examination. Although the sensitivity of

MRI in breast cancer detection has been reported to

be as high as 100% in some series, the reported

specificity is lower, ranging from 37% to 97%. To

benefit from breast MR imaging, it is necessary to

have the capability to perform biopsy of lesions

identified with MR only [20].

Early experience with MR-guided core breast

biopsy has been reported. Heywang-Koebrunner et al.

[21] performed successful MR-guided directional vac-

uum-assisted biopsy in 99 (99%) of 100 MR-detected

lesions, of which 25 were found to be carcinoma. In 78

lesions that had MR-guided 14-gauge automated core

biopsy, Kuhl et al [22] reported that histologic diag-

nosis was possible in 99% (77/78) and changed treat-

Fig. 1. 14-gauge automated core biopsy needle.

Fig. 2. 11-gauge vacuum-assisted biopsy probe.

L. Liberman / Radiol Clin N Am 40 (2002) 483–500484

ment in 70% (54/77); in 59 lesions with established

validation, the diagnostic accuracy of MR-guided core

biopsy was 98% (58/59).

MR-guided percutaneous breast biopsy poses

several challenges, including the necessity to remove

the patient from the closed magnet to perform the

biopsy, limited access to the medial breast tissue, the

transient nature of contrast enhancement, and diffi-

culty in confirming lesion retrieval [23]. Develop-

ment of dedicated MR-guided biopsy equipment

would be invaluable, including coils, breast immobi-

lization and compression devices, needle guides,

localizing markers, and nonferromagnetic needles

with minimal artifact.

Advantages of percutaneous breast biopsy

The patient care advantages of percutaneous

breast biopsy have been well documented. Percuta-

neous biopsy is fast, less invasive than surgery, does

not deform the breast, and causes minimal to no

scarring on subsequent mammograms [11,24–26].

Complications are unusual, with the frequency of

hematoma and infection in two large series each less

than 1 per 1000 [27,28]. Women who have percuta-

neous biopsy undergo fewer operations [29–36] and

have a lower cost of diagnosis [37–41,45].

Fewer operations

The goal of percutaneous breast biopsy is to

obtain a histologic diagnosis of a lesion that is of

sufficient concern to warrant biopsy. Approximately

70 to 80% of lesions referred for biopsy are benign. If

percutaneous image-guided biopsy yields a benign

diagnosis concordant with the imaging characteris-

tics, surgery can usually be avoided.

Percutaneous biopsy can also decrease the number

of operations performed in women with breast cancer.

Smith et al [35] found that the average number of

surgeries performed was 1.25 in women with percu-

taneously-diagnosed cancer versus 2.01 in women

with surgically-diagnosed cancer. Other investigators

have reported a single operation was performed in 75

to 100% of women with percutaneously-diagnosed

cancer versus 0 to 38% of women with surgically-

diagnosed cancer (Table 2) [29–36]. The likelihood

of clear margins at the first operation is also higher

among women with cancers diagnosed percutane-

ously (75 to 100%) rather than surgically (45% to

64%) [29–33,35,36].

Some women with percutaneously-diagnosed

invasive breast cancer may undergo breast conserving

surgery with sentinel lymph node biopsy, a minimally

invasive approach to diagnosis and treatment [42].

Percutaneous biopsy results may also indicate the

presence of carcinoma that is multifocal (multiple

sites in the same quadrant) or multicentric (multiple

sites in different quadrants), altering treatment rec-

ommendations [43].

The surgeon’s approach is different when per-

forming a diagnostic surgical biopsy as compared to

a therapeutic operation after a percutaneous diagnosis

of breast cancer. The goal of a surgical biopsy is to

obtain a tissue diagnosis. Many surgeons prefer to

excise the minimal amount of tissue necessary in

order to minimize potential cosmetic deformity for a

Table 1

14-Gauge automated core breast biopsy studies with surgical correlation

Investigator/Year # Cases Concordance Insufficient # Passes Needle Gun Guidance

Parker/1993 [7] 49 100% 0% 4–5 14G Long Ultrasound

Parker/1991 [8] 102 96% 0% 3–4 14G Long Stereotactica

Elvecrog/1993 [5] 100 94% 0% � 5 14G Long Stereotactica

Gisvold/1994 [6] 104 90% 0% � 5 14G Long Stereotactica

Dronkers/1992 [4] 53 91% 6% 2 18G Short Stereotacticb

Parker/1990 [9] 102 87% 1% 3–4 18G (n = 65) Short (n = 2) Stereotacticc

16G (n = 9) Long (n = 101)

14G (n = 29)

Gisvold/1994 [6] 56 80% 2% < 5 14G Long Stereotactica

Dowlatshahi 1991 [3] 250 67–69% 17% 2–3 20G Short (n = 120) Stereotactica

Long (n = 130)

From Liberman L. Clinical management issues in percutaneous core breast biopsy. Radiol Clin N Am 2000;38(4):791–807;

with permission.a Prone.b Upright.c Upright in 30, prone in 73.

L. Liberman / Radiol Clin N Am 40 (2002) 483–500 485

lesion that may be benign. The goal of a therapeutic

operation to remove all of the cancer with clear

histologic margins, a procedure that usually requires

excision of a greater volume of tissue. A percuta-

Fig. 3. Asymptomatic woman with abnormal screening mammogram. (A) Craniocaudal view right mammogram shows an

irregular, spiculated mass (arrow) measuring approximately 1 cm at maximal diameter in the upper outer quadrant. (B)

Ultrasound of the right upper outer quadrant shows hypoechoic, solid, irregular mass which is taller than wide. (C) After

identifying the mass with ultrasound, cleansing the breast with iodine soap, and injecting local anesthesia, the radiologist inserts

the 14-gauge automated needle into the breast. (D) Ultrasound image confirms that the needle tip is immediately adjacent to the

mass. (E) Ultrasound image obtained after ‘‘firing’’ the automated gun shows that the needle has traversed the mass. An average

of four specimens are obtained per lesion through the same incision. Histologic analysis showed infiltrating ductal carcinoma. (F)

Specimen radiograph from the patient’s single therapeutic operation (needle localization, wide excision, and sentinel lymph node

biopsy) shows the localizing wire, spiculated mass, and faint calcifications in the specimen. Surgical histology showed

infiltrating ductal carcinoma (1.5 cm) and ductal carcinoma in situ with clear margins, and negative sentinel nodes.

L. Liberman / Radiol Clin N Am 40 (2002) 483–500486

neous diagnosis of cancer facilitates operative plan-

ning, usually allowing the surgeon to achieve a

therapeutic result in a single procedure [32].

Lower cost of diagnosis

Percutaneous biopsy can decrease the cost of

diagnosis of indeterminate or suspicious nonpalpable

breast lesions. Lindfors and Rosenquist [41] found

that use of stereotactic 14-gauge automated biopsy

rather than surgical biopsy reduced the marginal cost

per year of life saved by 23%. In other studies,

stereotactic 14-gauge automated core biopsy spared

a surgical procedure in 76 to 81% lesions, decreasing

cost of diagnosis by 40 to 58% (Table 3). Liberman

et al [38] estimated that use of stereotactic 14-gauge

automated core biopsy rather than surgical biopsy for

nonpalpable breast lesions could lead to potential

national savings approaching $200 million.

Ultrasound-guided 14-gauge automated core

biopsy also yields substantial cost savings. Liberman

et al [12] found that ultrasound-guided 14-gauge

automated core biopsy spared a surgical procedure

in 128 (85%) of 151 lesions, yielding a 56% decrease

in the cost of diagnosis (Table 3). The authors found

that for masses amenable to either stereotactic or

ultrasound-guided biopsy, cost savings are likely to

be greater if the biopsy is performed under ultra-

sound guidance.

Vacuum-assisted biopsy devices are more expen-

sive than automated needles but may in fact be cost

saving. Liberman et al [40] studied 200 consecutive

solitary nonpalpable lesions that had stereotactic

11-gauge vacuum-assisted breast biopsy. Stereotactic

11-gauge vacuum-assisted biopsy spared a surgical

Fig. 3 (continued ).

Table 2

Frequency of 1 operation after diagnosis of cancer

Frequency ofBiopsy method

1 operation Percutaneous # (%) Surgical # (%)

Jackman [29] 121/135 (90) 27/111 (24)a

Yim [36] 21/21 (100) 0/31 (0)a

Liberman [32] 76/90 (84) 31/107 (29)a

Smith [35] 49/65 (75) 57/610 (9)a

Lind [33] 43/48 (90) 26/69 (38)a

Kaufman [30] 52/66 (79) 10/47 (21)a

Morrow [34] 225/267 (84) 47/142 (33)a

a P< 0.001.

Table 3

Percutaneous breast biopsy: frequency of sparing surgery

and cost savings

Study Method

Frequency of

sparing surgery

(%)

Cost savings

(%)a

Liberman Stereotactic 140/182 (77) 893/1626 (55)

[38] 14G ALCBB

Lee Stereotactic 328/405 (81) 741/1278 (58)

[37] 14G ALCBB

Hillner Stereotactic 757/1000 (76) 804/2000 (40)

[105] 14G ALCBB

Liberman Ultrasound 128/151 (85) 744/1332 (56)

[12] 14G ALCBB

Liberman Stereotactic 151/200 (76) 182/1180 (15)

[40] 11G DVABB

Abbreviations: ALCBB, automated large core breast biopsy;

DVABB, directional vacuum-assisted breast biopsy.

From Liberman L. Clinical management issues in percuta-

neous core breast biopsy. Radiol Clin N Am 2000;38(4):

791–807; with permission.a Ratio of cost saving (in dollars) attributable to per-

cutaneous biopsy to the cost of diagnostic surgical biopsy.

L. Liberman / Radiol Clin N Am 40 (2002) 483–500 487

L. Liberman / Radiol Clin N Am 40 (2002) 483–500488

procedure in 76%, decreasing the cost of diagnosis

by 20% (Table 3). The 11-gauge vacuum-assisted

biopsy technology expands the spectrum of lesions

amenable to steretotactic biopsy, increasing cost sav-

ings in the population. The authors calculated that

selective use of stereotactic 11-gauge vacuum-assis-

Fig. 4. Asymptomatic woman with abnormal screening mammogram. (A) Craniocaudal view mammogram shows cluster of

pleomorphic calcifications spanning 1 cm at maximal diameter (closed arrow), new from prior mammograms. Adjacent 2 mm

focus of calcification (open arrow) had been stable. (B) The patient is positioned prone on the stereotactic table with her breast

dependent and in compression. (C) Scout digital image of the breast demonstrates the calcifications. (D) Two stereotactic images

at 15-degree angles from the scout film demonstrate the calcifications. A specific focus within this cluster of calcifications is

targeted for biopsy, and the stereotactic unit indicates the location of this point in three dimensions for accurate needle

placement. (E) After cleansing the breast with iodine soap and injecting local anesthesia, the 11-gauge vacuum-assisted biopsy

probe is inserted in the breast to the appropriate position. (F) Images obtained after placing the probe show that it has traversed

the calcifications. (G) The specimen is retrieved without removing the probe from the breast. (H) Radiographs of the specimens

obtained through the single insertion of the probe demonstrate calcifications. (I) Because stereotactic images after tissue

acquisition suggested that the calcifications had been removed, a localizing clip is introduced through the probe to mark the

biopsy site. (J) Craniocaudal view of the breast obtained as part of two-view mammogram after stereotactic biopsy shows the

clip at the biopsy site. The tiny cluster of calcifications was removed, although some adjacent calcifications remain. Air is

present in the tract of the probe superficial to the biopsy site. (K) After the procedure, a tiny skin nick is observed which heals

without scarring. (L) Sterile strips are placed over the skin nick, which is then covered with sterile gauze. Histologic analysis

yielded a benign fibroadenoma with calcifications, concordant with imaging findings, and the patient was spared the need

for surgery.

L. Liberman / Radiol Clin N Am 40 (2002) 483–500 489

ted biopsy could yield annual national cost savings of

$50 million [40].

The reductions in surgeries and cost savings of

percutaneous biopsy in clinical practice were recently

demonstrated by Rubin et al [15]. They found that

incorporation of percutaneous image-guided breast

biopsy into their practice increased the breast carci-

noma yield for needle localization biopsies from 21%

in 1984 to 68% in 1998 (P< 0.0001). Selective use of

ultrasound alone and percutaneous fine- and large-

core needle biopsy resulted in a substantial reduction

in benign open surgical biopsies. Cost analysis

showed a 50% reduction in the mean cost of breast

cancer diagnosis. The breast cancers detected after

introduction of percutaneous biopsy had good prog-

nosis, with 66% measuring less than 1 cm and 88%

measuring 1.5 cm or less [15].

Limitations

Calcification retrieval

Stereotactic 14-gauge automated core biopsy has

recognized limitations in the assessment of calcific

lesions [44]. Diagnosis of calcific lesions (as opposed

to masses) often requires a larger volume of tissue.

Failure to sample the lesion, histologic underestima-

tion, and failure to spare a surgical procedure are more

frequently observed in calcific lesions rather than ma-

sses: in previous studies, stereotactic 14-gauge auto-

mated core biopsy spared a surgical procedure in

84% to 87% of mass lesions versus 66 to 72% of le-

sions evident as calcifications [37,38]. The difficulties

encountered at stereotactic breast biopsy of calcifica-

tions reflect lesion geometry and histologic hetero-

geneity [44].

Directional vacuum-assisted biopsy instruments

are helpful in the assessment of calcific lesions

(Fig. 4) [45]. The vacuum-assisted probes obtain

larger tissue specimens: the median specimen weights

approximately 17 mg for the 14-gauge automated

needle, 35 mg for the 14-gauge directional vacuum-

assisted biopsy probe, and 100 mg for the 11-gauge

directional vacuum-assisted biopsy probe [45–47].

The vacuum device allows multiple specimens to be

obtained with a single insertion, facilitates contiguous

sampling, and enables the operator to suction blood

from the biopsy cavity. Calcification retrieval rates of

99 to 100% have been reported for 14- or 11-gauge

directional vacuum-assisted breast biopsy, signifi-

cantly higher than the 86 to 94% calcification

retrieval rate observed with 14-gauge automated large

core biopsy (Table 4) [37,44,48–52].

Histologic underestimates

Histologic underestimation occurs when percuta-

neous biopsy identifies the presence of a high risk or

malignant lesion but incompletely characterizes the

pathology. Examples of histologic underestimation

include lesions yielding a stereotactic biopsy diag-

Table 4

Calcification retrieval at stereotactic breast biopsy

No. of lesions with Ca++ retrieved

at 14-gauge automated large-core

No. of lesions with Ca+ retrieved at

vacuum-assisted breast biopsy

Investigator breast biopsy (%) 14-gauge 11-gauge

Liberman [49] 65/72 (90)

Lee [37] 133/151 (88)

Liberman [50] 50/55 (91)a

Meyer [51] 118/130 (91) 106/106 (100)b

Jackman [48] 1122/1196 (94) 1195/1209 (99) 720/723 ( > 99)c

Liberman [44] 106/112 (95)d

Reynolds [52] 36/42 (86) 64/64 (100)

From Liberman L. Clinical management issues in percutaneous core breast biopsy. Radiol Clin N Am 2000;38(4):791–807;

with permission.a Frequency of calcification retrieval was 19/24 (79%) in the first half of the eight month study period and 31/31 (100%) in

the second half.b P= 0.0006.c Frequency of retrieving calcifications was significantly higher for 14-gauge directional vacuum-assisted biopsy versus

14-gauge automated large core biopsy (P < 0.0001), and significantly higher for 11-gauge directional vacuum-assisted biopsy

versus 14-gauge automated large core biopsy (P< 0.0001), but did not differ significantly for 11- versus 14-gauge directional

vacuum assisted biopsy (P= 0.15).d P= 0.003

L. Liberman / Radiol Clin N Am 40 (2002) 483–500490

nosis of atypical ductal hyperplasia (ADH) for which

subsequent surgery yields carcinoma (‘‘ADH under-

estimate’’) and lesions yielding a stereotactic biopsy

diagnosis of ductal carcinoma in situ (DCIS) for

which subsequent surgery yields invasive carcinoma

(‘‘DCIS underestimate’’). Because most lesions con-

taining ADH and/or DCIS contain calcifications,

histologic underestimates at percutaneous biopsy are

most often encountered in calcific lesions [53].

There are a variety of pathologic definitions of

atypical ductal hyperplasia, including a lesion that

has some but not all of the features of DCIS, a lesion

that has all of the features of DCIS but only involves

one duct, or a lesion that has all of the features of

DCIS but measures less than 2 mm [53]. There is

therefore the potential that a small sample of a DCIS

lesion may be interpreted by the pathologist as

representing ADH. Because some lesions may con-

tain both ADH and DCIS, or DCIS and infiltrating

carcinoma, sampling error may also lead to histologic

underestimation. Histologic underestimation can

decrease the frequency with which percutaneous

biopsy spares a surgical procedure: an ADH under-

estimate leads to a recommendation for surgical

biopsy, and a DCIS underestimate may require that

the patient have a second operative procedure to

assess the axilla [32].

The problem of ADH underestimation is dimin-

ished but not eliminated by directional vacuum-assis-

ted biopsy. Of lesions yielding ADH at 14-gauge

automated core biopsy, approximately 20 to 56%

have carcinoma at surgery; of lesions yielding ADH

at directional vacuum-assisted biopsy, approximately

0% to 38% have carcinoma at surgery (Table 5)

[13,44,53–60]. ADH underestimates have also been

reported with the Advanced Breast Biopsy Instru-

mentation (ABBI) System [61]. Some investigators

have suggested that it may be possible to identify

some lesions yielding ADH at percutaneous biopsy

that do not require surgical excision [62,63]. Until

such a subgroup can be confidently identified, how-

ever, it is prudent to suggest that a diagnosis of ADH

with any existing percutaneous biopsy technology

warrants surgical excision.

DCIS underestimation is also less common for

directional vacuum-assisted biopsy than automated

core biopsy. Jackman et al [64] found that the like-

lihood of DCIS underestimation was significantly

higher with stereotactic 14-gauge automated core

biopsy rather than stereotactic vacuum-assisted

biopsy (76/373 = 20.4% versus 107/953 = 11.2%,

P< 0.001), if the lesion yielding DCIS at percuta-

neous biopsy was a mass rather than calcifica-

tions (35/144 = 24.3% versus 148/1182 = 12.5%,

P < 0.001), and if fewer than 10 specimens were ob-

tained rather than 10 or more specimens (88/502 =

17.5% versus 92/799 = 11.5%, P < 0.02). In other

reports, the frequency of invasion at surgery was 16

to 35% for lesions yielding DCIS with the 14-gauge

automated needle versus 0 to 19% for lesions yield-

ing DCIS with the vacuum-assisted biopsy device

(Table 6) [13,55,56,58,64–68]. These data indicate

that acquiring larger volumes of tissue percutaneous-

ly reduces, but does not eliminate, underestimation.

False negative diagnoses

In four validation studies of stereotactic 14-gauge

automated core biopsy, the frequency of missed can-

cers ranged from 2.9 to 10.9% (average, 7.2%)

[5,6,8,9]. In clinical follow-up studies after stereo-

tactic 14-gauge automated core biopsy, the frequency

of missed carcinomas averaged 2.8% (range, 0.3% to

8.2%), with 70% of missed cancers identified shortly

after biopsy (‘‘immediate false negatives’’) and 30%

identified subsequently (‘‘delayed false negatives’’)

[69,70]. Although this frequency is comparable to the

frequency of missed cancers at needle localization and

surgical biopsy, which has an average cancer miss rate

of 2.0% (range, 0% to 8%) [71], it indicates the

possibility of a delay in the diagnosis of breast cancer.

The radiologist can take several steps to diminish

the likelihood and potential impact of a false-negative

diagnosis. Optimizing technique, particularly with

respect to lesion targeting, can maximize the chance

that the needle will sample the lesion [53]. For

Table 5

Atypical ductal hyperplasia (ADH) underestimates at

percutaneous breast biopsy

# Underestimates

with 14G

# Underestimates

with DVABB (%)

Investigator ALCBB (%) 14G 11G

Jackman [58] 9/16 (56)

Liberman [59] 11/21 (51)

Liberman [53] 20/37 (54)

Burbank [55] 8/18 (44) 0/8 (0)

Liberman [44] 1/10 (10)

Brem [54] 4/16 (25)

Philpotts [60] 6/30 (20) 4/15 (27)

Jackman [57] 26/54 (48) 13/74 (18) 4/31 (13)

Meyer [13] 10/18 (56) 9/24 (38) 1/9 (11)

Darling [56] 11/25 (44) 11/28 (39) 16/86 (19)

Abbreviations: ALCBB, automated large-core breast biopsy;

DVABB, directional vacuum-assisted breast biopsy.

From Liberman L. Clinical management issues in percuta-

neous core breast biopsy. Radiol Clin N Am 2000;38(4):

791–807; with permission.

L. Liberman / Radiol Clin N Am 40 (2002) 483–500 491

calcific lesions, retrieval of calcifications on speci-

men radiographs is important; if calcifications are not

identified on specimen radiographs and the diagnosis

is benign, additional tissue sampling may be war-

ranted even if calcifications are identified histologi-

cally [49]. Careful imaging-histologic correlation will

allow the radiologist to identify discordant lesions

prospectively and recommend prompt rebiopsy,

avoiding delay in diagnosis [72]. The radiologist

should emphasize to the patient the importance of

follow-up mammography after benign percutaneous

biopsy, so that any interval change can be identified

and evaluated [69].

Learning curve

A learning curve exists for all endeavors in life,

and percutaneous breast biopsy is no exception.

Liberman et al [73] recently reviewed 923 consec-

utive lesions that had stereotactic biopsy by one of six

radiologists with 14-gauge automated (n = 414) or

vacuum-assisted (n = 509) equipment. Significantly

higher technical success rates and lower false-nega-

tive rates were observed after the first 5 to 20 cases

for 14-gauge automated core biopsy and after the first

5 to 15 cases for 11-gauge vacuum-assisted biopsy.

Even after the radiologists had experience with ster-

eotactic biopsy, changes in equipment resulted in a

new learning curve. These data indicate the need for

adequate training, with phantoms and under the

guidance of more experienced individuals, so that

we can appropriately disseminate this technology

while delivering high quality care.

Controversies

Lesion selection

Percutaneous core biopsy is most often used to

evaluate nonpalpable lesions that are suspicious for

malignancy, that is, Breast Imaging Reporting and

Data System (BI-RADS) category 4 [74]. Carcinoma

is identified in approximately 20% to 40% of BI-

RADS of BI-RADS category 4 lesions [75,76]. If

percutaneous core biopsy of a category 4 lesion

yields a benign diagnosis concordant with the imag-

ing characteristics, diagnostic surgical biopsy usually

can be avoided [38].

The utility of percutaneous core biopsy in the

evaluation of lesions that are highly suggestive of

malignancy (BI-RADS category 5) has been de-

bated. Approximately 75 to 90% of BI-RADS cat-

egory 5 lesions are malignant [75,76]. The utility of

percutaneous core biopsy for category 5 lesions

depends on the surgical protocol. If the protocol in

the absence of percutaneous biopsy would be to

perform a diagnostic surgical biopsy followed by a

second (therapeutic) surgery if cancer is found,

percutaneous biopsy can spare a surgical procedure.

If the protocol in the absence of percutaneous

biopsy would be to confirm the diagnosis of cancer

with frozen section and then to perform a 1-stage

therapeutic operation, percutaneous biopsy would

not spare a surgical procedure.

In prior studies of stereotactic 14-gauge auto-

mated core biopsy, the frequency of sparing surgery

was higher for BI-RADS category 5 masses (76% to

77%), which usually represent invasive cancer, than

for BI-RADS category 5 calcifications (42% to 55%),

which usually represent DCIS [37,77,78]. Stereotac-

tic 11-gauge vacuum-assisted biopsy may be more

useful for women with calcifications highly sugges-

tive of malignancy. Liberman et al [39] found that

women with BIRADS category 5 calcifications who

had stereotactic biopsy, as opposed to surgical biopsy,

Table 6

Ductal carcinoma in situ underestimates at percutaneous

breast biopsy

# Underestimates

with 14G

# Underestimates

with DVABB (%)

Investigator ALCBB (%) 14G 11G

Jackman [58] 8/43 (19)

Liberma [66] 3/15 (20)

Burbank [55] 9/55 (16) 0/32 (0)

Liberman [44] 1/21 (5)

Liberman [67] 4/28 (14)

Won [68] 7/20 (35) 3/20 (15)

Meyer [13] NS (19)a NS (19)a 1/28 (4)

Lee [65] 11/25 (44) 6/34 (18)b

Darling [56] 14/67 (21) 8/47 (17) 18/175 (10)

Jackman [64] 76/373 (20) 38/348 (11) 69/605 (11)

Abbreviations: ALCBB, automated large-core breast biopsy;

DVABB, directional vacuum-assisted breast biopsy.

From Liberman L. Clinical management issues in percuta-

neous core breast biopsy. Radiol Clin N Am 2000;38(4):

791–807; with permission.a In 19/105 (19%) lesions yielding DCIS at 14G

ALCBB or 14G DVABB, surgery revealed infiltrating

carcinoma.b Among 74 lesions evident as calcifications that had

surgical biopsy yielding DCIS as the initial procedure, sub-

sequent re-excision showed invasion in six (6/74 = 8% all

cases and 6/56 = 11% lesions that had re-excision). The

frequency of histologic underestimation at 11-gauge vacuum-

assisted biopsy did not differ significantly from the frequen-

cy of underestimation in lesions that were diagnosed at

surgical biopsy.

L. Liberman / Radiol Clin N Am 40 (2002) 483–500492

were significantly more likely to undergo a single sur-

gical procedure (61/89 = 68.5% versus 19/50 = 38.0%,

P< 0.001) and to obtain clear histologic margins at the

first operation (58/77 = 75.3% versus 8/37 = 21.6%,

P < 0.001). Stereotactic 11-gauge vacuum-assisted

biopsy, as opposed to stereotactic 14-gauge automated

core or 14-gauge vacuum-assisted biopsy, was sig-

nificantly more likely to spare surgery (36/47 = 76.6%

versus 16/42 = 38.1%, P < 0.001) and had higher cost

savings ($315 per case, a 22.2% decrease in cost of

diagnosis) [39].

Controversy exists regarding the role of percuta-

neous core biopsy in the evaluation of ‘‘probably

benign’’ (BI-RADS category 3) lesions, which have

a 0.5% to 2% frequency of carcinoma [79,80].

The traditional management of BI-RADS category

3 lesions is short-term follow-up mammography,

which is less invasive and less expensive (by a

factor of eight) than percutaneous core biopsy

[81]. Biopsy could be considered in a small subset

of category 3 lesions, for example if follow-up is

unavailable or compromised (due to geographic

considerations, an impending pregnancy, or impend-

ing breast augmentation or reduction surgery), if a

synchronous carcinoma is present (especially in the

ipsilateral breast and breast conserving surgery is

planned), if the patient is at high risk for developing

breast cancer, or if the patient’s anxiety precludes

short-term follow-up.

Percutaneous imaging-guided core biopsy may

also be used in the evaluation of selected palpable

lesions. Liberman et al [82] reported 115 palpable

lesions that had percutaneous imaging-guided core

biopsy, including lesions that were small, deep,

mobile, vaguely palpable, or multiple. Biopsy was

performed under ultrasound guidance in 100 and

under stereotactic guidance in 15. Among these 115

lesions, 98 (85%) were referred by surgeons and 88

(77%) underwent percutaneous biopsy on the day of

the initial evaluation. Percutaneous imaging-guided

core biopsy spared the need for additional tissue

sampling in 79 (74%) cases.

Complete lesion removal

Complete removal of the lesion identified at

imaging may occur during percutaneous breast

biopsy. In studies of stereotactic 14-gauge direc-

tional vacuum-assisted biopsy, complete removal of

the mammographic target occurred in 13% to 48%

of all lesions and in 58% to 93% of lesions

measuring 5 mm or less [83]. In studies of sono-

graphically-guided 11-gauge vacuum-assisted biop-

sy, complete removal of the sonographic target

occurred in 55% to 89% [17,18].

Complete removal of all imaging evidence of the

lesion does not ensure complete excision of the

pathologic abnormality. In prior reports of carcino-

mas in which the imaging finding was removed at

11-gauge vacuum-assisted biopsy, surgery revealed

residual carcinoma in 50% to 73% [83,18]. There-

fore, if the lesion identified on imaging studies is

removed, it is desirable to place a localizing clip at

the biopsy site to facilitate subsequent localization if

necessary (Fig. 4) [84,85].

Although complete lesion removal is generally

not the goal of percutaneous biopsy, it may be

advantageous. Complete lesion removal may de-

crease the likelihood of growth on follow-up,

which has been reported in 7% to 9% of lesions

yielding benign results at 14-gauge automated core

biopsy [69,70]. Perhaps complete lesion removal

can reduce sampling error, with resultant decrease

in the frequency of histologic underestimation,

imaging-histologic discordance, and rebiopsy. With

the increased use of larger tissue acquisition devi-

ces, additional study is needed to assess the bene-

fits of complete removal of the imaging finding

versus sampling.

Advanced breast biopsy instrumentation

The Advanced Breast Biopsy Instrumentation

(ABBI) system (US Surgical, Norwalk, CT) is a

stereotactic table coupled with a tissue acquisition

device available with cannulas ranging in size up to

2 cm. The ABBI device can obtain a specimen ex-

tending from the subcutaneous tissue to beyond the

lesion, potentially removing the entirety of a small

mammographic target in a single specimen. In spite

of initial enthusiasm for this device, the ABBI system

has many disadvantages, including large (up to

13 cm3) volume of tissue with potential for scarring

and deformity, high (1.1%) complication rate, high

(64% to 100%) frequency of tumor at the margins of

the biopsy specimen, excision, and high cost (over

$500 for ABBI cannulas, versus $215 for 11-gauge

vacuum-assisted biopsy probes and $15 to $25 for

14-gauge automated needles) [86].

Epithelial displacement

Breast needling procedures (anesthetic injection,

suture placement, needle localization, fine needle

aspiration, core biopsy, or vacuum-assisted biopsy)

can displace benign or malignant epithelium into

tissue away from the target lesion. Epithelial dis-

L. Liberman / Radiol Clin N Am 40 (2002) 483–500 493

placement can cause interpretive problems for the

pathologist because displaced DCIS can mimic

invasive cancer. Specific histologic findings suggest-

ing epithelial displacement include morphologic

evidence of a needle track hemorrhage, fat necrosis,

inflammation, hemosiderin-laden macrophages, or

granulation tissue), fragments of epithelium in arti-

factual spaces, and absence of surrounding tissue

reaction. Epithelial displacement may be less fre-

quent after vacuum-assisted biopsy than after auto-

mated core biopsy [67].

In a study of 352 surgical excision specimens

in women with a prior diagnosis of cancer by

large-core needle biopsy, Diaz et al [87] found

displacement of malignant epithelium in 32%. The

frequencyof tumor displacement was 37% after

automated gun biopsy, 38% after palpation-guided

biopsy, and 23% after vacuum-assisted biopsy.

Tumor displacement was seen in 42% of patients

with less than 15 days biopsy and excision, in

31% of patients with an interval of 15 to 28 days,

and in 15% of tumors excised more than 28 days

after core biopsy (P < 0.005). The inverse relation

between time to excision and observed tumor

displacement suggests that tumor cells do not sur-

vive displacement.

Although there is no evidence that epithelial

displacement is of biological importance, few data

address the issue. Berg and Robbins [88] noted no

difference in 15-year survival between women diag-

nosed by aspiration biopsy as compared to open

surgical biopsy in a study of stage-matched palpable

invasive breast cancers treated with mastectomy.

Kopans et al [89] found no evidence of local re-

currence attributable to needle localization in a study

of 74 women with nonpalpable breast cancer diag-

nosed by needle localization and surgical biopsy.

Limited conclusions can be drawn from these two

studies because mastectomy was performed in

most [89] or all [88] of the patients. Other inves-

tigators have reported no significant difference in the

frequency of recurrence when comparing cancers

diagnosed by percutaneous biopsy versus surgical

biopsy [90].

Management after percutaneous breast biopsy

Rebiopsy

In published series, repeat biopsy has been rec-

ommended after percutaneous image-guided core

breast biopsy in 9% to 18% of cases [12,13,60,

91,92]. The diagnosis of atypical ductal hyperplasia,

which accounted for 16% to 56% of lesions referred

for repeat biopsy in prior reports, was the most

common reason for rebiopsy after stereotactic core

biopsy (Table 5). Other reasons for repeat biopsy

include discordance between imaging and histologic

findings, possible phyllodes tumor, pathologist’s rec-

ommendation, and (rarely) inadequate tissue [93–97].

Among lesions referred for rebiopsy after percutane-

ous biopsy, surgery revealed carcinoma in 0% to 44%

(Table 7) [12,13,60,91,92].

Controversy exists regarding the need for surgical

excision after percutaneous core biopsy diagnosis

of other specific histologies, including papillary

lesions [14,96,98], radial scar [69,92,96,100], atyp-

ical lobular hyperplasia [94–96,99], and lobular car-

cinoma in situ [1] (Table 8) [93–97,99]. Because of

Table 7

Rebiopsy after percutaneous breast biopsy

Investigator/Year Method Rebiopsy rate (%) Malignancy at rebiopsy (%)

Dershaw [91] 14G Stereo ALCBB 56/314 (18) 22/50 (44)

Meyer [92] Variablea 112/1032 (14) 18/112 (16)

Liberman [12] 14G US ALCBB 15/151 (10) 2/15 (13)

Philpotts [60] 14G Stereo ALCBB 88/592 (15) 10/73 (14)

Philpotts [60] 11G Stereo DVABB 32/354 (9) 5/27 (19)

Meyer [13] Variableb 202/1836 (11) 32/202 (16)

Liberman [40] 11G Stereo DVABB 35/200 (18) 5/35 (14)

Abbreviations: ALCBB, automated large core breast biopsy; US, ultrasound.

From Liberman L. Clinical management issues in percutaneous core breast biopsy. Radiol Clin N Am 2000;38(4):791–807;

with permission.a Guidance was stereotaxis in 824 (80%) of 1032 lesions and ultrasound in 208 (20%); tissue was acquired with a 14-gauge

automated needle in 926 (90%) and a 14-gauge directional vacuum-assisted biopsy probe in 106 (10%).b Guidance was stereotaxis in 1388 (76%) and ultrasound in 448 (24%); tissue was acquired with acquisition device was a

14-gauge automated needle in 1333 (73%), a 14-gauge vacuum-assisted device in 372 (20%), and an 11-gauge vacuum-assisted

device in 131 (7%).

L. Liberman / Radiol Clin N Am 40 (2002) 483–500494

the low frequency of each of these diagnoses, these

issues may best be addressed in multi-institutional

collaborations. Philpotts et al [60] found that the rate

of repeat biopsy was significantly lower after stereo-

tactic 11-gauge directional vacuum-assisted biopsy

(9%) rather than 14-gauge automated core biopsy

(15%), suggesting that the larger volume of tissue

or more contiguous sampling provided by vacuum-

assisted biopsy may improve lesion characterization.

Imaging-histologic discordance

Imaging-histologic discordance occurs when the

histologic findings do not provide a sufficient expla-

nation for the imaging features [72]. In published

reports, percutaneous biopsy has yielded discordant

results in up to 6% of cases; among discordant

lesions, subsequent surgical excision has demonstrat-

ed carcinoma in 0% to 64% [72]. At our institution,

the radiologist does not finalize the percutaneous

biopsy report until the histologic analysis is complete.

The radiologist then puts an addendum on the report,

discussing the histologic findings and stating whether

they are concordant; if discordance exists, a repeat

biopsy (usually surgical excision) is suggested. Care-

ful imaging-histologic correlation by an individual

with expertise in breast imaging is necessary to

minimize the likelihood of delayed diagnosis of

breast cancer.

Fibroepithelial tumors

Phyllodes tumors account for less than 1% of

all breast neoplasms and approximately 2% to 3%

of fibroepithelial tumors of the breast [101].

Although 50% to 75% of phyllodes tumors are

benign, they can be locally aggressive. In core

biopsy specimens, it may not be possible for the

pathologist to distinguish between a cellular fibroa-

denoma and a phyllodes tumor. If the percutaneous

biopsy findings suggest the possibility of phyllodes

tumor, surgical excision is warranted: in one series,

the diagnosis ‘‘fibroepithelial tumor: fibroadenoma

versus phyllodes tumor’’ was the most common

reason for recommending surgical excision after

ultrasound-guided core biopsy [12]. In prior reports

of fibroepithelial neoplasms thought to possibly

represent phyllodes tumors at percutaneous biopsy,

surgery revealed phyllodes tumors in 22 to 43%

(Table 8).

Radial scars

Radial scars (radial sclerosing lesions) are char-

acterized by a sclerotic central nidus composed of

fibrosis and elastosis, elastin in duct walls and

stroma, and partial or complete obliteration of ductal

structures. Radial scars may be an independent risk

factor for subsequent development of breast cancer

and may be associated with an adjacent cancer, such

as DCIS or tubular carcinoma [102]. In two series

including a total of 13 radial scars at percutaneous

biopsy that had subsequent excision, carcinoma was

found in two (15%) [69,103], including DCIS in one

and infiltrating ductal carcinoma in one. Although

data are limited, it has been suggested that excision

may be appropriate when percutaneous biopsy yields

a diagnosis of radial scar.

Table 8

Lesions for which surgical excision was suggested after

percutaneous biopsy in larger published seriesa

Percutaneous

biopsy findings Frequency (%)

# Malignant at

excision (%)

Discordance

Liberman [72] 56/1785 (3) 11/45 (24)

Meyer [92] 65/1032 (6) 2/65 (3)

Philpotts [60] 23/946 (2) 0/14 (0)

Fibroepithelial tumor

Possible phyllodes

Dershaw [91] 7/314 (2) 0/7 (0)a

Meyer [92] 9/1032 (1) 2/9 (22)b

Liberman [12] 5/151 (3) 1/3 (33)b

Radial scar

Jackman [69] 5/483 (1) 2/5 (40)

Philpotts [103] 9/1236 ( < 1) 0/8 (0)

Papillary lesions

Rubin [14] 8/200 (4) 0/8 (0)

Liberman [98] 12/1077 (1) 1/9 (11)

Philpotts [103] 16/1236 (1) 1/6 (17)

ALH

Liberman [95] 7/1315 ( < 1) 0/4 (0)

Lechner [94] 154/35,424 ( < 1) 18/84 (21)

Berg [99] 15/1400 (1) 1/6 (17)

LCIS

Liberman [95] 16/1315 (1) 3/14 (21)

Lechner [94] 89/35,424 ( < 1) 20/58 (34)

Berg [99] 10/1400 ( < 1) 0/5 (0)

Philpotts [103] 5/1236 ( < 1) 1 (20)

Abbreviations: ALH, atypical lobular hyperplasia; LCIS,

lobular carcinoma in situ.

From Liberman L. Clinical management issues in percuta-

neous core breast biopsy. Radiol Clin N Am 2000;38(4):

791–807; with permission.a Among seven fibroepithelial tumors that were excised,

three (43%) were benign phyllodes tumors.b Phyllodes tumors.

L. Liberman / Radiol Clin N Am 40 (2002) 483–500 495

Papillary lesions

Papillary lesions of the breast, often histologically

heterogeneous, account for less than 10% of benign

breast neoplasms that undergo biopsy and 1% to 2%

of breast carcinomas [98]. In three studies which

have included 34 benign papillary lesions at per-

cutaneous biopsy that had subsequent surgical exci-

sion, carcinoma was found in two (6%) [14,98,103].

One of these two lesions was a spiculated mass

yielding papillomatosis at percutaneous biopsy, a

diagnosis considered discordant with the imaging

characteristics; surgery revealed a radial scar and

DCIS [98]. The other was an unusual microscopic

papillary lesion for which excision was suggested by

the pathologist; surgery revealed borderline DCIS

[103]. Although no carcinomas have been reported at

surgery in lesions yielding benign papilloma at per-

cutaneous biopsy (to my knowledge), additional

study with long-term follow-up is necessary to assess

the clinical course of benign papillary lesions with-

out atypia that are not excised after percutaneous

breast biopsy.

Lobular carcinoma in situ and atypical

lobular hyperplasia

Lobular carcinoma in situ (LCIS) is a disease of

small lobular ducts and lobules. LCIS without other

evidence of carcinoma has been reported in 1 to 3%

of breast biopsy specimens. It is often multicentric

and bilateral. Women with LCIS diagnosed at sur-

gical biopsy are at increased risk of developing

infiltrating carcinoma (ductal or lobular) in either

breast. Atypical lobular hyperplasia (ALH) has been

described as a lesion that has some but not all of the

features of LCIS, or a lesion that has all of the

features of LCIS but only involves up to 50 to

75% of the lobule. Some pathologists have sug-

gested use of the term ‘‘lobular neoplasia’’ to

indicate a variety of lobular lesions ranging from

atypical lobular hyperplasia to LCIS, while others

feel that the term is too broad [95].

Surgical excision is warranted in some lesions

yielding LCIS or ALH at percutaneous biopsy.

Liberman et al [95] reported carcinoma in three

(21%) of 14 lesions yielding LCIS at percutaneous

biopsy, including DCIS in two and infiltrating carci-

noma in one. In two of the lesions yielding cancer at

surgery, percutaneous biopsy findings overlapped

with those of DCIS; in one, there was an associated

high-risk lesion (radial scar). Philpotts et al [103]

reported carcinoma in one (20%) of five lesions

yielding LCIS at percutaneous biopsy, which was

evident as a mass at mammography. Berg et al [99]

reported carcinoma in one (17%) of six lesions

yielding ALH at percutaneous biopsy; in this lesion,

residual suspicious calcifications were present after

the percutaneous biopsy, and surgical histology

yielded DCIS.

In a multi-institutional study by Lechner et al [94],

LCIS was found in 89 (0.3%) of 35,424 lesions that

had percutaneous biopsy. Surgical excision, per-

formed in 58 (65%) of these LCIS lesions, yielded

carcinoma in 20 (34%), of which 12 were infiltrating

carcinomas (infiltrating lobular carcinoma in eight,

infiltrating ductal carcinoma in two, and tubular carci-

noma in two) and eight were DCIS. Percutaneous

biopsy revealed ALH in 154 (0.5%) of 32,424 lesions.

Of the 84 (55%) ALH lesions that had surgical

excision, surgery revealed carcinoma in 18 (21%),

including DCIS in 13 and infiltrating carcinoma in five

(three ductal and two lobular); LCIS was found in an

additional 18 (21%) of these 84 lesions. The authors

concluded that surgical excision after percutaneous

diagnosis of LCIS or ALH is warranted in selected

cases, but do not suggest specific selection criteria.

The published experience suggests that lesions

yielding LCIS or ALH at percutaneous biopsy war-

rant surgical excision if there is imaging-histologic

discordance, if an associated high-risk lesion is

present, or if the histologic features overlap with

ADH or DCIS. Histologic differentiation of ductal

and lobular carcinomas can be facilitated by staining

for E-cadherin, a transmembrane glycoprotein that is

present in ductal but not lobular carcinomas [93].

Georgian-Smith and Lawton [93] have suggested

that excision may also be warranted if percutaneous

biopsy yields calcifications associated with necrosis

in ‘‘pleomorphic’’ LCIS. Although the existing data

do not mandate routine excision of all lesions yield-

ing benign findings concordant with imaging fea-

tures as well as an ‘‘incidental’’ microscopic focus of

LCIS at percutaneous biopsy, further study is

needed. In addition, all women with LCIS at percu-

taneous biopsy should be informed about their

increased risk of breast cancer and opportunities

for prevention.

Follow-up

Follow-up is essential after benign percutaneous

biopsy, but the follow-up interval is not standardized.

For lesions yielding benign results concordant with

the imaging characteristics, Lee et al [70] suggest

annual mammography if the percutaneous biopsy

histologic diagnosis is specific and short-interval

L. Liberman / Radiol Clin N Am 40 (2002) 483–500496

follow-up (the ipsilateral breast at six months and both

breasts at 12, 24, and 36 months) if the percutaneous

biopsy histologic diagnosis is nonspecific. Jackman

et al [69] recommend that the first follow-up study be

obtained six months after percutaneous biopsy for all

lesions yielding benign findings concordant with the

imaging characteristics. Further work is necessary to

determine the optimal follow-up protocol.

Obtaining follow-up poses challenges. In a study

of 160 breast lesions that had percutaneous biopsy,

Goodman et al [104] reported that only 52 (74%) of

70 lesions referred for surgical excision had docu-

mented surgical outcomes. Among 90 lesions re-

ferred for mammographic surveillance, 10 (11%)

were resolved at the time of the study, 49 (54%)

were on track toward 3-year lesion stability, 21

(23%) were being followed up elsewhere, four

(4%) were lost to physicians, and six (7%) were lost

to follow-up for other reasons. Follow-up requires a

substantial commitment of time and resources, but is

necessary for patient care and to improve our under-

standing of the false-negative rate of percutaneous

core biopsy of the breast.

Future directions

Percutaneous biopsy has revolutionized breast

diagnosis, but further work is needed. Future studies

should include evaluation of new technology with

respect to safety, accuracy, and cost-effectiveness;

optimization of choice of biopsy method for different

lesions; long-term follow-up studies; and develop-

ment of technology for MRI-guided breast biopsy.

With this additional study, percutaneous biopsy may

afford even more women a less invasive, less expen-

sive alternative to surgery for the histologic diagnosis

of breast lesions.

Acknowledgment

The author thanks David C. Perlman for his

invaluable support.

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L. Liberman / Radiol Clin N Am 40 (2002) 483–500500

Breast imaging and the conservative treatment

of breast cancer

D. David Dershaw, MD

Breast Imaging Section, Department of Radiology, Memorial Sloan-Kettering Cancer Center,

1275 York Avenue, New York, NY 10021, USA

When the breast containing cancer is treated by

mastectomy, issues of multifocality and multicen-

tricity of disease are obviated by removal of the

entire breast. When breast conservation is per-

formed, however, it is presumed that residual cancer

may be present postoperatively in the breast and can

be sterilized with postoperative radiation. The suc-

cess of radiation in eradicating residual tumor

depends, at least partially, on the volume of residual

disease within the breast. Therefore, it is necessary

for the breast imager to determine, as accurately as

possible, the extent of disease within the breast

undergoing treatment. After treatment, the breast is

monitored to detect recurrent tumor, if it occurs, at

the earliest stage possible. Additionally, the opposite

breast is screened because of its increased risk of

developing carcinoma.

Whereas the goal of both mastectomy and con-

servation is to cure, conservation also considers the

cosmetic result. Unnecessary biopsy of the treated

breast can compromise cosmesis; therefore, the

breast imager should be able to differentiate the

usual benign sequelae from possible malignant dis-

ease to minimize the likelihood of unnecessary

biopsy. Also, physicians need to understand the

appropriate role of needle biopsy techniques in this

population, sparing these women additional surgery

when possible.

Evidence supporting breast conservation

From 1972 to 1989, six prospective randomized

trials of 4108 women were conducted comparing the

outcome of women with invasive breast carcinoma

treated with breast-conserving surgery and whole-

breast radiation versus mastectomy. Results are

shown in Table 1 [1–6]. Mastectomies performed

were either radical or modified radical mastectomies.

Breast-conserving surgery was classified as local or

wide excision or quadrantectomy. Except for the

Danish Breast Cancer Group, which included women

with stage III tumors, studies included only women

with stage I (Milan I, Gustave-Roussy) or stage I-II

(EORTC, NCI, NSABP B06) breast cancers. All

trials included whole-breast irradiation of 45–50

Gy. Except for the NSABP study, in which no boost

dose was given, conservation treatment in the other

five studies included radiation to the primary tumor

site boosting the total dose at this site to � 60 Gy. In

these trials, there was no significant difference in the

outcomes of women treated with conservation or

mastectomy (Table 1). Patterns of local recurrence

reported in these trials show 3% to 20% recurrence at

3 to 18 years of follow-up.

