Benign Breast Diseases Epidemiology, Evaluation,.17[1]

Benign BreastDiseases:Epidemiology,Evaluation, andManagement

BUNJARUNGRUANG,MD, and JOSEPHL. KELLEY, III, MD

Department of Gynecologic Oncology, Magee-Womens Hospital,Pittsburgh, Pennsylvania

Abstract: Benign breast diseases are common andencompass a spectrum of disorders. The majority ofdiagnoses will stem from a patient presenting withsymptoms such as a mass or discomfort, or as a resultof breast imaging which shows abnormalities leadingto percutaneous biopsy. When mammographic andpathologic findings are disconcordant or when a high-risk lesion that can be associated with a preinvasiveor invasive malignancy is found, formal excisionalbiopsy is recommended.Key words: benign breast disease, palpable masses,radiographic abnormalities, fibrocystic change, be-nign neoplasms, mastalgia

Benign breast diseases are common andinclude presentations involving palpablemasses, radiographic abnormalities, andmastalgia. The incidence of benign breastlesions begins to rise during the seconddecade and peaks in the fourth to fifthdecades, as opposed to malignant dis-

eases, where the incidence continues toincrease after menopause with a peakincidence at the age of 70 years.1–12

The majority of patients presentingwith breast complaints will be found tohave benign conditions.1–8 With thebreast imaging and percutaneous needlebiopsy, a diagnosis can be accomplishedrapidly and without requiring additionalsurgical management in the majority ofthese lesions. After establishment of anonmalignant diagnosis, treatment is gen-erally aimed at symptomatic relief andpatient education.

Fibrocystic ChangeThe most frequent benign disorder of thebreast is fibrocystic changes, affectingpremenopausal women aged 20 to 50years.1–8 Fibrocystic changes are gener-ally multifocal and bilateral. Patientspresent with breast pain and tender no-dules. Although the exact pathogenesis

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Correspondence: Joseph L. Kelley, III,MD,Division ofGynecologic Oncology, Magee-Womens Hospital, 300Halket Street, Suite 2130 Pittsburgh, PA 15228.E-mail: [email protected]

CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 54 / NUMBER 1 / MARCH 2011

CLINICAL OBSTETRICS AND GYNECOLOGYVolume 54, Number 1, 110–124r 2011, Lippincott Williams & Wilkins

is unclear, a hormonal imbalance withestrogen predominance seems to be afactor in its development.13

Fibrocystic changes are observed clini-cally in up to 50% and histologically in90% of women.14,15 Pathologic correlatesinclude the presence of cysts (macro andmicro), adenosis (increased number orsize of glandular components), ductalepithelial hyperplasia, apocrine metapla-sia, radial scar, and papillomas. The in-distinct clinical and pathologic findingscall into question the validity of referringto it as a disease. On account of theimportance of determining whether theselesions are a risk factor for the subsequentdevelopment of breast cancer, they areevaluated under a classification systemproposed by Dupont and Page,16 as non-proliferative lesions and proliferative le-sions without and with atypia [atypicalhyperplasia (AH)]. The majority of breastbiopsies (up to 70%) show nonprolifera-tive lesions.

The subsequent risk for breast cancerfor each of these lesions is classified basedon the histologic appearance of the le-sion.16,17 There is no elevated breast can-cer risk in women with biopsy-provennonproliferative lesions, whereas prolif-erative disease without atypia and withatypical ductal or lobular hyperplasiahave an increased breast cancer risk, ran-ging from relative risks of 1.3 to 1.9 and3.9 to 13.0, respectively, when comparedwith the general population.16,18,19 Abso-lute risk, however, for both proliferativediseases with and without atypia is quitelow. More than 80% of patients with adiagnosis of AH do not develop invasivecancer during their lifetimes.

