Minimally invasive breast_biopsies__recent_results_in_cancer_research_

Recent Results in Cancer Research 173

Managing EditorsP. M. Schlag, Berlin ● H.-J. Senn, St. Gallen

Associate EditorsP. Kleihues, Zürich ● F. Stiefel, LausanneB. Groner, Frankfurt ● A. Wallgren, Göteborg

Founding EditorP. Rentchnik, Geneva

Renzo Brun del Re (Ed.)

Minimally Invasive Breast Biopsies

EditorProf. Dr. Renzo Brun del ReFMH Gynäkologie und GeburtshilfeAarbergergasse 30 3011 Bern [email protected]

ISSN: 0080-0015ISBN: 978-3-540-31403-5 e-ISBN: 978-3-540-31611-4DOI: 10.1007/978-3-540-31611-4 Springer Dordrecht Heidelberg London New York

Library of Congress Control Number: 2009921986

© Springer-Verlag Berlin Heidelberg 2009

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1 Documentation and Correlation of Senologic Findings ............................................. 1Renzo Brun del Re

1.1 Introduction ..................................................................................................... 11.2 Senometry ....................................................................................................... 11.2.1 Material ........................................................................................................... 11.3 Mapping Clinical Findings .............................................................................. 11.4 Mapping Mammographic Lesions Smaller than 2 cm .................................... 31.4.1 Mapping the Lesion on the Mammogram ....................................................... 31.4.2 Transferring the Mammographic Dimensions onto the Breast ....................... 71.5 Intraoperative Senometric Needle Localization .............................................. 151.6 Mapping Mammographic Lesions Larger than 2 cm ...................................... 151.6.1 Mapping the Lesion on the Mammogram ....................................................... 151.6.2 Transferring Dimensions onto the Breast ....................................................... 17 1.7 Nonpalpable Lesion Detected by Ultrasound ................................................. 191.8 Advantages of Senometry ............................................................................... 21References ........................................................................................................................ 21

2 Comparison of Large-Core Vacuum-Assisted Breast Biopsy and Excision Systems ..................................................................................................... 23Robin Wilson and Sanjay Kavia

2.1 Introduction ..................................................................................................... 232.2 Large-Core Biopsy Systems: Overview .......................................................... 242.2.1 Single Large-Core Biopsy System .................................................................. 242.2.2 Vacuum-Assisted Mammotomy Systems ........................................................ 262.3 Indications and Limitations ............................................................................. 352.3.1 Limitations ...................................................................................................... 362.3.2 Diagnostic Biopsy ........................................................................................... 372.3.3 Therapeutic Excision....................................................................................... 382.3.4 Image-Guided Biopsy Technique .................................................................... 39

Contents

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vi Contents

2.4 Conclusions ..................................................................................................... 40References ........................................................................................................................ 40

3 Sonographically Guided Vacuum-Assisted Breast Biopsy Using Handheld Mammotome ............................................................................................... 43Luc Steyaert, Filip Van Kerkhove, and Jan W. Casselman

3.1 Introduction ..................................................................................................... 433.2 Equipment ....................................................................................................... 433.3 Technique ........................................................................................................ 483.4 Indications ....................................................................................................... 673.4.1 Probably Benign or Indeterminate Nodular Lesions ....................................... 683.4.2 Very Small Suspicious Lesions ....................................................................... 703.4.3 Areas of Localized Attenuation....................................................................... 723.4.4 Isolated, Complex Fibrocystic Areas ............................................................... 733.4.5 Papillomas ....................................................................................................... 753.4.6 Clusters of Microcalcifications ....................................................................... 763.4.7 Lesions in Difficult Locations ........................................................................ 823.4.8 Very Hard Lesions with Inconclusive Previous Biopsy or FNAC .................. 823.4.9 Inadequate FNAC or Microbiopsy Results ..................................................... 823.4.10 Removal of Benign Lesions ............................................................................ 823.4.11 Indications Discussed: Radial Scar, Large Intracystic Lesions ....................... 833.4.12 Other Indications ............................................................................................. 853.5 Processing the Cores ....................................................................................... 853.6 Needle Size ..................................................................................................... 883.7 Clip Placement ................................................................................................ 903.8 US Versus Mammographic Guidance ............................................................. 903.9 Results ............................................................................................................. 92References ........................................................................................................................ 93

4 The Vacora Biopsy System ............................................................................................. 97R. Schulz-Wendtland

4.1 Introduction ..................................................................................................... 974.2 Technique ........................................................................................................ 974.3 Indications and Contraindications ................................................................... 984.3.1 US-Guided Transcutaneous Vacuum Biopsy .................................................. 984.3.2 Stereotactic Vacuum Biopsy ........................................................................... 1014.3.3 MRI-Guided Vacuum Biopsy .......................................................................... 1014.4 Side Effects ..................................................................................................... 1014.5 Results ............................................................................................................. 1014.6 Limitations ...................................................................................................... 1024.7 Practical Hints ................................................................................................. 102References ........................................................................................................................ 102

Contents vii

5 Available Stereotactic Systems for Breast Biopsy ........................................................ 105Ossi R. Köchli

5.1 Introduction ..................................................................................................... 1055.1.1 Prone Position Techniques .............................................................................. 1055.1.2 Upright Systems .............................................................................................. 1095.2 Cost of the Systems ......................................................................................... 1125.3 Cost of the Procedures .................................................................................... 112References ........................................................................................................................ 113

6 MRI-Guided Minimally Invasive Breast Procedures .................................................. 115Harald Marcel Bonel

6.1 Introduction: Role of MR Mammography ...................................................... 1156.1.1 Indications ....................................................................................................... 1166.1.2 Technique and Practical Tips ........................................................................... 1176.1.3 Limitations ...................................................................................................... 1266.2 Conclusion ...................................................................................................... 128References ........................................................................................................................ 128

7 Ductoscopy of Intraductal Neoplasia of the Breast ..................................................... 129Michael Hünerbein, Matthias Raubach, Y.Y. Dai, and Peter M. Schlag

7.1 Introduction ..................................................................................................... 1297.2 Methods for Sampling Intraductal Breast Cells .............................................. 1297.2.1 Technique of Ductoscopy ................................................................................ 1307.2.2 Ductoscopic Biopsy ........................................................................................ 1327.2.3 Ductoscopy in Women with Nipple Discharge ............................................... 1327.2.4 Ductoscopy in Breast Cancer .......................................................................... 1337.3 Summary ......................................................................................................... 134References ........................................................................................................................ 134