Multiple single institutions have also reported

retrospective data of their experience with breast con-

servation [7]. Among the 5600 women included in

these studies, 10-year results showed overall survival

rates ranging from 63% to 86%, with disease-free

survival rates ranging from 63% to 74%. Local recur-

rence rates were 8% to 20% at 10 years and 17% to

18% at 15-year follow-up. Again, these data support

the comparable survival rates of women treated with

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00003 -3

E-mail address: dershawd@mskcc.org (D.D. Dershaw).

Radiol Clin N Am 40 (2002) 501–516

conservation versus mastectomy and a roughly 1% lo-

cal recurrence rate in the first 15 years after treatment.

Selection of women for breast conservation

Clinical contraindications to breast conservation

are listed in Table 2. These contraindications are

based on the inability to deliver radiation to the

breast, the inability to resect tumor with a cosmeti-

cally acceptable result, or the inability or unreliability

of the patient to complete a course of radiation

(Fig. 1). Note that there is no contraindication based

solely on tumor size. Active collagen vascular disease

increases the breast’s sensitivity to radiation and may

make it impossible to deliver a therapeutic dose. If

collagen vascular disease is inactive, this is frequently

not a problem. Also, the presence of palpable, non-

matted axillary adenopathy does not contraindicate

breast conservation.

Preoperatively, it is the role of breast imaging to

accurately determine the extent of tumor within the

breasts. This assessment may be accomplished in

some women with mammography. In others, the use

of sonography and MRI may more accurately evaluate

the extent of tumor. Accurate preoperative assessment

can save the patient multiple surgeries necessitated by

repeatedly positive margins of the excised tissue.

Failure to detect multicentric disease can result in

local treatment failure and the need for mastectomy.

Complete evaluation of the breast with mammog-

raphy may require additional views, including mag-

nification. Comparison with prior studies may make

subtle changes caused by carcinoma more obvious.

Care should be taken to be certain that nothing

suspicious is present in the contralateral breast.

Several studies have suggested that additional

imaging techniques may be of value in detecting

otherwise hidden carcinoma in women with a known

malignant lesion in the breast. In women with known

breast carcinoma, sonography has detected foci

of carcinoma not apparent on mammography [8].

Although these additional sites of carcinoma are

usually caused by invasive disease, areas of ductal

carcinoma in situ (DCIS) have also been identified.

For MRI, the reported sensitivity in the diagnosis of

invasive carcinoma has approached 100%, with sen-

sitivity for DCIS ranging from 40% to 100% [9]. This

level of sensitivity has made it possible to perform

more accurate preoperative staging of local disease

within the breast with MRI than with mammography

or physical examination in some women. However,

false-positive MRI examinations make it necessary to

have histologic confirmation of positive MRI findings

if they will change the treatment of the disease. One

group has demonstrated that, whereas MRI results

changed therapy in 14% of women with breast cancer,

3.5% of studies led to an unnecessary open biopsy

[10]. MRI may be particularly useful in the preoper-

ative staging of invasive lobular carcinoma. One study

found that, whereas mammography was able to accu-

rately delineate the extent of this tumor within the

breast in only 32% of cases, MRI was accurate in 85%

[11]. MRI may also be useful in determining the

involvement of the pectoralis major muscle in women

with posterior breast cancers [12].

Specimen radiography

In women with nonpalpable cancers or with

tumors that have areas extending beyond the area of

the palpable tumor, specimen radiography is useful to

determine if the suspicious lesion has been excised or

if some tumor remains within the breast. It also is

useful in directing the pathologist to the areas of

interest in the excised specimen.

Specimen radiography can be performed with

mammography equipment or with special specimen

Table 1

Survival results of prospective randomized trials of breast

conservation

Overall

survival (%)

Disease-free

survival (%)

Study

Conser-

vation

Mastec-

tomy

Conser-

vation

Mastec-

tomy

Gustave-Roussy [1] 73 65

Milan I [44] 65 65

EORTC [42] 65 66

NCI [22] 77 75 72 69

NSABP B06 [14] 63 59 50 49

Danish Breast

Cancer Group [3]

79 82 70 66

Table 2

Contraindicators to breast conservation

Absolute contraindications

First or second trimester of pregnancy

History of prior breast therapeautic radiation

Large tumor-to-breast ratio

Multiple, synchronous carcinomas, especially if widely

separated or in different quadrants

Relative contraindicators

Collagen vascular disease

Inability to travel to radiation facility

Unreliable to complete course of treatment

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516502

radiography units [13]. Especially for uncalcified

areas of tumor, compression of the specimen may

be helpful in identifying the tumor. Views of the

specimen obtained in multiple projections can help

identify tumor extending to the margin of resection

(Fig. 2). When areas of worrisome calcification are

not found by the pathologist on histopathologic

slides, radiography of the tissue imbedded in paraffin

Fig. 1. Craniocaudal view of a breast of a woman who presented with a palpable mass at 12 o’clock. The mass was caused by

two adjacent spiculated masses (two central arrows). Mammography revealed two additional spiculated carcinomas (two

peripheral arrows). Although the central masses could be removed with conservation, the presence of multiple masses over a

wide volume of the breast necessitated mastectomy.

Fig. 2. Specimen radiography shows areas of calcification at (thick arrow) and near (thin arrow) the margin of resection.

Removal of additional tissue from at the time of surgery was performed for in situ and invasive ductal carcinoma.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516 503

can assist in locating foci of calcification that have

not been sliced and stained so that additional slides of

these areas can be prepared (Fig. 3).

At the time that the specimen radiograph is

interpreted, the preoperative mammogram should be

available so that the mammographic characteristics of

the carcinoma can be compared with the findings on

the specimen radiograph. Areas of architectural dis-

tortion and asymmetry can be difficult to appreciate

on specimen radiography, and the specimen radio-

graph is least useful for tumors presenting with these

imaging characteristics [14]. The specimen radio-

graph should be examined while the patient is still

in surgery. Absence of the area of suspicion should

result in the removal of more tissue to successfully

biopsy the suspicious lesion. Extension of tumor

mass or calcifications to the margin of the specimen

suggests that tumor has been transected. Removal of

more tissue from that margin of the biopsy cavity is

appropriate to obtain negative margins at the time of

the original surgical procedure. The excised specimen

can be marked with surgical clips to orient the

Fig. 3. Biopsy was performed in this patient for suspicious calcifications that could not be identified on initial examination of the

pathology specimen. Radiography of tissue slices allowed the pathologist to identify the sites of calcification (arrows), which

were caused by ductal carcinoma in situ.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516504

Fig. 4. A postlumpectomy mammographic view shows residual tumoral calcifications (arrows) next to the lumpectomy site. At

re-excision, residual ductal carcinoma in situ was found associated with the calcifications.

Fig. 5. A persistent seroma underwent sonography because of clinical concern over failure of the seroma to resolve. Although

there was no residual carcinoma, the irregular echo pattern of seromas makes it impossible to exclude malignancy.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516 505

margins of the specimen to the walls of the lumpec-

tomy cavity.

In addition to specimen radiography, margins of the

excised specimen are routinely painted with India ink,

and the inked margins are examined by the pathologist

to determine if tumor is present at or near the margin.

The specimen radiograph may not show margin

involvement because of the orientation of the speci-

men to the x-ray beam or because of mammographi-

cally inapparent carcinoma. Also, the pathologist

samples only some of the inked edges of the specimen,

possibly failing to sample sites with tumor involve-

ment. Therefore, these two techniques are complimen-

tary in evaluating the margins of the excised tissue.

For lesions that are identified only on sonography,

sonography of the excised specimen can confirm

removal of the lesion and localize it within the speci-

men [15]. Because MRI identification of carcinoma is

dependent upon contrast enhancement, no method of

MRI specimen assessment is currently available.

Immediate postoperative mammography

For women whose carcinomas contain calcifica-

tions that are detectable by mammography, complete

determination of the adequacy of excision of the

tumor includes a postoperative mammogram, usually

done before radiation therapy commences. Adequacy

of excision cannot be reliably determined on the basis

of the specimen radiograph [16]. This assessment is

appropriately performed by mammography following

tumorectomy [17]. These films are usually done 2 to

4 weeks after surgery and before radiation therapy is

initiated (Fig. 4). They can, however, be done as soon

as the same day as surgery, if necessary. Routine

mediolateral oblique (MLO) and craniocaudal (CC)

views of the breast should be obtained. If no residual

tumoral calcifications are seen, then magnification

mammography may demonstrate residual calcifica-

tions that are not apparent on the routine views.

Images should be compared with preoperative mam-

mograms so that the morphology of calcifications

associated with the patient’s carcinoma is known.

Although these postoperative mammograms are not

of value for women whose tumors did not contain

calcifications, it may be worthwhile to schedule all

patients undergoing conservation to have mammo-

graphy before radiation so that women for whom

these studies are valuable always have them done. If

re-excision of residual calcifications is performed,

postoperative mammography must again be done

before radiation to be certain that all worrisome cal-

cifications have been removed.

Fig. 6. (A) Conservation was performed on this patient with

invasive ductal carcinoma (arrow). (B) Mammography

done 1 year after treatment shows architectural irregularity

and ill-defined density at the lumpectomy site caused by

surgery. Skin thickening and stromal coarsening are

secondary to radiation.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516506

Completeness of tumor excision cannot be deter-

mined on the basis of these images. Although all

tumoral calcifications may have been excised, resid-

ual, uncalcified tumor can be present in the breast

[18]. The presence of this tumor can be suggested by

positive histologic margins of the lumpectomy speci-

men. Also, because benign and malignant processes

containing calcifications can coexist, the presence of

residual calcifications, particularly when they are few

in number and not of BI-RADS 5 type, can be caused

Fig. 7. Postoperative seromas at the lumpectomy may take long periods to involute. (A) Preoperative mammography shows a

small invasive ductal carcinoma (arrow) in the lateral aspect of this breast. (B) Mammogram done 1 year later shows clips at the

surgical site, surrounding ill-defined density that is centrally caused by a seroma. (C) Mammogram 2 years after surgery shows

partial involution of the seroma.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516 507

by benign entities [17]. Therefore, some re-excisions

for residual calcifications will fail to find tumor in

the breast.

For women with positive margins histologically,

assessment of residual disease within the breast can

also be done with MRI. This is particularly valuable

for women whose carcinomas are uncalcified and

whose breasts are dense. In one study of 47 patients,

contrast-enhanced MRI had a positive predictive

value for residual tumor of 82% and a negative

predictive value of 61% [19]. Among women included

in this study, 4 of 14 with residual multifocal or diffuse

carcinoma had their treatment changed from conser-

vation to mastectomy. These results have been sup-

ported by other investigators [20].

The normal, acute postoperative pattern at the

lumpectomy site is a thin rim of enhancement around

the seroma cavity. Clumped enhancement at the

margins of the seroma and enhancing lesions else-

where in the breast suggest residual tumor; how-

ever, in some instances, clumped granulation tissue

around the seroma cavity can have a pattern suggest-

ing residual disease. Also, nonmalignant lesions

within the breast can show patterns of enhancement

that are identical to those seen in carcinomas. Treat-

ment decisions should be made on the basis of

histologic assessment of enhancing lesions suggest-

ing tumor and should not be made solely on the basis

of MRI findings.

Sonographically, the tumorectomy bed appears as

a complex mass. The extent of solid material within

the seroma cavity is variable. However, irregularity of

the seroma wall and variability of the echo pattern

within the lumpectomy site usually make sonography

of little value in assessing completeness of tumor

excision (Fig. 5).

Long-term follow-up: usual mammographic

changes

The long-term follow-up of the irradiated breast is

performed to detect any recurrence of carcinoma in

the breast. The breast imager needs to be familiar with

the expected changes in the conservatively treated

breast so that these are not mistaken for recurrence.

Unnecessary biopsy of these breasts can compromise

the cosmetic result of conservation. Because of the

compromise of microvasculature by radiation, exag-

gerated patterns of scarring can occur after surgical

biopsy. It is important to identify recurrence as early

as possible to optimize the likelihood of cure [21,22].

The first post-treatment mammogram of the irra-

diated breast is usually done 3 to 6 months after

radiation [23]. Bilateral mammography is then per-

formed 12months after the preoperative mammogram.

At this time, the untreated breast undergoes its annual

screening, and assessment of the treated breast is

synchronized with the contralateral side. Thereafter,

screening can be performed annually, although some

radiologists have recommended mammography of the

treated breast every 6 months for the first 3 years.

Post-treatment changes should be most pro-

nounced on the first postradiation mammogram

[24,25]. Changes may show stability, regression, or

return to normal with the passage of time. Increases

in these changes on studies done after the first

posttreatment mammogram should not be accepted

as normal, and the reason for any increase in these

findings should be investigated because the cause can

be new or recurrent carcinoma.

The usual alteration in the mammogram after

treatment consists of an increase in breast density,

architectural distortion and scar formation, and the

Fig. 8. Dystrophic calcifications commonly develop at the

lumpectomy site after radiation. Three years after treatment,

coarse and punctate calcifications are present in this patient.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516508

development of calcifications (Fig. 6). In any single

patient, all, some, or none of these changes can occur.

Density changes are identical to those that can be

seen with inflammatory carcinoma, mastitis, obstruct-

ed lymphatic or venous drainage, and diffuse infiltra-

tion by lymphoma. Differentiation from these other

entities is based on clinical history.

Increase in density of the treated breast is initially

caused by postoperative edema. After radiation, post-

radiation inflammation occurs, followed by postradia-

tion fibrosis [26]. All of these processes have an

identical mammographic pattern. Skin thickening

may be present, and this is the most common post-

treatment change found on these mammograms

[27,28]. It is best appreciated by comparison with

the nontreated breast or the pretreatment mammo-

gram. In addition to skin changes, the stromal pattern

of the breast can become coarsened. Ductal and

glandular elements can also become thickened. These

individual changes contribute to a pattern of diffusely

increased mammographic density of the treated breast.

Architectural distortion and scar formation are

caused by the surgical intervention. On the initial

postoperative mammograms, it is common to see a

postoperative seroma. These are round or oval soft-

tissue-density masses. Resorption of seroma fluid can

be slow, and these masses can persist for many

months and occasionally for 2 or more years [24]

(Fig. 7). If they are studied with sonography, they

appear as a complex mass, and the findings do not

differentiate them from carcinoma. Their presence

should not be a cause of concern, however. If

aspirated, they will reaccumulate. Therefore, their

persistence over extended periods should not lead to

intervention. On serial examination, they should

decrease in size (or at least not increase). As they

regress, fibrosis of the surgical cavity can develop as

a scar forms at the operative site. Although the

pattern may be grossly spiculated, the volume of

the changes at the operative site should be stable or

decreasing. These changes can become more obvious

as postsurgical edema resolves. It is the volume of the

changes that is significant; as long as the size of the

area of surgical change is stable or decreasing, these

changes should not be a cause of concern.

Calcifications can be caused by radiation with

dystrophic calcifications and fat necrosis calcifica-

tions developing in about one third of women under-

going breast irradiation [23–25,29] (Fig. 8). These

may not appear until 3 to 5 years after treatment.

Coarse calcifications, characteristic of fat necrosis,

should cause no problems in the interpretation of

Fig. 9. Heavy, linear calcifications with rounded regions at the lumpectomy site are caused calcified, knotted suture material.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516 509

Fig. 10. (A) The upper portion of this mediolateral oblique view shows surgical clips surrounding a lumpectomy scar. (B) One

year later, 3 years after conservation, a new mass (arrow) has developed, caused by recurrent invasive ductal carcinoma.

Identification of the recurrence would be difficult without the prior post-treatment mammogram for comparison.

Fig. 11. (A) The upper portion of a mediolateral oblique view shows postsurgical distortion in the tail of the breast 1 year after

treatment. (B) One year later, three masses have developed at the lumpectomy site caused by recurrent invasive ductal carcinoma.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516510

mammograms of these patients. Calcified suture

material and surgical clips at the lumpectomy site

can also be seen (Fig. 9). These are also not a cause of

concern. The development of pleomorphic micro-

calcifications within the breast, however, raises the

possibility of local treatment failure. Their workup is

addressed in the following section.

Local treatment failure

Recurrence of carcinoma in the treated breast

occurs at a constant rate of 1% to 2% per year during

the first 2 to 8 years after treatment [30,31]. Local

recurrence rates of 5% to 10% at 5 years and 10% to

15% at 10 years for adequately treated cancers should

be expected. Women who are at increased risk for

local treatment failure include those with positive

margins [32,33], those not treated with radiation

[34], those with multiple cancers in the breast at the

time of initial presentation [35], and those whose

tumors have an extensive intraductal component

without a large negative surgical margin [36]. Some

also believe that those who are treated at a young age

are at greater risk for recurrence [37]; however, the

possibility of recurrent tumor exists in any breast

previously treated with conservation.

Local treatment failure that occurs within the first

5 to 7 years after treatment is most likely to be located

at or near the site of the original cancer [38,39]; it is

caused by recurrence of the original carcinoma that

was not fully eradicated. The greatest tumor burden

within the breast is usually near the site of the original

carcinoma, and the ability of radiation to sterilize the

tumor is related to tumor volume. Therefore, if tumor

cells are present in the breast after radiation, they are

Fig. 12. Six years after treatment for invasive ductal carcinoma, new microcalcifications (arrows) developed in the region of

coarse, fat necrosis calcifications at the site of prior lumpectomy. Biopsy revealed ductal carcinoma in situ.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516 511

most likely present at the site of the original carci-

noma. Local failure after 5 years is commonly caused

by carcinomas growing elsewhere in the breast. Small

tumors present within the breast that were undetected

at the time of treatment of the original cancer are

usually sterilized by postoperative radiation. There-

fore, growth of tumor outside the area of the original

cancer requires that new tumors form and grow for a

long enough time to become detectable.

Because of this pattern of recurrence, the breast

imager should attempt to include the entire site of

lumpectomy on follow-up mammograms, especially

in the first decade after treatment. This often requires

additional views beyond the routine MLO and CC

views. Routine magnification of the lumpectomy bed

is not necessary unless there are findings on non-

magnification views that warrant magnification [40].

If the surgeon has placed clips around the lumpec-

tomy cavity at the time of tumorectomy, identification

of all of these clips on the mammographic images is

helpful in documenting that the lumpectomy site has

been completely examined. It is helpful to establish

which extra views are needed on the first posttreat-

ment mammogram and to include these on all follow-

up studies, which makes it possible to compare the

size of the scar and other changes in the same

projection on serial examinations.

The ability of mammography to detect local recur-

rence is compromised by the presence of postoper-

ative distortion and increased density of the irradiated

breast. Mammography is able to detect only two thirds

of recurrences [23,38]. Therefore, the physical exami-

nation is of increased importance in detecting tumor

within the conservatively treated breast, and subtle

findings on physical examination should be carefully

correlated with subtle changes on mammography.

Patterns of recurrence on mammography are

generally those findings that are suspicious for car-

cinoma in the nonirradiated breast superimposed on

findings of lumpectomy and radiation. These include

suspicious microcalcifications and new masses not

caused by a simple cyst (Figs. 10, 11). Inflamma-

Fig. 13. An axillary view shows adenopathy (arrow) in the low axilla. This was new 5 years after conservation and was caused

by an axillary recurrence.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516512

tory recurrences can appear as diffusely increas-

ing breast density. Subtle or obvious enlargement

of the lumpectomy scar also can herald recurrent

carcinoma [38].

Calcifications that are associated with recurrences

tend to be highly suspicious (BI-RADS 5 category)

(Fig. 12) [41,42]. Less worrisome calcifications can

sometimes indicate the presence of recurrent tumor,

however. Recurrent DCIS is almost always indicated

by the development of microcalcifications. Detecting

these microcalcifications on mammography was

found to be the method of detecting recurrence in

92% of DCIS recurring as pure DCIS [43]. If an

immediate postoperative mammogram has not been

obtained for women whose cancers contain mammo-

Fig. 14. (A) Five years after conservation, this view of a

lumpectomy bed had been stable over several years,

showing unchanged architectural distortion and fat necrosis.

(B) One year later, a new mass (arrow) was evident near the

lumpectomy bed. Biopsy showed only fat necrosis.

Fig. 15. Sonography was performed for this woman with a

questionable new mass near her scar. (A) Sonogram of the

scar shows an angulated, spiculated, echo-poor shadowing

mass. (B) The palpable mass near the scar has similar

sonographic characteristics. It was caused by recurrent

carcinoma. Differentiation of scar and recurrence based on

their echo pattern is not possible.

D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516 513

graphically evident microcalcifications, the signifi-

cance of microcalcifications at the lumpectomy site

on the first post-treatment mammogram cannot be

determined. These can be caused by residual tumor or

recurrent disease or may indicate decreasing tumor

that is responding to treatment.

Although enlarging axillary nodes can appear

acutely postoperatively and are reactive, the presence

of axillary nodal enlargement later after treatment can

be caused by an axillary recurrence (Fig. 13). It is

necessary to determine the reason for developing

adenopathy. This might require biopsy, often done

using fine needle aspiration.

Benign sequelae resembling recurrent tumor

Fat necrosis and other dystrophic changes caused

by radiation can resemble tumor recurrence. Other

entities, such as sclerosing adenosis, can also occur

and produce findings that are also worrisome for new

or recurrent carcinoma. It is important to determine the

cause of these findings, without surgical intervention if

possible. When necessary for a definitive diagnosis,

however, surgical biopsy should be performed.

The characteristic pattern of fat necrosis is that it

develops at or near the lumpectomy site, usually

approximately 2 years after treatment. Because

enlargement of the surgical scar is a sign of recur-

rence, findings on physical examination and mam-

mography are suspicious for cancer (Fig. 14). MRI

may assist in the differentiation between scar and

recurrence. Because postoperative scarring is avascu-

lar after 18 months and recurrent breast carcinoma,

especially if invasive, is hypervascular, recurrences

will enhance with gadolinium on MRI, and enlarging

areas of fibrosis are generally nonenhancing [44,45].

Stereotactic core biopsy of suspicious areas has also

been demonstrated to be accurate in differentiating

scar from recurrence [46].

Sonographically, scars and carcinoma usually are

hypoechoic and ill defined (Fig. 15). The differentia-

tion of the two using sonography is therefore not

possible; however, sonography can be useful in

guiding needle biopsy of suspicious areas. Some have

also found it to be of value in following the size of

scars that are located in areas of the breast that are

difficult to fully image with mammography.

Summary

Breast conservation, where appropriate, offers

effective treatment for breast cancer while preserving

the breast. The increased use of mammographic

screening has led to increased detection of small,

curable breast cancers that are amenable to breast-

conserving surgery. Mammography and other imag-

ing modalities, such as sonography and MRI, assist in

the determination of the appropriateness of breast

conservation and in the differentiation of recurrence

from benign sequelae of treatment.

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D.D. Dershaw / Radiol Clin N Am 40 (2002) 501–516516

Breast imaging: a breast surgeon’s perspective

Kimberly J. Van Zee, MD

The Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center,

1275 York Avenue, New York, NY 10021, USA

The patient presenting with a lesion detected by

screening exam

A patient whose screening mammogram reveals an

abnormality is often referred to a surgeon who treats

diseases of the breast. The surgeon thus becomes the

treating clinician for a radiologic finding. The surgeon

is highly dependent upon the radiologist’s ability to

communicate his or her findings from the mammo-

gram. A thorough description of the abnormality—

including the type (eg, calcifications, mass, distortion),

descriptive characteristics (eg, punctate versus pleo-

morphic calcifications or well circumscribed versus

spiculated mass), size, location (eg, quadrant, distance

from nipple), and level of suspicion—is necessary if

the surgeon is to have a clear understanding of the

ramifications of the finding. Ideally, as the surgeon

reviews the written report describing themammogram,

he or she is able to inspect the actual film. Often,

however, the patient will arrive without the films. In

such cases, having a complete description greatly

facilitates the surgeon’s understanding of the finding

and communication with the patient.

I have found that the adoption of the Breast

Imaging Reporting and Data System (BI-RADSTM)

[1] lexicon, discussed by Liberman and Menell in

this volume [2], has greatly improved clear commu-

nication regarding level of suspicion for a lesion. By

means of this straightforward system of five numeric

assessment categories, the radiologist succinctly con-

veys to the surgeon an abundance of information.

As a result, the surgeon can appropriately discuss

with the patient the likelihood of malignancy and the

need for biopsy.

Noting the size, location, and type of lesion is also

very useful to the surgeon. In the patient referred with

an abnormal mammogram, knowledge of these

characteristics assists in determining whether any

physical examination findings correlate with the

mammographic findings. In a patient with a palpable

mass, a correlative mammogram or sonogram done

after the mass is marked by the surgeon can deter-

mine whether the radiologic abnormality corresponds

to the palpable one.

Given the widespread adoption of percutaneous

image-guided breast biopsy [3], a comment by the

radiologist regarding the feasibility of percutaneous

biopsy under stereotactic or ultrasound guidance is

also greatly appreciated. With this information, the

appropriate biopsy modality can be recommended.

In women with dense breasts and at high risk for

breast cancer by virtue of a prior personal history of

breast cancer, lobular carcinoma in situ, atypical

ductal hyperplasia, or because of a strong family

history of breast cancer, screening with sonography

[4] and MRI [5] is becoming increasingly common,

as discussed by Gordon [6] and Morris [7]. As with

mammography, a careful description of all relevant

findings helps the surgeon in his/her communication

with the patient. In experienced hands, sonography

and MRI of high-risk women may have an acceptable

false-positive rate and can occasionally detect cancer

that is nonpalpable and mammographically occult.

The patient presenting with a physical finding

The radiologist can also play a very important role

in the assessment of a patient presenting to the

surgeon with a finding on physical exam. Mammo-

graphic, sonographic, and/or MRI evaluation can

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00006 -9

E-mail address: vanzeek@mskcc.org (K.J. Van Zee).

Radiol Clin N Am 40 (2002) 517–520

often support or change the surgeon’s impression of a

palpable mass. Percutaneous core biopsy under ultra-

sound guidance can be helpful for tissue diagnosis in

women with palpable lumps, particularly if the lump

is deep, mobile, or vaguely palpable; ultrasound-

guided core biopsy in this setting can spare surgery

in women with benign disease and can expedite

treatment in women with breast cancer [3].

In the case of nipple discharge, the location of the

causative lesion can usually be identified by galac-

tography. Duct imaging can be of great utility to the

surgeon attempting to do a precise and accurate duct

excision for diagnosis [8]. In patients with nipple

discharge in whom a galactogram is unsuccessful,

MRI may be helpful in localizing the causative lesion

and in suggesting the presence of malignancy [9].

Image-guided biopsy

Probably the greatest change in the radiologist’s

contribution to the diagnosis of breast cancer has

been that effected by the widespread adoption of

image-guided core biopsy under stereotactic or ultra-

sound guidance, as discussed in this volume by

Liberman [3]. This technique represents a minimally

invasive method of obtaining breast tissue for histo-

logic diagnosis and has markedly changed the algo-

rithm used in the diagnosis of breast abnormalities.

The use of image-guided core biopsy has reduced the

number of surgical biopsies performed and has

increased the number of breast cancers that can be

treated with one surgical procedure. Through the

widespread use of this technique, many women are

now able to discuss surgical options with their

surgeon following a definitive diagnosis of breast

cancer but prior to any surgery.

In a patient undergoing stereotactic biopsy for

calcifications, communication of the findings of

specimen radiography and the postbiopsy mammo-

gram is very useful. Also, in patients in whom all

calcifications are removed, placement of a clip

greatly facilitates subsequent surgical excision should

histologic examination reveal malignancy [3]. In

these patients, knowing that no residual calcifications

remain after stereotactic biopsy also allows the

patient to forego the usual postoperative mammo-

gram to document removal of all calcifications.

The patient with breast cancer

In the patient with biopsy-proven breast cancer,

or in a patient whose physical or mammographic

findings are highly suspicious (BI-RADSTM cate-

gory 5), the radiologist makes important contribu-

tions to patient management.

In a patient with a relatively large mass or area of

calcifications, I often discuss the feasibility of breast

conservation with my radiologic colleagues while

reviewing the films. Sometimes the physical exami-

nation findings can underestimate or overestimate the

extent of disease, and radiologic findings can guide

one to a more appropriate treatment plan. In recent

years, sonography has played a larger role in the

characterization of palpable masses [10], and size

estimation by sonography may be better than that

by physical exam or mammography.

For women who are considering breast conserva-

tion, it is important to scrutinize the mammogram for

evidence of other sites of carcinoma in the ipsilateral

or contralateral breast. Sonography may identify

additional sites of disease that are mammographically

occult, altering surgical management [11]. MRI is

also being used more frequently in assessing extent of

disease, especially in women with dense breast tissue

and in those with infiltrating lobular carcinoma

[7]. Likewise, in women with positive margins after

attempted wide excision, MRI may be helpful in the

assessment of residual disease [12].

In patients with a radiologically detected non-

palpable lesion, preoperative localization is utilized.

While mammographic localization has been used for

many years, sonographic and MRI localization are

now also used. At our institution, localization is

performed with a thin hooked wire that has a 2-cm

reinforced portion. Ideally, the reinforced portion is

placed through the lesion so that, if the tissue sur-

rounding the reinforced portion and the hook of the

wire is excised, the entire radiologic lesion is resected.

Communication between surgeon and radiologist can

increase the likelihood of complete resection.

The recently developed ability to place a wire

under MRI guidance allows localization of lesions

that are nonpalpable and mammographically occult

but visible on MRI. In spite of the lesion’s being

mammographically occult, I have found that a

mammogram performed after the MRI-guided wire

placement is still helpful in guiding the surgeon

during the excision. The surgical procedure is similar

to that used for excisional biopsy with preoperative

mammographic localization, except that a specimen

radiograph usually does not demonstrate the lesion.

A postoperative MRI may be helpful to confirm

lesion retrieval.

In a patient with a large radiologic abnormality

that is either impalpable or vaguely palpable, it is

often useful to place multiple wires to bracket the

K.J. Van Zee / Radiol Clin N Am 40 (2002) 517–520518

area. This technique utilizes multiple mammograph-

ically or MRI-guided wires to delineate the bounda-

ries of the lesion, thereby increasing the likelihood

that the surgeon will completely excise the entire

lesion and achieve negative margins [13]. This tech-

nique may also be utilized for a mammographic mass

with calcifications extending from it, allowing the

surgeon to excise the mass and calcifications en bloc.

After excision of carcinoma with associated calci-

fications, a postoperative mammogram is generally

obtained, usually no earlier than 2 weeks after surgery.

In the presence of negative histologic margins, the

radiologist assists the surgeon in assessing the com-

pleteness of excision by reporting the presence or

absence of any residual calcifications that could

be associated with residual microscopic disease.

Although this applies to mammographic calcifi-

cations alone, it also applies to masses with associated

calcifications. Because of the high positive predictive

value of residual calcifications in this setting [14],

we generally perform needle localization and re-

excision for residual calcifications if the breast is

being conserved.

The patient with findings suspicious for

local recurrence

In the patient with a history of breast cancer

treated with breast conserving surgery, it is important

to distinguish between postoperative changes and

recurrence, as discussed by Dershaw in this volume

[15]. Having prior films is particularly useful in this

setting. I find it very helpful when their availability or

lack thereof is mentioned in the report because I am

then able to understand the level of concern of the

radiologist or encourage the patient to obtain her prior

films [15].

Magnetic resonance imaging is another tool that

is increasingly used in assessing patients for recur-

rence. Scar tissue that appears dense mammograph-

ically can sometimes be better imaged with MRI,

allowing the breast radiologist greater certainty in

interpretation [7].

In a patient with a history of DCIS treated with

breast conservation, new calcifications on mammog-

raphy raise the possibility of local recurrence. We

have found that, among patients in whom DCIS was

originally associated with mammographic calcifica-

tions, recurrences are usually manifest as calcifica-

tions with the same mammographic pattern and

calcification morphology as the original DCIS [16].

A comment from the radiologist to convey his or her

impression regarding the similarities or differences

between current mammograms and those obtained at

the time of the original DCIS diagnosis is useful to

the surgeon.

New modalities in breast imaging

Patients are interested in learning about new

modalities in breast imaging, as described by Leung

in this volume [17]. Although new techniques show

promise, we emphasize to our patients the proven

value of screening mammography, as discussed by

Lee [18]. We continue to take advantage of mammo-

graphic screening, a method that has been shown to

decrease breast cancer mortality, as we explore new

techniques that may assist in breast cancer detection.

Summary

Many changes have occurred in the past decade in

the imaging of the breast. These improvements have

led to more sensitive and specific breast imaging and

to the widespread use of minimally invasive biopsy

techniques. They have also facilitated a closer work-

ing relationship between breast imager and surgeon

and have contributed greatly to the surgeon’s ability

to optimally diagnose and treat breast cancer.

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Hylton NM. MR imaging of the breast in patients with

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time interval between lumpectomy and MR imaging.

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[13] Liberman L, Kaplan JB, Van Zee KJ, Morris EA,

LaTrenta LR, Abramson AF, et al. Bracketing wires

at pre-operative breast needle localization. AJR 2001;

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[14] Gluck B, Dershaw DD, Liberman L, Deutch BM. Mi-

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K.J. Van Zee / Radiol Clin N Am 40 (2002) 517–520520

What do we expect from imaging?

Richard R. Barakat, MD*, Hedvig Hricak, MD, PhD

Academic Office, Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center,

1275 York Avenue, New York, NY 10021, USA

The objectives of imaging in gynecologic cancer

include tumor detection, tumor diagnosis, staging,

and follow-up. In addition, monitoring the response

to treatment and differentiating tumor recurrence

from post-treatment changes are important indica-

tions for imaging. In 2002 it is estimated that there

will be 39,300 cases of endometrial cancer, 23,300

cases of ovarian cancer, and 13,000 cases of cervical

cancer [1]. This article reviews the information

required by the practicing gynecologist or gyneco-

logic oncologist before surgery and briefly summa-

rize state-of-the-art imaging in answering clinically

pertinent questions.

Endometrial cancer

Since 1972, carcinoma of the epithelial lining

(endometrium) of the uterine corpus has been the

most common female pelvic malignancy. The Amer-

ican Cancer Society estimates that 39,300 cases will

occur in 2002 in the United States. Carcinoma of the

endometrium is primarily a disease of postmeno-

pausal women, although 25% of the cases occur in

premenopausalwomen, with 5% occurring in women

younger than 40 years of age [2]. In 75% of all cases,

the tumor is confined to the uterine corpus at the time

of diagnosis, and uncorrected survival rates of 75% or

more are expected [3].

The mainstay of treatment for endometrial cancer

is surgery. The majority of these cases are operated

on by the general obstetrician/gynecologist. In some

cases, pelvic lymph node sampling is indicated. This

procedure consists of taking a sample of lymph

nodes taken from the distal common iliac and from

the superior iliac artery and vein. A third sample of

lymphatics is obtained from the group of nodes that

lie along the obturator nerve. For some patients,

para-aortic node sampling is also indicated and can

be performed through a midline peritoneal incision

over the common iliac arteries and aorta. A sample

of lymph nodes is resected along the upper common

iliac vessels on either side and from the lower

portion of the aorta and vena cava. On the left side,

the lymph nodes and lymphatics are slightly poste-

rior to the aorta; on the right side, they lie primarily

in the vena caval fat bed. Unfortunately, many

patients who require lymph node sampling do not

undergo this procedure because the general gynecol-

ogist is not usually trained to perform a lymph node

sampling. Lymph nodes may be palpated, plucked,

or perhaps worst of all ignored. Patients who have

not been comprehensively staged are often subjected

to the morbidity of whole pelvic radiation therapy.

The key, then, is to determine preoperatively which

patients require lymph node sampling so that appro-

priate referral to or intraoperative consultation with a

gynecologic oncologist can be obtained.

The group of patients at greatest risk for nodal

metastases has been identified by the staging studies of

the Gynecologic Oncology Group (GOG) [4]. Pelvic

and para-aortic lymph nodes should be sampled for

the following indications: myometrial invasion,

greater than one half (outer half of myometrium);

regardless of tumor grade, tumor presence in the

isthmus-cervix; adnexal or other extrauterine metasta-

ses; presence of serous, clear-cell, undifferentiated, or

squamous types; and lymph nodes that are visibly or

palpably enlarged. In the GOG study, 46% of the

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00002 -1

* Corresponding author.

E-mail address: barakatr@mskcc.org (R.R. Barakat).

Radiol Clin N Am 40 (2002) 521–526

positive para-aortic lymph nodes were enlarged, and

98% of the cases with aortic node metastases came

from patients with positive pelvic nodes, adnexal or

intra-abdominal metastases, or outer one-third myo-

metrial invasion [5]. These risk factors affected only

25% of the patients, yet they yielded most of the

positive para-aortic node patients. Identifying these

patients is crucial because they can achieve long-term

survival with radiation therapy. In the GOG study [6],

37 of 48 patients with positive para-aortic nodes

received postoperative irradiation, and 36% remained

tumor free at 5 years, whereas 13 (72%) of 18 patients

with positive pelvic nodes were disease free at 5 years

after treatment.

How can one identify the high-risk endometrial

cancer patient who requires surgical staging? Preop-

eratively, one knows from the endometrial sampling

procedure if a patient has a poorly differentiated

lesion or a high-risk histologic subtype that requires

pelvic and aortic nodal sampling. The presence of a

tumor in the isthmus or cervix can usually not be

determined by physical examination. Intraoperatively,

one can detect adnexal or peritoneal metastases and

enlarged lymph nodes, although in the GOG study,

only 10% of positive nodes were palpably enlarged.

The depth of myometrial invasion and cervical exten-

sion can be assessed clinically by opening the excised

uterus intraoperatively, preferably away from the

operating table. The clinical impression can be con-

firmed by microscopic frozen section [7]. Doering

and colleagues [8] reported a 91% accuracy rate for

148 patients for determining the depth of myometrial

invasion by gross visual examination of the cut

uterine surface. This is acceptable for a gynecologic

oncologist who can act on the information and

perform the required staging procedure.

The key issue that remains is the preoperative

identification of the high-risk patient who requires

nodal sampling. This is where radiologic imaging can

help the most. Specifically, imaging can predict the

presence of deep myometrial invasion or involvement

of the isthmus-cervix. Ultrasound is used in the

evaluation of stage I disease, with an emphasis on

detecting deep myometrial invasion [9]. A limitation

of ultrsound is suboptimal tissue contrast resolution,

so endometrial carcinoma may have an echogenicity

similar to the surrounding myometrium. As a result,

the reported accuracy for the differentiation of deep

(stage IC) from absent or superficial (stages IA and

IB) myometrial invasion by ultrasound ranges from

69% to 93% [9,10]. Similarly, difficulty in assessing

the depth of myometrial invasion is a major limitation

of computed tomography (CT) [9,10]. The reported

accuracy of CT for detecting myometrial invasion is

58% to 61% [9,11]. Because of difficulties in demar-

cating the anatomic landmarks between the cervix

and uterine corpus on axial imaging planes, CT is

limited in the evaluation of cervical tumor extension.

CT is more useful in advanced disease, by demon-

stration of pelvic sidewall extension, parametrial

invasion, lymph node enlargement, and distant meta-

stases to liver and lung [12]. Magnetic resonance

imaging (MRI) is the preferred modality in deter-

mining the depth of myometrial invasion and cervical

extension [9,12–14]. The use of MRI, with rapid

dynamic scanning after intravenous gadolinium con-

trast medium, significantly improves the assessment

of the depth of myometrial invasion [12]. The re-

ported accuracy of noncontrast MR is 55% to 83%,

compared with 85% to 94% for contrast-enhanced

MR studies [9,10,13,15]. In the evaluation of cervical

extension, the reported MR imaging accuracy ranges

from 91% to 95%. In the evaluation of lymph node

involvement, MRI has an accuracy of 88%, but, like

CT, MRI cannot distinguish between malignant and

hyperplastic nodes [9,11,12].

Cervical cancer

Carcinoma of the uterine cervix is the sixth most

common solid malignant neoplasm in American

women, after carcinoma of the breast, lung, color-

ectum, endometrium, and ovary. The American Can-

cer Society estimates that in 2002 there would be

13,000 new cases of invasive carcinoma of the cervix

in the United States and 4,100 deaths from the

disease [1]. The International Federation of Gynecol-

ogy and Obstetrics (FIGO) staging system is based

on clinical evaluation (inspection, palpation, colpo-

scopy); roentgenographic examination of the chest,

kidneys, and skeleton; and endocervical curettage

and biopsies. Lymphangiograms, arteriograms, CT

findings, MRI, and laparoscopy or laparotomy find-

ings are not used for clinical staging. Suspected

invasion of the bladder or the rectum should be

confirmed by biopsy. Bullous edema of the bladder

and swelling of the mucosa of the rectum are not

accepted as definitive criteria for staging.

As revised by FIGO [6] in 1995, stage Ia1

represents microscopic disease, and any clinically

apparent case is classified as stage IB. Stage IA is

further divided as follows: stage IA1: invasion up to

3 mm deep and 7 mm wide; stage IA2: invasion

between 3 and 5 mm deep and 7 mm wide. Stage IB

will be divided as follows: stage IB1: lesions no

greater than 4 cm in diameter; stage IB2; lesions

greater than 4 cm in diameter. Stage IIA disease

indicates involvement of the upper vagina, and

R.R. Barakat, H. Hricak / Radiol Clin N Am 40 (2002) 521–526522

stage IIB connotes spread beyond the cervix into the

parametria. To be classified as stage IIIB, the tumor

should definitely extend to the lateral pelvic wall,

although fixation is not required. Patients with hydro-

nephrosis or a nonfunctioning kidney ascribed to

extension of the tumor are classified as stage IIIB,

regardless of the pelvic findings. Stage IVA disease

(bladder or rectal invasion) is usually treated with

irradiation, whereas patients with distant metastatic

disease (stage IVB) receive chemotherapy. The crit-

ical distinction for the gynecologic oncologist is

between operable disease, which usually includes

stage IIA and below, and disease that is effectively

treated by radiation therapy (stages IIB – IV).

Although both definitive irradiation and radical oper-

ation are accepted treatments for stages IB and IIA

carcinoma of the cervix, surgery has often been

preferred in young women because of the desire to

preserve ovarian function. In addition, many gyne-

cologists believe that the sexually active patient will

be left with a more functional vagina after a surgical

procedure. The key is to select the right patient for

surgery to avoid the need for postoperative adjuvant

treatment. Patients with certain high-risk features (eg,

positive nodes, positive margins, or parametrial

extension) are now treated with postoperative chemo-

radiation after a recent GOG randomized trial

revealed a 17% improvement in progression-free

survival at 4 years approach [16]. If one could predict

ahead of time which patients had these features, one

could consider treating with radiation therapy to

avoid the combined morbidity of surgery followed

by chemoradiation.

Bulky endocervical tumors and the so-called

‘‘barrel-shaped cervix’’ have a higher incidence of

central recurrence, pelvic and para-aortic lymph

node metastasis, and distant dissemination [17].

The exact definition of a barrel lesion varies, but

most authorities consider lesions > 4 cm to be bulky

(stage IB2). Because of the inability of the intra-

cavitary sources to encompass the entire tumor in a

high-dose volume, larger doses of external radiation

to the whole pelvis, extrafascial hysterectomy, or

both have been advocated to improve therapeutic

results. Keys and colleagues [18], in a prospective,

randomized GOG study, found no significant differ-

ence in the survival of patients treated with irradi-

ation alone or irradiation followed by an extrafascial

hysterectomy. A recent follow-up study GOG trial

[19] revealed a 49% improvement in the risk of

recurrence and a 46% reduction in death for stage

IB2 patients treated with radiation and chemother-

apy followed by surgery, compared with radiation

alone followed by surgery.

Radiographic imaging before surgery should aid

the gynecologic oncologist in determining which

patients might be better treated by up-front chemo-

radiation rather than radical hysterectomy. This

includes patients with occult parametrial extension

and possibly positive pelvic nodes. These patients

will incur the morbidity of postoperative chemora-

diation following surgery and should be treated by

chemoradiation alone without surgery. Patients with

bulky (stage IB2) lesions are best treated by up-front

chemoradiation followed by simple hysterectomy.

The role of preoperative imaging in this group of

patients is to determine which patients have such

lesions so that they won’t undergo radical hysterec-

tomy followed by chemoradiation if the clinical

examination is incorrect [20,21].

Advances in pelvic imaging have improved the

diagnostic accuracy of cervical cancer staging.

Although ultrasound and CT have been used to

supplement clinical staging, MRI has become the

preeminent method for imaging cervical cancer. As

knowledge of cancer risk factors and the value of

cross-sectional imaging have been disseminated,

extended clinical staging utilizing imaging techniques

has developed without having to change the official

FIGO guidelines. In this setting, the use of CT or

MRI has gained wide acceptance in treatment plan-

ning, whereas the use of conventional radiological

examinations (intravenous urogram, barium enema,

and lymphangiography) is decreasing [21,22]. In

particular, the use of lymphangiography in the pre-

treatment evaluation of cancer of the cervix is no

longer recommended [23].

MRI is significantly better than CT in the evalua-

tion of parametrial invasion (MR imaging versus CT

accuracy, 85% to 93% versus 70% to 80%) [21,

22,24]. The presence of a low signal intensity stripe

of peripheral cervical stroma on MRI is 95% specific

in excluding parametrial invasion. The high predictive

value of MRI in determining the absence of para-

metrial invasion is valuable in identifying lesions that

could be surgically resected [21,22,24–26]. Further-

more, MRI is valuable in the evaluation of primary

endocervical lesion in cases where tumor origin

(endometrial versus endocervical) is in question.

MRI is not only valuable in evaluating the cervix

and parametrium but is also beneficial in evaluating

advanced-stage disease. Vaginal invasion (stages IIA

and IIIA) can be identified on MR imaging. Stage IIIB

disease (pelvic wall invasion and/or hydronephrosis)

is demonstrated as high-signal tumor infiltration

within adjacent pelvic musculature. The use of MRI

in the pretreatment evaluation of cervical cancer

results in fewer examinations and net cost savings.

R.R. Barakat, H. Hricak / Radiol Clin N Am 40 (2002) 521–526 523

Epithelial ovarian cancer

With 13,900 deaths expected in 2002, epithelial

ovarian cancer is the leading cause of death from

gynecologic cancer in the United States [1]. The

stage, defined by the extent of disease at diagnosis,

must be determined surgically. Unfortunately, only

23% of patients will present with disease confined to

the ovaries (stage I); 13% will have disease confined

to the pelvis (stage II), and 63% will have advanced

disease (stages III or IV) at presentation. Survival is

closely correlated with stage, with stage I patients

enjoying a 90% 5-year survival compared with 80%

for stage II and only 15% to 20% for stage III.

One of the most important prognostic factors in

epithelial ovarian cancer is the volume of disease that

remains after surgical cytoreduction. Numerous stud-

ies have demonstrated that there is a survival advan-

tage at the time patients with advanced ovarian cancer

undergo ‘‘optimal’’ versus ‘‘suboptimal’’ primary

surgical cytoreduction, or ‘‘debulking’’ [27–29]. Sur-

gical debulking refers to the resection of as much

tumor as possible even if grossly visible tumor is left

behind. The tumor left behind is termed ‘‘residual’’

disease. Because of the sensitivity of ovarian cancer

to chemotherapy, patients with small-volume residual

disease can often be put into long-term remission or

even cured.

Residual disease in patients with ovarian cancer

is quantified by measuring the diameter of the largest

tumor nodule remaining after the debulking surgery.

Patients are said to have undergone ‘‘optimal’’ ver-

sus ‘‘suboptimal’’ cytoreduction on the basis of

residual disease diameter. Various cutoff points

between 0.5 and 3.0 cm have been used for this

division. For those patients who undergo suboptimal

cytoreduction, the survival is equivalent regardless if

they are left with 4-, 5-, 6-, or even 10-cm tumor

nodules [29]. Therefore, surgery offers no survival

benefit to these patients. The current GOG definition

of optimal residual disease status uses 1 cm as a

cutoff point.