NONPROLIFERATIVE BREASTLESIONS

Nonproliferative lesions include cysts, pa-pillary apocrine change, epithelial-relatedcalcifications, ductal ectasia, nonscleros-ing adenosis, and periductal fibrosis.Nonproliferative breast lesions are not

associated with an increased risk of breastcancer.20

Breast CystsCysts are fluid-filled, round or ovoidmasses derived from the terminal ductlobular unit. These are common and areseen in as many as one-third of womenaged 35 to 50 years. Most are foundincidentally, but about 20% to 25% ofwomenwill have a palpablemass.17 Acuteenlargement of cysts may cause sudden,severe, and focal pain. Ultrasound eva-luation provides rapid and accurate eva-luation and is the preferred imaging test,as cysts cannot be distinguished fromsolid masses by clinical examination ormammography. Alternatively, a fine-needle aspiration (FNA) can be per-formed to establish the diagnosis.

Simple cysts are circumscribed and an-echoic, with posterior acoustic enhance-ment and absence of solid componentson ultrasound. These cysts are benign bydefinition and if asymptomatic, no inter-vention is necessary. Aspiration can beperformed to relieve pain. The cyst shouldresolve with removal of the fluid, and thepatient can be reassured. If the cyst recurs,reaspiration is reasonable. If a breast cystrecurs a third time, the patient should beevaluated by a surgeon for considerationof excision.21 If clear fluid is obtained onaspiration of a cyst, no further investiga-tion is required; however, if the fluid isbloody, it should be sent for cytologicanalysis. As gross cysts are not associatedwith an increased risk of carcinoma devel-opment, the current consensus on themanagement is routine follow-up withoutfurther therapy.17

Complicated cysts do not meet all cri-teria for simple cysts on ultrasound ex-amination. Sonographic characteristicsinclude internal echoes, fluid or debrislevels, thin septations, a thickened orirregular wall, and lack of posterioracoustic enhancement.22 Incidence is re-ported in approximately 5% to 5.5% of

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all breast ultrasound examinations. Theselesions are rarely malignant (0.4%) butshould be aspirated to confirm diagno-sis.22–24 However, if the lesion also in-cludes an intracystic mass, it should beregarded as ‘‘suspicious for neoplasm’’and managed as solid lesions, with eithera core needle biopsy or surgical exci-sion.22,25

PROLIFERATIVE BREAST LESIONSWITHOUT ATYPIA

Proliferative lesions without atypia includeductal hyperplasia, sclerosing adenosis,radial scar, and intraductal papillomaor papillomatosis. These lesions are asso-ciated with a slightly increased risk of de-veloping breast cancer, approximately 1 to2 times that of the general population witha relative risk of 1.3 to 1.9.10,16,18,19,26–29

However, as the risk of subsequent breastcancer in this population is small, in-creased surveillance and chemopreven-tion are not indicated.

Ductal HyperplasiaThe most common proliferative breastlesion without atypia is epithelial hyper-plasia.Normally, breast ducts are lined by2 layers of low cuboidal cells with specia-lized luminal borders and basal contrac-tile myoepithelial cells. Any increase incell number within the ductal space isregarded as ductal epithelial hyperplasia.Further classification is based on thedegree of architectural and cytologic fea-tures of the proliferating cells. Usual duc-tal hyperplasia or simple hyperplasiadenotes an increased number of cells thatmay vary in cell size and shape but retainthe cytologic features of benign cells with-out architectural distortion.30 This entitycan be stratified into 3 types. In mildhyperplasia, proliferating epithelial cellsare a 3 to 4-cell layer, whereas moderatehyperplasia describes epithelial prolifera-tion more than 4 cells thick, often withaccompanying bridging of the luminalspace. In florid hyperplasia, the lumen

is distended and may be obliterated.The most important cytologic features ofmild, moderate, or florid epithelial hyper-plasia are an admixture of cell types(epithelial cells, myoepithelial cells, andmetaplastic apocrine cells) and variationin the appearances of epithelial cells andtheir nuclei.31 No additional treatment isneeded for this pathologic entity and it isnot associated with an increased risk ofbreast cancer.