8 Pathology of Breast Tissue Obtained in Minimally Invasive Biopsy Procedures .......................................................................................................... 137Gad Singer and Sylvia Stadlmann

8.1 Introduction ..................................................................................................... 1378.2 Pathology of Breast Disease in Minimally Invasive Biopsies ......................... 1378.3 Benign Epithelial Lesions ............................................................................... 1388.3.1 Periductal Mastitis ........................................................................................... 1388.3.2 Fibrocystic Change.......................................................................................... 1388.3.3 Sclerosing Adenosis ........................................................................................ 1398.3.4 Columnar Cell Lesions ................................................................................... 1408.3.5 Usual-Type Epithelial Hyperplasia ................................................................. 1408.3.6 Lobular Neoplasia ........................................................................................... 141

viii Contents

8.4 Fibroepithelial Lesions .................................................................................... 1428.4.1 Fibroadenoma .................................................................................................. 1428.4.2 Phyllodes Tumor .............................................................................................. 1438.4.3 Benign Papillary Lesions ................................................................................ 1438.5 Malignant Noninvasive Lesions ...................................................................... 1448.6 Invasive Carcinoma ......................................................................................... 1458.7 Grading of Breast Carcinoma ......................................................................... 1468.8 Predictive Factors in MIBS ............................................................................. 147References ........................................................................................................................ 147

9 Limitations of Minimally Invasive Breast Biopsy ........................................................ 149Mathias K. Fehr

9.1 Technical Failures ............................................................................................ 1499.2 Underestimation of Breast Pathology on Minimally

Invasive Breast Biopsy Specimens .................................................................. 149References ........................................................................................................................ 155

10 Advances in Breast Imaging: A Dilemma or Progress? .............................................. 159Daniel Flöry, Michael W. Fuchsjaeger, Christian F. Weisman, and Thomas H. Helbich

10.1 Introduction ..................................................................................................... 15910.2 Ultrasound ....................................................................................................... 15910.2.1 Multiplanar Display Mode .............................................................................. 16110.2.2 Niche Mode View............................................................................................ 16110.2.3 Surface Mode .................................................................................................. 16110.2.4 Transparency Mode ......................................................................................... 16110.2.5 Static 3D Volume Contrast Imaging ................................................................ 16210.2.6 4D Volume Contrast Imaging .......................................................................... 16210.2.7 Inversion Mode ............................................................................................... 16310.2.8 Volume Calculation ......................................................................................... 16310.2.9 Tomographic Ultrasound Imaging .................................................................. 16310.2.10 Glass Body Rendering .................................................................................... 16410.2.11 Power Doppler, Color Doppler, and High-Definition Flow ............................ 16410.2.12 Extended View Documentation ....................................................................... 16510.2.13 Conclusion ...................................................................................................... 16710.3 Magnetic Resonance Imaging ......................................................................... 16710.3.1 1.5-Tesla Systems and Gadopentetate ............................................................. 16710.3.2 3.0-Tesla Systems ............................................................................................ 16810.3.3 Macromolecular Contrast Agents.................................................................... 16810.3.4 Tumor-Specific Contrast Agents ..................................................................... 17010.3.5 Functional Breast Imaging Techniques (Spectroscopy,

Diffusion-Weighted Imaging) ......................................................................... 171

Contents ix

10.4 Positron Emission Tomography....................................................................... 17210.4.1 Imaging of Cellular Proliferation and Apoptosis ............................................ 17210.4.2 Receptor Imaging ............................................................................................ 17310.5 Optical Imaging............................................................................................... 17310.5.1 Imaging of Hemoglobin .................................................................................. 17410.5.2 CTLM Device ................................................................................................. 17410.5.3 Optical Imaging of Extrinsic Contrast Agents ................................................ 17510.6 Electrical Impedance Scanning ....................................................................... 17610.6.1 Targeted EIS with TransScan TS2000 ............................................................. 17710.6.2 Screening EIS with T-Scan 2000ED ............................................................... 17910.7 Conclusion ...................................................................................................... 180References ........................................................................................................................ 180

11 Cost–Benefit Analyses .................................................................................................... 183Renzo Brun del Re and Regula E. Bürki

11.1 Introduction ..................................................................................................... 18311.2 Frequency of Mammography .......................................................................... 18311.3 Recall Rate ...................................................................................................... 18411.3.1 Recall Rate in Screening Programs ................................................................. 18411.3.2 Recall Rate Outside of Screening Programs ................................................... 18511.4 Distribution of Further Investigations ............................................................. 18511.4.1 Open (Surgical) Biopsy ................................................................................... 18511.4.2 Substitution of Open Biopsies ........................................................................ 18511.4.3 Substitution of Other Diagnostic Procedures .................................................. 18611.5 Trends and Scenarios ...................................................................................... 18711.6 Comparison of Costs ....................................................................................... 18711.6.1 Costs and Savings ........................................................................................... 18911.7 Decision Makers Have Changed ..................................................................... 19011.8 Conclusions ..................................................................................................... 192References ........................................................................................................................ 192

12 Systematic Review and Meta-analysis of Recent Data ................................................ 195Renzo Brun del Re and Regula E. Bürki

12.1 Evidence for the Clinical Relevance of Minimally Invasive Breast Biopsy .................................................................................................. 195

12.1.1 Older Systematic Reviews .............................................................................. 19512.2 Literature Search Methods .............................................................................. 19512.2.1 Evidence on Performance ............................................................................... 19512.2.2 Evidence on Risks and Safety ......................................................................... 19712.2.3 Presentation and Analysis of the Data ............................................................. 19712.3 Presentation and Analysis of the Data ............................................................. 20012.3.1 Evidence Used................................................................................................. 20012.3.2 Results ............................................................................................................. 207

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12.4 Safety of MIBB ............................................................................................... 21212.4.1 Open Biopsy as Gold Standard ....................................................................... 21212.4.2 Fourteen-G Core Biopsies and 11-G Vacuum-Assisted Biopsies ................... 21212.4.3 Conclusions on the Safety of MIBB ............................................................... 21512.5 Quality of Life (HRQoL) ................................................................................ 21512.6 Summary and Discussion of the MIBB Data Presented ................................. 21712.7 Conclusions ..................................................................................................... 220References ........................................................................................................................ 222

Harald Marcel BonelInstitute for Diagnostic Pediatric and Interventional Radiology, InselspitalUniversity of BerneFreiburgstrasse 103010 BernSwitzerland