The actual percentage of patients with advanced

ovarian cancer who can be successfully cytoreduced

to optimal status varies in the literature from 17% to

87%, with a mean of 35% [30]. The most recent

review of patients with stage III ovarian cancer

operated on primarily at Memorial Sloan-Kettering

Cancer Center between 1995 and 1997 reported an

optimal (< 1 cm residual) cytoreduction rate of 45%

[31]. Therefore, it seems that the majority of patients

with advanced ovarian cancer may undergo a primary

surgical procedure that does not significantly improve

their overall survival.

To date, no preoperative test has been demonstra-

ted to accurately predict optimal versus suboptimal

cytoreduction in patients with advanced ovarian can-

cer. If such a test or group of tests could be identified,

then, as implied above, a significant number of

patients could be spared an unnecessary laparotomy.

Preliminary retrospective studies have evaluated the

ability of preoperative serum CA-125 levels and

preoperative CT scan of the abdomen and pelvis in

predicting optimal versus suboptimal cytoreduction.

In a review of 100 patients with stage III ovarian

cancer operated on at Memorial Sloan-Kettering

Cancer Center, a cutoff value of 500 U/mL for the

preoperative serum CA-125 level was determined to

predict residual status with a sensitivity of 78%, a

specificity of 73%, a positive predictive value of

78%, and a negative predictive value of 73% [31].

Five studies have evaluated the accuracy of CT

scan in predicting residual status. With a total of

188 evaluable patients in these five studies, CT

scan showed a sensitivity of 50% to 92%, a

specificity of 63% to 100%, a positive predictive

value of 61% to 100%, and a negative predictive

value of 75% to 96% [32–36]. These small studies

using retrospective film review have demonstrated

that cross-sectional imaging can also be helpful in

surgical planning (eg, in predicting the need for

sigmoid resection). If an accurate method of pre-

diction could be identified, then patients thought to

have disease not amenable to optimal cytoreduction

could be offered neoadjuvant chemotherapy with

attempted debulking at a later date. Preliminary

studies have demonstrated beneficial results with

this approach [37,38].

Frequently, bulky disease in the upper abdomen

involving the diaphragms, liver, porta-hepatis, spleen,

or suprarenal lymph nodes is cited as the reason that

optimal cytoreduction could not be achieved [39].

Knowledge of disease in these or other sites on the

basis of preoperative CT scan of the abdomen and

pelvis would be useful for surgical planning. It would

help in obtaining appropriate preoperative surgical

consultations and would allow for having the neces-

sary surgical equipment in the operating room.

The concept of residual disease status is based on

the surgeon’s informal measurement of the diameter

of the largest remaining tumor nodule after debulking

surgery [27–31,39]. This measurement is subjective

and not routinely confirmed by any objective means.

Because response to chemotherapy and survival are

clearly linked to size of residual disease, it is impor-

tant to compare the reported intraoperative assessment

of residual disease to that found on postoperative CT

scan of the abdomen and pelvis. This would allow for

R.R. Barakat, H. Hricak / Radiol Clin N Am 40 (2002) 521–526524

a more accurate assessment of disease status before

administering chemotherapy and would more accu-

rately assess patient prognosis. Clearly then, preoper-

ative imaging using CT scan can aid in predicting

which patients may not be amenable to optimal

debulking and which patients may be better served

by neo-adjuvant chemotherapy. In addition, it may

allow for appropriate surgical consultations before

surgery so that the appropriate surgeons are available

to perform the required procedure. Finally, postoper-

ative CT scan may provide objective confirmation of

the surgeon’s assessment of residual disease, allowing

for more accurate determination of prognosis and

proper stratification into clinical trials.

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R.R. Barakat, H. Hricak / Radiol Clin N Am 40 (2002) 521–526526

Postmenopausal bleeding: value of imaging

Caroline Reinhold, MDa,b,c,*, Ida Khalili, MDa

aDepartment of Radiology, McGill University Health Center, 1650 Cedar Avenue, Montreal, PQ, H3G 1A4, CanadabDepartment of Gynecology, McGill University Health Center, 1650 Cedar Avenue, Montreal, PQ, H3G 1A4, Canada

cSynarc, Inc., San Francisco, CA, USA

Postmenopausal bleeding is a common clinical

problem accounting for approximately 5% of office

visits to a general gynecologist [1]. Postmenopausal

bleeding has been defined as (1) vaginal bleeding

occurring at least 6 months after complete cessation

of menses in women not on hormonal replacement

therapy (HRT), or (2) noncyclic vaginal bleeding

occurring in postmenopausal women who are receiv-

ing HRT [2]. Abnormal vaginal bleeding may be

caused by a number of gynecologic or nongyneco-

logic disorders. Endometrial atrophy is reported to be

the most common cause of postmenopausal bleeding

[2–4]. Other causes of postmenopausal bleeding

include endometrial hyperplasia, endometrial polyps,

endometrial carcinoma, and submucosal leiomyomas

[2,4]. Although most reports in the clinical literature

indicate that endometrial atrophy is the most common

cause of postmenopausal bleeding, the results of

recent studies with hysterosonography (HSG) indi-

cate that anatomic abnormalities, such as leiomyo-

mata and polyps, are much more common than has

been generally believed [5–9]. In addition, approx-

imately 10% of patients presenting with postmeno-

pausal bleeding are diagnosed with endometrial

carcinoma [4]. A diagnosis of endometrial carcinoma

should be excluded in all women of perimenopausal

or postmenopausal age presenting with abnormal

vaginal bleeding [2]. Intermenstrual and postmeno-

pausal bleeding is the initial symptom in 75% to 90%

of patients with endometrial carcinoma [10,11]. Early

diagnosis and treatment are important because the

5-year survival of patients varies from 90% to 100%

in patients with little or no myometrial involvement,

to 40% to 60% in patients with deep myometrial

invasion [12–15].

This article reviews (1) the relative role of endo-

metrial biopsy procedures and imaging in the evalua-

tion of patients with postmenopausal bleeding, and

(2) the imaging strategies for detecting and diagnos-

ing pathologic conditions of the uterus presenting

with postmenopausal bleeding. A discussion on the

role of imaging in women with a documented diag-

nosis of endometrial cancer is beyond the scope of

this article and is addressed elsewhere in this issue.

Role of diagnostic techniques

Endometrial biopsy procedures

Although dilatation and curettage (D and C) is

generally considered the standard of reference for

obtaining the necessary diagnostic intrauterine path-

ology, support for this assertion in the literature is

lacking. The sensitivity and specificity of D and C are

difficult to assess because few large series confirm

the histology with a subsequent hysterectomy speci-

men. In a series of 512 patients in whom the uteri

were removed immediately after the D and C, endo-

metrial lesions were missed in up to 10% of cases

including 38 endometrial polyps, 4 submucosal fib-

roids, 2 endocervical polyps, 2 placental polyps, and

1 undisturbed pregnancy [16]. For diagnosing endo-

metrial hyperplasia or carcinoma, false-negative rates

ranging from 2% to 6% have been reported [16–19].

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01)00008 -2

* Corresponding author. Department of Radiology,

McGill University Health Center, 1650 Cedar Avenue,

Montreal, Quebec, Canada, H3G 1A4.

E-mail address: reinhold@rad.mgh.mcgill.ca

(C. Reinhold).

Radiol Clin N Am 40 (2002) 527–562

In a study of 50 consecutive patients who underwent

D and C immediately before hysterectomy, Stock

and Kanbour [19] found that in 60% of patients less

than half of the endometrial surface was sampled

and in 16% less than a quarter of the surface was

actually sampled. In addition, as emphasized by Word

et al [16] in a review of over 6000 D and Cs, this

procedure is invasive and may be associated with

complications, such as infection, bleeding, and ute-

rine perforation.

Office-based endometrial sampling procedures,

such as Pipelle and Vabra, have gained widespread

acceptance since the convenience to the patient, lower

complication rate, and cost containment of these

procedures have been firmly established in the

literature [20]. Office biopsy procedures may be

technically impossible in 10% of patients, however,

because of cervical stenosis [21]. In addition, out-

patient endometrial sampling techniques may result

in specimens inadequate for histologic interpretation

in up to 15% of cases [22]. Dubinsky et al [1]

recently reported a 66% false-negative rate for detect-

ing endometrial carcinoma with endometrial biopsy.

Most studies, however, report the sensitivity of endo-

metrial sampling for detecting carcinoma to be 85%

or greater, with the two largest series reporting

sensitivities of 94% and 96%, respectively [22,23].

In general, the sensitivity for diagnosing endometrial

hyperplasia is more modest, ranging from 58% to

86% [18,22,24–29]. None of the series on endome-

trial sampling reported a false-positive diagnosis for

endometrial carcinoma.

Although the accuracy of endometrial sampling

procedures seems to be comparable with D and C for

diagnosing endometrial carcinoma, a lower accuracy

is achieved in the setting of endometrial hyperplasia,

polyps, or submucosal leiomyomas [14,17,18,24,26–

29]. This is clinically relevant, because endometrial

polyps or submucosal myomas have been reported in

up to 90% of patients with recurrent postmenopausal

bleeding [30]. The detection of pedunculated benign

conditions in the uterine cavity is a limitation of all

blind sampling procedures, including D and C. Hys-

teroscopy, which allows direct visualization of the

endometrial cavity, is superior in making an accurate

diagnosis of endometrial polyps and submucosal

myomas [31,32]. Hysteroscopy is, however, an inva-

sive method that carries a small but real risk of

perioperative complication. Because of these limita-

tions, it is generally recommended that a combination

of endovaginal sonography and endometrial sampling

be used in the diagnosis of endometrial disease in

women presenting with postmenopausal bleeding

[28,33–35].

Endovaginal sonography

Endovaginal versus transabdominal sonography

The use of transabdominal sonography in the

detection of endometrial pathology has been well-

documented [11,36–38]. Limited spatial resolution,

obesity, retroflexion, and multiple leiomyomas of the

uterus, however, can make assessment of the endo-

metrial stripe using transabdominal sonography tech-

nically difficult. With the advent of endovaginal

sonography these technical limitations have largely

been overcome. Furthermore, the greater resolution

afforded with the higher-frequency endovaginal probe

can improve the detection of endometrial carcinoma

and other endometrial abnormalities [39–41]. A pro-

spective comparison of endovaginal and transabdo-

minal sonography by Coleman et al [42] reported that

endovaginal scans yielded new information in 60% of

cases and allowed better visualization of pelvic struc-

tures in 22% of cases. The clinical diagnosis was

altered on the basis of endovaginal sonographic find-

ings in 24% of patients and confirmed with certainty

in 72% of patients. The authors believe that any

patient presenting with postmenopausal bleeding

should undergo endovaginal sonography [39,43].

Endometrial thickness

The advent of high-resolution endovaginal probes

has revolutionized the ability to visualize the endo-

metrium sonographically and to detect endometrial

pathology [39–42,44–48]. The use of endovaginal

sonographic measurements of maximal endometrial

thickness, as a predictor of disease in postmeno-

pausal women with bleeding, has recently been

well established in the literature [49]. Large trials

have been conducted to define an endometrial

thickness below which no pathology is found, in

the hopes of using this measurement as a screening

tool in postmenopausal women with abnormal ute-

rine bleeding [7,50–55]. Threshold values ranging

from 4 to 10 mm (double-layer endometrial thick-

ness) have been proposed. The role of endovaginal

sonography is to define a threshold value for

endometrial thickness below which routine histo-

logic sampling cannot be justified, because of a

low posttest probability of disease. Above this

threshold value, however, endometrial sampling is

indicated for the following reasons: (1) a high

posttest probability for endometrial pathology, and

(2) the lack of specificity of endovaginal sonogra-

phy in differentiating benign from malignant causes

of endometrial thickening.

The role of endovaginal sonography in detecting

endometrial cancer and other endometrial abnormal-

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562528

ities in postmenopausal women with vaginal bleed-

ing is well summarized in the following meta-anal-

ysis of English-language and non–English-language

articles published between 1966 and 1996 [56]. This

meta-analysis comprised 35 studies and includes

5892 women. Using a threshold value of greater

than 5 mm to define abnormal endometrial thicken-

ing, 96% (95% CI: 94% to 98%) of women with

cancer had an abnormal endovaginal sonogram,

whereas 92% (95% CI: 90% to 93%) of women

with endometrial pathology had an abnormal test

result (Fig. 1). Corresponding specificities were 61%

(95% CI: 59% to 63%) and 81% (95% CI: 79% to

83%), respectively. The false-negative rate of 8% for

detecting endometrial pathology with endovaginal

sonography compares favorably with that achieved

using office-based endometrial biopsy devices. For a

postmenopausal woman with vaginal bleeding and a

10% pretest probability of endometrial cancer, the

posttest probability decreases to 1%, given a neg-

ative endovaginal sonogram. These authors con-

cluded that endovaginal sonography is highly

sensitive for detecting endometrial carcinoma, and

can identify patients at low risk for endometrial

disease obviating the need for endometrial sampling

in this subgroup of patients. Women on HRT had a

significantly higher false-positive rate (specificity

77%; 95% CI: 75% to 79%) compared with patients

not taking hormones (specificity 92%; 95% CI: 90%

to 94%). These results are not surprising, because

endometrial thickness is known to increase after the

initiation of HRT. The degree of increase in endo-

metrial thickness, however, varies depending on the

type of hormonal regimen used. It is most marked

with the ingestion of sequential estrogen-progester-

one, followed by unopposed estrogen and is least

affected by continuous combined estrogen-progester-

one regimens [57]. For this reason, some authors

advocate a higher threshold value for endometrial

thickness in postmenopausal women on HRT com-

pared with controls (8 versus 5 mm) [58–60].

Endometrial morphology

Although the threshold values described in the

literature vary considerably, endometrial thickness is

often used as the sole criterion in the sonographic

assessment of the endometrium in postmenopausal

women. As evidenced from the preceding meta-

analysis, the proposed threshold value of 5 mm for

detecting endometrial carcinoma and other pathology

results in a high sensitivity but a relatively low

specificity, particularly for women on hormonal

replacement regimens. Nevertheless, most authors

recommend using a low cutoff value, such as 4 or

5 mm, which maintains the sensitivity but sacrifices

specificity. This results in many unnecessary sam-

Fig. 1. Endometrial carcinoma. Transverse endovaginal sonogram (EVS) in a 55-year-old woman on hormonal replacement

therapy (HRT) presenting with abnormal vaginal bleeding. The endometrium (E) is diffusely thickened (17 mm, calipers) and is

homogeneously echogenic. The borders are well-defined. The increased endometrial thickness in a patient on HRT ( > 8 mm)

mandates endometrial sampling. Using morphologic criteria on EVS, however, this endometrium could be misclassified as

benign. Endometrial biopsy revealed well-differentiated adenocarcinoma.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 529

pling procedures being performed not to miss sig-

nificant endometrial pathology. By increasing the

threshold value, the specificity improves, at the cost,

however, of increasing the number of false-negative

examinations. To address this issue, a number of

investigators have recently studied morphologic fea-

tures in addition to measuring endometrial thickness

with the hopes of improving the positive predictive

value of endovaginal sonography.

Weigel et al [61] in 1995 emphasized this point by

publishing an article entitled ‘‘Measuring the thick-

ness—is that all we have to do for sonographic as-

sessment of the endometrium in postmenopausal

women?’’ This group of investigators prospectively

examined 200 patients to ascertain the value of using

morphologic features on gray-scale ultrasound imag-

ing in patients with an endometrial thickness in the

indeterminate range for pathology (3 to 10 mm). These

authors concluded that combining metric and morpho-

logic parameters improved not only the predictability

of pathologic findings, but also the overall accuracy of

the sonographic evaluation. Similar conclusions have

been drawn by Brandner et al [62], who evaluated 221

postmenopausal women with endovaginal sonogra-

phy, including 139 (63%) who presented with abnor-

mal vaginal bleeding. This group of investigators used

various morphologic criteria and endometrial thick-

ness to classify patients as having endometrial atrophy,

proliferative endometria, endometrial hyperplasia or

polyps, or endometrial carcinoma.

Other investigators, however, remain more skep-

tical as to the role of endometrial morphology for

improving the accuracy of endovaginal sonography for

detecting endometrial carcinoma (Fig. 2) [44,63,64].

Hanggi et al [65] studied 203 consecutive women with

endovaginal sonography before a scheduled diagnos-

tic D and C or hysterectomy, of whom 91 presented

with symptoms of postmenopausal bleeding. Criteria

for malignancy on endovaginal sonography included

an endometrial thickness of greater than 5 mm, areas

of decreased echogenicity or heterogeneity, and poor

definition of the endomyometrial junction. Applying

these sonographic criteria, endometrial carcinoma was

diagnosed with a sensitivity of 85%, a specificity of

78%, a positive predictive value of 52%, and a

negative predictive value of 95%. When these results

are compared with those reported using measurements

of endometrial thickness alone, one notes a decrease

in sensitivity from 97% to 85%, with a corresponding

increase in specificity from 61% to 78%. These

observations parallel the authors’ findings in a pro-

spective study of 557 women presenting with post-

menopausal bleeding [64]. Using an endometrial

thickness of greater than 5 mm to define a positive

test result, the authors detected endometrial carcinoma

with a sensitivity of 97% (95% CI: 83% to 100%) and

Fig. 2. Atypical hyperplasia and polyp. Oblique endovaginal sonogram in a 75-year-old woman presenting with postmenopausal

bleeding. There is diffuse endometrial thickening (14 mm) with several small cystic areas. In addition, within the thickened

endometrial complex, there is a poorly defined hypoechoic area (arrows) that is suspicious for a carcinoma in the setting of

endometrial hyperplasia. Endometrial biopsy and subsequent hysterectomy revealed atypical hyperplasia and an endometrial

polyp originating from the ventral wall.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562530

a specificity of 47% (95% CI: 42% to 52%). The

addition of morphologic criteria decreased the sensi-

tivity from 97% to 77% (95% CI: 59% to 90%),

however, and resulted in an increase in specificity

from 47% to 84% (95% CI: 80% to 87%).

The addition of morphologic criteria tends to

improve the specificity, however, at the cost of

sensitivity, in effect raising the threshold for detecting

endometrial carcinoma. These results are not surpris-

ing when one considers the following. First, endova-

ginal sonography is unlikely to detect a significant

number of endometrial abnormalities in the setting of

a thin endometrium, defined as a maximal endome-

trial thickness less than or equal to 5 mm. Although

the rate of detection of small endometrial polyps or

early carcinomas is improved with the addition of

HSG, this technique is not routinely used to evaluate

a normal-appearing endometrial complex [66]. Sec-

ond, the risk of falsely classifying a malignant endo-

metrium as benign is not negligible, given the

considerable overlap of morphologic features

between benign and malignant endometrial pathology

(see Fig. 1). Finally, benign and malignant endome-

trial pathology frequently coexist in the same patient.

The decision to emphasize sensitivity versus specif-

icity when evaluating the test performance of endo-

vaginal sonography depends largely on the clinical

indication for performing the test. Because the role of

endovaginal sonography in evaluating patients with

postmenopausal bleeding is primarily to identify

patients who require further evaluation, an abnormal

test result must have a high sensitivity for diagnosing

endometrial carcinoma. Although this diagnostic

pathway has a false-positive rate of 23% [56], this

is considerably less than is obtained if all patients

with postmenopausal bleeding are referred for tissue

diagnosis. Using a combination of endovaginal

sonography and endometrial sampling in evaluating

patients with postmenopausal bleeding has been

demonstrated to be cost effective [56].

Although the decision to obtain histologic tissue is

based primarily on biometric criteria, detailed mor-

phologic information should be obtained during

every endovaginal ultrasound. In particular, a distinc-

tion between diffuse and focal causes of endometrial

thickening should be made whenever possible. Dif-

fuse causes of endometrial thickening on endovaginal

sonography are most often the result of proliferative

change, hyperplasia, or carcinoma, and are accurately

diagnosed with endometrial sampling techniques.

Conversely, focal endometrial thickening is most

often caused by endometrial polyps. The accuracy

of all blind sampling techniques is low in the setting

of endometrial polyps, frequently resulting in pathol-

ogy reports with inconclusive findings, such as ‘‘tis-

sue insufficient for diagnosis’’ or ‘‘scanty fragments

of atrophic tissue.’’ For patients with endometrial

polyps or submucosal fibroids, endometrial sampling

and removal is performed best under direct hystero-

scopic visualization. Endovaginal sonography in

some instances can be used to determine which

patients can undergo blind endometrial sampling

successfully versus those who would benefit from

hysteroscopic guidance.

Hysterosonography

Hysterosonography is a minimally invasive proce-

dure that plays an important role in the detection and

characterization of endometrial pathology [5, 66–76].

Several studies have shown that the accuracy of

HSG in diagnosing endometrial pathology exceeds

that achieved using endovaginal sonography alone

[6,69,77,78]. Even in the setting of a thin endo-

metrium (�5 mm), HSG may identify the anatomic

cause of bleeding in some cases (Fig. 3) [5,8, 77–79].

Bree et al [67] performed HSG in 98 patients with

postmenopausal bleeding, and reported a sensitivity of

98%, a specificity of 88%, a positive predictive value

of 94%, and a negative predictive value of 97%

for detecting endometrial pathology. In addition,

HSG can make a more precise diagnosis in cases

where endovaginal sonography only shows abnormal

thickening of the endometrium [5,66–69, 71–76].

By accurately diagnosing endometrial polyps and

submucosal myomas with an intracavitary compo-

nent, HSG can select those patients who benefit most

from hysteroscopic-guided removal. Furthermore, as

is discussed later, endometrial carcinoma on HSG

usually presents as an irregular broad-based mass

[69]. This is in contradistinction to endovaginal

sonography, where endometrial carcinoma most often

presents as diffuse endometrial thickening. A priori

knowledge as to the location of an endometrial

malignancy may improve the accuracy of blind

sampling techniques.

Hysterosonography is more accurate than endo-

vaginal sonography for the detection, localization,

and characterization of endometrial pathology. In

addition, HSG can be helpful in patients with non-

visualization of the endometrium or to distinguish

true from apparent endometrial thickening on endo-

vaginal sonography (Figs. 3, 4). The exact role of

HSG in the evaluation of patients presenting with

postmenopausal bleeding has not yet been clearly

defined. The authors, however, propose the following

general guidelines for performing HSG in this clinical

setting: (1) patients with endometrial thickening on

endovaginal sonography and negative endometrial

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 531

biopsy results; (2) patients with indeterminate find-

ings on endovaginal sonography; and (3) patients

with persistent bleeding and negative findings on

endovaginal sonography or endometrial biopsy.

Doppler ultrasound

Several investigators have measured pulsed Dop-

pler indices and color Doppler vascularity of the

endometrium to differentiate benign from malignant

endometrial pathology. Opinions differ, however, as

to the role of Doppler ultrasound in this clinical

setting. Threshold values for resistive indices (RI)

ranging from 0.40 to 0.70 have been reported to

differentiate benign from malignant endometria accu-

rately, with most authors recommending a threshold

value of 0.40 [80,81]. Proposed values for the pulsa-

Fig. 3. Endometrial polyp. (A) Oblique sagittal endovaginal sonogram in a patient presenting with postmenopausal bleeding

shows minimal focal thickening of the dorsal endometrium (calipers) relative to the ventral endometrium. The localized

thickening of the dorsal endometrium does not exceed 5 mm, and is located adjacent to an intramural leiomyoma (L). This raises

the possibility of apparent focal thickening caused by distortion of the endometrium by the leiomyoma. (B) Hysterosonography

shows that the focal thickening of the dorsal endometrium represents a small endometrial polyp (arrows).

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562532

tility index (PI) range from 1.00 to 2.00 [82,83]. In

these studies, values of RI and PI obtained below the

given threshold indicated malignant disease, whereas

values above were consistent with benign disease

[80–83]. Other investigators, however, found endo-

metrial thickness to be a better predictor of endome-

trial pathology than any of the Doppler indices

evaluated to date (Fig. 5A) [84–87].

Although earlier studies reported high accuracy

rates using RI or PI to differentiate malignant from

benign endometria [82,83,88], these results have not

been corroborated by the authors’ findings or those of

other investigators [64,84–87]. Considerable overlap

between measures of impedance for benign and

malignant endometria exists. For example, benign

polyps frequently demonstrate RI values less than

Fig. 4. Poor visualization caused by adenomyosis. (A) Oblique transverse endovaginal sonogram in a patient presenting with

postmenopausal bleeding. The endometrium is poorly seen because of coexisting adenomyosis, which is most marked along the

dorsal myometrium (arrows). (B) At hysterosonography, the atrophic endometrium (4 mm, arrows) is well outlined. No

endometrial mass or other abnormality is present.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 533

Fig. 5. Doppler and benign endometrial disease. (A) Transverse endovaginal sonogram shows a thickened endometrium with

stalk flow on color Doppler imaging. Spectral analysis obtained from the stalk results in a resistive index of 0.4. (B) Sagittal

section in the same patient demonstrates the stalk flow (arrow), suggesting the presence of a polyp. In addition, although the

vascularity is sparse at the level of the fundus consistent with benign disease, the vascularity in the body of the uterus and lower

uterine segment is increased. At histopathology only endometrial hyperplasia and an endometrial polyp were found.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562534

or equal to 0.4. The authors do not recommend that

measures of impedance be used routinely to evaluate

patients with postmenopausal bleeding. Differences

in patient selection, study design, and Doppler equip-

ment used may account in part for the discrepancy

among published results. For example, many studies

reporting on the role of Doppler in detecting endo-

metrial pathology have excluded patients on a hor-

monal regimen. This falsely improves the accuracy

for differentiating malignant from benign endometria,

given the lower impedance to pelvic blood flow, in

this group of patients [58,89–91].

In a recent study of 557 women with postmeno-

pausal bleeding, the authors used receiver-operator

curve analysis to determine which of the endometrial

Doppler indices had the highest accuracy for diag-

nosing endometrial carcinoma [64]. It was found that

the best predictors of case status were the presence of

endometrial vascularity on color Doppler and the

maximal venous velocity [64]. These findings are in

keeping with the results of Sladkevicius et al [87],

who found that the best Doppler variable for differ-

entiating between benign and malignant endometria

was the presence of color flow within the endome-

trium (sensitivity 88% [95% CI: 66% to 97%];

specificity 81% [95% CI: 75% to 89%]).

The appropriate use of color Doppler can provide

important information when evaluating the postme-

nopausal patient with vaginal bleeding. First, the

presence of color flow eliminates a blood clot as

the diagnosis of an intraluminal mass. In contra-

distinction, absence of color flow in a mass does

not necessarily exclude a neoplastic process even

with state-of-the-art Doppler systems. Second, color

Doppler can be used to search for feeding vessels in

the setting of an endometrial mass. A mass with a

single feeding vessel is more likely to be a benign

polyp on a stalk. Masses associated with endometrial

carcinoma tend to be broad based, and as a conse-

quence have multiple feeding vessels. In general,

moderate to marked vascularity is associated more

commonly with malignant endometria, where-

as benign endometria show sparse flow (Fig. 5B).

Considerable overlap exists between the vascularity

of benign and malignant endometrial processes, how-

ever, and this sign in isolation is neither sensitive nor

specific [64].

MRI

Endovaginal sonography in combination with

HSG is a highly effective screening tool in patients

with postmenopausal bleeding. In some patients,

however, endovaginal sonography is not technically

possible. In addition, accurate visualization of the

endometrium may not be possible because of a

vertical orientation of the uterus, marked uterine

enlargement, the presence of multiple leiomyomas,

or extensive adenomyosis. Under these circumstan-

ces, MRI may provide additional information on the

appearance of the endometrium, particularly in

patients in whom endometrial sampling is difficult

(eg, patients with cervical stenosis) (Fig. 6). Cur-

rently, MRI has no established role in screening for

endometrial pathology, and the accuracy of MRI in

evaluating this subgroup of patients has not been

fully evaluated.

Imaging findings for diagnosis

The normal postmenopausal endometrium

In the postmenopausal woman, the endometrial

lining becomes atrophic because of lack of hormo-

nal stimulation. Small ulcerations of the thin and

atrophic endometrium may result in abnormal vag-

inal bleeding. Endometrial biopsy in this setting

frequently reveals ‘‘atrophic tissue’’ or ‘‘insufficient

tissue for diagnosis.’’

Estrogen replacement therapy is frequently advo-

cated to reduce the symptoms of hypoestrogenemia

associated with menopause. Three of the more

commonly used hormonal regimens include (1)

estrogen and continuous progesterone, (2) estrogen

and cyclic progesterone, and (3) unopposed estro-

gen. Progesterone reduces the risk of adverse effects

associated with unopposed estrogen, such as endo-

metrial hyperplasia and endometrial carcinoma [92].

The combined use of estrogen and progesterone

results in variable findings at endometrial histopa-

thology. Proliferative and secretory changes are

frequently seen and may coexist in the same tissue

sample. Additional findings include glandular

hyperplasia ranging from simple to atypical, epithe-

lial metaplasia, and inactive or atrophic endome-

trium [93]. Aside from glandular hyperplasia, all

other changes listed are physiologic and of no

clinical significance.

The thickness of the endometrium is usually larger

in patients on unopposed estrogen or sequential

hormones than in patients receiving no hormones or

those on a continuous hormonal regimen [94,95].

Patients on sequential hormones show the greatest

variation in endometrial thickness over the course of

a cycle, with the maximal thickness occurring on

days 13 to 23 [94,95]. These patients should undergo

imaging either at the end or the beginning of a cycle

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 535

[95,96]. It is preferable to image the endometrium

after the cyclic bleeding has ceased, to avoid false-

positive findings associated with blood in the endo-

metrial cavity. Patients on continuous hormonal regi-

mens show no significant increase in endometrial

thickness over controls [94].

Endovaginal sonography and hysterosonography

The normal postmenopausal endometrium meas-

ures less than or equal to 5 mm (double-layer thick-

ness); is homogeneous; and moderately echogenic

relative to the myometrium on endovaginal sono-

graphy and HSG [56,69,74]. The normal endome-

Fig. 6. Atrophic endometrium not visualized at transabdominal sonography. (A) Transabdominal sonogram in a 56-year-old

woman presenting with postmenopausal bleeding. Transverse section through the uterus does not demonstrate the endometrial

stripe. A central hypoechoic area (arrows) is present, which may represent prominence of the subendometrial halo; however,

replacement of the endometrium by tumor cannot be excluded. Sagittal T2-weighted image of the uterus (B), gadolinium-

enhanced early image of the uterus (C), and late image of the uterus (D) demonstrate an atrophic endometrium (arrows) with

normal signal intensity and enhancement pattern. The junctional zone (long arrow) is prominent and ill-defined (B), suggesting

the presence of uterine adenomyosis. This may have contributed to the abnormality seen on ultrasound.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562536

trium on HSG is distensible and should expand with

the administration of normal saline. The appearance

of the endometrium shows greater variability in

patients on HRT (Figs. 7, 8). The endometrium of

patients on estrogen and cyclic progesterone parallel

that of the premenopausal patient and the maximal

endometrial thickness is greater than in patients not

receiving HRT [97]. This is the rationale for recom-

mending 8 versus 5 mm as a threshold value for

detecting endometrial pathology in patients on un-

opposed estrogen or sequential hormone therapy

[60,69,74].

MRI

In postmenopausal women, the normal endome-

trial complex can be identified as a thin hyperintense

structure relative to the adjacent myometrium on T2-

weighted sequences, and is usually isointense on T1-

weighted sequences. The endometrial complex is

hypointense during the early postcontrast images

and becomes isointense or slightly hyperintense rel-

ative to the adjacent myometrium on delayed con-

trast-enhanced images (see Fig. 6).

The normal range of endometrial thickness in post-

menopausal women with MRI has not been exten-

Fig. 6 (continued ).

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 537

sively studied. A few small series have reported a

maximal endometrial thickness of 3 mm in women not

receiving exogenous hormones, and 4 to 6 mm in

women receiving HRT [98–100]. In the authors’

experience, using a threshold value of 3 mm results

in a high number of false-positive examinations. The

Fig. 7. Proliferative endometrium on hormone replacement therapy. A 58-year-old postmenopausal woman presenting with

noncyclic vaginal bleeding. Sagittal section through the uterus on endovaginal sonogram shows the endometrium to be of

uniform thickness measuring 6 mm (arrows). The endometrium is homogeneously echogenic. The myometrium is heterogenous

because of the presence of adenomyosis. The endometrial biopsy revealed a proliferative endometrium.

Fig. 8. Proliferative endometrium with polyp on hormone replacement therapy. A 70-year-old woman on estrogen replacement

therapy presenting with breakthrough bleeding. Transverse endovaginal sonogram of the uterus demonstrates diffuse endometrial

thickening (9 mm, long arrows). In addition, along the right ventral aspect of the endometrium, there is an echogenic mass (short

arrows) consistent with an endometrial polyp. This polyp was made visible by the lower echogenicity of the background

proliferative endometrium.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562538

authors performed MRI in a series of 126 postmeno-

pausal women with a distribution of endometrial

histology as follows: normal (n = 17); benign (n =

26); and malignant (n = 83). Receiver-operator curve

analysis for differentiating benign from malignant

endometria resulted in a sensitivity, specificity, and

accuracy of 94%, 28%, and 71%, respectively, using a

3-mm cutoff; and 89%, 44%, and 74%, respectively,

Fig. 9. Tamoxifen and cystic hyperplasia. A 66-year-old woman with postmenopausal bleeding on tamoxifen therapy. Sagittal

endovaginal sonogram of the uterus shows a thickened endometrium (15 mm, arrows) of mixed echogenicity. The

endomyometrial junction is poorly defined. There are multiple endometrial and subendometrial cysts.

Fig. 10. Tamoxifen and endometrial polyp. A 70-year-old woman with postmenopausal bleeding on tamoxifen therapy. Oblique

sagittal endovaginal sonogram of the uterus shows a well-defined mass (M) with multiple cystic spaces distending the

endometrial cavity. The endometrial lining can be identified seperately from the mass, which proved to be an endometrial polyp

at histopathology.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 539

using a 5-mm cutoff [101]. The differences in sensi-

tivity between the 3- and 5-mm cutoff values did not

reach statistical significance. The authors use 5 mm as

the maximal endometrial thickness on MRI in post-

menopausal women.

Tamoxifen

Tamoxifen citrate is an antiestrogen agent used as

adjuvant chemotherapy in patients with breast cancer.

It functions as a weak estrogen agonist on the post-

Fig. 11. Tamoxifen and cystic atrophy, polyp. A 72-year-old woman on tamoxifen therapy presenting with postmenopausal

bleeding. (A) Sagittal endovaginal sonogram shows a diffusely thickened endometrium with cystic change (14 mm, calipers).

Centrally, a small mass of intermediate echogenicity (arrow) consistent with a polyp is identified. The diagnosis of endometrial

polyp in this setting is considerably facilitated by hysterosonography (not shown). (B) T2-weighted sagittal image of the uterus

shows diffuse thickening of the endometrial complex. The polyp (arrow) is difficult to visualize in the background of cystic

atrophy. (C) T1-weighted sagittal image obtained immediately after the administration of a gadolinium chelate shows the

enhancing stalk (arrow) of the polyp. Note the contrast enhancement of the endomyometrial interface. This finding is nonspecific

but has been reported in patients receiving tamoxifen.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562540

menopausal endometrium. Tamoxifen therapy is

associated with a wide spectrum of endometrial

pathology including proliferative change, hyperpla-

sia, polyps, adenomyosis, and carcinoma [102–106].

Postmenopausal patients on tamoxifen have a signifi-

cantly thicker endometrium than controls. In one

study the mean endometrial thickness of patients on

tamoxifen was 13 mm [107]. The endometrial thick-

ening decreases significantly 6 months after discon-

tinuation of tamoxifen therapy [108].

Endometrial cystic atrophy is frequently found at

histopathology in patients receiving tamoxifen. The

histologic findings include multiple cystic spaces

lined by an atrophic endometrium, with a small

amount of fibrous stroma. These cystic spaces may

be situated within the endometrium or extend into

the endometrial-myometrial junction to form suben-

dometrial cysts [102]. At endovaginal sonography,

these patients typically present with diffuse endo-

metrial thickening.

Endometrial hyperplasia is classified as (1) with

cytologic atypia and (2) without cytologic atypia.

This classification is not unique to patients on tamox-

ifen but applies to all patients with endometrial

hyperplasia. The differentiation has prognostic sig-

nificance, because patients with cytologic atypia have

a higher risk of developing endometrial carcinoma

(23% versus 2%) [109].

Unfortunately, imaging cannot distinguish between

hyperplasia with and without cellular atypia. Polyps

associated with tamoxifen therapy tend to be larger in

size. At histopathology these show cystic glandular

dilatation, prominent stromal fibrosis, and metaplastic

change [110]. Tamoxifen may result in the growth of

new leiomyomas, or increase the size of previously

existing ones [111]. Tamoxifen is also associated with

the development of adenomyosis in postmenopausal

women [112].

Tamoxifen therapy carries an increased risk (1.3-

to 7.5-fold) of developing endometrial cancer [102].

This risk increases with the duration of therapy and

the cumulative tamoxifen dose. Endometrial cancers

associated with tamoxifen use are usually high grade

and more aggressive [113].

Endovaginal sonography and hysterosonography

In 1996, the American College of Radiology

published appropriateness criteria on the role of

imaging in patients receiving tamoxifen therapy

[114]. In this report, it was recommended that endo-

vaginal sonography be used as the first-line imaging

modality for evaluating the uterus in women under-

going tamoxifen therapy. The strength of endovaginal

sonography is in the assessment of endometrial thick-

ness. Furthermore, it may provide information about

endometrial texture or focal masses. In cases where

endovaginal sonography is nondiagnostic or is sug-

gestive of an abnormality, hysterosonography (HSG)

can provide additional information. HSG can be used

to image polyps and subendometrial cysts with con-

fidence and can help direct sampling procedures

when necessary.

The most common sonographic pattern in patients

on tamoxifen is a thickened endometrium with mul-

Fig. 11 (continued ).

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 541

tiple cystic spaces (Figs. 9–11) [103,105,106,115–

117]. The histologic counterpart to this sonographic

appearance includes cystic atrophy, hyperplasia,

polyps, subendometrial cysts, and adenomyosis.

Although endometrial carcinoma infrequently

presents with cystic spaces, the sonographic appear-

ance of endometrial carcinoma is nonspecific. Endo-

metrial sampling is recommended in all patients on

tamoxifen presenting with vaginal bleeding. Imaging

plays an important role at directing the type of

sampling procedure to be performed in this patient

population. For example, imaging may suggest the

need for a more aggressive intervention (D and C

versus endometrial biopsy). Alternatively, in the

Fig. 12. Tamoxifen and adenomyosis. A 66-year-old woman on tamoxifen therapy presenting with postmenopausal bleeding.

Sagittal (A) and parasagittal (B) endovaginal sonogram of the uterus shows a thickened endometrium (13 mm, calipers) with

cystic change and poorly defined endometrial borders. The hypoechoic inner myometrium, myometrial cysts, and linear

echogenic striations extending out from the endometrium into the myometrium are signs of adenomyosis. The presence of

adenomyosis frequently results in an overestimation of the true endometrial thickness. (C) Sagittal T2-weighted image shows the

true endometrial thickness to be 5 mm (arrows). Note the increased thickness of the junctional zone and multiple hyperintense

foci within the inner myometrium consistent with adenomyosis.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562542

setting of a polyp, hysteroscopic-guided removal

may result in optimal management, particularly in

patients for whom endometrial biopsy results were

negative or inconclusive.

Several studies have shown discrepancies between

a thickened endometrium on endovaginal sonography

and normal findings at endometrial biopsy [1,48,118].

This most often occurs when endometrial thickening

is the result of polyps, cystic atrophy, or adenomyosis.

HSG is useful in this setting, because it can diagnose

endoluminal lesions accurately, in addition to differ-

entiating endometrial from subendometrial disease

[102]. Adenomyosis presenting as increased echoge-

nicity of the inner myometrium may result in pseu-

Fig. 13. Endometrial hyperplasia. A 70-year-old woman presenting with vaginal bleeding. Sagittal oblique endovaginal

sonogram through the uterus shows diffuse endometrial thickening (7 mm, calipers). The endometrium (E) is echogenic and

contains two small cystic areas. Endometrial biopsy revealed complex hyperplasia. This imaging appearance is nonspecific and

may be seen with endometrial carcinoma.

Fig. 12 (continued ).

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 543

dothickening of the endometrium on endovaginal

sonography (Fig. 12).

MRI

Despite the proved effectiveness of MRI for

demonstrating endometrial abnormalities [119,120],

little has been published in the literature regarding

the MRI appearance of the uterus in women under-

going tamoxifen therapy [21]. Ascher et al [121]

reported on the MRI appearance of the uterus in 35

postmenopausal patients with breast cancer who

were undergoing tamoxifen treatment, and correlated

the imaging findings with histopathologic results.

This group of authors noted two imaging patterns.

Fig. 14. Atypical hyperplasia and polyp. A 75-year-old woman presenting with vaginal bleeding. (A) Sagittal endovaginal

sonogram shows a retroverted uterus with diffuse endometrial thickening (14 mm, arrows) of heterogeneous echotexture. The

differential diagnosis comprises a wide range of endometrial pathology. (C) Sagittal T2-weighted fast spin echo image of the uterus

shows diffuse thickening of the endometrial complex (arrows) with an intact junctional zone. The endometrial complex is

heterogeneous. The imaging appearance is nonspecific. Endometrial sampling diagnosed atypical hyperplasia. The patient

underwent hysterectomy, which confirmed the diagnosis of atypical hyperplasia. In addition, an endometrial polyp originating from

the ventral aspect of the endometrium was found. (See also color Fig. 14B, page 545.)

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562544

(1) An endometrium with homogeneously high

signal intensity on T2-weighted sequences (mean

thickness, 0.5 cm) associated with contrast enhance-

ment of the endomyometrial interface, and a non-

enhancing lumen on gadolinium-enhanced images.

This pattern was most often associated with an

atrophic or proliferative endometrium at histopatho-

logic analysis. (2) An endometrium with heteroge-

neous signal intensity on T2-weighted sequences

(mean thickness, 1.8 cm), associated with enhance-

ment of the endomyometrial interface and lattice-

like enhancement of the endometrial complex on

gadolinium-enhanced images (see Fig. 11). The

latter pattern was most often associated with polyps,

one of which harbored a focus of endometrial

carcinoma. Gadolinium enhancement significantly

improves the characterization of the endometrial

process. Specifically, with gadolinium enhancement

Fig. 14. (B) Color Doppler imaging demonstrates localized stalk flow toward the ventral aspect of the endometrium, suggesting the

presence of a polyp.

Fig. 16. (B) Color Doppler imaging shows the stalk flow feeding the endometrial polyp.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 545

an enhancing stalk is seen in many of the polyps,

improving the diagnostic confidence. Additional

imaging findings include subendometrial cysts, leio-

myomas, and adenomyosis.

Although the role of MRI in this patient popula-

tion is not well-defined, MRI can demonstrate both

endometrial and myometrial pathology associated

with tamoxifen use. MRI may be appropriate in

patients with an equivocal or abnormal endovaginal

sonogram who are unable to undergo HSG because of

cervical stenosis.

Endometrial hyperplasia

Endometrial hyperplasia is a common cause of

abnormal uterine bleeding, and in postmenopausal

Fig. 16. Endometrial polyp. A 54-year-old woman presenting with postmenopausal bleeding. (A) Sagittal endovaginal sonogram

of the uterus shows an echogenic mass (arrows) within the endometrial cavity. Note the displacement of the endometrial lining

around the mass. (See also color Fig. 16B, page 545.)

Fig. 15. Endometrial polyp. A 47-year-old woman presenting with perimenopausal bleeding. Transverse endovaginal sonogram

of the uterus shows a uniformly echogenic, well-defined mass (calipers) within the endometrial cavity consistent with a polyp.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562546

women is most often caused by unopposed estrogen.

Histologically, there is excessive proliferation of

endometrial glands and an increased ratio of glands

to stroma. Endometrial hyperplasia can be classified

broadly into (1) hyperplasia without cellular atypia

and (2) hyperplasia with cellular atypia or atypical

hyperplasia. Approximately 25% of patients with

atypical hyperplasia harbor coexisting foci of endo-

metrial carcinoma or develop endometrial carcinoma

in the future. Patients with atypical hyperplasia at

endometrial sampling are typically treated with hys-

terectomy. The risk of malignant degeneration in

patients without cellular atypia is low [109]. Never-

theless, these patients usually undergo a trial of

Fig. 17. Endometrial polyp. A 46-year-old woman presenting with postmenopausal bleeding on hormone replacement therapy.

Sagittal T2-weighted (A) and contrast-enhanced T1-weighted (B) images of the uterus. (A) A hypointense area (arrow) is seen at

the fundus. This corresponds to the fibrous stalk of the polyp. The remainder of the polyp is isointense to the surrounding

endometrium. (B) The polyp (arrow) shows intense early enhancement relative to the surrounding endometrium. (From Reinhold

C, Gallix BP, Ascher SM. Uterus and cervix. In: Semelka RC, Ascher SM, Reinhold C, editors. MRI of the abdomen and pelvis:

a text atlas. New York, Wiley-Liss; 1997. p. 585–660; with permission.)

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 547

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562548

progesterone therapy with follow-up endovaginal

sonography or endometrial sampling to document a

decrease in the endometrial thickness.

Endovaginal sonography and hysterosonography

In patients with endometrial hyperplasia, the

endometrium is thickened and echogenic with well-

defined margins (Fig. 13). This imaging appearance

is similar to endometrial carcinoma confined to the

endometrium (stage 1A). Small cystic changes repre-

senting dilated glands may be present. On HSG,

endometrial hyperplasia presents as focal or diffuse

endometrial thickening without a localized mass. At

times it can be difficult to distinguish localized

endometrial hyperplasia from a sessile polyp. The

endometrial cavity remains distensible.

MRI

On MRI, endometrial hyperplasia presents as

diffuse or less commonly localized thickening of

the endometrial complex [122]. The endomyometrial

border remains well-defined. The signal intensity is

isointense, or slightly hypointense relative to the

normal endometrium on T2-weighted sequences.

Endometrial hyperplasia, like the normal endome-

trium, is hypointense relative to the myometrium

during the early postcontrast images, and becomes

isointense or hyperintense relative to the adjacent

myometrium on delayed contrast-enhanced images.

In addition, small hypointense foci representing

cystic glandular dilatations may be seen within the

thickened endometrial complex on delayed sequen-

ces. This imaging appearance is nonspecific and

overlaps with that of stage 1A endometrial carcinoma

(Fig. 14A).

Endometrial polyps

Endometrial polyps are a common cause of post-

menopausal bleeding [5,7–9,85]. They are seen most

frequently in perimenopausal and postmenopausal

women. Although polyps are usually asymptomatic,

they may result in uterine bleeding if ulceration or

necrosis occurs. Polyps are multiple in approximately

20% of cases and can be broad-based or pedunculated

with a thin stalk. Endometrial polyps may occur in

isolation or in the setting of endometrial hyperplasia

or less commonly carcinoma. Polyps, however, are a

more frequent cause of abnormal endometrial thick-

ening than either hyperplasia or carcinoma [7,8].

Histologically, polyps represent a localized over-

growth of endometrial tissue covered by epithelium,

and contain a variable number of glands, stroma, and

blood vessels [2]. Patients with postmenopausal

bleeding and endometrial polyps usually undergo

endometrial sampling and removal of the polyps for

the following reasons: (1) to alleviate the symptoms

of bleeding; (2) foci of atypical hyperplasia or carci-

noma may be present at histopathology in benign-

appearing polyps; and (3) endometrial polyps and

carcinoma may coexist in the same patient [66].