Sclerosing AdenosisAdenosis is characterized by an increasednumber or size of glandular componentsinvolving the lobular units. Sclerosingadenosis of the breast is defined as alobular lesion of disordered acinar, myo-epithelial, and connective tissue elements,which can mimic infiltrating carcinomaboth grossly and microscopically.32 His-tologically, it is characterized by increasedfibrous tissue and interspersed glandularcells. It can present as a palpable mass oras a suspicious finding at mammo-graphy.32,33 Sclerosing adenosis is stronglyassociated with other proliferative le-sions, including epithelial hyperplasia,intraductal or sclerosing papilloma,complex sclerosing lesion, and apocrinechanges. In addition, it can coexist withboth invasive and in-situ cancers.34 Scler-osing adenosis has been shown to be a riskfactor for invasive breast cancer indepen-dent of its association with other prolif-erative lesions of the breast but the risk issmall (RR 1.7) and chemoprevention isnot indicated.32,35

Radial ScarsRadial scars are pseudoproliferative le-sions of uncertain significance. They arecharacterized microscopically by a fibro-elastic core with radiating ducts and lobulesdisplaying variable epithelial hyperplasia,adenosis, duct ectasia, and papillomatosis.Radial scars are a histopathologic diagno-sis, usually an incidental finding on eitherpercutaneous or excisional biopsy. Radial

112 Rungruang and Kelley


scars are occasionally large enough tobe detected by mammography, but theradiographic features are nonspecificand cannot reliably be differentiated fromcarcinoma.36–39

Radial scars may serve as a milieu forthe development of atypical epithelialproliferations, including atypical ductalhyperplasia (ADH), atypical lobular hy-perplasia (ALH), lobular carcinoma insitu, and ductal carcinoma in situ.40 Forthis reason, when radial scars are foundon core biopsy, the entire lesion must beexcised. In addition to the possibility offinding an unrecognized in situ or invasivecomponent, there is some evidence thatthe radial scars may be premalignant le-sions.41 The risk of subsequent breastcancer in this population is small and noadditional treatment beyond excision isrecommended.

Intraductal Papilloma and PapillomatosisIntraductal papilloma is a discrete tumorof the epithelium of mammary ducts. Itcan arise at any point in the ductal systemand shows a predilection for the extremeends of the ductal system, the lactiferoussinuses and the terminal ductules.42 Thecentral papillomas tend to be solitary,whereas the peripheral ones are usuallymultiple, with 5 or more papillomas re-presenting papillomatosis. Solitary ormultiple intraductal papillomas may pre-sent as a palpable mass, a spontaneousserous or serosanguinous discharge,nodule on mammographic or ultrasono-graphic evaluation, or as a filling defecton ductography.43

A solitary papilloma consists of amonotonous array of papillary cells thatgrow from thewall of a cyst into its lumen.In particular, they are characterized bythe formation of epithelial fronds thathave both the luminal epithelial and theouter myoepithelial cell layers, supportedby a fibrovascular stroma. The epithelialcomponent can be subjected to a spec-trum of morphologic changes, ranging

from metaplasia to hyperplasia, atypicalintraductal hyperplasia, and in-situ carci-noma. The risk represented by the occur-rence of such abnormalities in anotherwise benign papilloma is currentlydebated.44 Central single papillomas havenot been considered premalignant ormar-kers of risk when they are not associatedwith atypia. There is a significant correla-tion between the presence of ADH inpapillary lesions on core biopsies and thepresence of invasive or preinvasive carci-noma of the breast in excisional biop-sies.45,46 The standard recommendationfor management of papillomas is that exci-sional biopsy be performed when diag-nosed by percutaneous needle biopsy.29,47–50

Once the diagnosis of solitary papilloma isconfirmed by excisional biopsy, no addi-tional treatment is needed. It has beensuggested that the recurrence of papillo-mas is related to the presence of prolifera-tive breast lesions (including usual ductalhyperplasia, ADH, and lobular neoplasia)in the surrounding breast tissue.44