Renzo Brun del ReSwiss Study Group for Minimally Invasive Biopsies of the Swiss Society for Senology Spezialabteilung für BrusterkrankungenLindenhofspital BernAarbergergasse 303011 BernSwitzerland

Regula E. BürkiDepartment of Gynecology, Salem-SpitalSchänzlistrasse 33CH-3013 BernSwitzerland

Jan W. CasselmanDepartment of Radiology and Medical ImagingSt-Jan General HospitalRuddershove 108000 BrugesBelgium

Yiyang DaiDepartment of Surgery and Surgical Oncology Charité Universitätsmedizin BerlinCampus Berlin Buch and Helios Hospital 13122 Berlin BuchGermany and Zheijang HospitalHangzhouChina

Mathias K. Fehr Department of Obstetrics and Gynecology Cantonal Hospital 8501 Frauenfeld Switzerland

Daniel FlöryDepartment of RadiologyUniversity of ViennaWaehringer Guertel 18-201090 Vienna Austria

Michael W. FuchsjaegerDepartment of RadiologyUniversity of ViennaWaehringer Guertel 18-201090 Vienna Austria

Contributors

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xii List of Contributors

Thomas H. HelbichDepartment of RadiologyUniversity of ViennaWaehringer Guertel 18-201090 ViennaAustria

Michael HünerbeinDepartment of Surgery and Surgical Oncology Charité Universitätsmedizin BerlinCampus Berlin Buch and Helios Hospital 13122 Berlin BuchGermany

Sanjay KaviaGuys and St. ThomasGuy’s Campus, Great Maze PondLondon SE1 9RTUK

Filip Van KerkhoveDepartment of Radiology and Medical Imaging, St-Jan General Hospital, Ruddershove 10 8000 Bruges Belgium

Ossi R. KöchliBreast Center Zürich-BethanienToblerstrasse 518044 ZürichSwitzerland

Matthias RaubachDepartment of Surgery and Surgical Oncology Charité Universitätsmedizin BerlinCampus Berlin Buch and Helios Hospital 13122 Berlin BuchGermany

Peter M. SchlagDepartment of Surgery and Surgical Oncology Charité Universitätsmedizin BerlinCampus Berlin Buch and Helios Hospital 13122 Berlin BuchGermany

R. Schulz-WendtlandInstitute of Radiology,Gynaecological Radiology,University of ErlangenUniversitätsstrasse 21-23 91056 ErlangenGermany

Gad SingerInstitut für Pathologie Kantonsspital Baden 5404 Baden Switzerland

Sylvia StadlmannInstitut für Pathologie Kantonsspital Baden5404 BadenSwitzerland

Luc SteyaertDepartment of Radiology and Medical Imaging, St-Jan General Hospital Ruddershove 108000 BrugesBelgium

Christian F. WeismanPrivate University Institute of Diagnostic Radiology, St. Johanns Hospital Landeskliniken Salzburg Muellner Hauptstrasse 48 5020 Salzburg Austria

Robin WilsonKings College HospitalDenmark HillLondon SE5 9RSUK

1.1 Introduction

Documentation of the results of a breast exami-nation is extremely important. Without accurate documentation, communication is impossible. Owing to the increased use of mammography and ultrasound, nonpalpable lesions of unknown origin are increasingly being detected. The demands on doctors involved in the diagnostic investigation of nonpalpable lesions have greatly increased (Senofsky et al. 1998; Liberman et al. 2001; Stavros et al. 2004; Sittek et al. 2004; Florentine et al. 2004; Burkholder et al. 2007). Experience shows that the investigation of a large number of these lesions is not ideal. The proper practical procedure can usually only be learned by on-the-job training, as more than 2,000 participants have experienced in our workshops since 1977.

A precondition for diagnostic investigation is to know the localization, size, shape, and sur-rounding tissue of the lesion, irrespective of whether this is later marked stereotactically or isometrically (Brun del Re et al. 1979). It is essential to prove that possible clinical, sono-graphic, mammographic, and magnetic resonance

imaging (MRI) abnormalities are distinct or amalgamated lesions.

1.2 Senometry

In this chapter, the senometric technique is described, which can transmit the mammo-graphic findings on the breast and correlate them with instant sonographic and or clinical findings.

1.2.1 Material

– Senometer (AstraZeneca) (Fig. 1.1)– Wax pencil (for mammography)– Fluorescent screen (for mammography)– Felt marker (permanent)– Coins– Possibly needles– Compression plate, optional (Fig.1.2).

1.3 Mapping Clinical Findings

– Note whether the measurements are taken with the patient in a sitting or lying position.

– Mark the lesion on the breast (Fig. 1.3).– Measure the size of the lesion with the

Senometer.

Renzo Brun del Re (Ed.), Minimally Invasive Breast Biopsies, Recent Results in Cancer Research 173, 1DOI: 10.1007/978-3-540-31611-4_1, © Springer-Verlag Berlin Heidelberg 2009

Documentation and Correlation of Senologic Findings

Renzo Brun del Re

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Renzo Brun del Re Ärztlicher Leiter der Spezialabteilung für Brusterkrankungen der Lindenhofspitals Bern, Aarbergergasse 30, 3011 Bern, Switzerlande-mail: [email protected]

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Fig. 1.2 Compression plate (by BIP, Türkenfeld, Germany)

Fig. 1.1 Senometer

1 Documentation and Correlation of Senologic Findings 3

– Locate the axis that runs from 12 o’clock through the middle of the nipple to 6 o’clock.

– The measuring arm with the senometry imprint is placed directly on the skin.

– The axis line of the measuring arm without the imprint is moved to cover the 12 o’clock axis, so that the middle of the clock-face comes to lie on the middle of the nipple.

– The measuring arm with the senometry imprint is turned until its axis line runs through the middle of the marked lesion (Fig. 1.4).

– The angle is noted in the form of clock time (e.g., at 10.30, between 10 and 11 o’clock).

– Measure or read off the distance between the middle of the nipple and middle of the lesion (Fig. 1.5).

– The findings are preferably drafted on the report (Fig. 1.6).

1.4 Mapping Mammographic Lesions Smaller than 2 cm

1.4.1 Mapping the Lesion on the Mammogram

The coordinates and the lesion are plotted with the wax pencil (Fig. 1.7).Craniocaudal view (Fig. 1.8)

– Mark the nipple.– Draw a sagittal straight line through the middle

of the nipple (sagittal mamillary midline).– Draw a parallel sagittal line through the

middle of the lesion (sagittal lesion midline).