Endovaginal sonography and hysterosonography

On endovaginal sonography, endometrial polyps

present as focal or diffuse endometrial thickening [2].

When focal, they appear as round echogenic masses

within the endometrial cavity (Figs. 15, 16A) [123].

Small cystic areas may be seen within the polyps

[44,45,47]. A localized deviation of the central hyper-

echoic line representing the endometrial interface can

be a clue to the presence of an endometrial polyp

[124]. Polyps presenting as diffuse endometrial thick-

ening, however, are difficult to differentiate from

endometrial hyperplasia. Furthermore, polyps are

more difficult to diagnose in the setting of endome-

trial hyperplasia (Fig. 14B).

Hysterosonography, on the other hand, is highly

accurate at detecting endometrial polyps even in

the setting of endometrial hyperplasia. On HSG,

polyps appear as smooth marginated masses of

homogeneous echotexture that demonstrate no

interruption of the endometrial lining. The echoge-

nicity is similar to that of the endometrium

[66,74,75,123]. Polyps project into the endometrial

cavity on a stalk or make acute angles with the

underlying endometrium.

Color Doppler ultrasound can identify the feeding

artery of a pedunculated polyp [40] (Fig.16B). On

pulsed Doppler, the feeding artery frequently demon-

strates high-velocity, low-impedance flow. These

Fig. 18. Endometrial polyp. A 65-year-old woman presenting with postmenopausal bleeding and negative endometrial biopsy

results. Endovaginal sonogram and hysterosonography were nondiagnostic because of the large size of the uterine mass (not

shown). Sagittal T2-weighted (A) and contrast-enhanced T1-weighted (B) images of the uterus demonstrate a large

heterogeneous mass (M) confined to the endometrium. The findings are consistent with a large endometrial polyp; however, a

polypoid endometrial carcinoma cannot be excluded. The patient underwent D and C and a benign endometrial polyp was

removed. (From Reinhold C, Gallix BP, Ascher SM. Uterus and cervix. In: Semelka RC, Ascher SM, Reinhold C, editors. MRI

of the abdomen and pelvis: a text atlas. New York, Wiley-Liss; 1997. p. 585–660; with permission.)

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 549

Doppler indices overlap with those encountered in

endometrial carcinoma [80,81]. The presence of color

flow in an endometrial mass excludes the presence of

a blood clot.

MRI

Endometrial polyps are of intermediate signal

intensity on T1-weighted images [125]. On T2-

weighted images, polyps present as masses that are

slightly hypointense relative to the normal endome-

trium (Fig. 17). Polyps may be entirely isointense on

T2-weighted sequences, however, and present as

diffuse or localized endometrial thickening. Large

polyps are frequently heterogeneous in signal inten-

sity (Fig. 18) [122,125]. The presence of a central

fibrous core and intratumoral cysts favors the diag-

nosis of a benign polyp [125]. On T2-weighted

sequences, the fibrous core is seen as a hypointense

area within a polyp (see Fig. 17). Intratumoral cysts

are well-defined cystic structures of variable size

Fig. 19. Uterine leiomyoma. (A) Transverse endovaginal sonogram shows a large leiomyoma (L) in the center of the uterus,

suspicious for a submucosal myoma. (B) The hysterosonography clearly shows that the leiomyoma (L) indents the endometrium;

however, it is not submucosal in location. The cause for the postmenopausal bleeding was an endometrial polyp.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562550

[125]. The presence of intratumoral cysts is nonspe-

cific, however, and cysts may be encountered in

endometrial carcinomas. Endometrial polyps show a

variable degree of enhancement after gadolinium

administration. Small polyps enhance early and are

well delineated against the hypointense endometrial

complex on early dynamic scans (see Fig. 17). In

addition, a vascular stalk frequently can be identified

during the arterial phase. On delayed images, polyps

are slightly hypointense relative to the endometrium,

but remain isointense or hyperintense relative to the

adjacent myometrium [122]. Large polyps demon-

Fig. 20. Submucosal leiomyoma. A 48-year-old woman with postmenopausal bleeding. Sagittal hysterosonography shows an

anteriorly located submucosal leiomyoma (L) displacing the endometrium posteriorly (arrows).

Fig. 21. Endometrial carcinoma. A 60-year-old woman presenting with postmenopausal bleeding. Oblique transverse

endovaginal sonogram of the uterus shows a mixed echogenicity endometrial mass (arrows) with irregular borders. The mass is

confined to the endometrium. The imaging appearance is consistent with a stage 1A endometrial carcinoma.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 551

strate a heterogeneous pattern of enhancement (see

Fig. 18). The addition of gadolinium-enhanced

sequences significantly improves the detection rate

of endometrial polyps [119]. The enhancement

characteristics of polyps are not sufficiently specific,

however, to obviate the need for tissue sampling

[99,119,122,125].

Leiomyomas

Leiomyomas are well-circumscribed tumors com-

posed of smooth muscle cells arranged in a whorl-like

interlacing pattern, separated by fibrous connective

tissue. Leiomyomas are not encapsulated but contain

a pseudocapsule representing the compressed adja-

Fig. 22. Endometrial carcinoma. A 63-year-old woman presenting with postmenopausal bleeding. (A) Oblique sagittal endo-

vaginal sonogram shows a homogeneous, polypoid mass (arrows) within the endometrial cavity. The mass is slightly hypoechoic

relative to normal endometrium (long arrow). (B) Sagittal T2-weighted image shows the mass (arrows) to be hypointense to

normal endometrium. Note the relatively homogeneous appearance of the mass. (C) Sagittal T1-weighted image early

postcontrast administration shows the endometrial mass (arrows) to be hypointense relative to the adjacent myometrium. Note

the presence of an enhancing stalk (long arrow) dorsally.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562552

cent myometrium. Leiomyomas are common and are

present in 25% of women greater than 35 years of

age. Uterine leiomyomas are classified as subserosal,

submucosal, or intramural based on their location.

Submucosal leiomyomas may result in uterine bleed-

ing caused by congestion, necrosis, or ulceration of

their surface, or just by increasing the surface area of

the endometrial cavity. Myomas are responsive to

estrogen stimulation and diminish in size after men-

opause. Conversely, in patients receiving HRT or

tamoxifen therapy, leiomyomas may increase in size.

Leiomyomas can undergo different types of de-

generation including hyalinization (most common);

myxomatous; cystic; fatty; or hemorrhagic. In post-

menopausal women, myomas frequently become cal-

cified. Sarcomatous degeneration is rare but must be

suspected when a leiomyoma suddenly increases in

size in a postmenopausal woman [2]. The imaging

appearances of leiomyomas and ieiomyosarcomas are

not sufficiently specific to permit accurate differ-

entiation unless frank signs of invasiveness or meta-

static disease are present.

Endovaginal sonography and hysterosonography

On endovaginal sonography and HSG, leiomyo-

mas most commonly appear as hypoechoic, hetero-

geneous masses with sound attenuation [66,75].

Leiomyomas not infrequently contain areas of calci-

fication in the postmenopausal woman. When

densely calcified, myomas appear as echogenic

masses. Submucosal myomas impinge on the endo-

metrium and distort the endometrial cavity [2]. Leio-

myomas are classified as submucosal when at least

50% of the lesion protrudes into the endometrial

cavity. The exact location of a leiomyoma (ie, sub-

mucosal versus myometrial) can be difficult to ascer-

tain on endovaginal sonography (Figs. 19, 20). This

is particularly true in the postmenopausal patient,

where distortion of the endometrial cavity and attenu-

ation by leiomyomas result in poor visualization of

the atrophic endometrium.

These limitations are largely overcome by HSG,

because the endometrial lining and its relative position

to the leiomyoma are well outlined by the instillation

of normal saline. Intramural myomas may displace the

endometrium, but the lining itself is unaffected [74].

Submucosal myomas can be sessile or pedunculated.

Sessile myomas are broad-based and form obtuse or

right angles with the endometrium [74]. When there is

erosion into the uterine cavity, the overlying endome-

trial lining is no longer intact. Pedunculated myomas

can be differentiated from polyps by their continuity

with the myometrium, decreased echogenicity, hetero-

geneous appearance, round shape, and sound attenu-

ation. In addition, polyps typically demonstrate stalk

flow using color Doppler, whereas leiomyomas more

commonly demonstrate diffuse tumor vascularity or a

rim of peripheral flow [67].

MRI

MRI has been shown in several studies to be the

most sensitive and accurate modality for the detection

and localization of uterine leiomyomas [126,127].

The role of MRI in this clinical setting is that of a

Fig. 22 (continued ).

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 553

problem-solving modality, in cases where endovagi-

nal sonography and HSG are nondiagnostic. The

appearance of leiomyomas on MRI is variable and

depends on its cellular composition, and on the type

and extent of degenerative changes present. Leio-

myomas typically appear as sharply marginated

masses of low signal intensity relative to the myome-

trium on T2-weighted images, and are hypovascu-

lar after gadolinium administration [21,126]. When

leiomyomas enlarge and degenerate, they attain

mixed signal intensity on T2-weighted images. Cel-

lular leiomyomas with little or no collagen are hy-

perintense on T2-weighted images, and show early

intense enhancement. Submucosal leiomyomas proj-

ect into the endometrial cavity and may be sessile or

pedunculated. When sessile, at least 50% of the

leiomyoma is surrounded by the endometrial lining.

Contrast-enhanced images play little role in the

Fig. 23. Endometrial carcinoma. A 52-year-old woman presenting with postmenopausal bleeding. (A) Sagittal endovaginal

sonogram shows diffuse thickening (8 mm, calipers) of the endometrium. The endometrium is homogeneously echogenic. (B)

Sagittal T2-weighted image shows the endometrium to be thickened (arrows) but of normal signal intensity. (C) On early

postcontrast T1-weighted images, the endometrial complex is hypointense (arrows). This imaging appearance is nonspecific and

can be seen in endometrial carcinoma and hyperplasia.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562554

detection, localization, or characterization of submu-

cosal leiomyomas, and are not routinely used. Sub-

mucosal myomas can be differentiated from polyps

by establishing their myometrial origin. Other MRI

characteristics that favor submucosal myomas but are

not entirely specific include low signal intensity on

T2-weighted images and a spherical shape.

Endometrial carcinoma

A discussion on the role of imaging in women

with a documented diagnosis of endometrial cancer is

beyond the scope of this article, and is addressed

elsewhere in this issue. This section focuses primarily

on the imaging findings of endometrial carcinoma

and presents morphologic characteristics for differ-

entiating malignant from benign disease.

Endometrial carcinoma is the most common inva-

sive malignancy of the female genital tract [59]. The

presenting symptom in over 75% of patients is uterine

bleeding. Approximately 90% of endometrial carci-

nomas are adenocarcinomas. Other histologic sub-

types include squamous, papillary, and clear cell

carcinomas. Although the histologic subtype is a

strong prognostic indicator, the histology of endome-

trial carcinomas cannot be predicted on the basis of

imaging characteristics.

Endovaginal sonography and hysterosonography

The sonographic appearance of endometrial carci-

noma is variable, and there is considerable overlap

between the morphologic characteristics of benign

and malignant endometrial pathology (Figs. 21–23).

Nevertheless, a number of imaging findings sugges-

tive of malignancy can be identified. The following

sonographic patterns of endometrial carcinoma have

been reported: (1) diffuse endometrial thickening,

hyperechoic with well-defined borders; (2) endome-

trial thickening with a heterogeneous echotexture and

irregular or poorly defined margins; and (3) a hetero-

geneous mass-like lesion [44,45,67,74]. Occasion-

ally, a well-defined cystic area may be seen within

an endometrial carcinoma (Fig. 24). The findings of a

diffusely thickened endometrium of increased echo-

genicity with well-defined borders are nonspecific

and indistinguishable from benign endometrial path-

ology (see Fig. 23). Endometrial thickening or an

endometrial mass that is heterogeneous with irregular

borders is suggestive of malignancy. Several small

series using HSG have shown poor distensibility of

the uterine cavity to be a useful sign for diagnosing

endometrial carcinoma [67,74]. Furthermore, endo-

metrial carcinoma on HSG usually presents as an

irregular broad-based mass [69]. This is in contra-

distinction to endovaginal sonography, where endo-

metrial carcinoma most often presents as diffuse

endometrial thickening.

On color Doppler imaging, endometrial carcino-

mas typically have multiple feeding vessels and show

moderate vascularity [64]. Rarely, stalk flow may be

seen in polypoid endometrial carcinomas. Further-

more, hypovascular endometrial carcinomas are not

uncommon, and color vascularity or Doppler indices

cannot be used to predict case status accurately.

Fig. 23 (continued ).

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 555

MRI

Endometrial carcinomas most commonly present

as focal or diffuse widening (>5 mm) of the endo-

metrial complex on MRI (see Figs. 21–24) [100,

128,129]. With larger tumors, an irregular mass can

be seen distending the endometrial cavity. In patients

with myometrial invasion, the tumor borders are

frequently irregular or ill-defined. Endometrial

carcinomas are isointense to the myometrium on

T1-weighted sequences. On T2-weighted sequences,

the signal intensity is variable ranging from isoin-

tense or slightly hypointense relative to the normal

endometrium, to a signal intensity that is isointense to

the myometrium. Endometrial carcinomas tend to

have a relatively homogeneous appearance. Endome-

trial carcinomas enhance less than the myometrium on

dynamic contrast-enhanced MRI scans [21]. The

differential in enhancement becomes less marked on

Fig. 24. Endometrial carcinoma. A 69-year-old woman presenting with postmenopausal bleeding. (A) Transverse endovaginal

sonogram of the uterus demonstrates a well-defined, echogenic mass within the endometrial cavity. Note two small areas of

cystic change (arrows). Coronal oblique T2-weighted (B) and T1-weighted (C) images of the uterus demonstrate the cystic

change (arrow) within the endometrial carcinoma.

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562556

delayed scans. In the absence of myometrial invasion

(stage 1A), the imaging appearance of endometrial

carcinoma is nonspecific and does not permit differ-

entiation from endometrial hyperplasia or polyp (see

Fig. 23) [100,130]. Rarely, in polypoid endometrial

carcinomas, an enhancing stalk may be seen on early

contrast-enhanced MRI (see Fig. 22).

Technique

Endovaginal sonography and hysterosonography

High-resolution sonographic images are needed to

evaluate the endometrium adequately in postmeno-

pausal women presenting with vaginal bleeding.

Transabdominal sonography suffers from limited

spatial resolution. In addition, obesity, retroflexion,

and multiple leiomyomas of the uterus can make

assessment of the endometrial stripe using transabdo-

minal sonography difficult. With the advent of endo-

vaginal sonography these technical limitations have

largely been overcome. Furthermore, the greater

resolution obtained with the higher-frequency endo-

vaginal probes (5 to 7.5 MHz) can improve the

detection of endometrial pathology.

Hysterosonography is an important adjunct to

endovaginal sonography in the assessment of post-

menopausal bleeding. Hysterosonography is well

tolerated by most patients and does not require the

routine administration of analgesics. In preparation

for performing the HSG, the patient is placed in a

lithotomy position, and a speculum is inserted into

the vagina. The internal os is localized and cleansed

with povidone-iodine solution. A 5 or 7F hysterosal-

pingogram catheter is inserted into the lower uterine

segment. Before insertion, the catheter and balloon

should be flushed with a sterile saline solution to

prevent air from entering the endometrial cavity.

Dilating the balloon with 1 to 2 mL of normal saline

fixes the catheter in place. The speculum can be

removed and the endovaginal probe inserted into the

vagina. Approximately 20 to 60 mL of sterile saline

solution is infused into the uterine cavity to achieve

distention, and endovaginal sonography of the uterus

is performed simultaneously [74,75,131].

Hysterosonography is contraindicated if signs of

pelvic infection including pain, fever, and mucopur-

ulent discharge are present. The presence of vaginal

bleeding is not a contraindication to undergoing HSG.

Antibiotics are not given prophilactically [75]. A

theoretical concern is transtubal dissemination of

endometrial carcinoma into the peritoneal cavity. Slow

infusion and avoidance of high pressures prevent

visible accumulation of fluid in the cul-de-sac during

the procedure. In some instances it may be prudent to

deflate the balloon before infusing the normal saline to

minimize the pressure within the endometrial cavity.

Although transtubal spread of malignant cells is a

theoretic concern, there was no difference in survival

rates between patients who demonstrated intraperito-

neal spill of contrast medium and those who did not in

a study of patients with endometrial carcinoma who

underwent standard HSG [132].

Fig. 24 (continued ).

C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562 557

MRI

The MRI protocol for evaluating patients pre-

senting with postmenopausal bleeding is tailored

to provide optimal depiction of the endometrium.

Imaging the endometrium in two planes (sagittal and

coronal oblique or short-axis) improves the ac-

curacy of detecting small endometrial lesions and

establishing the location of a leiomyoma relative to

the endometrial complex. The use of a pelvic multi-

coil array improves the signal-to-noise ratio of the

image allowing the acquisition of high-resolution

T2-weighted fast spin echo images with the fol-

lowing imaging parameters: field of view, 20 to

24 cm; section thickness, 4 to 5 mm; and matrix

size, 512 � 256. High-resolution images are needed

to depict consistently the atrophic endometrium. Dy-

namic contrast-enhanced and delayed fat-suppressed

T1-weighted images are needed for the detection

and characterization of endometrial pathology. In

addition, contrast-enhanced sequences allow the dif-

ferentiation of debris and hemorrhage from true

endometrial pathology.

Summary

Endovaginal sonography in combination with

HSG is an effective screening tool in evaluating

patients with postmenopausal bleeding. Endovaginal

sonography is highly sensitive for detecting endome-

trial carcinoma and can identify patients at low risk

for endometrial disease obviating the need for endo-

metrial sampling in this subgroup of patients. In

patients with abnormal findings at sonography, a

detailed morphologic analysis can be used to deter-

mine which patients can undergo blind endometrial

sampling successfully versus those who would bene-

fit from hysteroscopic guidance. In patients in whom

endovaginal sonography and HSG are inadequate,

MRI may provide additional information on the

appearance of the endometrium, particularly in

patients in whom endometrial sampling is difficult

(eg, patients with cervical stenosis).

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C. Reinhold, I. Khalili / Radiol Clin N Am 40 (2002) 527–562562

Imaging of cancer of the endometrium

Susan M. Ascher, MDa,*, Caroline Reinhold, MD, MPHb

aDepartment of Radiology, Abdominal Imaging Division, Georgetown University Hospital, 3800 Reservoir Road NW,

Washington, DC 20007-2197, USAbDepartment of Radiology, Gastroenterology and Gynecology, Montreal General Hospital, 1650 Cedar Avenue, Montreal,

Quebec H3Q1A4, Canada

The most important prognostic factors for

women with endometrial cancer are stage of disease,

depth of myometrial invasion, and histologic grade

of tumor. These factors correlate strongly with

lymph node metastases and with survival [1,2].

Although surgical staging is the primary means to

assess these prognosticators, it is imperfect with

recognized drawbacks (eg, staging errors and obe-

sity or other causes of increased surgical risk). These

limitations have led to the investigation and imple-

mentation of cross-sectional imaging for women

with endometrial cancer. Specifically, a growing

body of literature suggests that preoperative cross-

sectional imaging in select women with endometrial

cancer is complementary to surgical staging by

impacting the type and extent of surgery, and in

some patients it may be performed in lieu of

surgical staging [1,3].

The goals of this article are to review the

epidemiology, staging, imaging strategies, and

impact of imaging on treatment decisions and plan-

ning in women with the diagnosis of endometrial

cancer. Detection of endometrial cancer is beyond

the scope of this chapter and is addressed in the

article entitled, ‘‘Postmenopausal bleeding: value

of imaging.’’

Epidemiology and cancer prognostic factors

Epidemiology

Approximately 37,400 women had endometrial

cancer in 1999, making it the most common invasive

gynecologic malignancy in North America. Approx-

imately 6400 women that same year died of the

disease [4]. Endometrial cancer strikes women during

the 6th and 7th decades of life, and most women seek

treatment for dysfunctional uterine bleeding (inter-

menstrual or postmenopausal) [5]. Although the exact

etiology of endometrial cancer remains unknown,

studies have suggested that two distinct mechanisms

may play a role in its origin: (1) unopposed estrogen

stimulation, which leads to endometrial hyperplasia

and then progresses to carcinoma, and (2) sponta-

neous carcinomas arising from atrophic or inert endo-

metrium [1]. These divergent origins may account for

the more favorable prognosis in women with estro-

gen-related carcinomas that have well-differentiated

tumors compared with the poorer prognosis in

women with an unknown carcinogen that has undif-

ferentiated tumors [5].

Recognized risk factors associated with endome-

trial cancer include obesity, diabetes mellitus, hyper-

tension, nulliparity, unopposed estrogen replacement

therapy, and adenomatous endometrial hyperplasia

(Table 1) [1]. Women on tamoxifen citrate for breast

cancer and chemoprevention are also at increased risk

(2.2- to 6.4-fold) for endometrial cancer; however,

the benefit of tamoxifen therapy for reducing breast

cancer recurrence, contralateral new breast cancers,

and the development of breast cancer in women at

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00013 -6

* Corresponding author.

E-mail address: aschers@gunet.georgetown.edu

(S.M. Ascher).

Radiol Clin N Am 40 (2002) 563–576

increased risk outweigh the potential increase in

endometrial cancers. Nutrition may also be a factor

in the development of endometrial cancer given that

the prevalence of this disease is extremely low in

Eastern countries with diets low in animal fats [6].

Up to 90% of endometrial cancers are adenocar-

cinomas. Depending on the glandular pattern, these

cancers range from well-differentiated (grade 1) to

anaplastic (grade 3) tumors. The remaining histologic

types of endometrial cancers include adenocarcinoma

with squamous differentiation, adenosquamous car-

cinoma, papillary serous carcinoma, and clear-cell

carcinoma. Papillary serous and clear-cell carcino-

mas mimic the spread and clinical behavior of

ovarian carcinoma and, as such, are associated with

a worse prognosis.

Prognosis

Surviving endometrial cancer depends on histo-

logic grade, stage, depth of myometrial invasion, and

lymph node status [2]. Of particular importance is the

surgical stage of the disease so much so that in

1988 the International Federation of Gynecology and

Obstetrics (FIGO) revised the staging of endometrial

cancer to incorporate surgical findings. These factors

affect tumor recurrence and ultimately 5-year sur-

vival. Depth of myometrial invasion is the factor

most responsible for variation in the 5-year survival

rate in patients with stage I disease: 40% to 60% in

stage I patients with deep invasion versus 90% to

100% in stage I patients with minimal or no myo-

metrial invasion [7–10]. Specifically, women with

tumors confined to the corpus (stage I) and with only

superficial myometrial invasion have a 3% preva-

lence of para-aortic lymphadenopathy, whereas

women with stage I disease and deep myometrial

invasion have a 46% prevalence of lymph node

involvement [11]. This distinction is also critical with

regard to treatment. The likelihood of lymph node

metastases affects whether lymphadenectomy is per-

formed and its extent. Lymph node involvement,

even in nonsurgical candidates, may also impact the

extent of radiation therapy.

Owing to early symptoms (eg, dysfunctional uter-

ine bleeding), approximately 75% of women with

endometrial cancer are diagnosed with stage I dis-

ease. This early presentation is credited with the

overall favorable prognosis (overall 5-year survival

rate of 84% [12]), and there has been a 28% decrease

in mortality over the past 20 years. The mean 5-year

survival rates for endometrial cancer according to

stage are: stage I, 85.3%; stage II, 70.2%; stage III,

49.2%; and stage IV, 18.7% [13].

Staging

The FIGO surgicopathologic staging system for

endometrial adenocarcinoma (Table 2) includes

exploratory laparotomy, total abdominal hyster-

ectomy, bilateral salpingo-oophorectomy, peritoneal

washings sampling, and lymphadenectomy in

patients with enlarged nodes or at increased risk for

extrauterine disease or lymph node metastases (eg,

certain histologies, isthmus or corpus extension, and

Table 1

Risks for endometrial carcinoma

Characteristic Increased risk

Obesity

> 30 lbs 3�>50 lbs 10�

Nulliparous 2�Late menopause 2.4�‘‘Bloody menopause’’ 4�Diabetes mellitus 2.8�Hypertension 1.5�Unopposed estrogen 9.5�Complex atypical hyperplasia 29�Modified from Barakat RR, Grigsby PW, Zaino SP. Corpus

epithelial tumors. In: Hoskins WJ, Perez CA, Young RC,

editors. Principles and practice of gynecologic oncology.

3rd edition. Philadelphia, PA: Lippincott Williams &

Wilkins; 2000. p. 919–59.

Table 2

FIGO endometrial cancer surgical staging

Stages–grades Characteristics

IA-1, 2, 3 Tumor limited to the endometrium

IB-1, 2, 3 Invasion to less than half myometrium

IC-1, 2, 3 Invasion to more than half myometrium

IIA-1, 2, 3 Endocervical glandular involvement only

IIB-1, 2, 3 Cervical stromal invasion

IIIA-1, 2, 3 Tumor invades serosa or adnexa

or positive peritoneal cytology

IIIB-1, 2, 3 Vaginal metastases

IIIC-1, 2, 3 Metastases to pelvic or para-aortic

lymph nodes

IVA-1, 2, 3 Tumor invades bladder, bowel mucosa,

or both

IVB Distant metastases including

intra-abdominal and inguinal lymph nodes

Modified from Barakat RR, Grigsby PW, Zaino SP. Corpus

epithelial tumors. In: Hoskins WJ, Perez CA, Young RC,

editors. Principles and practice of gynecologic oncology.

3rd edition. Philadelphia, PA: Lippincott Williams &

Wilkins; 2000. p. 919–59.

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576564

deep myometrial invasion). The rationale for surgical

staging reflects the most common pathways for

spread of disease. Endometrial cancer spreads in four

ways: direct extension (most common); lymphatic

invasion; peritoneal metastases (transtubal egress);

and hematogenous metastases (lungs usually affec-

ted) [12].

The location of lymph node metastasis reflects

that portion of the uterus affected by cancer. The

middle and lower aspects of the uterus drain laterally

to the parametrium, paracervical, and obturator

lymph nodes. The upper corpus and fundus drain to

the common iliac and paraaortic lymph nodes. Addi-

tionally, the inguinal lymph nodes may be involved

through spread along the round ligaments.

Imaging strategies for detection, diagnosis,

and staging

Imaging strategies for detecting and diagnosing

endometrial carcinoma are covered in another article

in this issue. Although most women with endometrial

cancer undergo surgery for staging and for primary

therapy, pretreatment imaging can help triage patient

care. Imaging may identify a subset of patients who,

because of extensive disease, are no longer appropri-

ate surgical candidates. Rather, these patients may

benefit from extending the primary pelvic radiation

field to encompass para-aortic lymph nodes, abdom-

inal lymph nodes, or both. In other instances, pre-

treatment imaging may confirm extrauterine spread in

women with suspected advanced disease (eg, grade 3

adenocarcinoma, papillary serous carcinoma, or

clear-cell carcinoma). These patients may benefit

from referral to a tertiary care center for more

extensive surgery. Specifically, the decision to per-

form lymph node sampling and the extent of sam-

pling may be altered by the preoperative knowledge

of tumor extent. Finally, preoperative intracavitary

radiation therapy may be offered to some patients

with imaging findings of deep myometrial or cervi-

cal invasion.

Ultrasound, specifically transvaginal sonography

(TVS), is often used for the initial evaluation in

women with known or suspected endometrial carci-

noma. CT is usually reserved for staging; however, a

growing body of literature suggests contrast-enhanced

MRI should be performed in women with known

endometrial cancer in whom TVS is suboptimal or

in whom the results of imaging will directly impact

treatment and guide surgical planning [1,3].

TVS has had mixed results for determining depth

of myometrial invasion. Reported accuracy rates vary

from 68% to 99% [14–18]. This variability reflects

differences in patient populations and strictness in

assigning FIGO stage. Myometrial invasion is sug-

gested when a mass disrupts the subendometrial halo

or extends asymmetrically into the myometrium [16].

Unfortunately, TVS may overestimate or underesti-

mate disease extent. Overestimation of myometrial

invasion can be seen in patients with large intra-

luminal tumors, adenomyosis, or lymphovascular

space invasion [13,14,16]. In contradistinction, under-

estimation is frequent in patients with microscopic or

minimal myometrial invasion. Other factors that limit

TVS for staging endometrial cancer include small

field of view, which precludes assessment of the

cervix, parametrium, or lymph nodes; suboptimal soft

tissue contrast, such that the primary tumor, comorbid

conditions, and adjacent myometrium may all image

similarly; and body habitus, with obesity or a verti-

cally oriented cervix hampering complete evaluation.

CT (conventional and helical) has enjoyed wide-

spread use for the preoperative evaluation of endo-

metrial carcinoma. It is primarily used for staging to

include lymph node status and depth of myometrial

invasion. The accuracy of conventional CT staging of

endometrial cancer is reported to be from 84% to

88% [19,20]. There is a paucity of data for helical

CT. In the sole published study of helical CT in

25 patients with endometrial carcinoma, helical CT

was found to be less sensitive and less specific for

preoperative staging than MRI. The sensitivity and

specificity for helical CT to detect deep myometrial

invasion (stage IC) was 83% and 42%, respectively,

whereas the sensitivity and specificity for detecting

cervical invasion (stage II) was 25% and 70%,

respectively [21]. That the authors only evaluated

axial images and did not assess sagittal reconstructed

images might have contributed to their modest

results. At the time of this writing, there are no

published data on multidetector CT staging of endo-

metrial cancer

MRI is the most accurate modality for the pretreat-

ment evaluation of endometrial cancer. It is advan-

tageous because of its superior contrast resolution

and multiplanar capability. Moreover, recent advances

in software now allow reproducible, T1-weighted

(T1-W) contrast-enhanced, 3D isotropic voxel im-

aging [22]. The reported overall staging accuracy of

MRI for endometrial cancer ranges from 83% to 92%

[23–25]. When analyzing only patients with stage I

disease, MRI is 74% to 91% accurate for differenti-

ating superficial endometrial carcinoma (stages IA and

Ib) from deep endometrial cancers (stage IC).

A recent meta-analysis to compare the usefulness

of CT, TVS, and MRI in staging endometrial car-

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576 565

cinoma found that contrast-enhanced MRI performed

better than CT, ultrasound, or unenhanced MRI in

assessing depth of myometrial invasion [3]. In fol-

low-up meta-analysis and bayesian analysis, the use

of contrast-enhanced MRI significantly affected the

post-test probability of deep myometrial invasion in

patients with all grades of endometrial carcinoma

[26]. This last study has important economic impli-

cations for identifying a subset of patients who

might benefit from referral to a tertiary care center

for more aggressive management by a gynecologic

oncologist versus patients who can be treated by a

local general gynecologist.

Contrast-enhanced MRI results alter the likelihood

ratios for myometrial invasion, which, in turn, affects

the probability of lymph node metastases and hence

the extent of surgery performed. Specifically, Frei et al

[26] found the mean weighted pre-MRI probabilities

of deep myometrial invasion in patients with tumor

grades 1, 2, and 3 were 13%, 35%, and 54%, respec-

tively, whereas post-MRI probabilities for deep myo-

metrial invasion for grades 1, 2, and 3 increased to

60%, 84%, and 92%, respectively, for positive and

decreased to 1%, 5%, or 10%, respectively, for nega-

tive MR findings. Practically speaking, deep myome-

trial invasion can be reliably excluded in patients with

grade 1 or 2 tumors in whom MRI does not dem-

onstrate deep myometrial invasion. With this know-

ledge, frozen section or lymph node sampling is not

necessary, nor does the patient need referral to a

specialist. Similarly, in a patient with grade 3 adeno-

carcinoma, lack of deep myometrial invasion on MRI

significantly decreases the chance of lymph node

metastases, and lymphadenectomy may be deferred.

Conversely, positive MRI findings would support the

need for lymph node sampling.

Women are often diagnosed with endometrial

cancer after dilation and curettage. The MRI changes

in the uterus after dilation and curettage do not appear

to negatively impact image interpretation for staging,

and there are no strict guidelines for how long one

should wait before having a woman with a newly

diagnosed endometrial cancer [27] undergo scanning.

We opt to image women once post-procedural vaginal

bleeding has ceased or has nearly resolved.

Imaging protocol

Patient preparation is minimal. Patients are

instructed not to eat or drink 4 to 6 hours before the

examination to limit peristalsis artifact; alternatively,

glucagon may be administered before imaging.

Patients are also asked void prior to imaging. They

are scanned in the prone position using a torso-phased

array coil, and the field of view is as small as is

appropriate to body habitus. A basic examination

includes orthogonal T2- weighted (T2-W) sequences,

transverse T1-W sequence, and sagittal dynamic con-

trast-enhanced T1-W sequences. This protocol seeks

to detect viable primary tumor (T2-W and Gd-T1-W

sequences); myometrial and cervical involvement

(T2-W and Gd-T1-W sequences); and loco-regional

spread (eg, pelvic sidewall) and lymphadenopathy

(T1-W and Gd T1-W sequences).

Highly resolved T2-W fast spin echo sequences

(FSE) are favored for evaluation of the primary tumor,

myometrial penetration, and cervical extension [28].

Intravenous contrast is routinely used to delineate

viable tumor versus debris and to highlight the

tumor-myometrial junction. Contrast studies im-

prove the sensitivity and negative predictive value

for deep myometrial invasion [29]. Dynamic contrast-

enhanced T1-W spoiled-gradient echo sequences have

been found to be incrementally more accurate in the

determination of myometrial invasion than T2-W and

contrast-enhanced T1-W sequences by 85%, 58%,

and 68%, respectively [30]. An advantage of the

dynamic sequence is that absence of the junctional

zone (JZ), a landmark used for determining the depth

of myometrial invasion on T2-W sequences, does not

hamper evaluation. This is especially important as

T2-W zonal anatomy becomes less conspicuous in

women after menopause, the same cohort that tends to

get endometrial cancer.

In addition to the absence of the JZ or indistinct

zonal anatomy, other circumstances that may interfere

with the MR evaluation in women with endometrial

cancer are (1) myometrial thinning by a large polypoid

tumor or obstructed endometrial canal, (2) poor

tumor–myometrial interface regardless of sequence,

(3) distorting multiple or large leiomyomata, (4) small

uteri, and (5) congenital anomalies [31].

Imaging findings

MR correlates for the FIGO staging system have

been devised (Table 3). In general, endometrial can-

cer presents as widening of the endometrial stripe

greater than 3 to 5 mm in a postmenopausal wom-

an. Tumors tend to be isointense to myometrium on

T1-W sequences and have a variable appearance on

T2-W sequences (isointense, hypointense, or hetero-

geneous compared with the myometrium). On the

images taken immediately after dynamic contrast

administration, endometrial cancers typically enhance

less than the normal myometrium. This difference in

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576566

enhancement becomes less marked with subsequent

image acquisitions [21,32,33].

Stage 0 tumor, or carcinoma in situ, appears as a

normal or widened endometrial canal. Stage I endo-

metrial cancers include tumors confined to the corpus.

Stage IA disease, tumor limited to the endometrium,

may image as a normal or widened (focal or diffuse)

endometrium (Fig. 1). The JZ on T2-W sequences,

subendometrial enhancement (SEE) on dynamic

sequences, and low-signal intensity zone of the inner

myometrium (LIZ) on delayed sequences are pre-

served. Regardless of sequence, the tumor–myome-

trial interface is smooth and sharp. For stage IB

disease, tumor extends less than 50% into the myome-

Table 3

MRI correlates of FIGO staging

Stage Findings

0 Normal or thickened endometrial stripe.

IA Thickened endometrial stripe with diffuse or focal abnormal signal intensity; endometrial stripe may be normal;

intact junctional zone with smooth endometrial–myometrial interface.

IB Signal intensity of tumor extends into myometrium < 50%; partial- or full-thickness disruption of junctional zone

with irregular endometrial–myometrial interface.

IC Signal intensity of tumor extends into myometrium >50%; full-thickness disruption of junctional zone; intact stripe

of normal outer myometrium.

IIA Internal os and endocervical canal are widened; low signal of fibrous stroma remains intact.

IIB Disruption of fibrous stroma.

IIIA Disruption of continuity of outer myometrium; irregular uterine configuration.

IIIB Segmental loss of hypointense vaginal wall.

IIIC Regional lymph nodes greater than 1 cm in diameter.

IVA Tumor signal disrupts normal tissue planes with loss of low signal intensity of bladder or rectal wall.

IVB Tumor masses in distant organs or anatomic sites.

MRI findings are based on T2-weighted or contrast-enhanced T1-weighted images.

Modified from Barakat RR, Grigsby PW, Zaino SP. Corpus epithelial tumors. In: Hoskins WJ, Perez CA, Young RC, editors.

Principles and practice of gynecologic oncology. 3rd edition. Philadelphia, PA: Lippincott Williams &Wilkins; 2000. p. 919–59.

Fig. 1. Stage IA endometrial adenocarcinoma. Sagittal T2-W FSE image (A) demonstrates an intermediate signal intensity mass

(asterisk) distending the endometrial cavity. The junctional zone is preserved, and the tumor–myometrial interface is smooth

(arrows). Endometrial polyp or endometrial hyperplasia may appear similarly, as in this T2-W FSE image (B) in a woman with

endometrial hyperplasia. (Fig. 1A from Reinhold C, Gallix BP, Ascher SM. Uterus and cervix. In: Semelka RC, Ascher SM,

Reinhold C, editors. MRI of the abdomen and pelvis. New York, Wiley-Liss; 1997. p. 585–660; with permission.)

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576 567

trium with associated disruption or irregularity of

JZ, SEE, or LIZ (Fig. 2). If these landmarks are not

present, stage IB tumor is suggested by an irregular

tumor–myometrial interface. With stage IC disease,

tumor not only disrupts the JZ, SEE, or LIZ, it extends

more than 50% into the myometrium (Fig. 3). There

should be, however, an intact stripe of normal outer

myometrial tissue. It is recommended that superficial

Fig. 2. Stage IB endometrial adenocarcinoma. Sagittal T2-W FSE (A) and gadolinium-enhanced fat-suppressed T1-W spoiled-

gradient echo (B) images show a large mass distending the endometrial canal and approaching the endocervix. There is superficial

myometrial invasion at the level of the lower uterine segment (arrows). (From Audet P, Pressacco J, Burke M, Reinhold C. MR

imaging of female pelvic malignancies. Magn Reson Imaging Clin North Am 2000;8:887–914; with permission.)

Fig. 3. Stage IC endometrial adenocarcinoma. Sagittal T2-W FSE (A) and coronal gadolinium-enhanced fat-suppressed T1-W

spoiled-gradient echo (B) image shows a mass (asterisks, A, B) originating in the endometrium and invading the underlying

myometrium. Depth of myometrial invasion is difficult to discern on the T2-W image because of coexistent adenomyosis. After

intravenous contrast imaging, the tumor myometrial interface is more conspicuous, and deep myometrial invasion is well seen

(arrows, B). (From Audet P, Pressacco J, Burke M, Reinhold C. MR imaging of female pelvic malignancies. Magn Reson

Imaging Clin North Am 2000;8:887–914; with permission.)

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576568

Fig. 4. Stage IIA endometrial adenosquamous. Sagittal T2-W FSE (A) and gadolinium-enhanced fat-suppressed T1-W spoiled-

gradient echo (B) images show an endometrial mass with deep myometrial invasion and extension into the cervix. The cervical

involvement is more conspicuous on the T2-W image (arrows, A) because the tumor and normal cervical tissue enhance

similarly. (From Audet P, Pressacco J, Burke M, Reinhold C. MR imaging of female pelvic malignancies. Magn Reson Imaging

Clin North Am 2000;8:887–914; with permission.)

Fig. 5. Stage IIB endometrial adenocarcinoma. Sagittal T2-W FSE (A) and gadolinium-enhanced fat-suppressed T1-W spoiled-

gradient echo (B) images show an endometrial cancer (straight arrows, A,B) extending into and invading the anterior cervix

(curved arrow, A). Incidental note is made of Nabothian cysts (N). Bl = urinary bladder. (From Reinhold C, Gallix BP, Ascher

SM. Uterus and cervix. In: Semelka RC, Ascher SM, Reinhold C, editors. MRI of the abdomen and pelvis. New York, Wiley-

Liss; 1997. p. 585–560; with permission.)

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576 569

Fig. 6. Stage IIIA endometrial carcinoma. Sagittal (A) and axial (B) T2-W single-shot fast spin-echo (FSE) images in a woman

with papillary serous carcinoma show low-signal– intensity tumor extending into the endocervical canal. There is bilateral

hydrosalpinx (asterisks, A,B) secondary to tumor involvement to the fallopian tubes. The sigmoid colon (arrow, B) is

compressed by the dilated tubes but is otherwise normal. In another patient, sagittal T2-W FSE (C) and gadolinium-enhanced T1-

W fat-suppressed spoiled-gradient echo (D) images show a mass distending the endometrial canal and invading the underlying

myometrium. Deep myometrial invasion is easier to define on the postcontrast image (arrows, D). The axial gadolinium-

enhanced fat-suppressed T1-W spoiled-gradient echo image (E) shows a complex right adnexal metastasis (asterisk, E). (Figs. 6A

and 6B from Reinhold C, Gallix BP, Ascher SM. Uterus and cervix. In: Semelka RC, Ascher SM, Reinhold C, editors. MRI of the

abdomen and pelvis. New York, Wiley-Liss; 1997. p. 585–560; with permission.)

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576570

and deepmyometrial invasion be confirmed on orthog-

onal views.

Caution should be used when evaluating myome-

trial penetration in women with adenomyosis. The

normal endometrial–myometrial interface in women

with adenomyosis is irregular; imaging an irregular

endometrial–myometrial interface in the absence of

other findings should not automatically confer a

diagnosis of superficial myometrial invasion. Con-

versely, full-thickness disruption of the JZ in women

with true deep myometrial invasion may not be

apparent in patients with adenomyosis.

Stage II disease includes tumor extension beyond

the uterine corpus into the cervix. Stage IIA, invasion

of the endocervix, appears as widening of the internal

os and the endocervical canal with preservation of the

fibrocervical stroma (Fig. 4). Widening of the endo-

cervical canal by polypoid extension of an endome-

trial cancer, debris, or coexisting cervical polyp should

not be misinterpreted as cervical invasion. Contrast-

enhanced scans, especially dynamic imaging, may

help sort out the reason for endocervical canal widen-

ing. For stage IIB, there is disruption of the fibrocer-

vical stroma (Fig. 5). Microscopic cervical invasion

may go undetected.

Stage III endometrial cancer is tumor that extends

outside the uterus but not the true pelvis. For IIIA

disease, in which tumor invades the serosa or adnexa

or peritoneal cytologic findings are positive, the

integrity of the outer myometrium is usually irregular,

disrupted, or both (Fig. 6). The ovaries may be

involved by direct extension or as discrete metastases.

Parametrial involvement images as disruption of the

serosa with direct extension into the surrounding

parametrial fat. In stage IIIB disease, tumor extends

into the upper vagina, and there is segmental loss of

the low-signal intensity vaginal wall.

Lymphadenopathy, stage IIIC, is diagnosed when

the short axis of regional lymph nodes is larger than

1 cm (Fig. 7). Unfortunately, SI does not distinguish

hyperplastic lymph nodes from metastatic lymph

nodes. If a patient’s cancer spreads through the

lymphatics, there may be abdominal lymph node

metastases (MR equivalent of stage IVB disease) in

the absence of pelvic lymphadenopathy. Lymph

nodes are especially well seen on T1-W and Gd-FS-

T1-W sequences. The use of contrast can help dif-

ferentiate pelvic vessels from pelvic lymph nodes.

Stage IV tumor is disease that extends beyond

the true pelvis or invades the bladder or rectum. In

stage IVA disease there is a focal loss of the low-

signal intensity wall of the bladder, rectum, or both

(Fig. 8). It may be difficult to distinguish tumor

applied to these hollow viscera versus frank inva-

sion. Stage IVB, distant metastasis, is self-explan-

atory though pelvic manifestations include ascites

(which may enhance on delayed images) and peri-

toneal deposits [34]. Peritoneal disease is most

conspicuous on fat-suppressed gadolinium-enhanced

T1-W images and in the presence of ascites [35,36].

Although some studies have shown MRI to be

superior to CT in the detection of peritoneal disease,

Fig. 6 (continued ).

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576 571

deposits smaller than 1 cm may remain occult

regardless of imaging modality.

Impact of imaging on treatment decisions

and planning

Of all the gynecologic malignancies, treatment

plans for endometrial cancer have the most variabil-

ity. This is especially true for endometrial cancer

confined to the uterine corpus, which represents

approximately 75% of the adenocarcinomas of the

uterus. The standard treatment is total abdominal

hysterectomy and bilateral salpingo-oophorectomy.

However, preoperative and postoperative radiation

therapy and even chemotherapy are performed in

some patients (Table 4).

Although there are recognized indications for

retroperitoneal lymph node sampling (deep myome-

trial invasion, isthmus–cervix extension, extrauterine

spread, unfavorable histologies and enlarged lymph

nodes), a gray zone exists for patients who may not

Fig. 7. Stage IIIC endometrial adenocarcinoma. Axial (A) and sagittal (B) T2-W FSE images show an enlarged right external

iliac lymph node (arrow, A) and a large endometrial mass (asterisk, A,B) extending into and invading the cervix (arrows, B).

Note several nonpathologically enlarged left external iliac lymph nodes. (From Audet P, Pressacco J, Burke M, Reinhold C. MR

imaging of female pelvic malignancies. Magn Reson Imaging Clin North Am 2000;8:887–914; with permission.)

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576572

meet these criteria but nevertheless have some prob-

ability of lymph node involvement. This is where

contrast-enhanced MRI may have a significant

impact on treatment planning. As stated earlier, find-

ings at MRI change the likelihood ratios for myome-

trial invasion, in turn affecting the probability for

lymph node involvement and the need for lymph

node sampling.

Adjuvant treatment is usually based on surgical-

pathologic staging (see Table 4). Patients are clas-

sified into 3 groups:

Low risk: patients with a high rate of cure without

postoperative therapy

High risk: patients with a low rate of cure without

postoperative therapy

Fig. 8. Stage IVA endometrial adenocarcinoma. Sagittal T2-W single-shot fast spin-echo (FSE) (A) image shows a large tumor

distending the endometrial canal and extending into and invading the cervix. The disrupted fibrocervical stroma is especially

well seen (arrows, A). On sequential axial (B,C) and sagittal (D) gadolinium-enhanced fat-suppressed T1-W spoiled-gradient

echo images, a solid cystic tumor involving the sigmoid colon is highlighted (arrows, B–D). Bowel involvement mimics the

normal colon on the single-shot FSE image (arrowhead, A).

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576 573

Intermediate risk: patients who demonstrate a

reduced rate of surgical cure but who may or

may not benefit from additional therapy

Low-risk patients do not benefit from postoper-

ative radiation therapy. High-risk patients do benefit

from radiation therapy, usually to the vaginal cuff

and pelvis. Para-aortic radiation and abdominal

radiation are reserved for patients with proven

para-aortic lymph node metastasis and extra-pelvic

spread. It is for the intermediate-risk patients that

there is controversy regarding radiotherapy. A phase

3 GOG study did find an overall survival benefit at

3 years in intermediate-risk patients undergoing

postoperative radiation; however, the survival bene-

fit was less clear for a subset of patients who, after

surgical staging, were found to have myometrial

invasion as the only risk factor [37]. Regardless of

definitive survival benefit, it seems reasonable to

conclude from the GOG study that radiation ther-

Fig. 8 (continued ).

S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576574

apy probably does improve local and regional

tumor control.

Summary

Transvaginal US is often the initial imaging

examination for women with dysfunctional (postmen-

opausal or intermenstrual) uterine bleeding. However,

once the diagnosis of endometrial cancer has been

made, contrast-enhanced MRI should be performed

in patients who require multifactorial assessment (eg,

depth of myometrial invasion, cervical involvement,

lymph node metastasis). The results of contrast-

enhanced MRI help distinguish patients who need

more aggressive therapy and referral to a gynecologic

oncologist from those who will do well treated by a

community gynecologist.