Papillomatosis is defined as aminimumof 5 clearly separate papillomas within alocalized segment of breast tissue, usuallyin a peripheral or subareolar location.Multiple papillomas tend to occur bilat-erally, and their probability of having anin-situ or invasive carcinoma is higherthan with the central papilloma. In pa-tients with multiple papillomas on exci-sional biopsy, thorough sampling of thespecimen and diagnostic radiographic ima-ging of contralateral breast tissue is sug-gested to rule out malignancy.51 Availabledata suggest that the finding of a solitary,central, benign duct papilloma does notcarry any increased risk for subsequentbreast cancer, whereasmultiple papillomasmay indicate a slightly elevated risk forsubsequent breast cancer but no addi-tional treatment is advised.52–54

When severe ductal papillomatosis oc-curs below the age of 30 years, it is termedjuvenile papillomatosis and is associatedwith a heightened risk for breast cancer.



The actual risk of breast cancer is un-known for this rare entity, but synchro-nous breast cancer has been reported inup to 15%of cases55 and long-term radio-graphic follow-up is recommended.

PROLIFERATIVE BREAST LESIONSWITH ATYPIA

Proliferative lesions with atypia includeatypical ductal and lobular hyperplasiaand atypical papilloma or papillomatosis.These lesions have an increased breastcancer risk, ranging from relative risksof 3.9 to 13.0, when compared with thegeneral population. However, absoluterisk is low and the majority of patientsdo not develop invasive cancer duringtheir lifetime.16,18,19 Various risk reduc-tion strategies exist including the use ofselective estrogen receptors modifiers de-pending on the individuals Gail Modelrisk assessment.56,57

AHAH is an incidental finding on percu-taneous biopsy of mammographic ab-normalities or palpable breast masses.Classifications include ADH and ALH,and together they are referred to as AH.Histologic appearance of these lesionsincludes ductal or lobular elements withuniform cells and loss of apical-basalcellular orientation. With the increasinguse of mammography and detection ofmicrocalcifications, ADH is being diag-nosed in 30% of patients undergoingpercutaneous biopsy. In contrast, this dia-gnosis is rare (4%) among patients havingbiopsies for a palpable mass.58 Similarly,ALH is usually detected on percutaneousbiopsy for microcalcifications.

The relative risk of invasive breastcancer associated with AH ranges from3 to 6-fold.16,19,59,60 Multifocal lesions,especially those associated with calcifica-tions, increase the risk to 10-fold.60 Pa-tients who also have a first-degree relativewith breast cancer have nearly a 10-foldincreased risk as well.58,61

AH is associated with an increasedrisk of developing both ipsilateral andcontralateral breast cancer.17 The riskfor breast cancer is higher in the affectedbreast, but the contralateral breast is alsoat risk.16,17,62,63

Women with ADH develop cancerusually within 10 to 15 years of the diag-nosis, and the risk declines after 15years.62,64 Patients with this diagnosis oncore biopsy require excisional biopsy toconfirm the diagnosis, and this results inan upgrade in diagnosis to ductal carcino-ma in situ in 15% to 50% of cases.65–67

ALH has a 4-fold increased risk of breastcancer and is 3 times more likely to arise inthe ipsilateral breast than the contralateralside.68 Patientswith these conditions shouldbe counseled regarding long-term surveil-lance and consideration for chemopreven-tion with tamoxifen or raloxifene.56,57,69

Benign Neoplasms ofthe Breast

FIBROADENOMA

Fibroadenoma is a common lesion of thebreast, reported in up to 25%of asympto-matic women.70 The peak incidence isbetween the ages of 15 and 35 years. Theetiology is unknown but a hormonal re-lationship is likely as they persist duringthe reproductive years, can increase in sizeduring pregnancy or with estrogen ther-apy, and regress after menopause.71,72 Adirect association had been noted betweenoral contraceptive use before the age of 20years and the risk of fibroadenoma.73

Clinically, a fibroadenoma can presentas a palpable,mobile, firm, andnontendermass. Fibroadenomas are solid tumorscontaining glandular and fibrous tissue.Macroscopically, a fibroadenoma is awell-circumscribed, firm mass, less than3 cm in diameter, and the cut surface of isboth lobulated and bulging. Microscopicappearance consists of a proliferationof epithelial and mesenchymal elements,



with stroma proliferating around tubu-lar glands (pericanalicular growth) orcompressed cleft-like ducts (intracanali-cular growth). Often both types of growthare seen in the same lesion.73 When thetumor is larger than 10 cm, it is termeda giant fibroadenoma and is seen com-monly in adolescents. Excision is recom-mended to exclude the presence of atypiaor a phylloides tumor and to restorecosmesis to the affected breast.