– Measure the distance between the parallel lines (“a”).

– Draw the frontal straight line through the base of the nipple (frontal mamillary baseline).

Fig. 1.3 Clinical finding

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Fig. 1.4 Positioning of the Senometer and reading the angle on the dial of the Senometer

Fig. 1.5 Measuring or reading of the distance from the middle of the nipple to the center of the lesion


Workshop Senologie BdR

5.5 cm

The lesion lies on the right at 10.30,5,5 cm away from the middle of thenipple.It is 1 cm in size, dense and poorlydefined.

12 o‘clock

6 o‘clock

10:3

0

Fig. 1.6 Documentation of clinical finding

Fig. 1.7 How to plot the coordinates and the lesion on the mammogram

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C-Cright

2.5

2

a

b

sagi

ttal m

amill

ary

mid

line

sagi

ttal l

esio

n m

idlin

e

frontal mamillary baseline

frontal lesion midline

Fig. 1.8 Craniocaudal view


mediolateralright

1.5

2.0

c

d

front

al m

amill

ary

base

line

fron

tal l

esio

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idlin

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sagittal mamillary midline

sagittal lesion midline

Fig. 1.9 Mediolateral view


– Draw a frontal straight line through the mid-dle of the lesion (frontal lesion midline).

– Measure the distance between the parallel lines (“b”).

Mediolateral view (Fig. 1.9)

– Mark the nipple.– Draw a sagittal straight line through the middle

of the nipple (sagittal mamillary midline).– Draw a parallel sagittal straight line through the

middle of the lesion (sagittal lesion midline).– Measure the distance between the parallel

lines (“c”).– Draw the frontal straight line through the base

of the nipple (frontal mamillary baseline).– Draw a frontal straight line through the mid-

dle of the lesion (frontal lesion midline).– Measure the distance between the parallel

lines (“d”).

Oblique view

– If there is an oblique view, measure accordingly.– Mark the nipple.– Draw a sagittal straight line through the middle

of the nipple (sagittal mamillary midline).

– Draw a parallel sagittal straight line through the middle of the lesion (sagittal lesion midline).

– Measure the distance between the parallel lines.– Draw the frontal straight line through the base

of the nipple (frontal mamillary baseline).– Draw a frontal straight line through the mid-

dle of the lesion (frontal lesion midline).– Measure the distance between the parallel

lines.

1.4.2 Transferring the Mammographic Dimensions onto the Breast

NOTE: It is important to remember that a breast can never be positioned and compressed in exactly the same way on repeated examinations. Nevertheless, every effort should be made to measure as accurately as possible.Craniocaudal compression of the breast (Figs.

1.10 and 1.11)

– Mark the sagittal line through the middle of the nipple (Fig. 1.12).

Fig. 1.10 Positioning of the compression plate

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– Measure the distance (a) from the sagittal mamillary midline (Fig. 1.13).

– Mark the sagittal line through the lesion (Fig. 1.14).

– Measure the depth (b) and distance of the frontal lesion line from the imaginary frontal mamillary baseline (Fig. 1.15).

– Mark the frontal line through the lesion (Fig. 1.16).

– Mark the intersection of the two lesion lines (sagittal and frontal) (Fig. 1.17).

– The lesion is located at right angles to the skin surface under this point of intersection with the breast compressed.

Fig. 1.11 Craniocaudal compression

Fig. 1.12 Marking the sagittal mamillary line


Fig. 1.13 Measuring the distance of the sagittal lesion line from the sagittal mamillary midline

Fig. 1.14 Marked sagittal lesion line

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Mediolateral compression of the breast (Fig. 1.18)

– Mark the sagittal line through the middle of the nipple (Fig. 1.19).

– Measure the distance (c) of the sagittal lesion line from the sagittal mamillary mid-line (Fig. 1.20).

– Mark the sagittal line through the lesion (Fig. 1.21).

Fig 1.16 Marking the frontal lesion line

Fig. 1.15 Measuring the distance of the frontal lesion line from the imaginary frontal mamillary baseline


– Measure the depth (d), distance from the imaginary frontal mamillary baseline.

– Mark the frontal line through the lesion (Fig. 1.22).

– Mark the intersection of the two lesion lines (Fig. 1.23).

– The lesion is located at right angles to the skin surface under this intersection point with the breast compressed.

If there is an oblique view, the breast should correspondingly be obliquely compressed.

Fig. 1.17 Intersection of the two lesion lines (sagittal and frontal)

Fig. 1.18 Mediolateral compression of the breast

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Fig. 1.20 Measuring the distance of the sagittal lesion line from the sagittal mamillary line

Fig. 1.19 Marking the sagittal mamillary line


Fig. 1.21 Marking the sagittal lesion line

Fig. 1.22 Measuring the distance and marking of the frontal lesion line from the imaginary frontal mamil-lary line and marking the sagittal lesion line

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Fig. 1.23 Intersection of the two lesion lines (sagittal and frontal)

Fig. 1.24 Patient in lying position. Ultrasound probe on the sagittal lesion line moving toward the intersec-tion of both lesion lines


The lesion lies under the point where the two lesion lines (craniocaudal and mediolateral) cross. After marking this on the skin, it is usu-ally easy to correlate the mammographic and sonographic findings (Figs. 1.24 and 1.25).

In a stereotactic procedure this point must simply be centered in the window of the mam-mography compression panel.

It is not uncommon for nonpalpable lesions discovered at mammography to be detectable by ultrasound as well. After mammogram-based measuring, it is easier to locate the lesion using ultrasound. In these cases, ultrasound marking or ultrasound-guided minimally invasive biopsy is quicker, less expensive, less unpleasant for the patient, and very accurate.

1.5 Intraoperative Senometric Needle Localization

If neither stereotactic nor isometric localization is possible, lesions can be localized intraopera-tively. A long needle simply needs to be inserted

vertically into the craniocaudal intersection and one into the mediolateral intersection with the breast suitably compressed. The lesion is located at the point where the needles cross (Fig. 1.26).

1.6 Mapping Mammographic Lesions Larger than 2 cm

If the lesion is larger than 2 cm, needle marking is unwise (unless several needles are used for the marking). However, the operation area may be accurately measured and marked preopera-tively with senometry.

1.6.1 Mapping the Lesion on the Mammogram

Craniocaudal view (Fig. 1.27)

– Mark the nipple.– Mark the borders of the lesion (medial,

lateral, ventral, dorsal).