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Contemporary treatment plan using FIGO staging

Treatment factors Low risk Intermediate risk High risk

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IB, IC (all grades) IVA, IVB (all grades)

IIA, IIB (all grades)

IIIA (+ cytology)

Postoperative treatment None Vaginal cuff radiation Vaginal cuff radiation

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Abdominal radiation (+ intra-abdominal spread)

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S.M. Ascher, C. Reinhold / Radiol Clin N Am 40 (2002) 563–576576

Imaging of cancer of the cervix

Juergen Scheidler, MDa,*, Andreas F. Heuck, MDb

aDepartment of Clinical Radiology, Ludwig-Maximilians-University of Munich, Klinikum Grosshadern, D-81366,

Munich, GermanybRadiology Associates, Radiologisches Zentrum Munchen-Pasing, Pippinger Strasse 25, D-81245, Munich, Germany

Rapid advances in imaging technology have

resulted in significant changes in imaging algorithms

of the female pelvis. Ultrasound is considered an

adjunct to physical examination and is often the

initial imaging study ordered. CT represents a tech-

nical advance over ultrasound for staging of pelvic

neoplasms. The relative lack of soft tissue contrast

resolution, the necessity for injection of contrast

material, and exposure of the patient to ionizing

radiation, however, detracts from its usefulness.

MRI has proved to be a most valuable diagnostic

tool in studying the female pelvis. As documented by

numerous studies during the last decade, MRI offers

a noninvasive assessment of normal anatomy, con-

genital anomalies, and benign and malignant diseases

of the uterus. For most conditions, it has proved to be

superior to clinical examination, ultrasound, and CT.

Continuing advances in MRI of the pelvis, including

the development of new pulse sequences and coil

techniques, the use of gadolinium chelates as para-

magnetic contrast media, and the growing experience

of radiologists, have further increased the potential of

MRI as a problem-solving modality and helped to

establish its immediate and cost-effective impact on

treatment alternatives [1,2].

This article reviews the current status of cross-

sectional imaging modalities for the diagnosis and

staging of cervical cancer. With emphasis on MRI,

imaging strategies and their impact on treatment

decision and planning in cervical cancer are discussed.

Epidemiology and cancer prognostic factors

In the United States, carcinoma of the cervix is the

second most common gynecologic malignancy in

women, accounting for 15,700 new cases (6% of all

cancers) and 4900 deaths in the year 2001. World-

wide, cervical cancer is second only to breast cancer

as the most common malignancy in both incidence

and mortality. More than 471,000 new cases are

diagnosed each year, predominantly among the eco-

nomically disadvantaged, in both developing and

industrialized nations. During the last 50 years in

the United States, the use of screening programs

based on the Papanicolaou smear and pelvic exami-

nation has led to a steep decline in incidence of and

deaths from cervical cancer.

Cervical cancer occurs more frequently in young

women of low socioeconomic standing. The average

age at diagnosis is about 50 years with peaks at 38

and 62 years. Risk factors include early age at first

intercourse, a high number of sexual partners, multi-

parity, cigarette smoking, and a history of sexually

transmitted diseases. Strong evidence suggests that

the human papilloma virus is a main cause of

cervical carcinoma.

Cervical intraepithelial neoplasia (CIN) is consid-

ered a precursor lesion of cervical cancer. CIN is

characterized into three groups: (1) CIN 1, minor

dysplasia; (2) CIN 2, moderate dysplasia; and (3)

CIN 3, severe dysplasia or carcinoma in situ. Up to

40% of CIN 3 lesions progress to invasive carcinoma

if left untreated.

Carcinoma arises at the squamocolumnar junction,

which is located exophytic in young women. In these

individuals, cervical carcinoma grows predominantly

exophytic and large parts of the tumor extend inferi-

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00007 -0

* Corresponding author. Associate Clinical Professor of

Radiology, Radiologic Center of Munich, Pippinger Str. 25,

D-81245 Munich, Germany.

E-mail address: scheidler@rzm.de (J. Scheidler).

Radiol Clin N Am 40 (2002) 577–590

orly into the vagina. In older women with atrophic

cervices, however, the squamocolumnar junction is

located in the endocervical canal. Tumors occurring

inside the endocervical canal account for approxi-

mately 20% of cervical carcinomas, more commonly

involve the supravaginal portion of the cervix, and

frequently extend laterally through the cervical wall.

Two main histologic types of cervical carcinoma

can be differentiated: (1) squamous cell carcinoma,

which accounts for 80% to 90% of cases; and (2)

adenocarcinoma, which carries the worst prognosis.

Other important prognostic factors are the histologic

grade of tumor; the location within the cervix (exo-

cervix versus endocervix); the tumor volume and the

depth of stromal invasion; adjacent tissue extension;

and lymph node involvement at the time of treatment.

Clinically, the leading symptoms of cervical car-

cinoma are bleeding and vaginal discharge. Physical

pelvic examination commonly reveals a more or less

necrotic and bleeding tumor. In a number of patients,

however, speculum examination may reveal a normal

cervix when the carcinoma is located within the

cervical canal or occult. In these cases, detection of

cervical carcinoma is often based on exfoliate cytol-

ogy (Papanicolaou smear). In cases with a grossly

visible mass the definite diagnosis is made with

biopsy. Primary clinical information about local

tumor spread is provided by bimanual vaginal and

rectal examinations.

Staging

The classic staging of cervical carcinoma is clinical

and uses the Federation Internationale de Gynecologie

et d’Obstetrique (FIGO) classification (Table 1). The

TNM staging classification is essentially based on the

same criteria as the FIGO system (see Table 1). In

addition to the standard physical examination, FIGO

staging may include findings from examination under

anesthesia, cystoscopy, rectosigmoidoscopy, barium

enema, biopsy, intravenous pyelography, and chest

radiography. When compared with intraoperative and

pathologic findings, however, clinical staging shows

errors of 20% to 35% depending on the stage of

disease [1,3–5]. In addition, up to 25% of patients

have metastasis to the locoregional pelvic or to the

para-aortal lymph nodes that cannot be detected by

clinical examination. Moreover, extension to the blad-

der or adjacent bowel is difficult to define clinically.

These shortcomings of the clinical FIGO staging

system underline the importance of an accurate imag-

ing evaluation of carcinoma of the cervix. Ultrasound

is considered an adjunct to physical examination.

Technical limitations (caused by the patient’s habitus,

operator dependence, and low signal-to-noise ratio)

and lack of tissue characterization severely decrease

the diagnostic value of sonography in cervical cancer.

In addition, ultrasound is inadequate for staging

pelvic malignancies [6,7].

CT is not well suited to evaluate tumor size or

stromal invasion because it cannot distinguish cancer

from the surrounding normal cervical tissue [8]. In

general, the accuracy of CT in staging cervical carci-

noma is limited. In evaluating the stage of disease,

MRI was found to have an accuracy of 90%, compared

with 65% for CT [8]. Both modalities, however, were

comparable in evaluating lymph node metastases

(86% each). In identifying parametrial involvement,

CT has an accuracy of 55% to 70% and the overall

staging accuracy is as low as 45% to 63% [5,8,9].

MRI performed at high field strengths is the most

reliable pretherapeutic modality for the detection or

exclusion of parametrial spread, the overall tumor

staging, and for lymph node assessment [4,5,10–16].

MRI plays an important role in selecting patients for

surgery or radiation therapy.

MRI appearance of cervical carcinoma

Cervical cancer appears as a relatively hyperin-

tense mass on T2-weighted imaging, and is easily

Table 1

Staging systems for cervical neoplasms

TNM Cervix FIGO

T1 Limited to uterus I

T1a Preclinical invasive carcinoma IA

T1a1 Depth � 3 mm, horizontal

spread � 7 mm

IA1

T1a2 Depth 3–5 mm, horizontal

spread � 7 mm

IA2

T1b Tumor greater than T1a2 IB

T2 Beyond uterus but not to pelvic

side wall or lower third of vagina

II

T2a No parametrial invasion IIA

T2b With parametrial invasion IIB

T3 Extends to the pelvic wall or

involves lower third of the vagina

or hydronephrosis

III

T3a Lower third of vagina,

not to pelvic side wall

IIIA

T3b Pelvic side wall or

hydronephrosis

IIIB

T4 Tumor invades bladder

mucosa or rectum; extends

beyond true pelvis

IVA

M1 Distant metastasis (including lymph

nodes beyond the true pelvis)

IVB

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590578

Fig. 1. Normal appearance of the uterus on T2-weighted sagittal (A) and transversal (B) images after vaginal opacification with

ultrasound jelly. Note the low signal intensity stroma (C ) and the excellent delineation of the dorsal vaginal fornix (white

arrow) and the dorsal and anterior (black arrow) vaginal wall. Small intramural leiomyoma (diamond ). OV= ovary;

UB= urinary bladder.

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590 579

distinguishable from the normal low signal intensity

cervical stroma (Figs. 1, 2). Adenocarcinomas

(approximately 10% of cervical carcinomas) usually

have higher signal intensity on heavily T2-weighted

images (Fig. 3) than squamous cell cancer (90%). As

has been demonstrated by histopathologic correlation,

location and size of an invasive tumor can be deter-

mined accurately on T2-weighted images even in

clinically problematic lesions [13,15–19]. The accu-

racy in determining the depth of stromal invasion is

also high (about 80%) [5,11]. Preinvasive disease,

however, usually cannot be identified with MRI.

The contrast uptake of cervical carcinoma varies

considerably. Both strong enhancing tumors and

lesions revealing intermediate enhancement are seen

after intravenous gadolinium administration. Viable

tumors and areas of necrosis can be distinguished

with the use of gadolinium chelates. Because contrast

enhancement may render the tumor isointense to the

surrounding high-signal cervical and parametrial tis-

sue on T1-weighted images, however, it has not been

shown to increase diagnostic performance in tumor

depiction, in the definition of the depth of stromal

invasion, and in the evaluation of early parametrial

involvement [14,20,21]. Even so, contrast-enhanced

imaging may be helpful in the evaluation of tumor

extension to the pelvic side wall or into adjacent

organs, such as rectum or urinary bladder [20].

Fig. 2. Cervical carcinoma FIGO stage Ib. Sagittal (A) and

axial (B) T2-weighted images. The tumor (star) is located

endocervically. No extension to the vagina is seen (A).

Parametrial invasion can be excluded because of the

preserved dark rim of normal cervical stroma surrounding

the tumor (star).

Fig. 3. Adenocarcinoma of the cervix. T2-weighted sagittal

image. Compared with the squamous cell carcinoma

presented in Fig. 2, the signal intensity of the tumor is

higher. The tumor presents with full-thickness stromal

invasion of the cervix (arrows). The occlusion of the

cervical canal leads to fluid retention within the dilated

uterine cavity (star).

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590580

Staging with MRI

Stage I

Stage I tumors are confined to the uterus. Pre-

clinical invasive stage Ia tumors are characterized by

either microscopic stromal invasion (stage Ia1) or

macroscopic spread of less than or equal to 7 mm in

the horizontal dimension or a stromal invasion of less

than or equal to 5 mm (stage Ia2). Many stage Ia

tumors are not depicted on MRI because of their

small size. The cervical stroma appears widely nor-

mal on T2-weighted images, with a low signal

intensity ring structure on axial scans.

In stage Ib carcinoma the tumor can be detected

by its increased signal intensity within the cervical

ring (see Fig. 2). Using MRI, the depth of stromal

invasion can be determined. In partial stromal inva-

sion the uninvolved cervical tissue is demonstrated on

T2-weighted images as a hypointense peripheral

stripe. The presence of this stripe, with a thickness

of greater than or equal to 3 mm, is a reliable finding

(specificity 96% to 99%) for the exclusion of para-

metrial invasion [5,11,13,15,16,18]. Complete dis-

ruption of the low signal intensity cervical ring

indicates full-thickness stromal involvement. In this

situation, the exclusion of parametrial involvement is

more difficult. When the vaginal fornices are intact,

however, the tumor is likely confined to the cervix. In

addition, MRI estimates the exact tumor size accu-

rately within a range of 0.5 cm [22].

Stage II

In stage II the tumor grows beyond the uterus but

does not infiltrate the pelvic side wall or the lower

third of the vagina. Stage IIa tumors (Fig. 4) are

characterized by infiltration of the upper vagina (less

than two thirds) in the absence of parametrial inva-

sion. Vaginal infiltration is indicated by loss of

normal low signal intensity or hyperintense thicken-

ing of the vagina. The sensitivity of MRI in the

depiction of vaginal invasion is as high as 93% [18].

Parametrial infiltration classifies the tumor as

stage IIb cervical carcinoma (Fig. 5). The infiltration

occurs when the tumor spreads directly from the

endocervix or the exocervix to the upper cervical

canal or lower uterine body. In most cases of para-

metrial involvement, full-thickness stromal invasion

is present. Parametrial invasion can be diagnosed

when the tumor extends directly through the entire

low signal intensity cervical stroma into the para-

metrium. Another confirmatory finding of parametrial

invasion is small tumor extensions beyond the cer-

vical contour. If parametrial spread is subtle, it is

more difficult to diagnose than in cases where a mass

Fig. 4. Sagittal T2-weighted MRI of a cervical carcinoma FIGO stage IIa with tumor extension to the upper third of the vagina.

The dorsal vaginal wall, the dorsal vaginal fornix (black arrow), and the anterior vaginal wall are involved. The dorsal bladder

wall (white arrow), however, presents with normal low signal intensity, a finding that excludes tumor invasion.

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590 581

of similar signal intensity to the cervical tumor is

found. Microscopic parametrial invasion may be

found in cases with broad full-thickness infiltration

of the supravaginal cervix even when no paracervical

tumor is found on MRI. The overall accuracy of MRI

in detecting parametrial invasion is high, ranging

from 86% to 92% [5,11,19].

Stage III

Stage III cervical carcinomas extend to the pelvic

side wall, involve the lower third of the vagina, and

cause hydronephrosis (Fig. 6). Involvement of the

lower third of the vagina, consistent with stage IIIa, is

indicated by the loss of normal hypointensity and

thickening of the vaginal wall in its distal part.

Usually the tumor spread is continuous from the

upper two thirds to the lower third of the vagina.

Pelvic side wall extension (stage IIIb) is con-

firmed when a solid tumor extends to either pelvic

musculature or the iliac vessels. In addition, fine

strands of tissue between the tumor and pelvic

muscles may indicate pelvic side wall invasion, even

in the presence of fat tissue or the complete loss of

parametrial high signal intensity associated with dis-

rupted cervical stroma. Hydronephrosis can be diag-

nosed if the tumor encases the ureter, leading to

dilatation of the ureter and renal pelvis (see Fig. 6).

Stage IV

Invasion of the bladder or the rectum appears in

FIGO stage IV. When the bladder is involved, the low

signal intensity of the normal muscular bladder wall

on T2-weighted images is replaced with higher signal

intensity tumor tissue (Fig. 7). Bullous edema may be

demonstrated by a hyperintense band accompanying

the interior surface of the (frequently disrupted)

bladder wall (see Fig. 7).

Direct infiltration of the rectum is rarely found,

probably because the rectum is separated from the

posterior vaginal fornix by the Douglas pouch. More

frequently, rectal involvement occurs through tumor

spread along the uterosacral ligaments. Rectal inva-

sion can be identified by segmental thickening and

loss of low signal intensity of the anterior rectal wall,

or by prominent strands between the main tumor bulk

and the rectum.

Lymph node evaluation

Cervical carcinoma spreads to the parametrial

lymph nodes (see Fig. 6) first, followed by the

obturator nodes and the internal and external iliac

lymph node chains. Signal intensity is not helpful in

differentiating between benign and malignant nodes.

As with CT, the determination of metastatic infiltra-

tion of lymph nodes by MRI is based on their size.

The size criterion for metastatic lymph nodes is

currently under debate. Most authors use a diameter

of greater than 1 cm as the threshold for metastatic

lymph node involvement and achieve accuracy rates

between 75% and 88% [5,9,16,23]. With a minimal

axial diameter of greater than 1 cm as a sign of lymph

node metastasis, Kim et al [24] reported a sensitivity

of 62% and a specificity of 98% with a resulting

accuracy of 93%. In a study using high-resolution

MRI obtained with a body phased-array coil and a

threshold parameter of greater than or equal to 8 mm

for metastatic nodes, a sensitivity of 89% and a

specificity of 91% were obtained in lymph node as-

Fig. 5. Cervical carcinoma FIGO stage IIb. Sagittal (A) and

axial (B) T2-weighted images. The tumor (star) is protrud-

ing into the vagina and extents into the dorsal vaginal wall

(black arrow). Paravaginal and parametrial invasion on the

left side are apparent on the axial image (white arrow).

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590582

sessment [10]. A comparative meta-analysis between

lymphangiography, CT, and MRI showed MRI to be

slightly better than lymphangiography in detecting

lymph node metastasis, whereas CT and MRI were

not significantly different [25].

Imaging strategies for detection, diagnosis,

and staging

The role of imaging in the diagnostic work-up of

cervical carcinoma is not to prove the presence of a

Fig. 6. Cervical carcinoma FIGO stage IIIb. Axial T2-weighted turbo spin echo (TSE) (A), axial HASTE (B), and coronal T2-

weighted TSE images (C, D). Left side parametrial invasion is evident both on axial T2-weighted TSE and HASTE images

(straight arrow); however, parametrial lymph node metastases on the right side (black arrows) are much better identified on the

high-resolution T2-weighted TSE sequence than on the low-resolution HASTE sequence. Parametrial tumor invasion is encasing

the left ureter (curved arrow), leading to dilatation and hydronephrosis.

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590 583

tumor, which is accomplished by biopsy or exfoliate

cytology, but to define precisely the tumor extent to

select the appropriate course of treatment.

In stage Ia tumors, with a size less than 2 cm, no

further imaging evaluation for diagnosis and staging is

usually necessary, as long as the patient can be

examined sufficiently clinically. When imaging eval-

uation is required, MRI should be the modality of

choice. MRI provides a more comprehensive staging

ability than clinical examination combined with ultra-

sound and has a significantly higher staging accuracy

than CT.

In early stage cervical cancer (FIGO stage I), MRI

may be advocated for obese patients. For bulky FIGO

stage I carcinomas and stage II and greater, MRI is

generally recommended. MRI provides a ‘‘one-stop’’

solution for the diagnosis of parametrial involvement,

pelvic sidewall, bladder and rectum invasion, and

ureteral obstruction and lymph node metastasis. MRI

can replace additional imaging studies, such as intra-

venous pyelography or rectal enema.

MRI: protocol considerations

MRI coils

The use of phased-array coils significantly im-

proves signal-to-noise ratios by a factor of 2 to 3.5

[26], allowing for excellent image quality with a

Fig. 6 (continued ).

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590584

reduction of the field of view to 16 cm and the slice

thickness to 4 mm. With these parameters, the spatial

resolution approaches an in-plane resolution of 0.6

mm2. Early technical problems of phased-array coils,

such as increased motion and ghosting artifacts

caused by very high signal intensity in the near field,

have been almost completely resolved. Very obese

patients or those with protuberance of the abdomen

caused by tumor or ascites, however, may not be

suited for phased-array coil imaging.

Endovaginal and endorectal coil imaging may be

applied to study cervical cancer. It allows for excel-

lent signal-to-noise levels with a reduction of the field

of view to below 10 cm. Endovaginal coil images

provide excellent details of the anatomy of the cervix,

including tumor presence and extent, and the para-

metrial space [27,28]. No study, however, has yet to

provide definitive evidence of the advantages of

endocoils over phased-array surface coils.

Pulse sequences and imaging planes

Heavily T2-weighted high-resolution images are

essential for depicting normal zonal anatomy and

pathologic changes of the uterus and vagina. T2-

weighted turbo spin echo (TSE) or fast spin echo

(FSE) sequences provide anatomic and pathologic

information superior to that provided by conventional

spin echo sequences. TSE sequences allow higher

signal-to-noise ratios and a significant decrease in

imaging time (by a factor of 3 to 4) leading to a

considerable reduction in motion artifacts [29,30].

TSE sequences have fully replaced conventional spin

echo sequences for T2-weighted imaging.

Breath-hold T2-weighted TSE sequences are

rarely used in the pelvis because they do not provide

the necessary resolution and are still susceptible to

motion artifacts. In contrast, single-shot T2-weighted

sequences of the half fourier single-shot turbo spin

echo (HASTE) or single-shot FSE (ss-FSE) type are

very robust against artifacts and even can be used in

free breathing and uncooperative patients [31]. The

HASTE (ss-FSE) technique, however, suffers from

insufficient resolution and T2 contrast to detect even

small lymph node metastases (see Fig. 6).

Short tau inversion recovery (STIR) sequences

provide two general features: (1) robust fat suppres-

sion and (2) positive T1 and T2 contrast. By sup-

pressing the normally intense signal from fat, STIR

sequences greatly increase the ability to identify

structures or lesions that are surrounded by fat, such

as the parametria or lymph nodes. Because of

sequence properties, T1 and T2 contrasts are additive

with STIR imaging, enhancing the contrast between

lesions and low signal fat tissue. Despite these

properties STIR sequences have not yet been shown

to be superior to T2-weighted TSE sequences in

imaging of the uterus [19].

Advances in shim procedures helped to make

spectral fat-saturation techniques available as a robust

technique even in phased-array coil studies. Fat

saturation may be applied to either T2- or T1-

weighted contrast-enhanced sequences. The useful-

ness of both fat-suppressed T2-weighted sequences

for staging and fat-suppressed contrast-enhanced T1-

weighted sequences for the detection of parametrial

involvement, however, did not surpass the diagnostic

value of standard T2-weighted TSE sequences with-

out fat suppression [19,32].

Motion artifact suppression

Suppression of motion artifacts should be per-

formed whenever possible. If special software to

compensate for respiratory motion is available, it

should be used. If it is unavailable, a strap band

over the pelvis is helpful. Pulsation artifacts should

be suppressed by flow compensation techniques.

For the reduction of artifacts caused by bowel

Fig. 7. FIGO stage IVa cervical carcinoma with invasion of

the dorsal bladder wall. Sagittal T2-weighted TSE images

with vaginal opacification using ultrasound jelly. The large

central necrotic (star) tumor is occluding the cervical canal,

leading to fluid retention within the uterine cavity. The

tumor extends to the lower third of the anterior vaginal wall

(white arrow) and invades the urinary bladder (black arrow).

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590 585

peristalsis, administration of butylscopolamine (Bus-

copan) or glucagon is recommended unless medi-

cally contraindicated.

Contrast media

Intraluminal contrast agents

Numerous bowel contrast agents are available or

under investigation to improve delineation of bowel

from abdominal or pelvic organs [33–35]. They

can be divided into positive (eg, Magnevist oral,

Ferriseltz) and negative contrast agents (eg, oral

magnetic particles, Abdoscan, Lumirem, perfluor-

octylbromide). There are no reports in the literature

on the use of intraluminal contrast agents in large

groups of patients with uterine cancer. Rectal filling

might be beneficial in patients with extensive dis-

ease and suspected rectal involvement.

Vaginal filling is helpful in patients with cervical

carcinoma caused by an improved delineation of the

dorsal vaginal fornix [36]. Because of its consistency,

the authors find ultrasound jelly to be very well

suited for vaginal (see Fig. 1) and, if appropriate,

rectal opacification. It is readily available, inexpen-

sive, and easy to handle. Using the standard plastic

bottles and a rectal enema tip, the patient often is

able to apply the jelly into the vagina herself without

any help.

Intravenous contrast agents

The use of intravenous contrast (gadolinium che-

lates) in the evaluation of patients with carcinoma of

the cervix is advocated only in selected cases. Carci-

nomas of the cervix are characterized by inhomoge-

neous perfusion and augmented vascularization of the

tumor periphery. Enhancement of the adjacent cer-

vical stroma is often seen, which decreases the

contrast between tumor and normal tissue. Conse-

quently, as shown in multiple studies, the use of

intravenous contrast does not improve MRI staging.

In particular, the detection of parametrial invasion,

which represents the most important parameter for

treatment planning and prognosis of cervical cancer,

does not improve with the administration of intra-

venous gadolinium [19,37]. The use of contrast

media causes consistent overestimation of tumor size

[37]. Fat-suppression techniques combined with

intravenous contrast were also not beneficial for

staging. One study did show promising results in

staging cervical carcinoma using a dynamic postcon-

trast sequence [38]. These results, however, have not

been confirmed in other series [21].

In patients with more advanced disease, contrast-

enhanced images are a useful adjunct to T2-weighted

images for the identification of invasion of the

rectum, urinary bladder, and pelvic sidewall, and

for the identification of pelvic fistulas [20]. Contrast

administration is also used to identify recurrent or

residual disease in postradiation and postoperative

patients [39].

Suggested MRI protocol

Cervical cancer staging of the abdomen should

be comprehensive. It is recommended that the

MRI protocol include para-aortic lymph nodes and,

although less likely, the search for liver metastasis.

Before the examination starts, patients should be

asked to empty their bladder. Vaginal opacification

with ultrasound gel is helpful for the delineation of

the anterior and posterior vaginal wall and the poste-

rior vaginal fornix. The MRI study starts with the

upper abdomen. The body phased-array coil is posi-

tioned at the level of the liver. The liver and the

abdomen are covered with axial breath-hold T1-

weighted fast low angle shot and T2-weighted

HASTE sequences. Then the patient is asked to move

upward in the scanner, which brings the coil to the

correct position to evaluate the pelvis. The lower

abdomen and pelvis are examined using T2-weighted

FSE sequences in sagittal, axial, and paracoronal

planes of section. To obtain high-resolution images,

these sequences are acquired in a non–breath-hold

technique after intravenous application of an antiper-

istaltic agent (glucagon or Buscopan). Finally, the

examination is completed with MRI urography

(Fig. 8C) using a single thick slab rapid acquisition

with relaxation enhancement (RARE) sequence

(Table 2). Intravenous contrast-enhanced studies are

optional and recommended only in patients with

extensive disease.

Impact of imaging on treatment decision

and planning

The choice of treatment depends on the presence of

Bulky, large tumors with a diameter greater than

4 cm

Parametrial invasion

Invasion to the ureter, bladder, and rectum

Lymph node metastases, in particular above the

level of the true pelvis, and distant metastasis

Surgery is often the treatment of choice in patients

with FIGO stage I tumors less than 3 to 4 cm in size.

The classic surgical approach is the Wertheim-Meigs

operation. It consists of a total abdominal hysterec-

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590586

tomy including the resection of the upper third of the

vagina, the excision of parametrial and paravaginal

tissue including the sacrouterine ligaments, and pel-

vic and para-aortic lymph node dissection. With the

advent of laparoscopic approaches, a number of new

techniques have been introduced.

There is no agreement on the recommended

approach in patients with large stage I tumors and

patients with early parametrial invasion (early FIGO

stage IIb). Several centers prefer to combine chemo-

therapy and radiotherapy, whereas few still perform a

radiohysterectomy. Surgery may have the advantage

of retaining the option of radiotherapy in the event of

tumor recurrence. Recent prospective studies have

revealed no difference in survival rates between

radiotherapy and surgery in these patients [40];

however, morbidity increases significantly when

radiotherapy is combined with surgery. This fact

underlines the importance of preoperative staging

for correct treatment assignment. Because of the

inaccuracy of clinical FIGO staging, preoperative

imaging plays an important role in identifying

patients who will benefit from surgery. In selecting

operative candidates (stage I and minimal stage IIa

tumors), MRI is more accurate than CT (94% versus

76%) [8]. After the inclusion of MRI in the pretreat-

ment work-up of patients with cervical cancer, sig-

nificantly fewer procedures and fewer invasive

studies are performed [1]. Additional studies to

exclude bladder and rectal invasion (eg, barium

enema, cystoscopy, or proctoscopy) are avoided and

significant cost savings are gained [1].

Fig. 8. Cervical cancer recurrence at the left pelvic wall. Axial (A) and coronal (B) T2-weighted TSE images and MRI urography

using a rapid acquisition with relaxation enhancement (RARE) sequence (C). The tumor recurrence (star) approaches the left

pelvic side wall (black arrow). No residual fat plane is left between the tumor recurrence and the pelvic wall. Ultrafast (7 s) thick-

slice (70 mm) MRI urography (C) using a RARE sequence nicely demonstrates the tumor-related encasement and stenosis of the

left distal ureter (white arrow).

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590 587

The impact of MRI on treatment decisions and

costs was examined by Schwartz et al [2] in an

unselected patient population that included patients

with cervical carcinoma. Their study demonstrates

that the use of pelvic MRI may alter treatment,

decrease the number of invasive surgical procedures

performed, and reduce total health care expenditures.

The presence of pelvic or para-aortic lymph node

metastasis excludes surgery in patients with cervical

cancer. CT and MRI perform equally in the assess-

ment of pelvic and para-aortic lymph node metastasis

with an accuracy of 86% to 93% [8,24]. The use of

lymphangiography for lymph node staging is no

longer advocated. The change in the evaluation of

lymph nodes results from the invasive nature of

lymphangiography, not the results that there are no

significant differences in the accuracy between lym-

phangiography, CT, and MRI [25]. In fact, a trend

toward better performance was noticed for MRI than

for lymphangiography or CT [25]. Because CT and

MRI are less invasive than lymphangiography and

also assess local tumor extent, the use of lymphan-

giography for patient selection cannot be justified

anymore and cross-sectional imaging should be con-

sidered the preferred adjunct to clinical evaluation of

invasive cervical cancer.

Recurrent cervical cancer may be found in up to

20% of cases. Therapeutic options include surgery,

radiation therapy, and chemotherapy depending on

the primary tumor therapy and the location and the

extent of tumor recurrence. MRI is well suited for the

diagnosis of cervical cancer recurrence because of its

high soft tissue contrast. Determination of the extent

of recurrence with MRI may offer clinical assistance

in the selection of optimal therapy. MRI is in partic-

ular useful for the differentiation of recurrent cervical

carcinoma from radiation changes [41]. The presence

of completely low signal intensity stroma around the

endocervical canal and normal paracervical tissues

exclude recurrence after radiation therapy with a

negative predictive value of 97% [42]. A distinct

mass of intermediate to high signal intensity on T2-

weighted images is highly suspicious of a recurrent

tumor (positive predictive value 86%). In contrast to

Table 2

Suggested MRI protocol for cervical cancer staging (body phased-array coil, vaginal opacification recommended)

Sequence type Plane of section NEX

SL

(mm)

FOV

(mm) Matrix Comment

Upper abdomen

GRE (FLASH) T1w Transversal 1 8 350 256 Breath-hold, covering the liver and the

upper abdomen

T2w-HASTE (ssFSE) Transversal 1 8 350 512 Breathhold, covering the liver and the

upper abdomen

Lower abdomen and pelvis

T2w-TSE (FSE) Transversal 2 5 350 512 After intravenous application of

Glucagon or Buscopan,

non–breath-hold

T1w-GRE or SE Transversal 1 5–8 350 256 or 512 Either breath-hold GRE (256 matrix,

8 mm SL) or non–breath-hold SE

(512 matrix, 5 mm SL)

T2w-TSE (FSE) Sagittal 2 4 350 512 Non–breath-hold

Optional

T2w-TSE Paracoronal 2 4 400 512 Non–breath-hold, orientated along the

axis of the cervical canal

RARE Coronal 1 80 400 512 Single-shot thick slab breath-hold

MRI-urography

Optional (postgadolinium intravenously)

T1w-GRE or SE Transversal 1 5–8 350 256 or 512 Either breath-hold GRE (256 matrix,

8 mm SL) or non–breath-hold SE

(512 matrix, 5 mm SL)

Abbreviations: FLASH, fast low angle shot; FOV, field of view; GRE, gradient recalled echo; HASTE, half fourier single-shot

turbo spin echo; NEX, number of acquisitions; RARE, rapid acquisition with relaxation enhancement; SE, spin echo; SL, slice

thickness; ss-FSE, single-shot fast spin echo; T1w, T1 weighted; T2w, T2 weighted; TSE, turbo spin echo.

J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590588

recurrent tumor, late fibrosis displays low signal

intensity on T2-weighted images. Within the first

year after therapy, however, early fibrosis, mainly

containing granulation tissue with a high degree of

vascularization, is often present. It may be difficult or

impossible to distinguish early fibrosis from residual

or recurrent tumor, even if intravenous contrast

medium is administered [42,43].

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J. Scheidler, A.F. Heuck / Radiol Clin N Am 40 (2002) 577–590590

Detection and characterization of adnexal masses

Stacey A. Funt, MD, Lucy E. Hann, MD*

Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Department of Radiology, Weill Medical College, Cornell University, 525 East 68th Street, New York, NY 10021, USA

Ultrasound (US) is usually the first imaging study

performed in women with pelvic symptoms and

suspected adnexal mass by physical examination.

Excellent results of US for detection of adnexal

masses have been confirmed in several studies, which

have demonstrated 60% to 97% of ovarian masses

may be visualized sonographically and 93% to 97%

of ovarian masses may be characterized by sono-

graphic morphology and Doppler imaging features

[1–5]. MRI also has proved beneficial in determining

the site of origin for adnexal masses and characteriz-

ing those masses that are indeterminate by sono-

graphic criteria [6–10]. CT is the primary modality

for ovarian tumor staging and diagnosis of recur-

rence. The applications of CT are discussed elsewhere

in this issue. This article focuses on:

� Rationale for imaging in ovarian cancer

detection� Key imaging features of specific malignant

adnexal masses� Ultrasound detection of adnexal masses� Characterization of adnexal masses by mor-

phology and Doppler� MRI for lesion characterization

Ovarian cancer epidemiology and

prognostic factors

Ovarian cancer is the leading cause of death from

gynecologic malignancies. It is diagnosed in approx-

imately 25,000 women annually and there are an

estimated 14,500 deaths each year. Although the

1.4% incidence of ovarian cancer in the general

population is relatively low, in high-risk women with

BRCA genetic mutations, the risk of ovarian cancer is

much higher, estimated at 16% to 65% [11]. Detection

of early stage I ovarian malignancies can have a

significant impact because 5-year survival for stage I

and II tumors is approximately 80% to 90% in contrast

to 5% to 50% 5-year survival for women with stage III

and IV disease. Unfortunately, 80% of women with

ovarian cancer present with advanced-stage disease.

Serum CA-125 is used for diagnosis of ovarian cancer

but it is limited by poor sensitivity for detection of

early stage ovarian cancer because CA-125 is insensi-

tive to germ cell and mucinous tumors and is

expressed in only 50% of stage I ovarian cancers. In

contrast to CA-125, US has been shown to be effective

for detection of stage I ovarian cancers [12–18].

Ovarian cancer screening trials using transvaginal

ultrasound (TVUS) have shown consistently that US

detects more stage I ovarian cancers than CA-125

alone [12–16,18]. Data demonstrating survival bene-

fit are lacking, but results from a study in which TVUS

was used for ovarian cancer screening indicate

decrease in case-specific ovarian cancer mortality with

93% 2-year and 84% 5-year survival in women with

ovarian cancer detected by TVUS [18].

Primary ovarian malignancies are classified by the

site of cell origin, such as surface epithelium, germ

cell, or stromal cell. Approximately 80% to 90% of

primary ovarian cancers are surface epithelial–stromal

tumors of the ovary. These include serous cystadeno-

carcinoma (40% to 50%); mucinous cystadenocarci-

noma (5% to 10%); endometrioid carcinoma (20% to

25%); and clear cell carcinoma (5% to 10%) [19,20].

Brenner tumors also arise from the surface epithelium

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00009 -4

* Corresponding author. Department of Radiology,

Memorial Sloan-Kettering Cancer Center, 1275 York Ave,

New York, NY 10021.

E-mail address: hannl@mskcc.org (L. Hann).

Radiol Clin N Am 40 (2002) 591–608

but are rare and almost always benign [19]. Primary

ovarian surface epithelial-stromal tumors are predom-

inately cystic and multilocular (Fig. 1), with the

exception of some endometrioid cancers and Brenner

tumors that are usually solid [20]. Prognosis is deter-

mined by tumor grade and stage rather than histologic

subtype and differentiation of the various epithelial

malignant neoplasms usually is not possible by imag-

ing. Sex cord stromal tumors derived from the embry-

onic gonad or ovarian stroma account for 1% to 2% of

ovarianmalignancies. These tumors are predominately

solid and may be hormonally active, allowing detec-

tion at an earlier stage and more favorable prognosis.

In particular, granulosa cell tumors have low malig-

nant potential. Malignant germ cell tumors, such as

immature teratoma, dysgerminoma, and endodermal

sinus tumors, represent less than 5% of ovarian malig-

nancies. Germ cell tumors differ from epithelial ovar-

ian cancer in that they occur in young women or

children, and may be cured by limited surgery and

chemotherapy [21,22].

Ultrasound detection of adnexal masses

Transvaginal ultrasound with a 5- to 10-MHz

transducer is the preferred method to detect ovarian

masses and to exclude ovarian pathology by demon-

stration of normal ovaries. Visualization of both

ovaries may require a combination of transvaginal

and transabdominal techniques, however, because the

limited field of view provided by TVUS may not

include the ovaries posthysterectomy or in women

with fibroids, and large masses or masses peripherally

positioned within the pelvis may be missed [23,24].

DiSantis et al [4] reported that only 76% of normal

premenopausal ovaries and 20% of normal postme-

nopausal ovaries were seen when TVUS was used

alone, but other studies have shown better results for

TVUS with one or more ovaries seen in approxi-

mately 80% to 97% of postmenopausal women and

both ovaries seen in 60% to 97% [18,25,26].

Alteration in ovarian size or volume may be an

early indication of ovarian malignancy. The upper

limit of normal ovarian volume for premenopausal

women is 20 cm3 [27] and 8 to 10 cm3 for post-

menopausal women, but ovarian volumes decrease

with age and years since menopause, and ovarian

volumes in women more than 70 years of age are

even smaller, in the range of 1 to 1.8 cm3 [26,28].

Any ovary enlarged for age or ovary exceeding twice

the volume of the contralateral side is considered

suspicious by sonographic criteria [19].

Characterization of adnexal masses by ultrasound

The goals of adnexal mass characterization are (1)

to differentiate benign from malignant disease and (2)

to discriminate between epithelial ovarian carcinoma

and other primary or secondary ovarian malignant

tumors (Table 1). Benign versus malignant differ-

Fig. 1. Cystadenocarcinoma of the ovary. Contrast-enhanced CT scan of the pelvis reveals an enhancing, complex cystic and

solid mass in the left adnexa adjacent to the iliac vessels (arrow) and ascites.

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608592

entiation is essential because women with suspected

ovarian malignancy should be referred to gynecologic

oncologists for adequate primary surgery and staging,

whereas women with presumed benign ovarian

masses may be treated with less invasive surgery by

general gynecologists.

Morphology

Although both benign and malignant ovarian

masses are often cystic, there are important differ-

entiating features. US features of benignity include

simple cyst, thin wall, and septations less than 3 mm.

Hyperechoic regions, as may be seen in benign cystic

teratoma, and uniform low-level echoes, as seen in

endometriomas (Fig. 2A) or hemorrhagic cysts, are

also considered benign (Fig. 2B) [1,29,30]. Reported

accuracy of US morphology for prediction of benig-

nity is approximately 95% [30,31].

Ovarian masses with mural thickening, septations

greater than 3 mm, nodularity, and papillary projec-

tions are suggestive of malignancy and solid compo-

nent within an ovarian mass is reported to be the

most statistically significant predictor of malignancy

(Figs. 3, 4) [1]. Because some benign lesions, such as

endometriomas and hemorrhagic cysts, may have

similar appearance to malignant ovarian tumors, the

reported accuracy of 50% to 94% for prediction of

malignancy by morphology is slightly lower than for

benign disease [1,3,32–34]. To avoid unnecessary

surgery, it is essential that any premenopausal woman

with an abnormal ovary by TVUS have a follow-up

sonogram in 6 weeks or after the next menses to

exclude transient physiologic cysts (Fig. 5).

Some investigators have developed a morphologic

scoring system to standardize diagnosis of ovarian

abnormalities. The scoring system or morphologic

index assigns numerical scores for various US fea-

tures, such as size, wall thickness, solid components,

and number and thickness of septations [1,14,34,35].

Excellent interobserver variability is reported with

use of the morphologic index [14], but Timmerman

et al [36] found similar interobserver variability

(Cohen’s kappa 0.85) when readers used subjective

assessment of ovarian morphology.

It is not possible to differentiate histologic subtypes

of primary ovarian tumors by morphology, but there

are some features that should be considered. Epithelial

ovarian tumors are typically cystic, but endometrioid

tumors and Brenner tumors may be solid (Fig. 6A).

Table 1

Sonographic morphology of adnexal masses

Simple cyst Complex cyst Solid

Benign Benign Benign

Simple ovarian cysts Cysts with low-level echoes Pedunculated fibroid

Follicular cyst Endometrioma Torsion

Corpus luteal cyst Hemorrhagic cyst Brenner tumora

Hydrosalpinx Cystadenoma Fibroma/thecoma

Cystadenoma Cysts with hyperechoic components Nongynecologic

Nongynecologic cysts Cystic teratoma Lymphadenopathy

Cysts of gastrointestinal origin Cysts with solid components/septations Gastrointestinal tumor

Bladder diverticulum Turbo-ovarian abscess Bladder tumor

Fibrothecoma Malignant

Cystadenoma Germ cell tumors

Cystic teratoma Endometrioid carcinoma

Peritoneal inclusion cyst Granulosa cell

Nongynecologic Metastases to ovary

Abscess

Hematoma

Lymphocele

Malignant

Mucinous cystadenocarcinoma

Serous cystadenocarcinoma

Clear cell carcinoma

Endometrioid carcinoma

Granulosa cell

Cystic teratocarcinoma

Metastases to ovary

a Uncommonly may be malignant.

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608 593

Mucinous cystadenocarcinomas are more septated

than serous cystadenocarcinomas and may have fluid

with low-level echoes. Malignant germ cell tumors are

predominately solid as are stromal tumors (Fig. 6B).

Metastases to the ovary have a variable appear-

ance and are most frequent from breast cancer, colon

cancer, gastric cancer, and lymphoma [37]. In a study

that compared morphology of 24 secondary ovarian

Fig. 2. Benign endometrioma. (A) Simple cyst (short arrow) and a complex cyst (curved arrow) that has uniform low-level

echoes consistent with benign hemorrhagic cyst or endometrioma. (See also color Fig. 2B, page 598).

Fig. 3. Primary clear cell carcinoma of the ovary in a woman with a history of breast carcinoma. Transverse sonogram reveals a

cystic ovarian mass with thick irregular internal solid component (arrow).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608594

neoplasms with 86 primary ovarian cancers, multi-

locularity was more frequently associated with pri-

mary ovarian malignancy [37]. The issue of primary

versus secondary ovarian neoplasm is particularly

relevant in women with breast cancer who have

increased risk of primary ovarian cancer secondary

to BRCA mutations [11]. Ovarian metastases from

breast cancer are reported to be predominately solid

and occur more often in women with documented

stage IV breast cancer (Fig. 7) [38]. Bilaterality is not

useful for discrimination of primary from secondary

ovarian tumors. An estimated 59% to 75% of ovarian

metastases are bilateral and primary ovarian carcino-

mas also are frequently bilateral as seen in 50% of

serous cystadenocarcinomas, 30% of endometrioid

carcinomas, 20% of clear cell tumors, and 15% to

20% of mucinous cystadenocarcinomas [19,20,37].

Doppler imaging techniques

Doppler imaging techniques aid characterization of

adnexal masses by providing information regarding

vascular compliance, vessel density, and distribution

of vessels within the mass. Tumor neovascularity has

vessels that lack muscular layers and typically have

low resistance flow patterns with high diastolic flow

relative to systolic flow. Pulsed Doppler techniques

allow sampling of blood flowwithin vessels, and ratios

of diastolic flow relative to systolic flow may be cal-

culated as measures of vascular resistance. Resistive

index (RI) is peak systolic velocity minus end-diastolic

velocity divided by peak systolic velocity, and value

less than 0.4 is considered abnormal. Pulsatility index

(PI) is peak systolic velocity minus end-diastolic

velocity divided by mean velocity, and any value be-

low 1 is abnormal. Multiple samples are taken within

the ovary and the lowest values are selected.

Initial reports using pulsed Doppler showed high

sensitivity and specificity for detection of ovarian

cancers, but subsequent studies have shown consid-

erable overlap of RI and PI ratios in benign and

malignant masses [2,19,30,39–41]. Whereas RI and

PI tend to be lower in malignant ovarian tumors,

these indices cannot reliably differentiate benign from

malignant masses because some benign tumors,

inflammatory conditions, and the normal corpus

luteum may have flow patterns similar to those found

in ovarian malignancies [2,42]. For this reason,

pulsed Doppler cannot be used as an independent

indicator of malignancy, but it may provide supple-

mental information that is useful in benign versus

malignant differentiation. For example, benign con-

Fig. 4. Metastatic colon carcinoma to ovary. Transverse ultrasound image of the right ovary reveals a cystic mass with multiple

thick septations (arrows).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608 595

ditions should be considered in the differential diag-

nosis if a morphologically complex mass has Doppler

indices that are entirely normal.

Location of blood flow within an adnexal mass is

displayed best by power Doppler that is angle-inde-

pendent and sensitive to low-amplitude flow. Vessels

within tumors are located centrally, in irregular areas

of mural thickening and within papillary projections

compared with benign masses that typically have

peripheral vessel distribution with regular branching

pattern (Fig. 8) [3,42]. Most malignant ovarian

masses have internal vascularity on color or power

Doppler imaging, although rarely flow may be absent

(see Figs. 2B, 6B) [2,3]. It has been suggested that

detection of vascularity within malignant tumors may

be related to the size of tumor vegetations with

decreased detection of internal flow if papillary

projections are smaller than 1 cm (Fig. 9) [3]. The

Fig. 5. Hemorrhagic cyst appears suspicious for malignancy, but resolves on follow-up. (A) Right ovarian cystic mass has

irregular solid components (straight arrow) and free fluid is noted (curved arrow). Asterisk = uterus. (B) Follow-up sonogram 6

weeks later reveals a normal ovary (arrow) with follicles.

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608596

role of three-dimensional US with power Doppler for

improved diagnosis of ovarian masses is yet to be

determined [43].

Comparison of morphology and Doppler for

differentiation of benign from malignant

ovarian masses

Current evidence is that the combination of ovar-

ian morphology and Doppler perform best for char-

acterization of adnexal masses. In a prospective

study, Buy et al [3] used gray-scale US, duplex

Doppler, and color Doppler to evaluate 132 adnexal

masses including 98 benign, 3 borderline, and 31

malignant masses. Adding color Doppler to gray-

scale morphologic information increased specificity

from 82% to 97% and increased positive predictive

value from 63% to 97% but there was no added

information from duplex Doppler indices.

In a study of 211 adnexal masses including 28

malignancies Brown et al [1] used stepwise logistic

regression to determine the best discrimination

between benignity and malignancy by gray-scale

US and Doppler. A nonhyperechoic solid component

within a mass, central blood flow on color Doppler

imaging, free intraperitoneal fluid, and septations

Fig. 6. Papillary serous and endometrioid carcinoma in a postmenopausal woman. (A) Sagittal sonogram reveals an enlarged

lobulated ovary (short arrows) with heterogeneous architecture and small cystic regions (curved arrow). (See also color Fig. 6B,

page 598.)

Fig. 7. Bilateral ovarian metastasis from breast carcinoma. Contrast-enhanced CT scan of the pelvis reveals bilateral solid

adnexal masses and a small amount of fluid in the cul-de-sac (arrows).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608 597

within a mass proved to be the best predictors of

malignancy with 93% sensitivity and 93% specificity.