The diagnosis of fibroadenoma is con-firmed by percutaneous core biopsy.Ultrasound alone or FNA cannot differ-entiate between a fibroadenoma and aphylloides tumor. Patient and physicianpreference often determines long-termman-agement of this condition. Excision or ob-servation are options depending on the ageof the patient, concordant imaging, clinicalcharacteristics, and pathologic findings onpercutaneous core needle biopsy.74,75 Dis-advantages of excisional surgery includecosmetic change, damage to the breast’sduct system, and confounding future mam-mographic imaging because of architecturaldistortion, skin thickening, and increasedfocal density. Ultrasound-guided cryoabla-tion is an excellent treatment option forsmall (<3cm) fibroadenomas in womenwho wish to avoid surgery.76–80 In the clin-ical scenario where the fibroadenoma in-creases in size or becomes symptomatic,surgical excision is recommended.76,77,81

Juvenile fibroadenoma is a variant offibroadenoma that presents between 10and 18 years of age, usually as a painless,solitary, unilateral mass, greater than5 cm in size. Juvenile fibroadenomas aredistinguished from adult fibroadenomasby exhibiting more glandularity and great-er stromal cellularity. These lesions growrapidly and can reach up to 15 or 20 cm indimension. Surgical removal is recom-mended to restore breast symmetry.82

PHYLLOIDES TUMOR

Phylloides tumor is a fibroepithelial tumorof the breast with a spectrum of changes.

Benign phylloides tumor is difficult todifferentiate from fibroadenoma. Al-though phylloides tumors may appearsimilar to fibroadenoma on ultrasound,they are characterized by rapid growthand local recurrence if excised withoutadequate margins. Hypercellular stromawith cytologic ayptia, increased mitoses,and infiltrative margins of the lesion arethe most reliable discriminators to sepa-rate lesions with recurrence and malig-nant behavior. If a phylloides tumor issuspected, core needle biopsy is manda-tory. In terms of surgical treatment ofthese tumors, it is important to recognizephylloides tumor because it should beexcised completely with clear margins toreduce local recurrence.83,84

LIPOMA

Breast lipomas are benign solitary tumorscomposed of mature fat cells. Thesepresent as soft, nontender, well-circum-scribed masses that can be smooth orlobulated. Usually, both mammographyand ultrasound imaging are unrevealingunless the tumor is large.85 FNA biopsyshows fat cells with or without epithelialcells. The diagnosis is confirmed with acore or excisional biopsy. If the clinicaldiagnosis of lipoma is confirmed by eitherFNA biopsy or core biopsy and the mam-mogram and ultrasound are concordant,the patient can be followed with clinicalexaminations.However, if the diagnosis isnot certain or the lesion grows rapidly, thetumor should be surgically removed.30,85

There is no increased risk of subsequentbreast cancer associated with lipomas.

ADENOMA

Adenomas are pure epithelial neoplasms ofthe breast. They are distinguished fromfibroadenomas by their sparse stromal ele-ments. The most common types are lactat-ing and tubular adenomas. Both lactatingand tubular adenomas occur during thereproductive ages, with lactating adeno-mas occurring during pregnancy. They



are well circumscribed and lobulated.Although they may require excisionbecause of their size, they do not havemalignant potential.30