Fig. 1.25 Ultrasound probe on the intersection of the two lesion lines

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Fig. 1.27 Mapping of the lesion on the craniocaudal mammogram

Workshop Senologie BdR cranio-caudalright

52.5

1.5

3.5

Fig. 1.26 Where the two needles cross, the lesion lies


– Draw a sagittal straight line through the mid-dle of the nipple (sagittal mamillary midline).

– Draw a parallel sagittal straight line level with the medial border of the lesion.

– Draw a parallel sagittal straight line level with the lateral border of the lesion.

– Measure the distances of the sagittal lesion parallels from the sagittal mamillary midline.

– Measure the extent of the lesion.– Measure the shortest distance to the skin.

Mediolateral view (Fig. 1.28)

– Mark the nipple.– Mark the borders of the lesion (cranial,

caudal, ventral, dorsal).– Draw a sagittal straight line through the

middle of the nipple (sagittal mamillary midline).

– Draw a parallel sagittal straight line level with the caudal border of the lesion.

– Draw a parallel sagittal straight line level with the cranial border of the lesion.

– Measure the distances of the sagittal lesionpar-allels from the sagittal mamillary midline.

– Measure the extent of the lesion.

– Measure the shortest distance to the skin.– If there is an oblique view, measure accord-

ingly. Localization is easier using a cranio-caudal and mediolateral mammogram. It is therefore advisable to request a mediolateral view subsequently.

1.6.2 Transferring Dimensions onto the Breast

Transferring dimensions on the breast is done according to the technique described above (Figs. 1.8–1.21), with the difference that there are two sagittal lesion lines on each mammogram. The frontal lesions lines do not need to be transferred.

Craniocaudal compression of the breast

– Mark the sagittal line through the middle of the nipple.

– Measure the distances of the sagittal lesion lines from the sagittal mamillary midline.

– Mark the sagittal line corresponding to the medial border of the lesion.

– Mark the sagittal line corresponding to the lateral border of the lesion.

Fig. 1.28 Mapping of the lesion on the mediolateral mammogram


medio-lateralright

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1.5

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Mediolateral compression of the breast

– Mark the sagittal line through the middle of the nipple.

– Measure the distances of the sagittal lesion lines from the sagittal mamillary baseline.

– Mark the sagittal line corresponding to the cranial border of the lesion.

– Mark the sagittal line corresponding to the caudal border of the lesion.

If there is only an oblique view available, the breast should be correspondingly compressed obliquely.

Transferred dimensions on the breast (Fig. 1.29)

– With the patient in the supine position and no breast compression, a rectangle is drawn.

– The lesion lies within these boundaries.

– The shape of the lesion can be drawn in, based on the mammograms.

– A larger or smaller safety margin is drawn in, depending on the strength of the suspicion.

– The skin incision is usually positioned within this rectangle.

– The distance of the lesion from the skin and the size of the lesion are known.

– The specimen to be excised is marked with sutures while still in situ.

– If the specimen is marked with sutures and clips, precise orientation and assessment can be made intraoperatively using an X-ray of the specimen (Fig. 1.30).

– After excision, the wound cavity is measured under craniocaudal and mediolateral com-pression as a check.

Fig. 1.29 Transferred dimensions on the breast


5

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2.5 3


Fig. 1.30 Marking the specimen with additional clips (microcalcifications at 11 o’clock at the border)

1.7 Nonpalpable Lesion Detected by Ultrasound

Topographic documentation of a nonpalpable lesion by means of ultrasound is thought to be very diff icult. This is true insofar as the photographic documentation only allows the position of the probe to be focused approxi-mately on the image. This is why senometry is essential for nonpalpable lesions.

Marking the lesion on the skin

– Photographic documentation of the ultra-sonic lesion in two planes.

– Measure the lesion in three planes.– Measure the distance between skin surface

and lesion.– Hold the probe so that the lesion lies exactly

in the middle of the image.– Lift the probe slightly and place a coin under

the middle of the probe (Figs. 1.31).– Remove the probe.

– The coin is located directly over the lesion detected by ultrasound.

– The coin will stick because of the gel, even in a lateral position.

– Measure the lesion with the Senometer.– Locate the axis that runs from 12 o’clock

through the middle of the nipple to 6 o’clock.

– The measuring arm with the senometry imprint is placed directly on the skin.

– The axis line of the measuring arm without the imprint is moved to cover the 12 o’clock axis, so that the middle of the clock-face lies on the middle of the nipple.

– The measuring arm with the senometry imprint is turned until its axis line runs through the middle of the marked lesion.

– The angle is noted in the form of clock time (e.g., at 1.30 or between 1 and 2 o’clock).

– Measure or read off the distance between the middle of the nipple and middle of the lesion (Fig. 1.32).

– Documentation (Fig. 1.33).

20 R. Brun del Re

1

Fig. 1.32 Mapping the lesion

Fig. 1.31 Marking a sonographic lesion on the skin with a coin


1.8 Advantages of Senometry

– It is noninvasive.– It is reproducible at any time.– It is the only way to prove that possible clini-

cal, sonographic, mammographic, or MRI abnormalities are distinct or amalgamated lesions.

– Localization is possible on the operating table by a simple measuring technique, with the patient positioned as during the ultra-sound examination.

– In most cases, this method replaces ultra-sonic needle marking.

References

Brun del Re R, Stucki D, Almendral A, Thorhorst J (1979) A new device for isometric localisation of nonpalpable breast lesions detectet ba mammog-raphy. Experience in over 100 cases. Gynecology

and Obstetrics. Proceedings of the IX World Congress of Gynecology and Obstetrics, Tokyo, pp 624–625

Burkholder HC, Witherspoon LE, Burns RP, Horn JS, Biderman MD (2007) Breast surgery tech-niques: Preoperative bracketing wire localisation by surgeons. Am Surg 73(6):574–579

Florentine BD, Kirsch D, Johnson RM, Senofsky G (2004) Conservative excision of wire-bracketed breast carcinomas. A community Hospital’s experience. Breast J 10(5):398–404

Liberman L, Kaplan J, Van Zee KJ, Morris EA, Latrenta LR, Abramson AF, Dershaw DD (2001) Bracketing wires for preoperative breast needle localisation. Am J Roentgenol 177(3):565–572

Sittek H, Kessler M, Untch M, Reiser M (2004) Minimal-invasive Biopsie und präoperative Markierung suspekter Mammaläsionen. Gynäkol. Geburtshilfliche Rundschau 44:69–83

Senofsky GM, Gierson ED, Craig PH, Gamagami PP, Silerstein MJ (1998) Local exzision, lumpec-tomy, and quadratectomy. In: Spear SL (ed) Surgery of the Breast. Principles and Art. Lippincott-Raven, Philadelphia

Stavros AT et al (2004) Targeted indication: mam-mographic abnormality. In: Stavros AT (ed) Breast Ultrasound. Lippincott Williams &Wilkins, Philadelphia, pp 124–146

Fig. 1.33 Documentation of the localization of the sonographic lesion


Example

6

The lesion lies on the right side at1:30, 6 cm away from the middle ofthe nipple.