A recent meta-analysis of 89 data sets and 5159

patients using current US technique compared results

of morphologic assessment, Doppler US, color Dop-

pler flow imaging, and combined techniques for

characterization of adnexal masses [44]. Summary

receiver-operator curves showed that the point where

sensitivity and specificity are equal was highest for

combined techniques (0.92), followed in decreasing

order by morphologic assessment alone (0.85); Dop-

pler indices (0.82); and color Doppler flow (0.73).

MRI characterization of ovarian masses

Ultrasound remains the primary modality for

evaluation of adnexal masses, but lesions that are

indeterminate, poorly visualized, or inadequately

localized warrant further characterization (Table 2)

Fig. 2. (B) Power Doppler image reveals vessel (arrow) within the thin septation, but no internal vascularity. Resistive index and

pulsatility index were normal.

Fig. 6. (B) Power Doppler image shows internal hypervascularity consistent with malignancy (arrows).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608598

[45]. The additional benefit of MRI for character-

ization of ovarian masses in selected patients has

been well documented [6,7,10,46,47]. Because most

women with adnexal masses have benign ovarian

histopathology, specific diagnosis of benign adnexal

masses may obviate the need for surgery and change

clinical management [6]. A prospective study of 103

women with adnexal masses found that MRI had

sensitivity and specificity of 96% and 100% for

diagnosis of pedunculated leiomyomas, 100% and

99% for dermoid cyst, and 92% and 91% for endo-

metriomas [7]. Although MRI is expensive, it may

prove cost effective when improved diagnosis

reduces the need for surgical intervention or other

imaging evaluation [6,7,48]. In a study of women

with a variety of gynecologic diseases, including

adnexal masses, pelvic MRI was shown to alter

treatment in up to 73% of patients, decrease the

number of invasive surgeries, and reduce overall

expenditures for care [49].

MRI protocol

There is varying uniformity among pelvic MRI

protocols because of the lack of evidence-based cri-

teria. Generally accepted sequences to evaluate the

ovaries include axial T1, axial T2, and sagittal T2-

weighted images (coronal T2-weighted images are

optional). The administration of gadolinium has been

shown to increase characterization and detection of

malignant masses [33,47] and fat saturation is docu-

mented to differentiate blood from fat in lesions high

in signal intensity on T1-weighted sequences [50]. A

pelvic phased array coil or body coil is typically used

to increase signal-to-noise ratio and glucagon may be

administered intramuscularly to decrease motion arti-

fact from adjacent bowel.

MRI criteria for differentiation of benign from

malignant ovarian masses

Characterization of lesions as benign or malignant

on MRI is improved with the use of gadolinium

[10,51]. Diagnostic accuracy for malignancy in the

range of 87% to 99% is achieved by demonstration of

solid, enhancing tissue on MRI with gadolinium

[33,46,47,51,52]. Komatsu et al [46] found that the

single criteria of enhancing solid tissue was 91%

sensitive and 88% specific for differentiation of

benign from malignant adnexal masses. In a study

of 91 benign and 96 malignant adnexal masses,

gadolinium-enhanced MRI depicted 94% of adnexal

masses and had an overall accuracy of 93% for

diagnosis of malignancy [51]. The MRI features most

predictive of malignancy were necrosis in a solid

lesion and vegetations in a cystic lesion [51].

Other significant findings suggesting malignancy

include papillary projections, septa greater than 3 mm

in thickness, and solid components within a mass

[10,53,54]. In a study of 115 ovarian masses, the

Fig. 8. Metastatic colon cancer. Transverse power Doppler image of the ovary reveals internal vascularity (open arrows)

localized to the nodular solid component of the mass (solid arrow).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608 599

most significant findings for malignancy based on a

logistic regression analysis were wall structure, inter-

nal architecture, and massive ascites [9]. These data

were then used to generate a computer-assisted model

to distinguish benign from malignant adnexal masses,

and when applied to 75 new cases, the model had an

accuracy of 87% [9]. In a prospective study of 60

adnexal masses, Stevens et al [54] suggested five

primary criteria for malignancy (size > 4 cm, solid

mass or large solid component, wall thickening >3

mm, septa >3 mm, and vegetation and nodularity and

necrosis) and four ancillary criteria (involvement of

pelvic organs and sidewall; peritoneal, mesenteric, or

omental disease; ascites; and adenopathy). A lesion

was considered malignant on contrast-enhanced MRI

if there were one or more primary criteria and a single

ancillary criterion. Three masses were not detected by

MRI. For the remaining 57 masses, a correct diag-

nosis was made in 23 (100%) of 23 malignant masses

and in 30 (88%) of 34 benign masses.

Benign-appearing lesions by MRI

Simple cystic lesions

Lesions that have a homogeneous, low signal

intensity on T1-weighted images and high signal

intensity on T2-weighted images are simple, fluid-

filled structures and are considered benign (Fig. 10).

These are most commonly physiologic cysts, such as

follicular cysts that occur because of failure of

ovulation. These thin-walled cysts may rarely have

mural enhancement or higher signal intensity on T1-

weighted images because of proteinaceous material

within the cyst [55]. The corpus luteal cyst, formed

after ovulation, is often larger and may have irregular

walls. These cysts may hemorrhage with resulting

high signal on T1-weighted images, indistinguishable

from endometriomas [51,56].

Location of cysts by MRI or US may provide

information regarding the benign nature of an adnexal

abnormality. Peripheral cysts in a young woman sug-

gest polycystic ovaries or an ovary within a cyst may

indicate benign peritoneal inclusion cyst [57,58].

Peritoneal inclusion cysts are usually seen in preme-

nopausal women with a history of prior pelvic or

abdominal surgery. Failure of peritoneal resorption of

ovarian exudate and peritoneal adhesions cause fluid

to collect around the ovary. Although these benign

cysts may be complex with septations, the cysts

usually conform to the shape of the pelvis and

identification of the normal ovary within the fluid

collection allows correct differentiation from ovarian

Fig. 9. Borderline serous carcinoma. Longitudinal ultrasound image of the left ovary reveals a cystic mass with fine mural

nodularity (arrows).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608600

malignancies (Fig. 11). Peritoneal inclusion cysts can

be differentiated from paraovarian cysts that are lo-

cated in the broad ligament and are separate from the

ovary [58].

Morphology of a cyst may also provide specific

diagnosis. A hydrosalpinx often appears serpiginous

in structure or has ‘‘cog-wheeling’’ on T2-weighted

images. Nongynecologic cysts in the adnexal region

include duplication cysts or an appendiceal mucocele,

although these may appear brighter on T1-weighted

images because of proteinaceous material. Serous

cystadenomas may be indistinguishable from simple

cysts or they may have thin septations and occasion-

ally papillary projections [56,59]. Mucinous cystade-

nomas more often have multiple septations and may

appear brighter on T1-weighted images because of

mucinous material [60].

High T1 signal intensity

Lesions with high signal intensity on T1-weighted

images usually contain blood products (hemorrhagic

cysts, endometriomas, or hematoma) or fat (mature

cystic teratoma) (Fig. 12). MRI with fat saturation has

proved to be extremely specific, sensitive, and accu-

rate in differentiating blood from fat-containing

lesions [50,53]. Following fat saturation, a fat-con-

taining mass loses signal, whereas a hemorrhagic

mass remains bright and even has an exaggerated

signal (Fig. 13). This apparent increase in signal is

caused by a narrowed dynamic range on fat saturation

that increases conspicuity [61]. Lesions containing fat

or blood may appear heterogeneous on T2-weighted

images because of chronicity and concentration of

blood products within the hemorrhage or the mixture

of fat, fluid, and the Rokitansky protuberance within

the dermoid [62].

Diagnostic features of mature cystic teratoma

include fat or coarse calcification on CT or loss

of T1-weighted bright signal on MRI when fat

saturation is applied [63]. Chemical shift artifact

on MRI also suggests the presence of fat. This

Fig. 10. Simple cyst. (A) T1-weighted axial image of the

pelvis (TR= 500, TE= 8) shows a homogeneous, low signal

lesion in the right ovary (arrow). (B) T2-weighted axial

image (TR= 6666, TE= 98) shows a homogeneous high

signal lesion in the right ovary (arrow).

Table 2

MRI signal characteristics of adnexal massesa

Low T1, High T2

Functional cysts

Peritoneal inclusion cysts

Cystadenomas

Hydrosalpinx

High T1

Dermoid

Endometrioma

Hemorrhagic cyst

Proteinaceous material

Low T1, Low T2

Leiomyoma

Fibroma or thecoma

Heterogenous signal

Many of the above secondary to hemorrhage, fluid,

septations, or degeneration

Malignancies (enhancing nodule, thick septation, or

papillary projection)

Tubo-ovarian abscess

Ovarian torsion

Ruptured ectopic pregnancy

a Listed are the most characteristic or common MRI

signal intensities for adnexal masses yet many of these

lesions may have varying appearances.

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608 601

artifact is seen on T2-weighted images as signal

reduction on one side of the mass and signal loss

on the other. Chemical shift artifact may not be

seen in all cases and is usually confirmed with fat

saturation [64].

Endometriomas cannot be differentiated adequate-

ly from hemorrhagic cysts, although multiplicity and

thick fibrous walls with adhesions to adjacent struc-

tures are more suggestive of endometriosis [59,65].

Shading, the loss of signal of T2-weighted images,

Fig. 11. Peritoneal inclusion cyst. Normal right ovary (curved arrow) with follicles (straight arrows) is contained within a

peritoneal inclusion cyst in a woman with history of prior abdominal surgery.

Fig. 12. Endometrioma. T1-weighted fat saturated axial image (TR= 500, TE= 8) shows persistent high signal intensity within

the lesion, consistent with blood (arrows).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608602

which represents a chronic hemorrhagic process,

hematocrit levels, and multilocularity have been used

to describe endometriomas but also may be seen with

hemorrhagic cysts [62,64,66,67].

Solid lesions

An adnexal mass that is low in signal intensity on

T1- and T2-weighted images is most likely a pedun-

culated leiomyoma [8,68]. This diagnosis can be

stated with near certainty when a stalk is seen con-

necting to the uterus or two normal ovaries are

identified. Leiomyomas may be heterogeneous on

T2-weighted images because of hyaline, myxoma-

tous, or fatty degeneration. Calcification may present

as areas of very low signal on T1- and T2-weighted

images. Contrast is not essential for evaluation but

when present, fibroids enhance. MRI cannot exclude

the rare case of malignant degeneration but other

signs, such as a rapidly enlarging fibroid or invasion

of adjacent structures, may suggest malignancy.

Ovarian fibromas also present with low signal

intensity on T1- and T2-weighted sequences, but on

T1-weighted images, fibromas often have lower sig-

nal intensity than leiomyomas (Fig. 14) [69–71]. A

variety of signal intensities may be seen on T2-

weighted images because of edema and cystic degen-

eration encountered mainly in larger lesions [71,72].

Brenner tumors, which are usually benign, may be

solid, cystic, or mixed. When solid, they can have

low signal intensities on T1- and T2-weighted

images. Amorphous calcifications, best seen on CT,

are commonly present in the solid portions of the

mass. Approximately 30% of Brenner tumors are

associated with a second neoplasm, such as a cystic

teratoma or a cystadenoma [73].

Heterogeneous signal intensities

Most of the lesions mentioned may appear heter-

ogeneous because of hemorrhage, fluid, septations,

necrosis, or degeneration. Some of these masses may

mimic malignancy warranting surgery or short-term

follow-up. Also included in the differential diagnosis

of heterogeneous adnexal masses are tubo-ovarian

abscesses, ovarian torsion, and ruptured ectopic preg-

nancy, but these conditions usually have specific

clinical or laboratory findings and are not typically

diagnosed by MRI. Tubo-ovarian abscesses are typ-

ically thick walled with central fluid. Hemorrhage,

surrounding edema, and engulfment of the ovary may

occasionally add to their complex appearance. Ovar-

ian torsion is typically seen with an associated ovar-

ian mass, yet may occur in a normal ovary. Edema,

hemorrhage, or an underlying mass create a hetero-

geneous appearance on MRI. Kimura et al [74]

described three findings of a torsed ovary with a

mass: (1) engorged blood vessels on the side of

torsion with a protrusion of the lesion toward the

uterus, (2) lack of enhancement, and (3) straight

blood vessels draped around the lesion. A ruptured

ectopic pregnancy is usually associated with hemor-

rhage that may become organized in a chronic setting

with surrounding inflammation [57,64]. Nongyneco-

logic masses, such as diverticular and appendicular

abscesses, may appear as adnexal lesions and mimic

ovarian abnormalities [75].

Fig. 13. Bilateral dermoids. (A) T1-weighted axial image

(TR = 500, TE = 8) shows bilateral heterogeneous high

signal adnexal masses (arrows). (B) T1-weighted fat

saturated axial image (TR= 500, TE= 8) shows a loss of

signal from both lesions (arrows). A small region of high

signal drops from the left dermoid (arrowheads).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608 603

Malignant-appearing lesions

A mass containing single or multiple solid,

enhancing nodules, papillary projections, or thick-

ened septations is suspicious for malignancy (Fig. 15)

[53]. MRI is superior to CT for diagnosis of malig-

nant ovarian masses and MRI has been shown to

increase specificity for diagnosis of malignancy in

adnexal masses considered suspicious by TVUS

[33,46,47,52,76,77]. MRI has also been used to

distinguish benign from borderline or malignant

lesions, yet it cannot histologically differentiate spe-

cific surface epithelial, germ cell, stromal cell, or

metastatic tumors. Outwater et al [78] reported that

papillary projections are distinctive of epithelial ovar-

ian neoplasms. A review of 15 cases suggested that

borderline tumors typically have profuse papillary

projections, whereas invasive tumors are more often

dominated by solid components with fewer projec-

tions [78]. It is generally accepted, however, that

borderline and malignant tumors cannot be differ-

entiated and are grouped together under the heading

of malignancy.

Serous and mucinous cystadenocarcinomas are

difficult to distinguish, although mucinous tumors

tend to be larger in size, more often unilateral, multi-

loculated, and may have slightly hyperintense signal

within a locule on T1-weighted images because of the

high protein concentration in mucoid material [60].

When an ovarian mass is seen in conjunction with

pelvic and abdominal gelatinous implants (high signal

intensity on T2-weighted images), pseudomyxoma

peritonei with a mucinous cystadenocarcinoma or a

mucinous appendiceal lesion is suspected. Serous and

mucinous fluids, however, cannot reliably be distin-

guished on MRI. Endometrioid carcinoma is consid-

ered when a nodule is seen within a predominantly

cystic endometrioma or there is a synchronous endo-

metrial carcinoma [79,80].

Granulosa cell tumors, the most common stromal

cell malignancy, are typically seen in postmenopausal

women and are often estrogen producing, which may

lead to uterine enlargement, endometrial hyperplasia,

and endometrial carcinoma. Granulosa cell tumors

may be hemorrhagic and solid or cystic. When cystic,

multiple small components in a characteristic sponge-

like appearance are characteristic [81,82]. Dysgermi-

noma, a germ cell tumor, is seen in younger women

and is the counterpart to the male seminoma. Mark-

edly enhancing fibrovascular septae with flow void in

vessels may suggest the diagnosis but this finding is

not pathognomonic [83].

Metastatic disease to the ovary is difficult to

differentiate from a primary ovarian malignancy, yet

surgical treatment and chemotherapy may vary

greatly. Kim et al [84] compared primary ovarian

lesions with metastases to ovary and found metasta-

ses to the ovary were more commonly bilateral,

maintained the oval shape of the ovary, and contained

well-demarcated intratumoral cysts with strongly

enhancing walls. Ha et al [85] found 14 of 21

metastases to ovary were solid and that identification

of hypointense solid components within an ovarian

mass on T2-weighted MRI was suggestive of meta-

Fig. 14. Fibroma. (A) T1-weighted axial image (TR= 400,

TE= 9) reveals a low signal intensity mass within the right

ovary (arrow). (B) The mass (white arrow) remains low in

signal intensity on the T2-weighted axial images

(TR= 5000, TE= 96). There is high signal consistent with

fluid in the cul-de-sac (black arrow).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608604

stases. In a study of adnexal masses in women with

breast carcinoma, breast metastases to the ovaries

were more commonly bilateral and solid in compar-

ison with primary ovarian masses that appeared cystic

[38]. Brown et al [37], however, reviewed 110

ovarian primary and metastatic neoplasms and found

only multilocularity was a significant distinguishing

factor on both MRI and US. There is limited ability

accurately to distinguish these lesions.

Summary

The main challenge to the radiologist is to differ-

entiate benign from malignant adnexal masses. Both

US and MRI perform well for prediction of benig-

nity. There is less specificity for diagnosis of malig-

nancy but features, such as papillary projections,

thickened septations, and internal vascularity within

nodules, aid in this differentiation. The combination

of morphology and Doppler characteristics provide

the most accurate US diagnosis. For sonographi-

cally indeterminate masses, MRI is useful for addi-

tional lesion characterization. Analysis of T1- and

T2-weighted signal intensities for benign-appearing

lesions with the addition of fat saturation for high

signal on T1-weighted sequences may lead to an

exact diagnosis or a narrow differential. For cases

considered suspicious by TVUS, more specific diag-

nosis by MRI may obviate the need for surgery or

otherwise change management by identification of

benign etiology.

Fig. 15. Cystadenocarcinoma. (A) T1-weighted axial image status post-gadolinium administration (TR= 170, TE= 4.2)

demonstrates a complex, irregular, enhancing mass in the pelvis (arrow). (B) T2-weighted axial image (TR= 5000, TE= 96)

demonstrates a heterogeneous cystic and solid pelvic mass (arrow).

S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608 605

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S.A. Funt, L.E. Hann / Radiol Clin N Am 40 (2002) 591–608608

Staging ovarian cancer: role of imaging

Fergus V. Coakley, MD

Abdominal Imaging, Department of Radiology, University of California San Francisco, Box 0628, L-308,

505 Parnassus Avenue, San Francisco, CA 94143, USA

Ovarian cancer is the commonest cause of death

from gynecologic malignancy, and is the fifth com-

monest cause of cancer deaths in women [1]. The

lifetime risk of ovarian cancer in women is 1.5%, and

the overall mortality is approximately 60%. As with

other tumors, it is important to distinguish the sepa-

rate radiological roles of detection, characterization,

and staging, although in practice these are often

combined. Ultrasound is the primary modality used

for the detection and characterization of adnexal

masses, and these issues are discussed in a separate

chapter. CT is the primary modality used for staging

of ovarian cancer, and CT is the main modality

discussed in this chapter. MRI is useful in the

characterization of ovarian masses and for the eluci-

dation of certain equivocal CT findings, and these

applications are also described. The role of imaging

in the staging of ovarian cancer is reviewed under the

following headings:

� Radiologically relevant pathology� Staging and management� Typical CT findings� Atypical CT findings� Clinical role of imaging in ovarian cancer

Radiologically relevant pathology

The pathology of ovarian cancers is complex, but

only a few basic concepts are essential for the

practicing radiologist. The germinal epithelium is

the single layer of columnar cells that line the ovary.

Approximately 90% of ovarian cancers are of epi-

thelial origin [2–4]. Epithelial cancers are graded as

well (10%), moderately (25%), or poorly (65%)

differentiated. More differentiated tumors have a

better prognosis. Epithelial tumors are subtyped as

serous (50%), mucinous (20%), endometrioid (20%),

clear cell (10%), or undifferentiated (1%). The cur-

rent consensus is that histologic subtype is not of

independent prognostic significance, allowing for

tumor grade and stage, and should not affect treat-

ment planning [2]. Clear cell cancer is a possible

exception, and may have a worse prognosis inde-

pendent of other factors. Epithelial cancers are typi-

cally cystic and have a propensity to spread within

the peritoneal cavity. Non-epithelial cancers include

malignant granulosa cell tumor, dysgerminoma,

immature teratoma, endodermal sinus tumor, and

metastases to the ovary.

Staging and management

Ovarian cancer is staged surgically, based on the

International Federation of Obstetrics and Gynecol-

ogy (FIGO) system introduced in 1964 and most

recently revised in 1985 [5]. The FIGO system

reflects the three primary mechanisms of spread of

ovarian cancer, i.e., local, peritoneal, and lymphatic

[6]. The FIGO staging system is summarized in

Table 1. Stage I ovarian cancer refers to tumor

confined to the ovaries. Stage II consists of ovarian

cancer with peritoneal metastases confined to the true

pelvis. Stage III consists of ovarian cancer with

extrapelvic peritoneal metastases or abdominopelvic

nodal metastases. Stage IV consists of ovarian cancer

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00012 -4

E-mail address: Fergus.Coakley@radiology.ucsf.edu

(F.V. Coakley).

Radiol Clin N Am 40 (2002) 609–636

with metastases outside of the abdomen and pelvis.

The distinction of stage III and IV disease contributes

to treatment planning and prognosis, and there are

two important related issues in imaging. First, the

commonest finding to result in the assignment of

stage IV disease at presentation is a malignant pleural

effusion. However, the radiological detection of an

effusion is not of itself sufficient to constitute stage

Table 1

FIGO staging system for ovarian cancer

Stage

Approximate

percentage at diagnosis Description

5 year

survival [2]

I 25% Grossly confined to one or both ovaries. 80%

IA: Intracapsular and unilateral

IB: Intracapsular and bilateral

IC: Actual or potential microscopic peritoneal contaminationa

II 25% Local extension; grossly confined to the true pelvis 60%

IIA: Involvement of Fallopian tubes or uterus

IIB: Involvement of other pelvic tissues, eg, sigmoid,

pelvic implants

IIC: Actual or potential microscopic peritoneal contaminationa

III 25% Nodal metastases, or peritoneal implants outside the pelvis. 20%

IIIA: Microscopic abdominal implants

IIIB: < 2 cm abdominal implants

IIIC: > 2 cm abdominal implants or positive nodes

IV 25% Distant spread, for example malignant pleural effusion,

intrahepatic metastases

10%

a Based on the presence of surface tumor, tumor rupture, ascites containing malignant cells, or positive washings.

Fig. 1. Axial contrast-enhanced CT section of the chest in a 56-year-old woman with epithelial ovarian cancer. A right pleural

effusion can be confidently characterized as malignant, because of co-existent pleural metastases (arrows). A pleural effusion is

an indication of stage IV disease only if the effusion is proven to be malignant.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636610

IV disease; the effusion must be demonstrated to be

malignant. CT rarely contributes to the determination

of whether an effusion is benign or malignant, except

when pleural thickening or nodules are identified

(Fig. 1). Another similarly important distinction is

the differentiation of liver surface implants (perito-

neal spread; stage III) from true intraparenchymal

metastases (hematogenous spread; stage IV). Surface

Fig. 2. Axial contrast-enhanced CT sections in two different patients with ovarian cancer, illustrating the differences between

perihepatic (A) and intrahepatic (B) metastases. Perihepatic metastases are surface peritoneal implants and are a feature of stage

III disease. Intrahepatic metastases are hematogenous intraparenchymal deposits and indicate stage IV disease.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 611

implants are usually well defined, biconvex, and

peripheral, and indent the liver rather than replace

liver parenchyma. True intraparenchymal implants

are often ill-defined, circular, and partially or com-

pletely surrounded by liver tissue (Fig. 2).

The management of ovarian cancer is closely

related to stage. The standard of care for suspected

early ovarian cancer is a comprehensive staging

laparotomy [7]. The established elements of a com-

prehensive staging laparotomy, based on the known

patterns of disease spread, are total abdominal hys-

terectomy (TAH), bilateral salpingo-oophorectomy

(BSO), infracolic omentectomy, random sampling

of multiple peritoneal sites (including pelvic side

walls, paracolic gutters, cul-de-sac, and surface of

bladder, rectum, and diaphragm), and pelvic and

para-aortic lymphadenectomy. Inspection and palpa-

tion are also performed, but in isolation are inad-

equate for the detection of peritoneal or nodal

metastases. The standard of care for operable

advanced ovarian cancer is primary optimal surgical

cytoreduction (ie, debulking) followed by adjuvant

combination chemotherapy with a platinum com-

pound and paclitaxel [7]. Optimal debulking refers

to the reduction of all tumor sites to a maximal

diameter of less than 1 to 2 cm. The 1 to 2 cm

threshold has been established empirically. Cytore-

duction with residual tumor over 1 to 2 cm confers no

benefit, while more aggressive cytoreduction to less

than 1 cm has no incremental benefit. Optimal cyto-

reduction improves survival, and probably improves

quality of life. Debulking is believed to act by remov-

ing hypovascular tumor which would receive inad-

equate chemotherapy, by increasing the number of

actively proliferating cells which are highly chemo-

sensitive, and by reducing the number of cancer cells

from which chemoresistant clones might develop.

Typical CT findings

Primary tumor

The majority of malignant epithelial tumors

appear as cystic masses lateral to the uterus. Because

of the mobility of the ovary, ovarian masses may also

be seen in the midline above the bladder or anterior to

Fig. 3. Axial contrast-enhanced CT section in a 56-year-old woman with stage I well-differentiated mucinous adenocarcinoma of

the right ovary. The large right cystic adnexal mass demonstrates the characteristic imaging features of malignancy in a cystic

lesion; the presence of thick septa (white arrow) and solid components (black arrow).

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636612

Fig. 4. Fifty-four-year-old woman with stage II poorly differentiated papillary serous carcinoma of the left ovary. Axial

T2-weighted MR image (A) shows large predominantly solid adnexal masses (asterisks) is inseparable from the sigmoid colon

(arrow). Sagittal T2-weighted MR image (B) confirms the sigmoid colon (arrow) is encased and compressed by tumor (asterisks).

At surgery, the sigmoid colon was extensively involved by tumor, and a sigmoid resection was required.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 613

the rectum [8]. Ovarian cancer is frequently bilateral,

and it is thought that in about half these cases the

contralateral tumor represents a synchronous second

malignancy (multicentric origin) while in the remain-

ing cases contralateral involvement is due to meta-

static spread from the primary tumor in the other

ovary [4]. Cystic adenocarcinomas are usually over

4 cm in diameter, and may be very large. Features

that suggest malignancy in a cyst are thick (>3 mm)

walls or septa, nodules, vegetations, or papillary pro-

jections (Fig. 3) [9,10]. Malignancy in a solid lesion

is suggested by necrosis. While these features are

usually detectable by contrast-enhanced CT, gadoli-

nium-enhanced MRI is slightly superior to both

contrast-enhanced CT and Doppler US in the charac-

terization of adnexal masses [11]. The administration

of gadolinium is important, because it may reveal

solid elements not appreciated on the pre-contrast T1

and T2 weighted images. It is sometimes possible to

suggest the histologic subtype of epithelial cancer

based on imaging findings. Calcification suggests a

serous tumor, but only 12% of serous tumors have

Fig. 5. Axial contrast-enhanced CT sections in three different patients with ovarian cancer, illustrating peritoneal implants

(arrows) in the left paracolic gutter (A), greater omentum (B), and perihepatic space (C). These are all frequent sites of peritoneal

metastases in ovarian cancer. The finding of confluent metastatic disease in the greater omentum is known as omental cake, and

is virtually diagnostic of ovarian cancer.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636614

calcification that is visible at CT [12]. High density

within the locules of a multilocular tumor is sugges-

tive of proteinaceous fluid in a mucinous tumor [13].

Endometrioid carcinomas are associated with hyper-

plasia or carcinoma of the endometrium in 20 to 30%

of cases. The endometrial pathology is thought to

represent an independent lesion, rather than meta-

static disease [13]; however, the primary radiological

distinction in the imaging of an adnexal mass is the

characterization of the mass as likely benign or

malignant, rather than identification of the histolog-

ical subtype.

Local spread

In addition to peritoneal implantation, ovarian

cancer also spreads by local continuity. Spread to

the opposite ovary occurs in 6 to 13% of patients with

disease that would otherwise be stage IA [14,15].

Tumor spread to the uterus occurs in 5 to 25% of

cases, possibly by a retrograde lymphatic route [16].

Surgically important local spread that may be

detected by imaging are invasion of the pelvic side-

wall, rectum, sigmoid colon, or urinary bladder [16].

Pelvic sidewall invasion should be suspected when

the primary tumor lies within 3 mm of the pelvic

sidewall or when the iliac vessels are surrounded or

distorted by tumor [17]. Imaging criteria for bladder

or rectosigmoid involvement have not been system-

atically described, but focal obliteration of the fat

plane between these structures and the tumor is

concerning, particularly when there is associated

tumor encasement (Fig. 4), and frank tumor invasion

is essentially diagnostic.

Peritoneal spread

Intraperitoneal dissemination is the commonest

route of spread of ovarian cancer, and likely occurs

when free tumor cells shed from gross or microscopic

tumor excrescences on the surface of the ovary [16].

These exfoliated cells are distributed by gravity into

the pouch of Douglas, and by the normal flow of

peritoneal fluid throughout the peritoneal cavity. The

normal peritoneal cavity contains less than 100 ml of

serous fluid, which circulates in the cavity and is

preferentially drawn upwards in the paracolic gutters

to the right subphrenic space, where it is absorbed

[18]. The mesothelial cells of the right subphrenic

peritoneum have wide intercellular gaps (stomas) that

facilitate absorption into the terminal lymphatics of

the mediastinum. These mechanisms explain the

commonly seen sites of peritoneal metastases in

ovarian cancer (Fig. 5):

� Pouch of Douglas� Paracolic gutters� Surface of the small and large bowel� Greater omentum� Surface of the liver (perihepatic implants)� Subphrenic space (right greater than left)

Other less common sites of peritoneal metastases

include (Fig. 6):

� Porta hepatis� Fissure for the ligamentum teres� Lesser sac� Gastrosplenic ligament

Fig. 5 (continued ).

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 615

� Splenic hilum� Gastrohepatic ligament

As noted, such peritoneal implants should not be

mistaken for intraparenchymal metastases in the liver

or spleen. Peritoneal metastases appear as nodular or

plaque-like enhancing soft tissue masses of varying

size, and may occur anywhere in the peritoneal

cavity. Delayed enhancement of perihepatic implants

has been described at MRI [19], though this may

actually represent contrast retention in the lesion with

washout in the adjacent liver. In either case, delayed

images may help. Ascites is a nonspecific finding, but

in a patient with ovarian cancer, usually indicates

peritoneal metastases [20]. Ascitic fluid may outline

small implants, which facilitates detection [8].

Previous studies examining the accuracy of CT in

the diagnosis of peritoneal metastases in ovarian

cancer have reported a sensitivity of 63% to 79%

and a specificity of 100% [21–23]. A more recent

study of 64 patients at Memorial Sloan-Kettering

Cancer Center, using spiral CT, demonstrated a sen-

sitivity of 85% to 93% and specificity of 91% to 96%

for the detection of peritoneal metastases outside the

Fig. 6. Axial contrast-enhanced CT sections in five different patients with ovarian cancer, illustrating peritoneal implants

(arrows) in the porta hepatis (A), fissure for the ligamentum teres (B), superior recess of the lesser sac (C), gastrosplenic ligament

(D), and splenic hilum (E). These are uncommon sites of metastatic disease in ovarian cancer, but are important to recognize,

because they may constitute unresectable disease. In addition, peritoneal implants (stage III) in the fissure for the ligamentum

teres, superior recess of the lesser sac, or splenic hilum should not be mistaken for intraparenchymal metastases (stage IV).

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636616

Fig. 6 (continued ).

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 617

true pelvis [24]. This increased accuracy likely re-

flects the increasing use of thinner sections and the

absence of slice misregistration artifact on spiral CT,

which aid the detection of small implants and help in

the distinction of unopacified bowel from tumor

implants. However, implants measuring 1 cm or less

in diameter remain difficult to detect, and CT sensi-

tivity falls from 25% to 50% for such small volume

disease [24]. While CT is the primary modality for

the demonstration of metastatic disease [11,17], MRI

may be equally or more accurate [17,25]. The use of

MRI is currently limited by expense, availability,

prolonged duration of scanning, and lack of wide-

spread reader experience.

Nodal spread

The ovarian lymphatic vessels are another impor-

tant route of metastatic spread. The ovary has three

routes of lymphatic drainage [16]. The main pathway

ascends with the ovarian vessels to the retroperitoneal

nodes of the upper abdomen. The second pathway

passes laterally in the broad ligament to reach the

internal iliac and obturator nodes in the pelvic side-

wall. The third group passes with the round ligament

to the external iliac and inguinal nodes, and explains

the occasional spread of ovarian cancer to the groin.

The frequency of nodal metastases in patients with

what would otherwise be stage I or II disease is 15 to

17%, and rises to 64% in stage IV disease [26]. In a

study of 71 unselected patients with ovarian cancer, 20

(28%) had pathologically proven nodal metastases

[17]. Using a size threshold of greater than 1 cm in

short axis to define adenopathy, the sensitivity and

specificity of preoperative CT for nodal staging was

50% and 95%, respectively. Therefore, while enlarged

nodes are likely to be involved (Fig. 7), CT is unable to

exclude disease in non-enlarged nodes. This empha-

sizes the importance of lymphadenectomy as part of

the routine surgical staging of suspected early stage

disease. Occasionally, patients are encountered who

have predominantly nodal rather peritoneal spread.

Disproportionate nodal disease may be seen in dys-

germinoma (see later), and this should be suggested as

a possible diagnosis, particularly in younger patients.

However, in our experience, disproportionate nodal

disease is more frequently encountered in the setting

of poorly differentiated adenocarcinoma (Fig. 8).

Interestingly, while nodal involvement indicates at

least stage III disease, there is evidence that patients

with ‘‘node only’’ stage III disease have a better

prognosis than patients with stage III disease due to

the presence of peritoneal metastases [27].

Distant metastases (stage IV disease)

The term ‘‘distant metastases’’ in the setting of

ovarian cancer refers to metastases beyond the status

of stage III disease, ie, metastases outside of the

peritoneal cavity and abdominopelvic lymph nodes

(Fig. 9). Such metastases are rare at presentation, but

are increasingly recognized during treatment because

of the sophistication of imaging technology and

because therapy is increasingly successful at control-

ling peritoneal disease, so patients live longer and die

of distant disease which would not otherwise have

Fig. 7. Axial contrast-enhanced CT sections in two different patients with ovarian cancer, illustrating nodal metastases (arrows)

in the obturator chain (A) and retroperitoneum (B).

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636618

become evident [28]. The common sites of distant

metastases at autopsy are listed in Table 2 [28–30].

Manifestations of stage IV disease, such as paren-

chymal hepatic metastases, pleural or pulmonary

nodules, and superior diaphragmatic adenopathy, are

important to recognize but do not necessarily contra-

indicate cytoreduction.

Atypical CT findings

The typical CT findings in a patient with

advanced ovarian cancer are cystic adnexal masses

with irregular internal solid components, omental

cake, and ascites. Other sites of peritoneal disease

may also be present; however, a significant propor-

tion of patients has atypical findings. These are

important to recognize, because they may have

important pathologic or clinical implications. In addi-

tion, several pathologic entities may result in unusual

or potentially confusing imaging findings. These

issues are described in this section.

Non-epithelial ovarian cancer

Ovarian cancers other than primary epithelial

cancers include malignant sex-cord stromal tumors,

malignant germ cell tumors, and metastases to the

ovary. Malignant germ cell and malignant sex-cord

Fig. 8. Axial contrast-enhanced CT sections in a 55-year-old woman with stage III poorly differentiated adenocarcinoma of the

right ovary. The primary tumor (asterisk) is predominantly cystic with mural nodules (A). A large nodal deposit (arrow) is seen

in the retroperitoneum (B), without visible peritoneal deposits or ascites. Disproportionate nodal disease is unusual, and may be

seen in poorly differentiated primary epithelial cancer, and dysgerminoma. An extra-ovarian primary cancer with nodal and

adnexal metastases is also a consideration.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 619

stromal tumors account for approximately 7% of

primary ovarian cancers [3].

Of the many subtypes of sex-cord stromal

tumors, only granulosa cell tumors are seen with

significant frequency [16]. Granulosa cell tumors are

characterized histologically by a significant content

of granulosa cells, which are the cells that surround

the ovarian follicles. During ovulation, these cells

mature from pregranulosa cells to granulosa cells,

and finally granulosa lutein cells. The latter secrete

estrogens and progesterone, and accordingly granu-

losa cell tumors are often functional (ie, hormonally

active). Granulosa cell tumors are divided into adult

and juvenile types. The later are almost always

benign [31]. Adult granulosa cell tumors usually

present in pre- or post- menopausal patients with

menstrual disturbance or uterine bleeding, due to

estrogen-induced endometrial hyperplasia. Endome-

trial hyperplasia progresses to endometrial carcinoma

in 5 to 25% of patients. The wide variation in the

reported incidence of secondary endometrial carci-

noma may be partially due to histologic difficulty in

distinguishing atypical hyperplasia and endometrial

carcinoma [32]. Occasionally, granulosa cell tumors

are androgenic and present with virilization. At

imaging, granulosa cell tumors are large encapsu-

lated multicystic masses that are predominantly solid

with variable cystic components [33,34]. The tumors

may have a characteristic ‘‘spongelike’’ appearance

on T2-weighted MRI. The masses are usually uni-

lateral and confined to the ovary. Associated endo-

metrial thickening or mass may be seen. Unilateral

salpingo-oophorectomy is the standard treatment

[16]. The histological appearance of granulosa cell

tumors does not correlate with biological behavior,

so prolonged follow-up is required to detect evi-

dence of malignancy, such as peritoneal metastases

(Fig. 10). Granulosa cell tumors have a particular

predisposition to hemorrhage. Hemorrhage may be

intratumoral or intraperitoneal. The latter is due to

tumor rupture and may result in an acute clinical

presentation with hemoperitoneum.

Malignant germ cell tumors account for less than

5% of all ovarian cancers [16], but are more frequent

in younger women, and account for two-thirds of

ovarian cancers in women less than 20 years of age

[35]. The commonest subtypes are dysgerminoma,

immature teratoma, and endodermal sinus tumor, and

these subtypes account for approximately 90% of

malignant germ cell tumors [4]. Dysgerminoma is the

female equivalent of seminoma. The tumor is fre-

Fig. 9. Axial contrast-enhanced CT sections in a 45-year-old woman with recurrent ovarian adenocarcinoma, 6 years after initial

surgery and chemotherapy for stage III disease. Two separate metastases (arrows) are seen in the mid (A) and lower (B) right

kidney. Hematogenous metastases are increasingly detected in patients with ovarian cancer, due to modern imaging technology

and better control of peritoneal disease. Such metastases may be seen in a wide variety of sites.

Table 2

Frequency of distant metastases in ovarian cancer at autopsy

by site

Site Frequency

Liver 45–48%

Lung 34–39%

Pleura 25%

Adrenal glands 15–21%

Spleen 15–20%

Bone and bone marrow 11%

Kidney 7–10%

Skin and subcutaneous tissues 5%

Brain 3–6%

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636620

quently unilateral and solid, but be partially cystic

and contain areas of hemorrhage and necrosis [36].

The finding of a multi-lobulated mass with prominent

enhancing septa has been described as a character-

istic feature on MRI [37]. The tumor is often local-

ized at presentation (stage I or II) [38]. If present,

metastatic disease tends to be nodal rather than

peritoneal. Many patients can be successfully treated

by unilateral oophorectomy and combination chemo-

therapy [16]. Immature (malignant) teratoma of the

ovary is also usually unilateral and solid, though

cystic areas are common [39]. About 70% of patients

have stage I or II disease at presentation. Calcifica-

tion and small amounts of fat may be seen within

mature teratoma [40]. In addition, a co-existent

mature teratoma is present in the ipsilateral ovary

in 26% of patients and in the contralateral ovary in

10% of patients [41]. Metastases, if present, are

usually peritoneal in location (Fig. 11). Endodermal

sinus tumor or yolk sac tumor of the ovary is a

malignant germ cell tumor characterized histologi-

cally by papillary projections that resemble the yolk

sac endodermal sinus of the rodent placenta [32]. The

tumor usually presents as rapidly growing unilateral

adnexal mass in a young woman. The imaging

features are variable, and the tumors may range from

predominantly solid to predominantly cystic [42]. A

co-existent mature teratoma (dermoid cyst) is seen in

Fig. 10. Axial contrast-enhanced CT sections in a 46-year-old woman with recurrent granulosa cell tumor, 4 years after initial

surgery for stage I disease. A predominantly solid peritoneal implant (arrow) is seen between the liver, right kidney, and

duodenum (A). Four weeks later, the patient complained of right upper quadrant pain, and a repeat CT scan (B) showed a large

hematoma (asterisk) adjacent to the implant, secondary to tumor rupture and hemorrhage. Granulosa cell tumors have a particular

predilection to hemorrhage, either within the tumor or into the peritoneal cavity.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 621

up to 15% of cases (Fig. 12). Hemorrhage and

hypervascular enhancement have been suggested as

imaging findings that may suggest the histologic

diagnosis, in the setting of a complex ovarian mass

in a young woman.

Metastases to the ovary usually arise from primary

malignancy in the stomach or colon, though other

primary sites such as the breast, lung, and pancreas

are also recognized [43]. The term Krukenberg tumor

is sometimes used as a synonym for metastases to the

ovary. However, this term is correctly used for a

metastasis consisting of mucin signet-ring cells in a

cellular stroma, usually arising from a carcinoma of

the gastric antrum [32]. Using this definition, only

30% to 40% of ovarian metastases are Krukenberg

tumors [4]. Metastases to the ovary are typically

bilateral, solid, and strongly enhancing [43,44].

Cystic and necrotic areas are common (Fig. 13).

Mucinous tumors may result in areas of increased

T2 signal on MRI, while fibrous stromal may result in

areas of reduced T2 signal [43]. The primary tumor is

often clinically overt, with other evidence of wide-

spread metastatic disease [45].

Superior diaphragmatic adenopathy

The superior diaphragmatic (or cardiophrenic)

nodes lie on the superior surface of the diaphragm,

and are divided into two groups [46,47]. The

anterior diaphragmatic (or paracardiac) nodes lie

behind the seventh costochondral junction and ster-

num. The lateral diaphragmatic (or juxtaphrenic)

nodes lie close to the entrance of the phrenic nerve

into the diaphragm, adjacent to the inferior vena

cava on the right and the cardiac apex on the left.

The diaphragmatic nodes are the principal drainage

site of the entire peritoneal cavity, and enlarged

superior diaphragmatic nodes are seen in approxi-

mately 15% of patients with advanced ovarian

cancer (Fig. 14) [48]. Because these nodes are

usually small, enlargement is defined as a short axis

diameter greater than 5 mm [47,48]. In a study of

FIGO stage III ovarian cancer at the Royal Marsden

Hospital, anterior diaphragmatic adenopathy was

seen at baseline CT scanning in 15 (28%) of 53

patients [48]. This finding was an independent

predictor of disease recurrence and death. This

suggests anterior diaphragmatic adenopathy should

be considered indicative of stage IV disease, but

such radiologic findings are not currently incorpo-

rated in the surgically-based FIGO staging system.

One limitation of the Marsden study was that the

pathological status of the nodes was not directly

assessed, but the inaccessible location of these nodes

is such that they are rarely biopsied or resected.

Mesenteric root disease

The small bowel mesentery may be involved by

surface peritoneal implants, such as in the greater

omentum or on the bowel wall. These implants are

usually peripherally located with respect to the small

Fig. 11. Axial contrast-enhanced CT sections in a 28-year-old woman with stage III immature teratoma. Relatively small and

predominantly solid ovarian masses (arrow) are seen in pelvis (A). Two larger additional masses (asterisks) lying in the pouch of

Douglas and superior to the bladder were found to be extra-ovarian peritoneal implants at surgery. (B) Tumor implants (arrows)

are also seen in the greater omentum (arrows). Solid ovarian masses in young women with suspected ovarian malignancy are

suggestive of primary non-epithelial cancer.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636622

bowel mesentery. Occasionally, tumor is present at

the root of the mesentery, and may be unresectable

and result in suboptimal debulking [17]. The fre-

quency and mechanism of mesenteric root involve-

ment has been poorly described. There are two

plausible mechanisms; tumor may seed along the

surface of the mesentery, spreading centrally towards

the mesenteric root, or malignant cells may be

absorbed from the greater omentum and mesenteric

surface, resulting in true mesenteric adenopathy

(Fig. 15). Whatever the mechanism, it is important

to scrutinize the mesenteric root at imaging, since this

is a clinically important disease site that may be

overlooked, particularly if there is extensive disease

elsewhere in the abdomen and pelvis.

Complex histology

The classification of ovarian cancers is com-

plex, and many tumors contain mixed histologic

patterns [4]. In general, treatment is determined by

the most malignant tissue pattern [16]. These

complexities indicate that attempts to assign a

histologic subtype to a malignant ovarian mass

based on radiological findings will be of somewhat

limited accuracy, and the primary aims of imaging

are the detection of malignant characteristics and

the assessment of stage. However, two histologic

issues are important to radiologists; malignant

transformation of benign tumors and cancer arising

in association with endometriosis.

Malignant transformation may occur in benign

epithelial tumors, and is a topic of considerable

interest in the pathogenesis of epithelial ovarian

cancer [49]. The most frequently encountered form

of malignant transformation in clinical practice, how-

ever, is the development of cancer in a mature cystic

teratoma (dermoid cyst). Between 0.2% and 2% of

dermoid cysts undergo malignant transformation

[4,50]. The risk of malignant transformation is higher

in postmenopausal women. A variety of cancers may

arise in dermoid cysts with malignant transformation,

but squamous cell carcinoma is the single commonest

Fig. 12. Axial contrast-enhanced CT sections in a 34-year-old woman with stage I endodermal sinus tumor. The tumor forms a

lobulated layer of enhancing tissue at the periphery of a dermoid cyst. The tumor was confined within the capsule of the ovary

at histopathologic examination. Approximately 15% of endodermal sinus tumors arise in association with a pre-existing

dermoid cyst.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 623

malignancy. The imaging findings in a series of

six patients with malignant transformation in der-

moid cysts have been reported [51]. A large non-

fatty solid component was seen in four cases, and this

mass invaded adjacent structures in three cases.

Therefore, these findings may indicate malignancy

when seen in a dermoid cyst, particularly in a post-

menopausal patient.

The co-existence of endometriosis and endome-

trial cancer was initially considered coincidental [4],

but is now generally accepted as a real association

[52,53]. The reported relative risk of ovarian cancer

in patients with long-standing endometriosis is 4.2

[54]. The mechanism of the association remains

obscure. The commonest histologic types of ovarian

cancer seen in association with endometriosis are

clear cell, endometrioid, and serous carcinoma [53].

The radiological appearances of ovarian cancer aris-

ing in endometriosis have not been systematically

described, but the detection of solid tissue in an

endometriotic cyst should be considered suspicious

(Fig. 16).

Primary papillary serous carcinoma of

the peritoneum

Occasionally, a female patient presents with

peritoneal carcinomatosis, an elevated CA-125, but

without large adnexal masses [55,56]. While this

may represent peritoneal spread from a non-ovarian

primary site, the constellation of findings should

raise the possibility of primary papillary serous

carcinoma of the peritoneum (Fig. 17). Papillary

serous peritoneal carcinomatosis is usually secon-

dary to ovarian papillary serous carcinoma. How-

ever, in about 10% of cases, the ovaries appear

grossly normal, or are only superficially involved by

tumor. In such cases, it is postulated that the tumor

has arisen from the extraovarian peritoneum, and the

term papillary serous carcinoma of the peritoneum is

used [57]. A primary origin from the extraovarian

peritoneum is supported by the occurrence of the

tumor many years after bilateral oophorectomy for

benign disease [58], and by one reported case in a

man [59]. Other terms that have been used to refer

to this condition include serous surface papillary

Fig. 13. Axial contrast-enhanced CT section in a 69-year-old woman with widely metastatic pancreatic cancer, including a

metastasis to the left ovary (arrow). The mass is heterogenous and hypodense, but predominantly solid.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636624

carcinoma, papillary tumor of the peritoneum, and

normal-sized ovary carcinoma syndrome. Imaging

findings resemble those of peritoneal carcinomatosis

due to ovarian carcinoma, except that the ovaries are

Fig. 14. Axial contrast-enhanced CT section (A) in a 59-year-woman with ovarian cancer showing an enlarged superior

diaphragmatic node (arrow). These nodes are rarely biopsied, because of the inaccessible location. In this case, a PET scan (B)

was performed, and confirmed increased metabolic activity (arrow) in the node.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 625

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636626

typically less than 4 cm in size. The presence of

peritoneal masses, extensive omental calcification,

and the absence of an ovarian mass on CT have

been reported as highly suggestive of primary papil-

lary serous carcinoma of the peritoneum, particularly

in postmenopausal women [55,60]. The distinction

from ovarian papillary serous carcinoma is largely

academic, since both are treated with cytoreduc-

tive surgery and platin-based chemotherapy, and

the prognosis is similar in both conditions [56,57].