Lactating adenoma is the most preva-lent breast mass during pregnancy andpuerperium. It presents as a solitary ormultiple, discrete, palpable, freely mova-ble breast mass that tends to be small(<3 cm). The lesion is well circumscribedand lobulated and is characterized byhyperplastic lobules lined by actively se-creting cells. Lactating adenomamay alsodevelop in ectopic locations, such as theaxilla, chest wall, or vulva.86,87 Althoughthe tumor may spontaneously involute,surgical removal or medical therapy toshrink the tumor may be necessary be-cause of its mass effect.86

Tubular adenoma of the breast pre-sents as a solitary, well-circumscribed,firm mass. Histologically, tightly packedacinar structures are seen in a sparselycellular stroma. This tumor may resemblea noncalcified fibroadenoma radiogra-phically. In addition, tiny, punctuate,and irregular microcalcifications in di-lated acini may be prominent onmammo-graphy and ultrasonography.88 Theselesions may require excision only becauseof mass effect, but they do not havemalignant potential.30

Inflammatory Conditionsof the BreastA variety of inflammatory and reactivechanges can be observed in the breast.Although some of these changes are aresult of infectious agents, others do nothave a well-understood etiology and mayrepresent local reaction to a systemic dis-ease or a localized antigen-antibody reac-tion, and are classified as idiopathic. It isimportant to recognize that inflammatorybreast cancer can mimic an infectiousor inflammatory condition. Most patientswith inflammatory breast cancer are

diagnosed after an initial treatment withantibiotics failed to show clinical improve-ment. Imaging and biopsies are helpful indistinguishing this cancer from an infec-tious etiology.

MASTITIS

Acute mastitis usually occurs during thefirst 3 months postpartum in the settingof breast feeding. It is a cellulitis of theinterlobular connective tissue within themammary gland and can result in abscessformation and septicemia. The diagnosisis based on clinical symptoms. Risk fac-tors include improper nursing technique,nipple cracks or fissures, stress, and sleepdeprivation. Microorganisms can thenenter through the open skin and populatewithin areas of milk stasis.89,90 Clinically,this results in a diffusely painful, swollen,and erythematous breast and is oftenassociated with a febrile reaction.

As the duration of symptoms beforestarting treatment is found to be the onlyindependent risk factor for abscess devel-opment, early diagnosis and early man-agement of mastitis is of value.91 There islittle consensus on the type or duration ofantibiotic therapy andwhen to begin anti-biotics. As lactation mastitis is a processof subcutaneous cellulitis, detection ofpathogens in breast milk may not alwaysbe possible; therefore, breast emptyingwith frequent nursing ormanual pumpingand beginning empiric antibiotic ther-apy, such as with dicloxacillin or otherbroad spectrum penicillin, seems to be themost appropriate approach. When anabscess occurs, incision and drainage orpercutaneous drainage are options formanagement.91

Mastitis can also be seen inwomenwhoare not lactating but evaluation for inflam-matory breast cancer is mandatory. Cellu-litis of the breastwith orwithout an abscessis common in women who are over-weight, have large breasts, or have hadprior surgery or radiation to the breast.92

This is usually seen in the lower half of



the breast, where sweat accumulates, andStaphylococcus aureus is themost commonresponsible organism. Similar to lacta-tional mastitis, acute episodes of infectionshould be treated with appropriate anti-biotics, with precutaneous or incisionaldrainage of the abscess if present. Forpatients with recurrent infections of thelower breast area, the skin should bekept clean and dry, creams and powdersshould be avoided, and cotton bras shouldbe worn.92

Miscellaneous BenignLesions of the Breast

MAMMARY DUCT ECTASIA

Mammary duct ectasia is a disease ofmiddle-aged to elderly parous women,who can present with nipple discharge, apalpable subareolarmass, noncyclicalmas-talgia, nipple retraction, or with a non-puerperal infection which may manifestwithout fever. Usually, this is an asympto-matic lesion and is detected by mammo-gram with a finding of microcalcifications.The most important histologic feature ofthis disorder is the dilatationofmajorductsin the subareolar region. These ducts con-tain eosinophilic, granular secretions andfoamy histiocytes both within the ductepithelium and the lumen, and these lumi-nal secretions may undergo calcificationsthat may be the presenting sign in manypatients.93

The clinical presentation of nipple in-version can mimic invasive carcinoma.The etiology is not well known, but smok-ing is an associated factor.93–96Mammaryduct ectasia generally does not requiresurgery and should bemanaged conserva-tively.96 There is no evidence that mam-mary duct ectasia is associated withincreased risk for breast cancer.