12o‘clock

6 o‘clock

1:30

2.1 Introduction

The past 30 years have seen dramatic changes in the diagnosis and management of breast prob-lems. Much of this change has been driven by the quest for early diagnosis and by the wide-spread use of imaging in the diagnosis of symp-tomatic breast disease and for breast cancer screening. The traditional approach of surgical biopsy for diagnosis has now been replaced by needle biopsy techniques that provide both accurate and reliable diagnosis. The aims are to prevent unnecessary surgery for benign proc-esses and to provide detailed information on borderline and malignant processes that allow for prospective fully informed treatment plan-ning (Teh et al. 1998). To achieve these aims, specialized techniques for needle biopsy of the breast have been developed that facilitate the removal of sufficient amounts of tissue required to ensure accurate diagnoses.

In the 1980s, the predominant technique for needle sampling of the breast was fine-needle aspiration for cytology (FNAC). The results achieved with FNAC were encouraging but the required reliability and acceptable sensitivity and specificity proved to be only achievable in

expert centers. Even then, false-negative results for sampling in situ disease represented by microcalcifications and for certain types of invasive breast cancer were disappointing. For this reason, in the 1990s there was a trend away from the use of FNAC to needle core biopsy techniques. Core biopsy provides histological material for morphological as well as cellular assessment and the skills required for interpreta-tion are much more widely available. The sensi-tivity for the more elusive disease, such as lobular invasive carcinoma, is also significantly better. In addition, when sampling microcalcifi-cations, core samples can be imaged to prove retrieval of representative tissue. Overall, com-pared to cytology, core biopsy histology pro-vides significantly better sensitivity and positive predictive values for both benign and malignant disease and has a reduced rate of false-negative results. Automated core biopsy is now accepted as the preferred technique for breast tissue sampling (Bassett et al. 1997; Teh et al. 1998; Litherland 2001; Parker et al. 1996; Schueller et al. 2008).

Using core biopsy, the vast majority of breast abnormalities can be accurately diagnosed and most breast lesions are amenable to ultrasound-guided biopsy (Philpotts et al. 2003). However, particularly for screen-detected impalpable lesions, there remain around 5–10% of abnor-malities where core biopsy either does not pro-vide sufficient material for accurate diagnosis or does not target the lesion accurately (Parker and Burbank 1996). For these abnormalities, either more tissue or more accurate targeting is

Comparison of Large-Core Vacuum-Assisted Breast Biopsy and Excision Systems

Robin Wilson and Sanjay Kavia

2

Robin Wilson ()King’s College HospitalDenmark Hill, London SE5 9RS UKe-mail: [email protected]


24 R. Wilson and S. Kavia

2necessary to achieve the tissue needed for reli-able histopathological assessment (Kettritz et al. 2003). With these two factors in mind, in the early 1990s techniques were developed to pro-vide both directional sampling capability and retrieval of larger volumes of tissue (Parker et al. 1994; Burbank 1993). These have been further developed and refined over the past 15 years and are now in routine use for both diag-nosis and therapeutic excision.

Two different approaches for large-core biopsy have been developed: multiple contigu-ous large-bore cores retrieved with the assistance of suction (vacuum-assisted mammotomy; VAM) and single very-large-bore core (SLCB). Both methods can be used under X-ray (stereotactic guidance) and ultrasound, but currently only VAM is recommended for magnetic resonance (MR)-guided biopsy. With these techniques, it is now possible to retrieve sufficient tissue using image-guided biopsy such that 98–99% accuracy of nonsurgical diagnosis can be achieved. In fact, so much tissue can be removed that these tech-niques are now being used for total excision of certain breast abnormalities. Compared to core biopsy, VAM and very-large-core biopsy reduce by half understaging of pathology (atypical hyperplasia and DCIS), on average from 20 to 10%. This means that repeat biopsy and further surgery for diagnosis and treatment are required half as often (Liberman et al. 2000). Vacuum-assisted biopsy is the technique of first choice for MR-guided breast biopsy (Liberman et al. 2005; Kuhl 2007).

2.2 Large-Core Biopsy Systems: Overview

Currently one single large-core radiofrequency biopsy system and four vacuum-assisted multi-ple-core biopsy systems are in routine use for breast diagnosis and excision. All of the VAM systems are suitable for use under ultrasound,

stereotactic (upright and prone table), and MR imaging guidance; the single intact biopsy sys-tem is described as being suitable for ultrasound and X-ray stereotactic-guided biopsy. All the systems are suitable for use in the out-patient setting with local anesthesia.

2.2.1 Single Large-Core Biopsy System

The Intact Breast Lesion Excision System (BLES; Intact Medical Corporation Inc.) is a breast excision system that combines the use of vacuum and radiofrequency (RF) cutting to remove the targeted lesion as a single specimen (Intact Medical Corporation 2008). The probe (or wand) (Fig. 2.1) is available in four sizes, designed to retrieve specimens that are 10, 12, 15, and 20 mm in diameter (Fig. 2.2). The Intact BLES probe is positioned under imaging guidance (ultrasound or X-ray stereotaxis) through a 6- to 8-mm skin incision and advanced to the periphery of the area to be excised. A cutting RF wire is activated and advanced to cut and ensnare the target lesion by means of four insulated struts that first expand and then contract to surround the lesion (Fig. 2.3). The single large sample is then withdrawn intact through the same tract. Vacuum is used to minimize the extent of the RF effect on the sample excised and into the surrounding breast tissue and to extract any bleeding that may occur during the procedure. The Intact BLES system is said to have the advantage over VAM of retaining the full histological architecture and potentially clear margins around the area of interest and with little RF artifact on histology (Sie et al. 2006). It has also been reported to be associated with reduced understaging compared to VAM (Sie et al. 2006; Killebrew and Oneson 2006). However, the RF function does limit its use for lesions close to the skin or the chest wall and for lesions in small breasts.