The distinction from primary peritoneal mesothe-

lioma can be difficult histologically, but is important

to make, since prognosis and management are dif-

ferent. The median survival for patients with papil-

lary serous carcinoma of the peritoneum is 2 years,

whereas patients with peritoneal mesothelioma

rarely survive for more than a year.

Calcified ovarian tumors

Calcification in an ovarian mass usually suggests

a benign etiology, such as mature teratoma, fibroma,

or Sertoli-Leydig cell tumor [61–63], but calcifica-

tion can also be seen in ovarian malignancies. Most

calcified ovarian cancers are serous carcinomas [12].

Other rare malignancies such as malignant Brenner

Fig. 15. Axial contrast-enhanced CT sections in two different patients with ovarian cancer, illustrating mesenteric root

involvement. Disease in the mesenteric root may appear as soft tissue nodules (arrow) adjacent to the superior mesenteric vessels

(A), which may represent nodal spread after absorption of malignant cells from the greater omentum or mesenteric surface, or as

soft tissue masses (arrows) distributed more randomly within the mesentery (B), which may represent peritoneal implants on the

mesenteric surface.

Fig. 16. Axial gadolinium-enhanced T1 axial MR image with fat suppression in a 41-year-old woman. A left ovarian cystic

lesion is of high T1 signal intensity (asterisk), despite fat saturation. This is suggestive of hemorrhage in an either endometriotic

cyst or a hemorrhagic ovarian cyst. However, in addition, an enhancing mural nodularity is visible (arrow). The lesion was

resected and histopathologic analysis showed a focus of clear-cell carcinoma arising in an endometriotic cyst.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 627

tumors and gonadoblastoma may also calcify [64,65].

Calcification in peritoneal metastases is helpful in the

detection of implants around the liver and spleen.

Calcified disease more inferiorly in the abdomen may

Fig. 17. Axial contrast-enhanced CT sections (A and B) in a 52-year-old woman with primary serous papillary carcinoma of the

peritoneum, showing the typical radiologic constellation of ascites, peritoneal implants (straight arrows) and non-enlarged ovaries

(curved arrows).

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636628

require careful scrutiny to allow distinction from

contrast-filled bowel (Fig. 18).

Pseudomyxoma peritonei

Pseudomyxoma peritonei is a form of peritoneal

neoplasia that is characterized by the progressive ac-

cumulation of mucinous ascites, and is usually due to

rupture of an ovarian or appendiceal mucinous ade-

noma or low-grade mucinous adenocarcinoma [66]. In

practice, the primary site is often unclear, and cases of

apparent pseudomyxoma peritonei secondary to ovar-

ian tumors may represent metastatic disease to the

ovaries and peritoneum from an unrecognized primary

tumor in the appendix or elsewhere [67,68]. Two

forms can be recognized, depending on whether the

histological appearance suggests an adenomatous or

adenocarcinomatous origin [69]. These have been

designated disseminated peritoneal adenomucinosis

(approximately 60% of cases of pseudomyxoma peri-

tonei) and disseminated peritoneal mucinous carcino-

matosis, respectively. This pathologic distinction is of

major clinical importance; disseminated peritoneal

adenomucinosis has an age-adjusted 5-year survival

of 84% compared to 7% for disseminated peritoneal

mucinous carcinomatosis. At CT, the condition may

superficially resemble simple ascites; however, the

mass-like nodular nature of the gelatinous material in

pseudomyxoma peritonei may result in suggestive

findings such as hepatic, splenic, and mesenteric

scalloping, and visible septations or locules (Fig. 19).

Benign mimics of metastatic ovarian cancer

Benign mimics of peritoneal metastatic disease are

rare. The major differential diagnosis for peritoneal

malignancy is infectious peritonitis, especially tuber-

culous peritonitis. There is considerable overlap

between the CT findings in peritoneal carcinomatosis

and tuberculous peritonitis [70], and definitive differ-

entiation is histological. Other reported non-cancerous

mimics of peritoneal carcinomatosis include mesen-

teric panniculitis, leiomyomatosis peritonealis dis-

seminata, extramedullary hematopoiesis, and chronic

leak from an ovarian dermoid cyst with granuloma-

tous peritonitis [71–74]. Prominent diaphragmatic

Fig. 18. Axial contrast-enhanced CT sections of the upper abdomen (A) and pelvis (B) in a 53-year-old woman with stage III

ovarian serous adenocarcinoma. Calcification within peritoneal metastases facilitates the detection of perihepatic (black arrow)

and gastrosplenic ligament (white arrow) implants. Conversely, calcified omental cake (curved arrow) could potentially be

mistaken for contrast-filled bowel.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 629

slips should not be mistaken for perihepatic implants

[75] (Fig. 20).

Clinical role of imaging in ovarian cancer

The previous sections have described the typical

and atypical imaging findings in ovarian cancer. The

ultimate role of the radiologist is to integrate these

findings with the clinical setting in order to optimize

patient care and develop a tailored patient-specific

management plan. The imaging observations that are

critical to management may be divided into those

related to characterization of the primary tumor,

identification of metastatic disease to prevent under-

staging, and identification of disease that may be an

indication for neoadjuvant chemotherapy.

Most ovarian malignancies are epithelial cancers

and appear as cystic adnexal masses with irregular

internal solid components. This is often accompanied

by omental cake, peritoneal implants, and ascites.

The clinical and imaging findings in non-epithelial

cancers have been described previously, and are

summarized in Table 3. These diagnoses are impor-

tant considerations in the appropriate setting, because

in young patients some of these tumors (granulosa

cell tumor, dysgerminoma, immature teratoma, and

endodermal sinus tumor) may be treated by unilateral

oophorectomy in order to preserve fertility. Con-

versely, metastatic disease to the ovary may be more

appropriately treated by systemic chemotherapy

rather than resection.

In practice, up to 90% of patients with apparent

stage I or II ovarian cancer do not have optimal

surgical staging, often because of failure to perform

a selective retroperitoneal lymphadenectomy [76]. As

a result, approximately 30% of such patients are

under-staged [77]. Accurate identification of ovarian

metastases by imaging helps prevent such under-

staging, and may guide subspecialist referral in

patients in whom the diagnosis of ovarian cancer

was not considered, or considered unlikely.

In practice, the percentage of women with ad-

vanced ovarian cancer who are successfully (opti-

mally) debulked varies from 17% to 87% [7]. This

wide variation likely reflects differences in surgical

Fig. 18 (continued ).

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636630

expertise, but indicates that even in specialist cen-

ters a significant fraction of patients will have

inoperable disease and will gain no benefit from

primary cytoreduction. The optimal management of

Fig. 19. Axial contrast-enhanced CT sections in a 45-year-old woman with pseudomyxoma peritonei. Mucin in the peritoneal

cavity resembles simple ascitic fluid, but the presence of scalloping (arrow) of the liver surface (A) and mass-like separation of

bowel loops (B) indicates the true diagnosis.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636 631

patients with inoperable ovarian cancer is not

established, but review of the clinical and radio-

logical literature suggests:

� Neoadjuvant chemotherapy (ie, preoperative)

with interval (or delayed) cytoreductive surgery

after tumor shrinkage is a viable management

option, and merits a randomized controlled trial

[78,79].� Cross-sectional imaging can help treatment

planning by identifying, with a high degree of

accuracy, those patients with inoperable dis-

ease [17,80,81].

The concept of using imaging to identify patients

with inoperable disease who may be more appropri-

ately managed by neoadjuvant chemotherapy appears

straightforward, but the problem is that there are no

clearly established surgical criteria for inoperable

disease. Some institutions consider radical surgery

appropriate to achieve optimal debulking, even if this

involves including resection of the liver, spleen, or

kidneys [7,82]. Therefore, the role of the radiologist

is not to describe disease as resectable or unresect-

able, but rather to alert the clinician to disease that

may complicate surgery. Depending on the institu-

tion, this may be an indication for neoadjuvant

chemotherapy. Findings that may indicate inoperable

disease include:

� Invasion of the pelvic sidewall, rectum, sig-

moid colon, or bladder� Tumor deposits greater than 1 to 2 cm in size

in the gastrosplenic ligament, gastrohepatic

ligament, lesser sac, fissure for the ligamen-

tum teres, porta hepatis, subphrenic space,

small bowel mesentery, or retroperitoneum

above the renal hila [17,80,81,83].

Summary

Ovarian cancer is relatively common, and often

presents at an advanced stage with widespread

intraperitoneal metastases. The constellation of com-

plex pelvic masses, ascites, omental cake, and other

peritoneal implants is virtually diagnostic. All

patients are potential surgical candidates, since

suspected early stage disease is treated by a com-

prehensive staging laparotomy including total abdo-

minal hysterectomy, bilateral salpingo-oophorectomy,

Fig. 20. Axial contrast-enhanced CT section of the upper abdomen, showing a prominent diaphragmatic slip (arrow). This should

not be interpreted as a perihepatic implant.

F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636632

and omentectomy. Operable advanced disease is

treated by surgical debulking and adjuvant combina-

tion chemotherapy. The role of imaging is to detect

and characterize adnexal masses as likely malignant,

recognize unusual findings that may suggest atypical

pathology, demonstrate metastases in order to pre-

vent under-staging, and detect specific sites of dis-

ease that may be unresectable. These aims are

directly related to clinical management; character-

ization of an adnexal mass as malignant guides

appropriate surgical referral, recognition of atypical

pathology such as malignant granulosa cell tumor in

a young woman may be an indication for fertility-

preserving surgery. Demonstration of metastatic sites

assists surgical planning, and detection of unresect-

able disease may be an indication for neoadjuvant

(ie, preoperative) chemotherapy with interval de-

bulking rather than primary debulking with adjuvant

(postoperative) chemotherapy.

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± Endometrial hyperplasia/carcinoma

± Intratumoral hemorrhage/hemoperitoneum

Metastases to the

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Dysgerminoma 1% Young woman

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± Nodal metastases

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F.V. Coakley / Radiol Clin N Am 40 (2002) 609–636636

Imaging of the vagina and vulva

Silvia D. Chang, MD

Department of Radiology, University of British Columbia, Vancouver Hospital and Health Sciences Centre,

899 West 12th Avenue, Vancouver, British Columbia, Canada V5Z 1M9

Imaging of the vagina and vulva has improved with

the advent of cross-sectional imaging modalities such

as ultrasound (US), computed tomography (CT) and

magnetic resonance (MR) imaging. This chapter gives

an overview of vaginal and vulvar pathology with an

emphasis on primary malignancies and includes a

discussion of embryology/anatomy, epidemiology,

diagnosis, staging, treatment with a focus on the im-

aging strategies for detection, diagnosis and treatment.

Vaginal and vulvar carcinomas are rare and

account for only 2% to 3% and 3% to 5% of gyne-

cologic malignancies, respectively [1–6]. The low

rate of carcinomas of the vagina may be due to the

classification criteria established by the International

Federation of Gynecology and Obstetrics (FIGO).

According to FIGO, a tumor that involves the cervix

or the vulva is considered a primary lesion from that

site [4]. Both carcinomas of the vagina and the vulva

usually occur in post-menopausal women [7,8]. The

most common cell type is squamous cell in origin and

accounts for 75% to 90% and greater than 90% of

primary vaginal and vulvar malignancies, respectively

[9,10]. The diagnosis of vaginal and vulvar carcino-

mas is usually made by physical examination and

biopsy. Cross-sectional imaging, however, can make a

valuable contribution to patient evaluation.

Embryology and anatomy of the vagina

The vagina is a fibromuscular tubular structure

lined by estrogen-sensitive mucus epithelium derived

from two mesodermal sources. The mullerian tract

gives rise to the upper two thirds of the vagina which

is lined by columnar epithelium. The lower one third

of the vagina is derived from the urogenital sinus or

the cloaca, which differentiates and proliferates into

the squamous epithelium. During the second gesta-

tional trimester, the urogenital squamous epithelium

migrates upwards to cover the columnar glandular

mullerian epithelium. By the eighteenth gestational

week this process is complete, having continued on to

cover the vaginal fornices and cervix, thus forming

the hollow, squamous epithelialized vagina.

The vagina has an extensive vascular supply that

arises from a number of sources. The vaginal artery

and uterine vessels all arise from the internal iliac

vessels and have a rich anastomosing network bet-

ween them. The middle rectal artery arises from the in-

ternal iliac artery and provides a portion of the blood

supply to the mid-vagina. The internal pudendal artery

arises from the internal iliac vessels and supplies the

lower vagina. Additionally, the lower vagina also re-

ceives a blood supply from the external pudendal ar-

tery, which arises from the femoral region. The venous

drainage is via the uterine and vaginal plexuses.

The vagina has a complex lymphatic drainage,

which generally parallels the embryologic develop-

ment of the vagina. The upper two thirds of the

vagina drain to the internal and external iliac chains,

which form the pelvic lymph nodes. Part of the upper

vagina also drains directly to the sacral lymph node

area. The lower one third of the vagina drains to the

inguinal region.

Normal cross-sectional imaging appearance of the

vagina and vulva

Normal ultrasound appearance

The mucosa of the vagina is hyperechoic and the

vaginal wall demonstrates medium echogenicity

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00010 -0

E-mail address: schang@vanhosp.bc.ca (S.D. Chang).

Radiol Clin N Am 40 (2002) 637–658

(Fig. 1). The vulva is seen as medium echogenicity

on ultrasound.

Normal CT appearance

The vagina is seen as a rectangular soft tissue

structure inferior to the cervix (Fig. 2). The vulva is

seen as a triangular soft tissue structure (Fig. 3).

Normal MR appearance

Current convention divides the vagina into thirds

for descriptive purposes. The upper third of the vagina

includes the vaginal fornices (Fig. 4). The middle third

of the vagina is at the level of the bladder base.

The lower third of the vagina is adjacent to the urethra.

On T1-weighted scans, the vagina displays medium

signal intensity, similar to the urethra anteriorly and

the rectum posteriorly. On T2-weighted images, the

vaginal muscosa appears as a central stripe of high

signal intensity surrounded by the intermediate signal

intensity of the vaginal wall (Fig. 4). The appearance

of the vagina varies depending on hormonal influen-

ces. The high signal intensity stripe may be thin or

absent in premenarchal girls and in postmenopausal

women not on hormone replacement therapy. Admin-

istration of intravenous gadolinium causes the vaginal

mucosa to enhance (Fig. 4). On both T1 and T2

weighted sequences the vulva demonstrates low to

intermediate signal intensity (Fig. 5).

Benign disorders of the vagina

Congenital anomalies such as vaginal atresia

(Fig. 6), vaginal duplication, abnormalities of gona-

dal differentiation and ambiguous genitalia can be

evaluated with magnetic resonance (MR). MR can

also assess associated abnormalities of the uterus,

cervix and ovaries. Gartner’s duct cysts are derived

from mesonephric and tubule remnants. These are

best seen on MR (Fig. 7) as low signal lesions on T1

and high signal lesions on T2-weighted sequences.

Neurofibroma, hemangioma (Fig. 8), fibroepithe-

lial polyp, leiomyoma, rhabdomyoma, and mullerian

mixed tumor are examples of the variety of benign

tumors that involve the vagina. Benign tumors of the

vagina typically present as mobile rounded submu-

cosal or polypoid masses. Simple excision is both

diagnostic and therapeutic in these cases.

Carcinoma of the vagina

Epidemiology and pathology

Carcinoma of the vagina mainly occurs in post-

menopausal females; usually in patients in their

sixties and seventies. Vaginal intraepithelial neo-

plasia (VAIN) often occurs with cervical intraepi-

thelial neoplasia (CIN) and is believed to have a

Fig. 1. Normal ultrasound of the vagina in the sagittal plane. The vaginal mucosa is demonstrated as a thin echogenic line (*) and

the adjacent wall is of medium echogenicity (arrows). u = uterus, c = cervix.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658638

similar etiology secondary to human papillomavirus

(HPV) [11]. Unlike the cervix, the vagina does not

have a transformation zone of immature cells sus-

ceptible to HPV infection, thus most vaginal HPV

lesions arise from healing areas of squamous meta-

plasia due to mucosal trauma such as tampon use or

coitus. Vaginal carcinoma is often found in associ-

ation with VAIN (dysplasia/carcinoma in situ).

VAIN is found in younger women and has been

presumed to precede invasive vaginal carcinoma

much like CIN precedes cervical carcinoma [12].

Unlike the strong association between CIN and

cervical carcinoma, however, no such association

between VAIN and invasive vaginal carcinoma has

been established to date.

Eighty to ninety percent of primary vaginal malig-

nancies are squamous cell carcinomas and approx-

imately 5% to 10% are adenocarcinomas. Risk factors

for primary invasive carcinoma of the vagina include:

advancing age, human papillomavirus (HPV) and

prior carcinoma involving the cervix or vulva. One

study showed an association between chronic irritant

vaginitis secondary to the use of pessaries with

vaginal cancers arising in the posterior fornix or

posterior wall [13]. Others argue that advancing age

requires the use of pessaries and may be the causative

Fig. 2. Normal intravenous contrast-enhanced CT of the vagina. (A) Axial image of the upper vagina (arrows) and (B) axial

image of the lower vagina (v). b = bladder, r = rectum, u = uterus.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 639

factor rather than the pessaries themselves [5,14].

Prior pelvic radiation has been linked with vaginal

cancers and proposed by some to be a predisposing

factor [2,8]; however, many of these patients received

radiation for carcinoma of the cervix or vulva and

a field effect may explain the development of

the vaginal carcinoma rather than exposure to radi-

ation therapy.

Clear cell adenocarcinoma of the vagina is a

subtype of adenocarcinoma associated with maternal

ingestion of diethylstilbestrol (DES) during preg-

nancy. Clear cell adenocarcinoma in women exposed

to DES is rare with only approximately 1 in every

1000 women exposed to DES in utero developing

clear cell carcinoma [15]; however, approximately

45% of DES-exposed women have areas of vaginal

adenosis and 25% have structural abnormalities of

the uterus, cervix, or vagina. These abnormalities are

both dose and time related with respect to DES

exposure. Typically, patients with clear cell carci-

noma of the vagina present at an early age with a

peak occurrence between the ages of 15 and 22 years

[16]. Women who have been exposed to DES require

careful observation. Treatment of clear cell carci-

noma of the vagina is similar to other cancers of the

vagina. Other rare primary vaginal carcinomas

include vaginal melanomas and vaginal sarcomas,

predominantly leiomyosarcomas [17–21]. In the

pediatric population, embryonal rhabdomyosarcoma

(sarcoma botryoides) is a malignant sarcoma present-

ing in children under the age of 6 [22]. In general,

metastases to the vagina are more common than

primary vaginal malignancies. Metastases usually

occur from direct tumor extension from the endome-

trium or cervix, but may also spread from the rectum

or bladder.

The most common symptom in patients with

vaginal carcinoma is abnormal bleeding. This affects

60% to 70% of patients with vaginal carcinoma and

typically is postmenopausal bleeding in an elderly

patient. Another third of patients with vaginal carci-

noma have vaginal discharge, which causes them to

seek medical care. Aside from these two common

symptoms, patients with vaginal carcinoma tend to be

asymptomatic. In advanced disease, symptoms such

as vaginal pain or hemorrhage may occur. The

diagnosis of vaginal carcinoma is made clinically

with biopsy.

Pattern of spread

Approximately half of all primary vaginal can-

cers originate in the upper third of the vagina,

typically presenting as nodular, exophytic or ulcer-

ated masses [23–25]. Vaginal cancer can spread by

direct extension into adjacent structures such as the

bladder, urethra, and rectum. Vaginal tumors also

spread via both the lymphatic and hematogenous

systems. Lymphatic spread is determined by the site

of the primary vaginal lesion. Generally, tumors

originating in the vaginal vault spread to the obtu-

rator and internal iliac nodes. Tumors arising from

the posterior wall tend to spread to the superior and

inferior gluteal nodes. Tumors arising from the

lower one-third of the vagina will usually spread

to the pelvic and/or inguinofemoral lymph nodes.

The most common location of hematogenous spread

of vaginal cancer is to the lungs. Less common

Fig. 3. Normal intravenous contrast-enhanced CT of the vulva. The vulva (arrows) is situated anterior to the anus (a).

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658640

sites of hematogenous spread include the liver and

bone [23].

Staging

Clinical staging of vaginal cancer is based on the

guidelines defined by the International Federation of

Gynecology and Obstetrics (FIGO). According to the

FIGO system both vaginal and cervical cancers are

staged in the same manner [4]. Staging of vaginal

cancer according to FIGO includes clinical examina-

tion, CXR, complete blood count and biochemical

profile. Often included in the FIGO staging of

vaginal cancer are cystoscopy, sigmoidoscopy, bar-

ium enema and IVP. Additionally, most staging of

vaginal cancer includes a CT to assess for lympha-

denopathy, which is not part of the FIGO system. It is

however, part of the TNM classification system

(Table 1) [26]. The incidence of lymph node meta-

stases is poorly documented with one report claiming

16% of patients with vaginal cancer presented with

nodal involvement [8] and another report stating as

many as 40% of patients with vaginal cancer have

nodal involvement [27]. Overall, FIGO stage II

disease is the most common stage of presentation,

accounting for approximately 40% of all vaginal

cancers [8,27–29].

Prognosis

Tumor stage is the most important predictive

factor with respect to survival [2,8,10,14]. The

overall survival rate for patients with vaginal cancer

is approximately 45%. This is based largely on

squamous cell disease that accounts for the major-

ity of patients with vaginal cancer. As with most

cancers, survival is directly related to stage. Tumor

size is also an important predictor of outcome.

Studies have shown a poor prognosis if tumor size

is greater than 5 cm [23] and a better survival rate

for patients with tumors less than 4 cm in diameter

[24]. The consensus at this time is that tumor

location, tumor grade, cell type and age of the

patient do not influence outcome [10]. Some

reports, however, have shown increased rates of

local recurrence in patients with posterior wall

tumors [23] and better survival rates in patients

with tumors of the upper third of the vagina [30].

Many studies have shown a correlation between

histological grade of a tumor and its recurrence,

[24,31] but an equal number of studies have found

no such correlation [2,8,10]. Similarly, some inves-

tigators have reported poorer survival rates with

adenocarcinoma, [23] while others have shown no

difference between the outcome in patients with ade-

nocarcinomas and squamous carcinomas [10,24,29].

Both melanoma of the vagina and the much less

common sarcomas of the vagina have decreased

survival rates compared with squamous cell carci-

nomas of the vagina. Few cases of small cell carci-

noma of the vagina have been reported and all have

been fatal.

Imaging evaluation of vaginal carcinomas

Conventional radiography

As previously mentioned, the FIGO staging

system for vaginal carcinoma is similar to that of

cervical carcinoma and incorporates the use of

chest radiograph, barium enema and intravenous

pyelography [4]. The chest radiograph is a standard

in the work up of gynecological malignancies

because it can detect pulmonary metastases and

other comorbid pulmonary disease common in the

elderly population. The double contrast barium

enema had traditionally been used to assess meta-

static rectal or colonic involvement in patients with

vaginal cancer. Barium enema findings in these

patients may include: fixation and tethering of the

bowel wall, irregular serrations, mucosal ulceration

and fistula formation [32]; however, these studies

tended to give a low positive yield. Today, the

barium enema has been largely replaced by

sigmoidoscopy and colonoscopy, which allow for

direct visualization and biopsy. The intravenous

pyelogram (IVP) is used to identify tumor spread

causing obstruction. IVP findings may include

delayed or persistent nephrogram, hydronephrosis,

hydroureter, or extrinsic compression of the ureter

by tumor. The use of IVPs in the work up of

vaginal cancers has declined over the years due to

a combination of low positive yield, increased use

of cross-sectional imaging, and direct visualization

with cystoscopy.

Lymphangiography

Lymphangiography, was the modality of choice

for assessment of nodal disease in the past. How-

ever, this is an invasive technique and the number of

centers where lymphangiography is routinely per-

formed is declining. Lymphangiography has largely

been replaced by cross-sectional imaging, which is

less invasive and provides comparable accuracy for

identification of nodal involvement as well as addi-

tional information about extra-nodal structures.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 641

Cross-sectional imaging

The advantages of CT and MRI have led to an

increase in their use in the evaluation of patients

with gynecological cancer. Although US is used

extensively in the assessment of ovarian and endo-

metrial abnormalities, it is limited in the assessment

of the cervix, vagina and vulva. Both US and CT are

limited in assessment of early localized disease due

to inferior soft tissue contrast when compared to

MRI. CT is most useful in the evaluation of more

advanced disease and in the detection and biopsy of

suspected lymph node metastases. MRI offers excel-

lent soft tissue contrast and allows assessment of the

extent of tumor as well as staging. For tumors

involving areas that are difficult to examine clini-

cally, such as the upper third of the vagina, MRI

may be helpful in determining whether the site of

origin is vaginal or cervical.

Magnetic resonance imaging

T1- and T2-weighted sequences both play a role

in the evaluation of the female pelvis. T1-weighted

images provide excellent contrast between fat and

soft tissue. T1-weighted images are used to char-

acterize soft tissues and lymphadenopathy. T2-

weighted sequences are essential in characterizing

pathological conditions as they differentiate the

layers of the vaginal wall the best. Thin (5 mm)

Fig. 4. Normal MR anatomy of the vagina. (A) On axial T1-weighted sequence the vagina (v) demonstrates intermediate signal

intensity similar to adjacent urethra (u) and rectum (r). On (B) axial and (C) sagittal T2-weighted images, the mucosa of the

vagina is demonstrated as a high signal intensity stripe (arrow). The anterior (curved arrow) and posterior (large white arrow)

vaginal fornices are best visualized in the sagittal plane. (D). On axial T1-weighted images with gadolinium, the mucosa of

the vagina (arrows) enhances greater than the surrounding muscular wall. u = urethra, r = rectum, b = bladder, ut = uterus. Figure

(C) modified from Chang SD, Hricak H [48].

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658642

sections are preferable. The optimal plane of imag-

ing is transaxial [33]. MRI cannot differentiate

primary tumors from metastatic lesions. Inflamma-

tory disease cannot be distinguished from tumors

by MRI. In spite of these limitations, MRI remains

the best imaging modality available for the assess-

ment of vaginal cancer. MRI is used to differentiate

tumor from fibrotic or granulomatous tissue, in

Fig. 4 (continued ).

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 643

staging vaginal tumors, and to evaluate tumor

extension into adjacent tissues [33]. MRI with

gadolinium-contrast enhancement is used to charac-

terize vesico-vaginal fistulas that can occur with

vaginal cancers.

On T2-weighted MRI sequences vaginal carcino-

mas appear as intermediate to high signal intensity

masses. On T1-weighted images vaginal tumors are

intermediate in signal intensity and may not be

visualized. Alteration of the vaginal contour may be

Fig. 5. Normal MR anatomy of the vulva. (A) Axial T1-weighted and (B) T2-weighted images demonstrate the vulva (straight

arrows) as intermediate in signal intensity. A tiny Bartholin cyst is present on the left (curved arrow). A/a = Anus.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658644

the only indication of disease on a T1-weighted

sequence [34]. FIGO staging is determined clinically

and pathologically. MRI staging of vaginal cancers

can be correlated with the FIGO clinical staging

system as shown below.

In FIGO stage I, tumors are confined to the vagina

and correspond to the MRI appearance of superficial

tumors. When the tumor is confined to the vaginal

wall, the normal low signal vaginal wall is preserved

on T2-weighted images. Sometimes there are areas of

Fig. 6. Vaginal and uterine agenesis. (A) Axial and (B) sagittal T2-weighted MR images demonstrate absence of the vagina and

uterus. b = bladder, r = rectum, u = urethra.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 645

abnormal medium signal intensity, which extend

through the vaginal wall. In these cases, the surround-

ing fat is of high signal intensity and remains distinct

from the vagina [35].

In FIGO stage II, tumor invades paravaginal

tissues, but does not extend to the pelvic wall. On

T2-weighted sequences, the extension of the vaginal

tumor into the paravaginal tissues appears as medium

Fig. 7. Gartner’s duct cyst. (A) Axial T1-weighted and (B) T2-weighted MR images demonstrate a Gartner’s duct cyst (arrow)

arising from the right vaginal fornix.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658646

to high signal intensity. The interface between fat and

tumor is indistinct and represents paravaginal soft

tissue involvement [35]. (Fig. 9)

In FIGO stage III, the tumor extends to the

pelvic wall. This appears as increased signal in

the pelvic floor muscles (levator ani, obturator

internus, or piriformis muscle) on T2-weighted

images [34].

In FIGO stage IVa, tumor invades the mucosa of

the bladder or rectum and/or extends beyond the true

Fig. 8. Hemangioma involving the vagina. (A) Axial T2-weighted and (B) with fat saturation MR images demonstrate the

hemangioma as high signal intensity involving the posterior wall of the vagina (straight arrows). The mons pubis (curved

arrows) is also involved. u = urethra.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 647

pelvis. This may be seen as direct tumor invasion or

as increased signal within the bladder or rectal wall

on T2-weighted images.

Treatment

MRI staging of vaginal cancers can facilitate

treatment planning by determining the initial extent

of the disease. Disease in stages I to III is usually

treated with external beam radiation with or without

brachytherapy. Patients with early disease in the

posterior upper vagina are usually treated with surgi-

cal resection. In advanced disease (stage IV), pelvic

exenteration in addition to radiation is used. The role

of chemotherapy in the treatment of vaginal cancer

has not yet been defined because of the rare nature of

this disease. Current chemotherapeutic regimens used

to treat vaginal cancers are extrapolations from cer-

vical cancer treatment protocols [36].

The vulva

The vulva is comprised of: the mons pubis, labia

major, labia minor, clitoris, vestibular bulb, vestibular

glands and vestibule of the vagina. Diseases of the

vulva constitute only a small fraction of gynecologic

practice. Disorders of the vulva include: Bartholin’s

cyst, vestibular adenitis, vulvar dystrophies, lichen

sclerosis and tumors of the vulva. Only vulvar disease

in which imaging plays a role will be discussed.

Fig. 9. Vaginal carcinoma, Stage II. Axial T2-weighted image shows a mass (t) arising from the lower third of the vagina with

invasion into the right anterior paravaginal muscles (arrows) with loss of the fat-tumor interface. u = urethra, r = rectum.

Table 1

TNM classification and clinical FIGO staging of vaginal

carcinoma

TNM FIGO

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 I Tumor confined to the vagina

T2 II Tumor invades the paravaginal

tissues but does not extend to the

pelvic wall

T3 III Tumor extends to the pelvic wall

T4 IVA Tumor invades mucosa of bladder

or rectum and/or extends beyond

the rule pelvis

NX Regional lymph nodes cannot

be assessed

N0 No regional lymph node metastasis

N1 Regional lymph node metastasis

MX Distant metastasis cannot

be assessed

M0 No distant metastasis

M1 IVB Distant metastasis

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658648

Benign disorders of the vulva

Bartholin’s cysts result from retained secretions

within the vulvovaginal glands and typically occur

due to chronic inflammatory reactions or trauma. Most

patients are asymptomatic unless the cysts become

infected and require drainage. On MRI, Bartholin’s

cysts appear as areas of abnormal signal intensity

located in the posterolateral aspect of the lower third

of the vagina (Fig. 5A). Depending on its fluid com-

position, the cyst is usually of medium to high signal

intensity on T2-weighted images. On T1-weighted

Fig. 10. Hemangioma involving the vulva. (A) Axial T1-weighted and (B) with fat saturation MR images demonstrating the

hemangioma as high signal intensity (arrows), which is best visualized with fat suppression.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 649

images the signal intensity can be increased due to the

proteinaceous content. Radiologically, Bartholin’s

cysts are usually an incidental finding noted during

the course of an MRI examination as they are usually

diagnosed clinically without specific need for imaging.

Other benign lesions of the vulva include neurofibro-

mas and hemangiomas (see Figs. 10, 12).

Carcinoma of the vulva

Epidemiology and pathology

Vulvar cancer is a rare malignancy, accounting

for approximately 5% of all female genital tract

cancers [3,4,37]. Two thirds of all vulvar carcino-

mas occur in women over the age of 60 [38]. The

median age of patients diagnosed with vulva cancer

is between 65 and 70 years. Approximately 85 to

90% of all vulvar cancer is squamous cell carci-

noma. The remaining 10% to 15% are comprised

of melanoma, Bartholin gland cancer, Paget’s dis-

ease, sarcomas, basal cell carcinomas, and adeno-

carcinomas. Most vulvar cancers present as pruritis

or irritation in the vulvar area. Up to 70% of

patients with vulvar cancer have pruritis as their

presenting complaint [39,40]. Another common

presenting complaint is of a lump or lesion in the

vulvar area. Other less common symptoms include:

ulceration of the vulva, bleeding, pain, discharge,

and urinary symptoms.

Fig. 11. Contrast-enhanced CT of vulvar carcinoma, stage III. An irregular and heterogeneous mass (arrows) is seen arising from

the vulva and extends posteriorly invading the anus (a). Bilateral hip prostheses (p) are present causing spray artifact.

Table 2

TNM and FIGO classification of vulvar carcinoma

TNM FIGO

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1a IA Tumor 2 cm or less confined to the

vulva, with stromal invasion 1 mm

or less

T1b IB Tumor 2 cm or less confined to the

vulva, with stromal invasion > 1 mm

T2 II Tumor greater 2 cm confined to the vulva

T3 III Tumor of any size invading the lower

urethra, vagina, perineum or anus

T4 IVA Tumor of any size invading the mucosa

of the bladder or rectum, or tumor fixed

to the pelvic bone

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Unilateral regional lymph node metastasis

N2 Bilateral regional lymph node metastasis

MX Distant metastasis cannot be assessed

M0 No distant metastases

M1 IVB Distant metastasis, including pelvic lymph

node metastasis

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658650

Vulvar tumors are usually separated into two

categories based on their association with human

papillomavirus (HPV). HPV-negative tumors usually

occur in women over the age of 60 and are

associated with vulvar inflammation or lichen scle-

rosis. Typically, these lesions are unifocal and are

usually well differentiated with exuberant keratin

formation [41–43]. HPV-positive tumors occur in

Fig. 12. Vulvar (Bartholin cyst) carcinoma, stage I. (A) Axial T1-weighted and (B) axial T2-weighted MR images show a small

< 2 cm mass (arrow) arising from the Bartholin gland.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 651

women under the age of 60 and are associated with

vulvar intraepithelia neoplasia (VIN). These tumors

tend to be multifocal and occur more frequently in

women who smoke.

Fig. 13. Vulvar carcinoma, stage II. (A) Axial T2-weighted with fat saturation and (B) sagittal T2-weighted images of one patient

and (C) axial T1-weighted image in a different patient show a mass >2 cm arising from the vulva. a = anus, b = bladder, v =

vagina, r = rectum.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658652

Carcinoma in situ, VIN, or Bowen’s disease tend

to occur in younger women and is considered a

precancerous change. The median age at time of

diagnosis is between the ages of 45 and 50 years.

Between 80% to 90% of all VINs contain HPV. These

lesions may be associated with similar lesions of the

cervix and vagina. Typically these lesions form less

keratin than HPV-negative tumors.

Pattern of spread

Approximately 70% of vulvar carcinomas involve

the labia majora or minora [44]. The labia majora is

more commonly involved. The clitoris and perineum

are each involved by 15% to 20% of vulvar cancers.

Up to 10% of cases have such extensive lesions that

the site of origin cannot be determined. Multifocal

lesions account for about 5% of all cases of vulvar

cancer. Vulvar tumors extend locally to invade adja-

cent structures including the vagina, urethra and anus.

In advanced disease, adjacent pelvic bones may

become involved.

Early in the course of vulvar carcinoma, the

tumor spreads to regional lymph nodes. The lym-

phatic drainage of the vulva is comprised of a rich

anastomatic network with multiple extensions

across midline. Typically, the initial regional meta-

stasis involves the superficial inguinal lymph nodes

and then spreads to the deep femoral lymph nodes

with subsequent involvement of the pelvic lymph

nodes. However, many different patterns of spread

have been reported. Vulvar carcinoma can also

spread via hematogenous metastasis, most com-

monly to the lungs.

Staging

The FIGO staging system uses a TNM staging

system (Table 2). As of 1988 the FIGO staging

system switched from that of clinical assessment to

surgical pathological evaluation of the resected

specimen which includes the primary lesion and

regional lymph nodes. This change was imple-

mented due to studies showing that clinical assess-

ment of lymph nodes was inaccurate [45–47]. In

1994, the staging system subdivided stage I into

superficial versus deep invasion.

Prognosis

The prognosis for cure following treatment is

correlated with various clinical and pathological

features. Tumor diameter is such a strong predictive

factor with respect to outcome that it is part of the

Fig. 13 (continued ).

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 653

current FIGO staging system [37]. Lymph node

metastasis is also a strong prognostic factor. Other

factors that consistently correlate with outcome and

are predictive of lymph node metastasis include:

depth of tumor invasion, tumor thickness, and the

presence or absence of lymphatic or vascular involve-

ment. The amount of keratin, the mitotic rate, and the

tumor growth pattern are other factors associated with

Fig. 14. Vulvar carcinoma, stage IV. (A), (B) Axial T2-weighted and (C) and sagittal T1-weighted with gadolinium MR images

show a mass (T) invading the urethra (*) and the vagina (v) and invades the left paravaginal tissues and the mucosa of the

bladder (arrows).

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658654

prognosis. Tumor grade has not been established as a

prognostic factor.

Imaging evaluation of vulvar carcinoma

Currently recommended investigations for the

staging of vulvar carcinoma include: history and

physical exam, chest radiograph, complete blood

count, renal and liver function tests, CT scan, and

electrocardiography (ECG) if indicated. Cystoscopy

and barium enema are recommended in patients

with suspected metastasis or extension to the adja-

cent organs [37]. CT is helpful to assess for

lymphadenopathy and in the evaluation of advanced

disease (Fig. 11). MRI provides superior soft tissue

resolution in displaying the perineal structures in

comparison to US and CT. Thus, MRI would be

the most useful imaging modality with respect to

local vulvar cancers. MRI imaging of vulvar car-

cinoma correlates with the FIGO staging system

as below:

FIGO stage I: Tumors less than 2 cm are seen

on T2-weighted sequences as an increased signal

intensity lesion localized to the vulva (Fig. 12). On

T1-weighted sequences these vulvar carcinomas

usually appear as intermediate signal intensity

lesions [35].

FIGO stage II: On MRI the tumor appears similar

to that described for stage I, but the tumor is greater

than 2 cm and still confined to the vulva. These

tumors may be associated with lymphadenopathy

(Fig 13).

FIGO stage III: Tumor invasion of the lower

urethra, with or without involvement of the vagina

or anus, is seen on MRI as an intermediate to high

signal intensity mass extending into these structures.

Unilateral regional lymph node metastases may or

may not be present.

FIGO stage IVa: Tumor invasion of the upper ure-

thra, bladder, rectal mucosa, or pelvic bony structures

(Fig. 14).OnMRI this is seen as areas of intermediate to

high signal intensity within these structures.

MRI with its excellent soft tissue resolution may

provide additional information regarding prognostic

factors such as lesion size, lesion type (exophytic or

infiltrative), and clitoral involvement. Both CT and

MRI provide information on deep inguinal and

pelvic lymph nodes that are difficult to assess

clinically. CT- or US-guided biopsies can provide

diagnostic information on suspicious lymph nodes,

thus impacting treatment.

Post-radiation changes can be assessed by MRI.

Fibrosis can be differentiated from recurrent tumor, as

the former is lower in signal intensity on T2 and does

not enhance with contrast (Fig 15).

Treatment

As with vaginal cancers, MRI facilitates treatment

planning by defining the extent of the disease. Early

Fig. 14 (continued ).

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658 655

stage disease (stages I and II) can be treated with

vulvectomy and unilateral lymph node dissection.

More advanced disease, however, may require pelvic

exenteration and bliateral lymph node dissection.

Summary

The imaging evaluation of female lower genital

tract cancers has undergone dramatic changes in the

Fig. 15. Post radiation changes of vulvar carcinoma. (A) Axial T2- and (B) T1-weighted post gadolinium MR images

demonstrate fibrosis as irregular low signal intensity strands (arrows) and do not show any appreciable contrast enhancement. v =

vulva, a = anus.

S.D. Chang / Radiol Clin N Am 40 (2002) 637–658656

last two decades. Technical improvements and

increased availability of cross-sectional modalities

(US, CT, MR) have increased their use to such an

extent that they have largely replaced more conven-

tional imaging techniques. US is of limited value in

the staging of vaginal and vulvar malignancies. CT

is most useful for staging more advanced disease of

the vagina and vulva. It is widely available and

provides quick imaging time. CT is used in the

detection and biopsy of suspected lymph nodes and

metastases. MRI provides the best soft tissue con-

trast and is the most useful imaging modality

available to evaluate carcinomas of the vagina and

vulva. Future advancements in the imaging evalua-

tion of vaginal and vulvar cancers will likely focus

on functional imaging.

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S.D. Chang / Radiol Clin N Am 40 (2002) 637–658658

Postsurgical pelvis: treatment follow-up

Kazuro Sugimura, MDa,*, Hiromi Okizuka, MDb

aDepartment of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 6500017 Kobe, JapanbDepartment of Radiology, National Defense Medical College, 3-2, Namiki, Tokorozawa, Japan

Cervical carcinoma

Postsurgical changes

Stage IA carcinoma is usually treated with coni-

zation or total abdominal hysterectomy (TAH). TAH

requires resection of the uterine corpus and cervix

and a small cuff of the upper vagina. The residual

vagina is sutured. During the procedure the uterosac-

ral, uterovesical, round, and broad ligaments are

incised; however, the cardinal ligaments, which are

intimately related to the ureters, are left intact. There

is minimal disturbance of the trigone of the bladder

and the ureters because these structures are not

removed from their beds [1].

Modified radical (extended) abdominal hyster-

ectomy appears to be well suited for patients with 3

to 5 mm of invasion and small lesions that do not

distort the anatomy. This procedure removes the

cervix and the upper vagina (proximal 1–2 cm),

including paracervical tissues. The ureters are dis-

sected in the paracervical tunnel to the point of entry

into the bladder. Because the ureters are unsheathed

and retracted laterally, parametrial and paracervical

tissue can be safety removed medial to the ureter.

This operation may be performed with or without

pelvic lymphadenectomy [1].

Radical abdominal hysterectomy is indicated for

most patients with stage Ib or IIb cancer of the cervix.

This procedure consists of removal of the uterus, the

upper third of the vagina, and the parametrial, para-

cervical, and upper paravaginal tissues. All uterine

ligaments are resected, including the cardinal liga-

ments that are dissected free of the ureters and are

severed at the pelvic sidewall. Lymph node dissection,

with removal of all nodes distal to and including the

common iliac chains, is undertaken at the same time.

Para-aortic lymphadenectomy is performed at the

discretion of the surgeon.

Pelvic exenteration is performed for a few selected

stage IVa lesions and recurrent or persistent carci-

noma of the cervix. Occasionally, pelvic exenteration

is indicated for severe radiation toxicity. In patients

with malignant disease, the most important criterion

for resectability is that the tumor be confined to the

central pelvis without evidence of extension to the

pelvic sidewall or of distant dissemination. Exentera-

tion may be total or partial. Total exenteration con-

sists of removal of the bladder, urethra, uterus,

vagina, and rectum, together with all the pelvic

supporting and connective tissues. Partial exentera-

tion is either anterior, with the rectum preserved, or

posterior, with retention of the bladder and the urethra

[2]. Most exenterations are supralevator, with the

pelvic floor musculature left in situ. Infralevator

exenteration is occasionally necessary, however, and

in these patients the pelvic floor muscles are resected

together with the vulva.

CT and MR appearance

After conization, extensive shortening and subse-

quent incompetence of the cervix may occur (Fig. 1).

Stenosis of the cervical canal, another complication of

cone biopsy, occasionally results in hematometra or

hematocervix. The CT and MR appearance of the

central pelvis is similar after total and radical hyster-

ectomy. In addition to the absence of the uterus, the

opposed vaginal fornices typically form a linear soft

tissue configuration on transaxial images. Nodularity

or fullness of the lateral fornix, seen on postcontrast

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (01 )00016 -1

* Corresponding author.

E-mail address: sugimura@kobe-u.ac.jp (K. Sugimura).

Radiol Clin N Am 40 (2002) 659–680

CTand T1-weighted MR images (T1-WI), may mimic

a mass lesion. In most cases, a normal vaginal cuff is

confirmed by visualizing a smooth, low-signal–

intensity muscular wall on T2-weighted MR images

(T2-WI) (Fig. 2). In some cases, however, fibrotic scar

tissue is present at the vaginal vault. The scar demon-

strates medium to low signal intensity on T2-WI

(Fig. 3) [3–5]. In addition, after radical hysterectomy,

the medium- to high-signal-intensity residual vagina

is short. Metallic clips along the pelvic sidewall can be

detected at the site of lymph node dissection. After

total exenteration, the pelvis is devoid of the bladder,

urethra, genitalia, and rectum. The patient has a

urinary diversion and a colostomy, which may be

visualized during CT or MR examination [5].

In patients who have undergone anterior pelvic

exenteration, there is no identifiable bladder or pelvic

genitalia, but the rectum remains in situ and the

potential space in the anterior pelvis is filled by bowel

(see Fig. 13). Sometimes the rectum occupies a more

anterior position. After posterior pelvic exenteration

(see Fig. 14), the rectum and pelvic genitalia are

Fig. 1. Conization. T2-WI (A) and fat-suppressed contrast-enhanced T1-weighted image (B) show shortening of the cervix.

Defect in the portio (arrows) is also seen.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680660

Fig. 2. After total abdominal hysterectomy. On T2-WI, vaginal cuff is demonstrated as linear low signal intensity. Metallic

clip (arrow).

Fig. 3. One year after radical abdominal hysterectomy (RH). The fibrotic scar demonstrated low signal intensity on T2-WI.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 661

absent and the bladder extends into the posterior

pelvis [5].

Postradiation follow-up

Advanced carcinoma of the cervix is commonly

treated with radiation therapy, usually combination

external beam therapy and brachytherapy [1]. A

residual tumor may be recognized on postcontrast

CT scans in which the tumor may appear as a soft

tissue mass enlarging the cervix with diminished

intravenous contrast enhancement compared with

normal cervical tissue.

A residual tumor displays high signal intensity on

T2-WI, similar to the corresponding primary tumor

(Fig. 4). MRI is superior to CT for delineating the

tumor. Most tumors that respond to therapy decrease

in size within 6 months, and most of these tumors also

Fig. 4. Cervical cancer after radiation. T2-WI 10 days after (A) and 1 year after (B) completion of radiation. Residual tumor displays

high signal intensity on T2-WI. After 1 year, size of the tumor has increased. Invasion of the bladder and the rectum is also seen.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680662

show decreased signal intensity because of radiation

fibrosis (Fig. 5); however, large primary tumors ( > 50

cm3) may show delayed response [6].