FAT NECROSIS

Fat necrosis of the breast is a benigncondition that most commonly occurs as

the result of breast trauma or surgery. Fatnecrosis can be confused with a malig-nancy on physical examination and radio-logic studies, appearing as a spiculateddensemasswith skin retraction, ecchymo-sis, erythema, and skin thickening.97 It issometimes necessary to biopsy these le-sions to confirm the diagnosis, althoughexperienced radiologists can usually de-termine that a lesion represents fat necrosison the basis of mammographic and ultra-sound findings such as oil cysts.30,98 Eventhe macroscopic appearance of the benignlesion can suggest a malignant tumor. His-tologically, the diagnosis of fat necrosis ischaracterized by anuclear fat cells, oftensurrounded by histiocytic giant cells andfoamy phagocytic histiocytes.99 Once thediagnosis is established, excision is notnecessary, and there is no increased riskof subsequent breast cancer.

GALACTOCELE

Galactoceles are cystic collections of fluid,usually caused by an obstructed milk duct.These present as soft cystic masses onphysical examination. On mammographicimaging, galactoceles may appear as anindeterminate mass, unless the classic fat-fluid level is seen, and ultrasound mayshow a complex mass. Diagnosis is madeby clinical history and aspiration, whichyields a milky substance.100 Once thediagnosis is established, excision is notnecessary.

HAMARTOMA

Hamartomas are uncommon benign tu-mor-like nodules that have varyingamounts of glandular, adipose, and fibroustissue. They either present as discrete, en-capsulated, painless masses or are foundincidentally on screening mammography.The classic mammographic appearance isa circumscribed area consisting of bothsoft tissue and lipomatous elements, sur-rounded by a thin translucent zone.101,102

Although the pathogenesis of the lesion isnot clear, it is thought to result from a



dysgenesis rather than a true tumorousprocess. Some cases have been reported tobe related to a genetic defect calledCowdensyndrome, which is associated with multi-ple hamartomas and increased risk ofearly onset breast and thyroid cancer.103

The diagnosis can be difficult to makewith limited tissue, as hamartomas do nothave specific diagnostic features. On ma-croscopic examination, hamartomas aretypically well-circumscribed lesions withsmooth contours. Histologically, the mostcharacteristic appearance is an otherwisenormal breast and fat tissue distributed ina nodular fashion within fibrotic stromasurrounding and extending to individuallobules, which obliterates the usual inter-lobular-specialized loose stroma.101,102,104

As coincidental malignancy can occur,surgical excision is recommended.30

PSEUDOANGIOMATOUS STROMALHYPERPLASIA

Pseudoangiomatous stromal hyperplasia(PASH) is a benign stromal proliferation,which may present as a mass on physicalexamination or radiologic imaging. Itsclinicopathologic spectrum ranges fromincidental, microscopic foci to clinicallyand mammographically evident breastmasses.105 In fact, PASH is found as anincidental microscopic finding in as manyof 25% of breast biopsy specimens.On gross examination, PASH is usually awell-demarcated mass with a smooth ex-ternal surface, and the cut surfaceconsists of homogeneous white and rub-bery tissue. The histologic appearance ischaracterized by anastomosing slit-likeempty spaces lined by spindle cells.Although PASH is benign, it should bedistinguished from a malignancy, suchas mammary angiosarcoma.30,106 If thereare any suspicious features on imaging, thediagnosis of PASHon a core biopsy shouldnot be accepted as a final diagnosis andexcisional biopsy should be performed.There is no increased risk of subsequentbreast cancer associated with PASH.