2 Comparison of Large-Core Vacuum-Assisted Breast Biopsy and Excision Systems 25

Fig. 2.1 The Intact disposable wand (probe) and driver

Fig. 2.2 Intact whole-tissue samples showing the size of samples achieved with the 10-, 12-, 15-, and 20-mm wands

Fig. 2.3 Diagram of how the Intact system operates


22.2.2 Vacuum-Assisted Mammotomy Systems

There are four systems in routine use based on the principle of single or multiple cores using 14 to 7 French gauge needles or probes. Although the principles of operation are similar for all of these VAM systems, there are significant differ-ences in their design, method of operation, and attributes. Table 2.1 shows a comparison of the various attributes of these systems. All of these systems are directional, allowing sampling around a full 360-degree arc either by manual rotation of the driver or manual or automated

rotation of the needle within the driver. The EnCor system has fully automated and program-mable directional functions. Each system is described here in greater detail.

2.2.2.1 Mammotome System

Mammotome (Breast Care, Ethicon Endo- Surgery), the first VAM system to be developed and originally marketed under the Biopsys name, has been available since 1995, and has been upgraded several times since. It is a well-proven

Table 2.1 Comparison of VAM systems

Attribute Mammotome Vacora Atec EnCor

Drivers required Separate for US, X-ray, and MRI

Same for all Same for all Separate for MRI

Command unit Same for all Self-contained Various options Same for allVacuum adjustment No No Requires different

unitsYes

Manual vacuum control

+++ No + (With lavage) +++

Needle gauge 11 and 8 14 and 10 12 and 9 10 and 7Multiple core retrieval Yes No Yes YesCutting method Rotating Rotating Rotating ScissorNeedle sharpness ++ + ++ +++Core sample size ++ ++ ++ +++Volume of tissue per minute

++ + +++ +++

Open or closed tissue collection

Open Open Closed Closed

Smaller chamber size Choice

No No Requires different probe

Selectable with the same probes

Speed of tissue retrieval

++ + +++ +++

Needle rotation Manual only Manual only Manual only Manual or automated

Lavage No No Full Sample chamberProgrammable functions

++ No No +++

Biopsy site marker system

Yes No Yes Yes

Local anesthetic function

++ No ++ +++

Probe offset Yes Yes No Yes


device with more than 3 million biopsy procedures performed worldwide and more than 200 papers reporting various aspects of its use published in the medical literature.

This system uses three different drivers for stereotactic, ultrasound, and MR-guided biopsy (Fig. 2.4a, b). All three drivers use the same unique double-lumen probe, one lumen used for providing the suction (at 23–25 mmHg) that draws the sample into the biopsy chamber and the other through which the internal rotating cutting trocar moves to cut the sample and for retrieval of the specimen (Fig. 2.5). All three drivers are controlled by the same command module (Fig. 2.6) that can be programmed to individual preference for automated or semi-automated function with variable pause periods between each sample, application of suction sequences, and “clear” mode for “dry tap” events (Fig. 2.7). The control module can be operated via a foot switch or a handheld control-ler for sterotactic and MR-guided biopsy and via buttons on the driver itself for MR- and ultra-sound-guided procedures (Fig. 2.4). The com-mand module provides the suction via plastic tubing for all three uses and provides real-time pictorial feedback of all the functions, including the position of the cutting trocar and where in the system suction is being applied. Suction can be applied manually at any time during a biopsy

procedure to extract any bleeding or hematoma. Additional local anesthetic can be delivered through a port in the vacuum tubing during a biopsy. The needle bore and the biopsy can also have lavage applied if blockage occurs by injec-tion of saline through the same vacuum tubing port.

For stereotactic biopsy, the drive for the rotation and retraction of the cutting trocar is via torsion cables driven from the command unit, while for MR- and ultrasound-guided procedures, the drive for the cutter is incor-porated into the handheld device, allowing for more flexible use (Fig. 2.5). The stereo-tactic driver incorporates a spring-loaded system that allows the needle to be fired for-ward 20 mm into the breast while it is held in the stereotactic holder (Fig. 2.8). In all appli-cations, the mammotome is an open biopsy system and each core sample must be retrieved

a b

Fig. 2.4 Mammotome biopsy probes (a) ultrasound EX system and (b) stereotactic ST system

Fig. 2.5 Close-up view of the Mammotome probe tip showing the double lumen system with fenes-trations used to suck in the samples for cutting by the rotating inner trocar. A scalpel-type blade is embedded in the tip to ease insertion of the probe


2

from the sample collection chamber after each biopsy (Fig. 2.9). The probes are dispos-able and are available in two sizes (11 and 8 G) for ultrasound, stereotactic, and MR use and are available with or without a cutting

scalpel embedded into the probe tip (Fig. 2.5). The 11-G probe provides approximately 100 mg and the 7-G probe approximately 175 mg of tissue per core sample. Special part-ceramic probes, guides, and introducers are

Fig. 2.6 The Encor (left), Atec (middle), and Mammotome (right) control modules

Fig. 2.7 The Mammotome control module monitor showing the operating functions


available to facilitate MR-guided biopsy using standard lateral grid MR biopsy coils. Various types of ultrasound and X-ray-visible biopsy site markers are available for use with the Mammotome probes, which are inserted through the probe directly into the biopsy cavity.

2.2.2.2 Vacora

The Vacora system (C.R. Bard Inc.) was the sec-ond device to become available for VAM (origi-nally marketed as the BIP VacuFlash). It is

a b

Fig. 2.8 The Mammotome ST system a showing the set-up for use with a lateral arm and b for biopsy of the inferior part of the breast using an upright dig-

ital stereotactic system (GE Medical Systems) with the patient in the lateral decubitus position

Fig. 2.9 The Mammotome ST system in use for biopsy of the upper breast in the craniocaudal position using an upright stereotactic system (GE Medical Systems) showing manual retrieval of a core sample