Immediately after radiation, inflammation, edema,

and capillary hypervascularity are seen. Pathologically

low-signal– intensity areas on T2-WI correspond to

Fig. 5. Cervical cancer after radiation. T2-WI before (A) and after (B) radiation. Before radiation, bladder invasion is seen. The

tumor has disappeared after radiation; however, vesicovaginal fistula is seen as fluid-filled tracks (arrow).

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 663

low cellularity, prominent fibrosis, and hemosiderin

deposits in the necrotic tissue; however, high signal

intensity on T2-WI after treatment may represent

residual tumor or peritumoral edema/inflammatory

tissue [6,7]. Post-treatment edema or inflammation is

especially prominent within the first 6 months of

treatment. As a result, the accuracy and the specificity

of MR examinations at less than 6 months after the

beginning of radiation therapy are significantly lower

than they are for examinations performed after more

than 6 months [7]. The use of contrast enhancement

may lead to an increase in false-positive findings;

however, gadolinium-enhanced T1-WI is helpful in

evaluating patients with adnexal or pelvic sidewall

recurrence and patients with fistula formation. Recent

studies report that dynamic MRI might be helpful in

making this distinction, with accuracy rates of 82% to

83% [8].

Fig. 6. Cervical cancer after chemotherapy. T2-WI before (A) and 4 months after (B) chemotherapy. Tumor size has decreased

after chemotherapy. Residual tumor demonstrates high signal intensity similar to that of the corresponding primary tumor.

Uterine leiomyoma (asterisk).

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680664

Postchemotherapy changes

Recently, presurgical chemotherapy was used in

patients with advanced cervical cancer to reduce

tumor volume and stage, providing optimal condi-

tions for surgical therapy. After chemotherapy, the

residual tumor demonstrates high signal intensity on

T2-WI, similar to that of the corresponding primary

tumor (Fig. 6). MRI is superior to CT for delineating

the tumor.

In most cases, the size of the tumor is correctly

estimated, but peritumoral inflammatory tissue may

sometimes result in slight overestimation. In the

presence of intratumoral necrosis, the necrotic area

images with low signal intensity on T2-WI. This

finding may be related to hemosiderin deposits in

necrotic tissue [9]. In patients with a completely

successful responses to chemotherapy, the area pre-

viously occupied by cancerous tissue shows low

signal intensity, corresponding to fibrosis and extens-

ive foreign body reaction [10].

Cancer recurrence

Although advances in surgical techniques, radi-

ation therapy, and chemotherapy have resulted in

improved survival rates, approximately 30% of

patients with invasive cervical carcinoma die as a

result of recurrent or persistent disease. The preva-

lence of recurrence of cervical carcinoma varies with

tumor grade, histologic tumor type, tumor size, and

presence of lymph node metastases at the time of

presentation [11].

Typical manifestations of recurrent cervical carci-

noma, such as pelvic masses and lymphadenopathy,

are well recognized; however, less typical manifes-

tations such as peritoneal carcinomatosis and solid

organ metastases also occur. The increasing preva-

lence of these less manifestations is related, in part, to

the use of intensive pelvic radiation therapy, which

has resulted in a shift away from pelvic recurrence

toward distant recurrence. Selected patients with

limited pelvic recurrence not fixed to the pelvic wall

and without evidence of extrapelvic metastasis can be

potentially salvaged by pelvic exenteration with cura-

tive intent [2].

For patients with recurrence in the pelvis after

surgery, a combination of external radiation, depend-

ing on the volume of the tumor, and an additional

parametrial dose with midline shielding is needed [1].

CT and MR appearance

Pelvic recurrence may be located centrally in the

pelvis in the preserved cervix or in the postsurgical

bed and vaginal cuff. Residual tumor may appear as

a heterogeneous soft tissue mass on postcontrast

CT scans.

Fig. 7. Recurrent cervical carcinoma. Recurrent tumor is seen at the vaginal vault (arrows). The tumor demonstrated high signal

intensity on T2-WI, similar to the primary tumor.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 665

On T2-WI, a recurrent tumor demonstrates in-

creased, often heterogeneous, signal intensity. After

contrast administration, a recurrent tumor shows

varying degrees of enhancement (Figs. 7, 8) [4,12].

MRI is superior to CT for delineating the tumor.

On MR images, lesions larger than 1 cm are

accurately depicted [10]. Smaller lesions, however,

may be affected by partial volume averaging and are

more difficult to assess. When recurrence occurs

within the preserved cervix, obstruction of the cervical

os may occur and may result in hydrometra.

Central recurrences may also grow anteriorly,

resulting in contiguous spread to the urinary bladder

and even to the anterior abdominal wall. Such local

recurrence with anterior extension may lead to

ureteral obstruction by direct encasement of the ureter

Fig. 8. Recurrent cervical carcinoma with anterior extension resulting in left hydroureter (arrows). T2-WI (A), fat-suppressed

contrast enhanced image (B). An enlarged lymph node is also seen (arrows).

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680666

or by tumor infiltration of the bladder wall, resulting

in obstruction at the ureteral orifice. It was reported

that hydronephrosis was detected in approximately

70% of pelvic recurrences in an autopsy series [13].

In addition to ureteral obstruction, tumor extension to

the urinary bladder predisposes the patient to vesico-

vaginal fistula. Central pelvic recurrences may extend

posteriorly to involve the rectum, with a recto-vaginal

fistula developing in some instances, or it may extend

laterally to involve the pelvic sidewall [11].

Tumor extension into the bladder and rectum is

suggested by abnormally high signal intensity in

their walls on T2-WI (see Figs. 4, 5). The use of

gadolinium chelates is helpful in the assessment of

bladder and rectal invasion [12]. Evidence of cancer

at the pelvic sidewall and the presence of lymph

node metastases make the patient ineligible for

curative exenteration.

The prevalence of lymphatic involvement by the

tumor varies with the histologic type of the tumor.

Patients with adenocarcinoma of the cervix have a

greater prevalence of metastases than patients with

squamous cell carcinoma [14]. Lymphatic involve-

ment in cervical cancer has traditionally been sepa-

rated into primary and secondary nodal groups

[15–17]. The significance of these two groups is

that the prognosis worsens as nodal involvement

progresses from the primary to the secondary group.

The primary group consists of the paracervical, para-

metrial, internal and external iliac, and obturator

nodes. The secondary group consists of the sacral,

common iliac, inguinal, and para-aortic nodes. Until

the advent of CT and MRI, the nodes in the abdomen

attained considerable size (>1 cm) and often resulted

in urinary tract and intestinal obstruction before com-

ing to clinical attention (Figs. 8, 9).

After the pelvis and lymph nodes, the solid organs

of the abdomen are the most frequent sites of

involvement by recurrent cervical carcinoma [13,14,

17]. CT is useful for detecting clinically unsuspected

extrauterine metastases and lymph node metastases.

The intraabdominal solid organ most commonly

involved is the liver [14]. Liver metastases have been

reported in approximately one third of patients with

recurrent cervical carcinoma [14]. Hepatic recurrence

of cervical carcinoma usually appears as multiple

focal lesions with variable enhancement patterns at

CT (Fig. 10). The adrenal gland is the next most

commonly involved intraabdominal solid organ [14].

Adrenal metastases have been noted in 14% to 16%

of patients with recurrent cervical carcinoma [14,17].

Lung metastases from recurrent cervical carcinoma

occurred in 33% to 38% of patients in three separate

autopsy series [13,14,17]. The prevalence of osseous

metastases in patients with recurrent cervical carci-

noma ranges from 15% to 29% as reported in

multiple autopsy series [17]. Vertebral bodies are by

far the most frequently involved bones, followed by

Fig. 9. Lymph node metastases of cervical carcinoma. Contrast-enhanced CT reveals enlarged paraaortic and inter-aortocaval

lymph nodes (arrows).

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 667

the pelvis, ribs, and extremities [17]. The prevalence

of peritoneal carcinomatosis has ranged from 5% to

27% [15,17].

Endometrial cancer

Postsurgical changes

In stage I, grade 1 lesions, total abdominal hys-

terectomy, bilateral salpingo-oophorectomy, and

cytologic examination of peritoneal washings are

considered sufficient. In stage I, grade 2 and 3

patients, who are at much higher risk, selective pelvic

and para-aortic lymphadenectomy are also performed

to determine the need for adjunctive therapy. Adjuv-

ant radiotherapy has demonstrated improved control

in patients with high grade or deep myometrial

invasion [18,19].

Cancer recurrence

Approximately 17% of patients primarily treated

for endometrial carcinoma experience local or distant

recurrence. Women at low risk of recurrence are

characterized by stage Ia, grade 1 or 2, or stage Ib

grade 1 adenocarcinoma and have recurrence rates of

3% to 15%. The remaining high-risk patients (grade 3

lesions, stage equal to or greater than Ic disease; stage

Ib, grade 2; and aggressive histologies consisting of

sarcoma, papillary serous, clear-cell, and adenosqu-

amous) have recurrence rates of 25% to 45% [20].

Seventy percent of treatment failures for endometrial

carcinoma occur within the first 3 years of therapy.

Recurrences after surgery may occur locally within

the vagina, regionally within the pelvic or para-aortic

lymph nodes, or systemically. For low-risk endome-

trial cancers that recur, the vagina is the sole site of

failure in 30% to 50% of the patients. It is well

recognized as risk, particularly in patients who do not

receive adjuvant therapy. Vaginal recurrences may

result from local spread through lymphatic channels

or implantation at the time of surgery. Although

vaginal recurrences occur anywhere in the vagina,

the most common location is at the vaginal apex

(Figs. 11, 12).

Distant dissemination of endometrial carcinoma

may develop secondary to local failure. When recur-

rence is isolated and occurs at the vaginal apex,

radiotherapy is performed. When recurrence is more

extended or extrapelvic, chemotherapy is usually

used. Recurrent intrapelvic endometrial carcinoma

Fig. 10. Liver metastases of cervical carcinoma. Contrast-enhanced CT reveals multiple low-attenuation lesions in the liver.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680668

or distal metastasis is visualized as is recurrent cer-

vical carcinoma. Hepatic, lung, and osseous meta-

stases and peritoneal carcinomatosis may develop.

Ovarian cancer

Postsurgical changes

All histologic types of ovarian carcinoma are

treated in the same way. The standard surgical proce-

dure for ovarian carcinoma is total abdominal hyster-

ectomy and bilateral salpingo-oophorectomy. Partial

or complete omentectomy should be performed, and in

advanced disease an attempt should be made to resect

as much metastatic tumor as possible [21].

Postsurgical CT or MR appearance depends on the

extent of the resection. The uterus and ovaries are

absent, and vaginal fornices typically form a linear

soft tissue configuration on transaxial images. The

potential space is occupied by small bowel and

fibrous tissue [4].

Fig. 11. Recurrent endometrial carcinoma is seen at the vaginal vault. T2-WI (A), fat-suppressed contrast-enhanced image (B).

Recurrent tumor shows high signal intensity on T2-WI and good enhancement (arrows).

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 669

Cancer recurrence

The recurrence rate of ovarian cancer is high,

primarily because two thirds of patients have tumors

that have spread beyond the pelvis by the time of

diagnosis. Aggressive surgical cytoreduction fol-

lowed by chemotherapy has been the therapeutic

keystone for primary and recurrent ovarian disease.

However, it has been reported that if the recurrent

lesion is larger than 2 cm in diameter, surgical

resection may improve survival [22,23].

Serial measurement of the serumCA-125 levels is a

routine practice in the management of ovarian cancer.

A CA-125 level that remains elevated after chemo-

therapy is a strong indication of a residual tumor. Con-

versely, it is well recognized that a normal CA-125

level does not exclude the presence of a tumor [23].

Even at laparotomy, the detection of all tumors is

not feasible; up to 50% of patients who have a

negative findings on second-look surgery eventually

have a recurrent tumor. The goals of reassessment

during and after adjuvant chemotherapy include not

Fig. 12. Pelvic sidewall recurrence of endometrial carcinoma. T2-WI (A), fat-suppressed contrast-enhanced image (B). Recurrent

tumor shows high signal intensity on T2-weighted image and good enhancement (arrows).

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680670

only determining the presence or absence of a tumor

but also establishing the volume of the residual

tumor, its location, and the degree of the tumor

response to the initial therapy. Recent developments

in consolidation to salvage chemotherapy, including

paclitaxel, topotecan, high-dose chemotherapy with

hematologic support, and intraperitoneal chemother-

apy, have increased the option in treating women with

residual or recurrent tumors.

CT and MR appearance

The ability of CT and MRI to depict a tumor is

influenced by the size and location of the tumor

recurrence. Although the accuracy for lesions smaller

than 2 cm is low, it increases for lesions larger than 2

cm [22,23]. Ovarian carcinomas usually spread by

wide implantation on the omental and peritoneal

surfaces. Tumor depiction is excellent for lesions

Fig. 13. Recurrent ovarian cancer (immature teratoma). T2-WI (A) and fat-suppressed contrast-enhanced image (B) show cystic

mass with fat component (arrows) and ascites. Signal intensity of the fat component decreased on fat-suppressed contrast-

enhanced image.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 671

located in the cul-de-sac, in the vaginal cuff, and on

the liver surface. Lesions located in the peritoneum

and mesentery, however, are not well displayed

[22,23]. Tumor implants are recognized as soft tissue

on postcontrast CT and marked enhancement nod-

ules or plaques with gadolinium chelates on MRI

Fig. 15. Peritoneal implants with ovarian cancer. Contrast-enhanced CT demonstrates peritoneal implants protruding into

ascites (arrow).

Fig. 14. Extensive ascites and peritoneal implants with ovarian cancer. T2-WI demonstrates extensive ascites and multiple

peritoneal implants (arrows).

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680672

(Figs. 13–15). The greater contrast resolution of

enhanced MRI allows better differentiation between

small peritoneal tumors and the adjacent soft tissues

and ascites. However, enhancement with gadolinium

chelates is a nonspecific finding. The site of peri-

toneal or bowel inflammation becomes enhanced and

has an appearance identical to that of peritoneal

tumors. Enhancement adjacent to the surgical inci-

sions is also a common finding anteriorly in the

middle region of the abdomen and the pelvis. In

addition, in the setting of acute bowel obstruction, it

is difficult to differentiate intestinal and mesenteric

enhancement caused by bowel obstruction from

recurrent tumor. CT performed after intraperitoneal

administration of iodinated contrast material may be

more useful for detecting small peritoneal metastases

than conventional CT.

Postoperative complications

Hematoma

The most common postoperative complications

are infection and hematoma formation. On CT scans,

attenuation characteristics of hematoma depend on the

duration of the hemorrhage. An acute hematoma

( + 70 to + 90 HU) has a higher attenuation value than

circulating blood because clot formation and retrac-

tion cause greater concentration of red blood cells. As

stated previously, contrast-enhanced dynamic CT may

document active arterial extravasation either as a focal

high-density area surrounded by a large hematoma or

as a diffuse area of high density. Subacute hematoma

often has a lucent halo and a soft tissue density center

(Fig. 16). Chronic hematoma appears as a low-density

mass ( + 20 to + 40 HU) with a thick, dense rim.

Peripheral calcification also may be present. Although

hyperdensity is specific for acute hematoma, a sub-

acute hematoma can be confused with a retroperito-

neal tumor; a chronic hematoma may have an

appearance similar to that of an abscess, a lymphocele,

a cyst, or an urinoma.

MRI appearance of hemorrhage depends not only

on the age of the hematoma but also on the magnetic

field strength. Signal intensity of an acute hematoma

imaged using a low magnetic field (0.15 to 0.5 T) is

less than that of muscle on T1-WI and slightly higher

than that of muscle on T2-WI. Acute hematoma

examined using a high magnetic field (1.5 T), how-

ever, has a signal intensity similar to that of muscle

on T1-WI and marked hypointensity on T2-WI. The

marked hypointensity on T2-WI is attributed to the

presence of intracellular deoxyhemoglobin. A fluid

level with a greater signal in the dependent layer on

T1-WI also has been described in large, acute hema-

tomas. MR findings at this stage are nonspecific

because abscesses and tumors may have similar

appearances [24].

Subacute hematoma often has three distinct layers

of signal on T1-WI: a low-intensity rim correspond-

ing to the hemosiderin-laden fibrous capsule, a high-

intensity (similar to fat) peripheral zone, and a

medium-intensity central core (slightly greater than

muscle) (Fig. 16). On T2-WI, the signal intensity of

the central core increases relative to that of the

peripheral zone, whereas the rim remains low in

intensity. With further maturation of the hematoma,

the central core, which represents the retracted clot,

continues to diminish in size, and the entire hema-

toma eventually becomes a homogeneous, high-sig-

nal– intensity mass surrounded by a low-intensity rim

on both T1- and T2-WI. Progressive increase in

signal intensity of a hematoma parallels the formation

of methemoglobin.

Abscess

The CT appearance of an abscess is variable

depending on its age and location. During its earliest

stage, an abscess consists of a focal accumulation of

neutrophils in a tissue or organ seeded by bacteria

and thus appears as a mass with an attenuation value

near that of soft tissue. As the abscess matures, it

undergoes liquefactive necrosis. Concomitantly,

highly vascularized connective tissue proliferates at

the periphery of the necrotic region. At this stage, the

abscess has a central region of near-water attenuation

surrounded by a higher attenuation rim that usually

enhances after the administration of intravenous con-

trast material. Approximately one third of abscesses

contain variable amounts of air, appearing on CT

scans as either multiple small bubbles or an air fluid

level (Fig. 17).

On T1-WI abscess can be seen as a predominantly

medium-signal– intensity mass, which increases in

signal intensity on T2-WI. The presence of multiple

foci of necrosis and liquefaction produces a more

heterogeneous appearance. Gas is present in slightly

more than one third of abscesses and may appear as

multiple small bubbles or as a large collection with an

air fluid level. Abscesses commonly obliterate adja-

cent fat planes and thicken surrounding muscles,

mesentery, and bowel wall. The presence of a long

air fluid level suggests communication with the gas-

trointestinal tract. Ancillary findings include displace-

ment of surrounding structures, thickening or

obliteration of adjacent fascial planes, and increased

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 673

density of adjacent mesenteric fat. Whereas most

abscesses are round or oval, those adjacent to solid

organs, such as the liver, may have a crescentic or

lenticular configuration.

Fistula or sinus tract

A fistula is an abnormal communication between

two epithelialized surfaces, and a sinus is a blind-

ending abnormal tract that can open onto the skin

surface. Fistulas and sinus tracts commonly arise

secondary to sepsis or to inflammatory gastrointesti-

nal conditions. Fistulas also may be caused by pen-

etrating tumors or radiation therapy.

Enterovesical fistulas most commonly affect the

peritoneal bladder dome, and vesicovaginal fistulas

involve the posterior bladder wall. Rectovaginal and

sigmoidovaginal fistulas are classified into (1) those

involving the peritonized portion of the vagina and

the Douglas pouch [7] (upper third), (2) direct con-

Fig. 16. Subacute hematoma. Contrast-enhanced CT (A) and T1-WI (B). Hematoma demonstrates heterogeneous mass on

contrast-enhanced CT. T1-weighted images displays a high-signal-intensity peripheral zone and a medium-signal-intensity

central core.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680674

nections through the rectovaginal septum (middle

third), and (3) communication between the anal

sphincter and the perineal body (lower third) [25].

Sinus tracts are frequently associated with intraabdo-

minal or pelvic abscesses. Fistulas are not easily

visualized on CT or MRI unless they are large, and

identification depends on indirect evidence, such as

air in an abnormal location.

On T2-WI fistulas appear as fluid-filled tracks

surrounded by lower signal intensity tissue represent-

Fig. 18. Lymphocele. Contrast-enhanced CT shows lymphocele in the left iliac region (arrow).

Fig. 17. Abscess. Contrast-enhanced CT shows gas-containing, low-attenuation fluid collection mass with an enhancing wall.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 675

ing fibrosis, granulation tissue, or tumor. A key

finding is the presence of a focal interruption in the

low-signal-intensity muscle of the bladder, rectum, or

vagina (see Fig. 5). The use of gadolinium chelates

improves fistula detection.

Sinus tracts are identified by their orientation and

communication with the skin surface. On MR

images, sinuses appear as linear or tubular structures

that run from the pelvis to the skin surface, usually

the perineum.

Injection of contrast material into the fistula

improves visualization and helps establish the pres-

ence of communication with adjacent abscesses or the

genitourinary tract. An iodinated contrast agent at a

concentration of 5% to 10% is useful for CT fistulo-

graphy; normal saline provides good contrast for MRI

studies [26].

Lymphocele

A lymphocele (lymphocyst) is an accumulation of

lymph fluid, contained by the parietal peritoneum,

adjacent to the pelvic sidewall [27]. It is a relatively

uncommon complication of lymphadenectomy and

occurs in less than 5% of patients. Factors implicated

in the development of lymphoceles include the extent

of lymphadenectomy, radiation therapy before sur-

gery, tumor invasion of the lymphatics, and treatment

with heparin as a prophylaxis against deep venous

thrombosis [27].

Lymphoceles are visualized as well-circumscribed

oval structures (Fig. 18). They may contain multiple

septa. Because of their protein content, they show

high signal intensity on T2-WI. The configuration

and position of a lymphocele, together with its signal

characteristics, facilitate recognition on imaging stud-

ies, particularly when there is a history of previous

lymph node dissection [4].

Postradiation changes

The recognition of changes in the irradiated pelvis

is important lest they be mistaken for recurrent neo-

plasms. MRI is superior to CT for demonstrating

those changes after radiation therapy. Acute radiation

leads to endarteritis of small blood vessels and

increased endothelial permeability, resulting in the

formation of interstitial edema and congestion. A

chronic radiation effect is caused by ischemia and

fibrosis, resulting in impaired organ function, stric-

ture, or fistula formation.

Uterus

In females of reproductive age, the uterus may

undergo several changes after radiation therapy, and

the myometrium and the endometrium are affected

[28]. The myometrium demonstrates a generalized

decrease in signal intensity on T2-WI that may be

seen as early as 1 month after treatment. Eventually

this leads to a loss of distinction of the zonal anatomy.

The endometrium undergoes atrophy. These changes

become apparent after approximately 6 months. Two

mechanisms account for these changes, a direct

radiation effect on the uterine tissues and radiation-

induced ovarian hypofunction, which causes reduced

hormonal stimulation of the uterus. Cervical os steno-

sis may occur 3 to 6 months after the completion of

high-dose radiotherapy [29].

Ovary

In females of reproductive age, the irradiated

ovaries become smaller and demonstrate a homoge-

neous, decreased signal intensity on T2-WI, reflect-

ing atrophy of the ovarian follicles, increased fibrosis,

and vascular sclerosis. [29].

Vagina

During the acute phase, the wall of the vagina

exhibits increased signal intensity on T2-WI because

of edema and hypervascular inflammatory change,

whereas the vagina becomes atrophic and shows a

homogeneously low signal intensity during the

chronic phase from fibrosis. More severe changes,

manifested by inflammation and tissue necrosis with

ulceration that can progress to fistula formation, can

also be seen.

Bladder

The severity of bladder radiation injury is not

directly related to the interval from the start of

therapy because the effects of severe radiation may

Fig. 19. Radiation cystitis with vesicovaginal fistula. (A) T1-W, (B) T2-W, and (C) contrast-enhanced images. Thickening of

the bladder wall, with heterogeneous high signal intensity on T2-WI. Vesico-vaginal fistula is clearly demonstrated on

contrast-enhanced image (arrow). Thickening of the perirectal fat and increased signal intensity of striated muscle on T2-WI

are also seen.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680676

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 677

be identified in the acute, subacute, or chronic phases.

Symmetrical thickening of the walls of the urinary

bladder is commonly seen in patients who have

received a total radiation dose of 54 Gy or greater.

Postradiation MR studies of the bladder demonstrate

a range of changes that correlate with the severity of

histologic findings. Although symptom severity gen-

erally parallels the MR grades of radiation change,

minor changes may be identified in totally asympto-

matic patients [30]. The earliest MR feature is high

signal intensity of the bladder mucosa on T2-WI,

which most likely represents mucosal edema. This

high signal intensity usually commences at the tri-

gone but may spread to involve the whole mucosa.

The normal bladder wall thickness (< 5 mm) is pre-

served. With more severe radiation injury, the bladder

wall increases in width to more than 5 mm, and it

demonstrates a uniformly high signal intensity on

T2-WI. After contrast administration, the bladder

wall enhances, but there may be differentially

increased enhancement of the mucosa [30]. During

the subacute or chronic stage, the inner aspect of the

bladder wall may remain as a thin band of low signal

intensity because of radiation-induced fibrosis,

whereas the rest of the wall is of high signal intensity.

In addition to thickening and abnormal signal char-

acteristics of the bladder wall, bladder radiation

changes in their most extreme form include the

formation of fistulae or sinus tracts arising from the

bladder (Fig. 19).

Rectum and perirectal tissue

Radiation-induced injury of the colon, or radiation

colitis, occurs in two time frames. In some patients, it

develops as an acute process, during or within a few

weeks of the time of radiation exposure. In others, it

develops as a late complication of therapy. The early

form presents as self-limited diarrhea and tenesmus

and is usually recognized clinically without the need

for imaging studies. The late form is a chronic,

relentlessly progressive process that begins 2 to 20

years after radiation exposure. It is a result of radi-

ation-induced, obliterative endarteritis, and it is, in a

sense, a form of ischemic disease [30]. CT findings

include narrowing and mural thickening of the irra-

diated segment. The presacral space is widened by

increased perirectal fat and perirectal fibrous tissue

that usually encircle the rectum and the perirectal fat

like a sleeve. The combination of increased perirectal

fat and thickened perirectal fascia can produce a

target appearance, with the thick-walled, stenotic

rectum forming the center of the target. The symmet-

rical increase in perirectal fibrous tissue found after

radiation helps distinguish radiation proctitis from the

general asymmetrical appearance of recurrent tumor

or postoperative fibrosis [31].

Radiation-induced changes have been studied

more extensively using MRI. The severity of these

changes is graded based on MRI signal intensity and

thickness of the wall of the involved organ. The first

MR evidence of radiotherapy change in the rectum is

increased signal intensity in the submucosa on T2-

WI. At this stage, the outer muscle layer of the rectal

wall retains its normal low signal intensity on T2-WI

sequences. With progression of radiation injury, the

rectal wall becomes thickened (> 6 mm in the dis-

tended state), and the outer muscle layer demonstrates

high signal intensity on T2-WI. As a result of these

changes, differentiation between the submucosa and

muscle layers is lost [30]. After the administration of

gadolinium chelates, rectal tissue enhances but there

is no distinction between the component layers. The

most severe rectal changes include evidence of a

fistula or a sinus tract from the rectum. As with

bladder radiation injury, the degrees of rectal change

are unrelated to the time from the start of treatment,

and minor rectal MR findings may be seen in

asymptomatic patients [30].

The perirectal fascia becomes thickened after

radiation therapy measuring more than 3 mm at

the S4/5 vertebral level. This is more commonly

seen in the subacute phase [30]. The presacral space,

which normally has a maximum diameter of less

than 1.5 cm at the S4/5 vertebral level, is widened,

usually during the chronic phase after treatment. The

space may be filled with fat (high signal intensity on

both T1- and T2-WI) or fluid (low signal intensity

on T1-WI and high signal intensity on T2-WI).

Alternatively, presacral tissue may demonstrate low

signal intensity on T1 and T2-WI, most likely

because of fibrosis.

Pelvic fat and striated muscles

Normal pelvic fat demonstrates homogeneous

high signal intensity on T1- and T2-WI. Radiation

therapy changes lead to a heterogeneous decrease in

signal intensity on T1- and T2-WI [30] within the

pelvic fat.

Normally, the striated pelvic muscles demonstrate

medium signal intensity on T1-WI and decreased

signal intensity on T2-WI. After radiation, however,

they demonstrate high signal intensity on T2-WI,

probably related to edema, with the involved muscles

corresponding to the radiation field (Fig. 19) [30].

Radiation muscle changes are commonly identified

during the subacute phase [31].

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680678

Bone marrow

MRI is excellent for the evaluation of radiation-

induced bone marrow changes. Normal bone marrow

demonstrates medium to high signal intensity (less

than the signal intensity of fat) on T1-WI. Radiation

results in myeloid depletion and an increase in fat

content, accounting for the high signal intensity of

irradiated bone marrow on T1-WI. Radiation-induced

osteonecrosis may cause bone marrow to display low

signal intensity on T1-WI and heterogeneous signal

intensity on T2-WI.

Insufficiency fractures occur as a result of normal

physiologic stress on bone with deficient elastic

resistance. They are often seen in postmenopausal

women, in patients who have had exposure to radi-

ation, or in patients with who have had high-dose

steroid therapy. The typical distribution of insuf-

ficiency fractures is sacroiliac joint in 61%, upper

sacrum (S1-2) in 28%, lower sacrum (S3-5) in 4%,

pubis in 4%, and ischium in 3%. The lesions dem-

onstrate low signal intensity on T1-WI and variable

signal intensity on T2-WI. Symmetrical fractures are

found in more than half the patients [32] (Fig. 20).

Fig. 20. Insufficiency fracture. T1-W (A) and contrast-enhanced (B) images. Bilateral sacroiliac joints demonstrate low signal

intensity on T1-weighted image (arrows) and slight contrast enhancement.

K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680 679

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K. Sugimura, H. Okizuka / Radiol Clin N Am 40 (2002) 659–680680

Index

Note: Page numbers of article titles are in boldface type.

A

Abscesses, after pelvic surgery, 683

Adenocarcinoma, clear cell, of vagina, 650

Adnexal masses, 597–617

benign versus malignant, 606

CA-125 levels in, 597

Doppler ultrasonography of, 602, 606

MR imaging of, 606–607, 609–610, 613–614

benign-appearing lesions, 607, 609–610, 613

heterogeneous signal intensities in, 610, 613

high T1 signal intensity in, 609

simple cystic lesions, 607, 609

solid lesions, 610

benign versus malignant, 607

malignant-appearing lesions, 614

protocol for, 607

prognosis for, 597–598

transvaginal sonography of, 598–599, 601–602

metastases in, 601

morphology in, 599, 601–602

Advanced Breast Biopsy Instrumentation system, in

core biopsy, of breast cancer, 493

Artificial neural network, to diagnose breast disease,

BI-RADS lexicon for, 417–418

Atypical ductal hyperplasia, core biopsy of, 490–491

Atypical lobular hyperplasia, core biopsy of, 496

B

Bartholin’s cysts, of vulva, 659–660

BI-RADS lexicon, 409–430, 492–493

and communication with referring physicians,

419–420

breast parenchymal density, 416–417

computer-aided diagnosis, 417–418

for mammography, 409–411

for MR imaging, 424–428

lexicon development, 424–428

potential usefulness of, 428

for ultrasonography, 420–424

lesion characterization, 420–421

lexicon development, 421–423

observer variability in, 423–424

limitations of, 418–419

potential usefulness of, 411–416

category 3: probably benign, 412–416

final assessment categories, 411–412

Biopsy

core, of breast cancer . See Core biopsy.

endometrial, for postmenopausal bleeding,

527–528

fine-needle aspiration, of breast cancer,

434–435, 437

image-guided, of breast cancer, 518

Bladder, postradiation changes in, 686, 688

Bleeding, postmenopausal.

See Postmenopausal bleeding.

Bone marrow, postradiation changes in, 688–689

BRCA genes, and risk of breast cancer, 400

MR imaging for, 465

Breast cancer. See also Breast disease.

Breast Imaging Reporting and Data System in .

See BI-RADS lexicon.

conservative treatment of, 501–516

and benign sequelae resembling recurrent

tumor, 514

evidence supporting, 501–502

local failure of, 511–514

long-term follow-up of, 508–509, 511

mammography after, 506–508

patient selection for, 502

specimen radiography in, 502–504, 506

core biopsy of . See Core biopsy.

digital mammography of .

See Digital mammography.

MR imaging of, 437, 443–466

difficult histologies in, 457–459

0033-8389/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.

PII: S0033 -8389 (02 )00032 -5

Radiol Clin N Am 40 (2002) 681–687

for occult primary breast cancer, 464

for staging, 459–462

for tumor recurrence, 462, 464

image acquisition in, 445–449

fat suppression in, 445

Memorial Sloan-Kettering protocol for,

445–449

proposed minimum requirements, 445

image analysis in, 449–451, 457

American College of Radiology lexicon

for, 449

clip artifact in, 453

delayed imaging time in, 456

fat suppression in, 453

kinetics in, 450–451, 453

misregistration in, 454–455

morphology in, 449–450

unilateral examinations in, 456–457

window levels in, 454

in high-risk patients, 464–465

sensitivity of, 443–445

to assess recurrence, 519

to assess residual disease, 462

to assess treatment response, 462

to guide core biopsy, 484–485

to localize lesions, 518–519

ovarian metastases from, 601, 614

positron emission tomography of . See Positron

emission tomography.

screening for, mammography in .

See Mammography.

sestamibi scintimammography of .

See Sestamibi scintimammography.

surgeon’s perspective on, 518–519

ultrasonography of, 431–441

barriers to acceptance of, 435–437

false-positives and nonstandard thresholds,

436–437

lack of proof of benefit, 435–436

nature of examination, 436

problems with reproducibility, 436

small footprint probes, 436

for screening, 434–435

for staging, 432–434

versus other modalities, 437–439

Breast disease. See also Breast cancer.

surgeon’s perspective on, 517–520

breast cancer, 518–519

findings suspicious for local recurrence, 519

image-guided biopsy, 518

lesions detected by screening, 517–518

new imaging modalities, 519

patient with physical findings, 518

Breast Imaging Reporting and Data System.

See BI-RADS lexicon.

Breast parenchymal density, BI-RADS lexicon for,

416–417

Brenner tumors, MR imaging of, 610

C

CA-125 levels

in adnexal masses, 597

in ovarian cancer, 524, 680

Calcifications, in breast

BI-RADS lexicon for, 409–410

recurrent breast cancer and, 513–514

stereotactic core biopsy of, 490

Calcified ovarian tumors, CT of, 637–639

Cancer

breast . See Breast cancer.

cervical . See Cervical cancer.

endometrial . See Endometrial cancer.

ovarian . See Ovarian cancer.

vaginal . See Vaginal cancer.

vulvar . See Vulvar cancer.

Cervical cancer, 579–595

CT of, 523–524

epidemiology of, 579

lymph node evaluation in, 585

MR imaging of, 523–524, 580–582

and treatment planning, 593–594

coils in, 587

contrast enhancement in, 589–592

motion artifact suppression in, 589

protocol for, 592–593

pulse sequences and imaging planes in,

587, 589

postchemotherapy changes in, 674–675

MR imaging of, 675

postoperative changes in, 669–670

after hysterectomy, 669–670

after pelvic exenteration, 669–670

CT of, 669–670

MR imaging of, 669–670

postradiation follow-up of, 672–674

MR imaging in, 672–674

prognosis for, 580

recurrence of, 675–677

CT of, 675–677

MR imaging of, 675–677

staging of, 580

MR imaging in, 582, 584–585

stage I, 582

Index / Radiol Clin N Am 40 (2002) 681–687682

stage II, 582, 584

stage III, 584–585

stage IV, 585

Cervical intraepithelial neoplasia, epidemiology and

pathology of, 648–649

Chemotherapy

for breast cancer, assessing response to, MR

imaging in, 462

for cervical cancer, 674–675

Clear cell adenocarcinoma, of vagina, 650

Color Doppler ultrasonography

in postmenopausal bleeding, 535

of endometrial cancer, 555

of endometrial polyps, 549

Computed tomography

of abscesses, after pelvic surgery, 683

of cervical cancer . See Cervical cancer.

of endometrial cancer, 522, 567

of hematomas, after pelvic surgery, 683

of ovarian cancer . See Ovarian cancer.

of vaginal cancer, 651–653

Computer-aided diagnosis, of breast disease, 471

BI-RADS lexicon for, 417–418

Contrast agents, in MR imaging, of cervical cancer,

589–592

Contrast-enhanced mammography, of breast

cancer, 472

Core biopsy, of breast cancer, 483–500

advantages of, 485, 487, 490

fewer operations, 485, 487

lower cost, 487, 490

controversies in, 492–494

Advanced Breast Biopsy Instrumentation

system, 493

complete lesion removal, 493

epithelial displacement, 493–494

lesion selection, 492–493

follow-up of, 496–497

for fibroepithelial tumors, 495

for lobular carcinoma in situ and atypical lobular

hyperplasia, 496

for papillary lesions, 495–496

imaging-histologic discordance in, 495

limitations of, 490–492

calcification retrieval, 490

false negatives, 492

histologic underestimation, 490–492

learning curve, 492

MR imaging in, 484–485

radial scars in, 495

rebiopsy after, 494–495

stereotactic, 483

ultrasonography in, 483–484

Cystadenocarcinomas, MR imaging of, 614

Cysts

adnexal, MR imaging of, 607, 609

Bartholin’s, of vulva, 659–660

D

Diaphragmatic adenopathy, CT of, 632

Digital mammography, of breast cancer, 437,

467–475

advanced adjunctive applications of, 470–471

clinical trials of, 472–474

computer-aided diagnosis in, 471

contrast enhancement in, 472

cost-effectiveness of, 474–475

dual-energy subtraction mammography in

functional components of, 467–468

image acquisition in, 468

image display in, 468–470

image processing in, 468

image storage and retrieval in, 470

stereomammography in, 472

systems for, 470

telemammography in, 471–472

tomosynthesis in, 472

Dilatation and curettage, for postmenopausal

bleeding, 427–528

Doppler ultrasonography

in postmenopausal bleeding, 532–533, 535

of adnexal masses, 60, 606

of endometrial cancer, 555

of endometrial polyps, 549

Dual-energy subtraction mammography, of breast

cancer, 472

Ductal carcinoma in situ

recurrence of, 519

stereotactic core biopsy of, 490–492

Dysgerminomas, CT of, 630–631

E

Endodermal sinus tumors, CT of, 631–632

Endometrial biopsy, for postmenopausal bleeding,

527–528

Index / Radiol Clin N Am 40 (2002) 681–687 683

Endometrial cancer, 565–578

and postmenopausal bleeding .

See Postmenopausal bleeding.

CT of, 522, 567

endometriosis and, 634

epidemiology of, 565–566

imaging findings in, 568–570, 573–574

and treatment planning, 574–577

stages 0, I, IA, IB, 569–570, 573

stage II, 573

stages III, IIIA, IIIB, IIIC, 573

stages IV, IVA, IVB, 573

imaging protocol for, 568

MR imaging of, 522, 567–568

contrast-enhanced, 568

postoperative changes in, 677–678

prognosis for, 566

radiation therapy for, 576–577

recurrence of, 678

staging of, 566–567

transvaginal sonography of, 567

Endometriomas, MR imaging of, 609

Endometriosis, and endometrial cancer, 634

Endometrium, in postmenopausal bleeding, 528–531,

546–547, 549

Endovaginal sonography, in postmenopausal

bleeding. See Postmenopausal bleeding.

Epithelial displacement, in core biopsy, of breast

cancer, 493–494

Estrogen replacement therapy, for postmenopausal

bleeding. See Postmenopausal bleeding.

F

Fat necrosis, of breast, resembling recurrent breast

cancer, 514

Fibroepithelial tumors, of breast, core biopsy of, 495

Fibromas, ovarian, MR imaging of, 610

Fine-needle aspiration biopsy, of breast cancer,

434–435, 437

Fistulas, after pelvic surgery, 683–686

Fluorodeoxyglucose, in positron emission

tomography, of breast cancer, 475

G

Germ cell tumors, CT of, 630–632

Granulosa cell tumors

CT of, 630

MR imaging of, 614

Gynecologic imaging, 521–526

of cervical cancer, 522–524 .

See also Cervical cancer.

of endometrial cancer, 521–522 .

See also Endometrial cancer.

of ovarian cancer, 524–525 .

See also Ovarian cancer.

H

Hematomas, after pelvic surgery, 683

Hodgkin’s disease, treatment of, and risk of breast

cancer, 400–401

Human papillomavirus, and vulvar cancer, 660–661

Hysterectomy, for cervical cancer, 669–670

Hysterosonography, in postmenopausal bleeding.

See Postmenopausal bleeding.

I

Intraluminal contrast agents, in MR imaging, of

cervical cancer, 589–590

Intravenous contrast agents, in MR imaging, of

cervical cancer, 590–592

K

Krukenberg tumors, MR imaging of, 632

L

Leiomyomas

and postmenopausal bleeding .

See Postmenopausal bleeding.

MR imaging of, 610

Lobular carcinoma in situ, core biopsy of, 496

Lymph node evaluation, in cervical cancer, 585

Lymphangiography, of vaginal cancer, 651

Lymphoceles, after pelvic surgery, 686

M

Magnetic resonance imaging

after breast-conserving treatment, 508

BI-RADS lexicon for . See BI-RADS lexicon.

Index / Radiol Clin N Am 40 (2002) 681–687684

in patient selection, for breast-conserving

treatment, 502

in postmenopausal bleeding .

See Postmenopausal bleeding.

of abscesses, after pelvic surgery, 683

of adnexal masses . See Adnexal masses.

of breast cancer . See Breast cancer.

of cervical cancer . See Cervical cancer.

of endometrial cancer, 522, 567–568

contrast-enhanced, 568

of endometrial polyps, 549–551

of fistulas, after pelvic surgery, 684–685

of hematomas, after pelvic surgery, 683

of lymphoceles, after pelvic surgery, 686

of postradiation changes, in pelvis, 686,

688–689

of vagina, normal anatomy in, 648

of vaginal cancer, 651–658

of vulvar cancer, 664–665

Mammography, 395–407

accuracy of, 401–404

false-negative interpretations in, 402

false-positive interpretations in, 402–404

observer variability in, 401–402

after breast-conserving treatment, 506–509, 511

to detect local recurrence, 512–514

BI-RADS lexicon for, 409–411

controversies in, 396–399

age to initiate screening, 396–397

decrease in mortality, 396

optimal screening interval, 399

stopping screening, 397–399

digital . See Digital mammography.

in high-risk women under 40, 399–401

proven benefit of, 395

Mesenteric root disease, CT of, 632–633

Metastases

from ovarian cancer, 628–629

to ovaries, 601, 614, 632

benign mimics of, 639–640

Motion artifacts, in MR imaging, of cervical

cancer, 589

Mucinous cystadenocarcinomas, MR imaging

of, 614

N

Nodal spread

by cervical cancer, 677

by ovarian cancer, 628

Non-epithelial ovarian cancer, CT of, 629–632

O

Ovarian cancer

CA-125 levels in, 524, 680

CT of, 524–525

imaging of, clinical role of, 640–642

postoperative changes in, 678–679

CT of, 681–683

MR imaging of, 681–683

recurrence of, 679–680

staging of, 619–646

and treatment planning, 619–622

CT in, 622, 624–626, 628–635, 637–640

benign mimics of metastatic disease,

639–640

calcified tumors, 637–639

complex histology in, 633–634

distant metastases, 628–629

local spread, 625

mesenteric root disease, 632–633

nodal spread, 628

non-epithelial cancer, 629–632

peritoneal spread, 625–626, 628

primary papillary serous peritoneal cancer,

634–635, 637

primary tumor, 622, 624–625

pseudomyxoma peritonei, 639

superior diaphragmatic adenopathy, 632

pathology in, 619

Ovarian fibromas, MR imaging of, 610

Ovaries

metastases to, 601, 614, 632

postradiation changes in, 686

P

Papillary lesions, of breast, core biopsy of,

495–496

Papillary serous carcinoma, of peritoneum, CT of,

634–635, 637

Pelvic exenteration, for cervical cancer, 669–670

Pelvic fat, postradiation changes in, 688

Perirectal tissue, postradiation changes in, 688

Peritoneal spread, by ovarian cancer, 625–626, 628

Phyllodes tumors, of breast, core biopsy of, 495

Plain films

in patient selection, for breast-conserving

treatment, 502–504, 506

of vaginal cancer, 651

Index / Radiol Clin N Am 40 (2002) 681–687 685

Polyps, endometrial, and postmenopausal bleeding,

549–551

Positron emission tomography, of breast cancer,

475, 477

applications of, 475

diagnostic accuracy of, 475

for distant metastases, 475–477

for regional nodal metastases, 475

to monitor treatment, 477

Postmenopausal bleeding, 527–563

Doppler ultrasonography in, 532–533, 535

endometrial biopsy for, 527–528

endometrial cancer in, 555–557

endovaginal sonography and

hysterosonography in, 555

MR imaging in, 556–557

endometrial hyperplasia in, 546–547, 549

endovaginal sonography and

hysterosonography in, 547, 549

MR imaging in, 549

endometrial polyps in, 549–551

endovaginal sonography and

hysterosonography in, 549

MR imaging in, 549–551

endovaginal sonography and hysterosonography

in, 528–532

endometrial morphology in, 529–531

endometrial thickness in, 528–529

techniques for, 557

estrogen replacement therapy for, 535–536

leiomyomas in, 551–555

endovaginal sonography and

hysterosonography in, 553

MR imaging in, 553–555

MR imaging in, 535

techniques for, 558

tamoxifen for, 539–546

endovaginal sonography and

hysterosonography in, 541–543

MR imaging in, 543–546

versus normal endometrium, 535–536

endovaginal sonography and

hysterosonography in, 536–537

MR imaging in, 537–539

Pseudomyxoma peritonei, CT of, 639

R

Radial scars, and risk of breast cancer, 495

Radiation therapy

effects of

on bladder, 686, 688

on bone marrow, 688–689

on ovaries, 686

on pelvic fat and striated muscles, 688

on rectum and perirectal tissue, 688

on uterus, 686

on vagina, 686

for cervical cancer, 672–674

for endometrial cancer, 576–577

Rectum, postradiation changes in, 688

S

Scars, of breast, resembling recurrent breast

cancer, 514

Scintimammography, sestamibi. See Sestamibi

scintimammography.

Serous cystadenocarcinomas, MR imaging of, 614

Sestamibi scintimammography, of breast cancer,

437–438, 477–479

applications of, 478–479

diagnostic accuracy of, 477–478

Sex-cord stromal tumors

CT of, 630

MR imaging of, 614

Sinus tracts, after pelvic surgery, 683–686

Stereomammography, of breast cancer, 472

Stereotactic biopsy, of breast cancer, 483

Striated muscles, postradiation changes in, 688

T

Tamoxifen, for postmenopausal bleeding.

See Postmenopausal bleeding.

Telemammography, of breast cancer, 471–472

Teratomas, CT of, 631

Tomosynthesis, in digital mammography, of breast

cancer, 472

U

Ultrasonography

after breast-conserving treatment, 508

BI-RADS lexicon for . See BI-RADS lexicon.

color Doppler . See Color

Doppler ultrasonography.

Doppler . See Doppler ultrasonography.

Index / Radiol Clin N Am 40 (2002) 681–687686

endovaginal, in postmenopausal bleeding .

See Postmenopausal bleeding.

in postmenopausal bleeding, 528

of adnexal masses . See Adnexal masses.

of breast cancer . See Breast cancer.

of endometrial cancer, 567

Uterus, postradiation changes in, 686

V

Vagina, 647–658

benign disease of, 648

cancer of . See Vaginal cancer.

embryology and anatomy of, 647

normal imaging appearance of, 647–648

postradiation changes in, 686

Vaginal cancer, 648–658

CT of, 651–653

epidemiology and pathology of, 648–650

lymphangiography of, 651

MR imaging of, 651–658

pattern of spread of, 650

plain films of, 651

prognosis for, 651

staging of, 650–651

treatment of, 658

Vaginal intraepithelial neoplasia, epidemiology and

pathology of, 648–649

Vulva, 658–665

benign disease of, 659–660

cancer of . See Vulvar cancer.

normal imaging appearance of, 647–648

Vulvar cancer, 660–665

epidemiology and pathology of, 660–662

MR imaging of, 664–665

pattern of spread of, 663

prognosis for, 663

staging of, 663

treatment of, 665

Y

Yolk sac tumors, CT of, 631–632

Index / Radiol Clin N Am 40 (2002) 681–687 687