MastalgiaBreast pain is classified as cyclical, non-cyclical, or extramammary. Breast cancermay present as breast pain, thus a breastexamination is indicated. Younger wo-men (less than 30 y of age) with com-plaints of cyclical diffuse breast painwho are at no increased risk for breastcancer and have a normal breast exam-ination should have a follow-up examina-tion scheduled in 2 to 3months to confirmthe initial impression of normalcy. Forwomenwho have localized breast pain, anincreased risk of breast cancer or anabnormal breast examination, furtherevaluation with a targeted breast ultra-sound and mammography is indicated.

CYCLICAL BREAST PAIN

Cyclical breast pain is caused by normalhormonal changes associated with ovula-tion that stimulate the proliferation ofnormal breast tissue. In addition, cyclicalbreast pain can be associated with phar-macologic hormonal agents such as oralcontraceptives. Minor discomfort is nor-mal and is usually bilateral and diffuse innature. Cyclical mastalgia is more severeand persistent than normal cyclicalpain.107 Fibrocystic breast changes canalso be painful in response to hormonalstimulation during ovulation. If moderateor severe breast pain has been presentfor less than 6 months, there is a highprobability of spontaneous remissionand the patient should be reassured with-out further treatment. In women above35 years of age without imaging in the lastyear, reassurance can be given after nor-mal mammography to exclude other find-ings. If the pain is present for more than6 months or more than 6 weeks withpersistent and very severe pain, symptom-atic treatment may be offered.108 A 3-month course of 10mg tamoxifen canreduce pain in 71% to 75% of womenwith few side effects, the most commonbeing hot flashes.109,110 Danazol hasalso been shown to be effective, but



with more side effects, such as nausea,headaches, depression, and menstrual ir-regularity.111–113 Danazol should onlybe considered if there is no response totamoxifen.108

NONCYCLICAL BREAST PAIN

Noncyclical breast pain is not related tohormonal changes associated with themenstrual cycle and may occur in bothpremenopausal and postmenopausal wo-men. These lesions tend to be unilateraland variable in the location in the breast.Large pendulous breasts may be painfulsecondary to stretching of Cooper’s liga-ments.Additional symptoms include neckand shoulder pain, headache, and a rashunder the breasts. These patients mayhave up to 85% relief in their symptomsfrom wearing a more supportive bra.114

Hormone replacement therapymay causenoncyclical breast pain in up to one-thirdof women, but this usually resolves spon-taneously over time.115,116 Other causes ofnoncyclical breast pain include inflamma-tory breast cancer, pregnancy, priorbreast surgery, thrombophlebitis (Mon-dor disease), andmedications.117Many ofthese conditions resolve spontaneously,but symptomatic treatments can be of-fered for persistent or severe pain. Non-steroidal anti-inflammatory drugs mayrelieve pain due to Mondor disease.108

EXTRAMAMMARY PAIN

Extramammary pain is referred pain fromsources outside the breast. This can includechest wall pain, spine problems, trauma, orscarring fromaprevious biopsy. Chestwallpain is usually lateral and burning in qual-ity,with either localizedordiffuse pain. It ismost frequently because of the pectoralismajor muscle, and this pain can be repro-duced by asking the patient to place herhand flat on the iliac wing and push in-ward. Spinal problems typically occur inolder women because of the accumulationof spinal disease in the neck and upperthorax with age. Trauma or trauma-in-

duced fat necrosis can also be a source ofextramammary pain. Gallbladder diseaseand ischemicheart diseasemayalsopresentas extramammary pain. Treatment is gen-erally aimed at the underlying cause ofpain.108

SUMMARY

Benign breast diseases are common andencompass a spectrum of disorders. Whena patient presents with a breast mass, care-ful history, physical examination, and in-dicated imaging and biopsies are key todiagnosis.Most patients will have a benigncondition, but some of these conditionsconfer increased risk of subsequent breastcancer, therefore accurate diagnosis is im-portant. Excisional biopsy should be re-commended for mass lesions that causebreast distortion or for high-risk lesionsfound on percutaneous sampling.

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