2

unique in that it is a self-contained system incor-porating the driver for the rotating cutting trocar and the suction unit within the handheld unit (Fig. 2.10a, b). The disposable probes are single-lumen and contain a rotating cutting trocar. The probes are available in 14- and 10-G sizes, pro-viding approximately 50 and 150 mg of tissue per core sample, respectively (Fig. 2.11). The needle is directional but needs to be rotated manually in the holder to achieve different biopsy directions for stereotactic biopsy; for ultrasound- and MR-guided biopsy, the com-plete holder can be rotated for multidirectional sampling (Fig. 2.12). The Vacora is a single-sample system and the probe must be with-drawn from the breast to retrieve each core sample. For this reason a plastic guiding canula is best inserted into the breast first to facilitate repeated insertion of the probe to the same site in the breast. This single-sample function means that it is not suitable for therapeutic excision of anything other than small lesions (10 mm or less). The suction is only applied while the core is being taken and again when each core is

extracted. It is not possible to apply manual suction, and this limits its use when bleeding occurs at the biopsy site. Additional local anesthetic injection and biopsy site marking must be delivered through the guiding plastic

ba

c

Fig. 2.10 The Bard Vacora vacuum biopsy system: a the handheld device showing insertion of the nee-dle and the self-contained vacuum system into the

driver, b the system ready for use, and c a close-up view of the operating panel

Fig. 2.11 Comparative core sample sizes achieved with 14-, 10-, and 7-G vacuum core needles


canula. The system incorporates a spring-loaded firing mechanism that allows the needle to be fired forward into the breast. The system is simple to use because its functions are all preset and are activated using the control panel on the side of the device; changes to its operation cannot be programmed by the user.

2.2.2.3 ATEC (Automatic Tissue Extraction and Collection)

The Automatic Tissue Extraction and Collection (ATEC) system (Suros Inc.) is similar in its function to the Mammotome ST system in that it is driven by cables from the command unit and uses an internal rotating cutter. However, it is a single-bore system and the whole driver unit is disposable (Fig. 2.13). There are three different command modules available that deliver differing suction levels depending or required usage (MR only, ultrasound and stereotactic only, and all three). The disposable handpieces are available in two needle sizes in several lengths and sampling chamber sizes. Twelve-gauge needles are avail-

able in 9- and 12-cm lengths, both with 20-mm sampling chambers. The larger 9-G needles are available in 9-, 12-, and 14-cm lengths with the two shorter lengths available with either 20- or 12-mm sampling chambers (Fig. 2.14). The sampling processes are preset and not programmable by the user. All handpieces include a closed sample collection system (Fig. 2.14).

There are two operation modes that are used for all methods of image guidance (Fig. 2.15). In the lavage mode the sample chamber is open and saline is continuously instilled through the system into the biopsy area and through the sampling filter (Fig. 2.15). The ATEC is the only system that uses lavage of the biopsy area. Manual suction can also be applied (Fig. 2.15). In the biopsy mode, the sample chamber is closed in the resting position until the foot pedal is used to trigger multiple rapid retrievals of samples (averaging 150–175 mg per core). The ATEC is the fastest-acting VAM system, although it does not deliver more tissue per time unit than the EnCor system (see below). Directional sampling is achieved by rotating the handpiece manually (Fig. 2.16). The needle of

Fig. 2.12 The Bard Vacora system in use for MRI-guided breast biopsy. The black line on the back of the device indicates the direction of sampling


2

the Suros ATEC system is not offset and this means that there may be restrictions on its use under stereotactic and MR guidance for lesions close to the chest wall and in breasts with a small compression thickness.

2.2.2.4 EnCor

The EnCor system (Senorx Corporation), like the Vacora and ATEC, is a single-bore VAM system. However, it differs from the other VAM systems in many ways. The inner cutting trocar, rather than rotating to cut the sample, uses a scissor oscillating action that is said to be more effective

for dense tissue and more prolonged use. The driver contains the mechanisms for driving the cutting device and for rotating the needle (Fig. 2.17). The driver has an electrical cable and plas-tic vacuum tubing that connects it to the com-mand module. The same command module is used for ultrasound-, X-ray stereotactic-, and MR-guided biopsy (Fig. 2.6). The functions are fully programmable by the user, including auto-mated rotation of the biopsy sampling chamber, which can be set for single, three (180°), six (270°), and eight (360°) rotations in any direction (Fig. 2.18). The automated function of the probe rotation is particularly useful for stereotactic and MR-guided biopsy, as the sample selection direc-tion and extent of rotation can be preset. The driver unit is lightweight and handheld for ultra-sound-guided procedures (Fig. 2.19). The same driver is attached to a holder for either prone table or upright stereotactic use (Fig. 2.20). The stereotactic probe holder has a spring-loaded mechanism that allows the driver and probe to be fired forward 20 mm into the breast.

The needle probes are available in 10- and 7-G sizes. Both have the patented tri-concave tip design that renders the probe extremely sharp so that it passes through all but the most dense breast tissue with ease (Fig. 2.21). The 7-G probe provides the largest samples of all the VAM systems at 300 mg per core sample. The sample

ba

Fig. 2.13 The Suros ATEC biopsy device a showing the component parts with the disposable driver and detached closed sampling chamber and b close-up of the closed sampling chamber in place

Fig. 2.14 The Suros ATEC needles showing the 9- and 14-cm lengths


chamber length (10 or 20 mm) for the two needle sizes can be set at the control module and avoids the need to select a different needle if a short core length is required. The strength of the vac-uum applied can also be doubled when particu-

larly dense tissue is encountered. The module also has a preset anesthetic function that allows for delivery of local anesthetic 360° around the biopsy site either before or during the biopsy procedure. The same system is used to deploy

Fig. 2.15 The Suros ATEC control system

Fig. 2.16 The Suros ATEC system in use for ultrasound-guided biopsy


2a b

c

Fig. 2.17 The EnCor biopsy system: a the driver unit and disposable needle, b close-up of the closed sample retrieval component, in place and c detached

Fig. 2.18 The Senorx EnCor control display


gel and clip markers at the biopsy site (Fig. 2.22). The closed sample collection system retrieves the samples in an easily removable basket that

can also be used for sample radiography. There is an optional lavage system that uses saline to cleanse the tissue samples in the collection chamber as they are retrieved. Like the Mammotome and ATEC systems, the EnCor device can be used with MRI-specific introducers and trocars (Fig. 2.23a, b)

2.3 Indications and Limitations

There are a number of diagnostic and therapeu-tic situations where VAM or SLCB should be considered as the primary technique. These include:

Fig. 2.19 The Suros EnCor system set up and ready for handheld use

Fig. 2.20 The Suros EnCor system in place for ster-eotactic-guided biopsy using a prone table

Fig. 2.21 Close-up of the Tri-concave EnCor needle tip


2

Diagnostic biopsy:

– Equivocal or failed core biopsy– Small lesion (sub 5 mm)– Architectural distortion– Clustered microcalcifications– Diffuse nonspecific abnormality– Complex cyst– Intraductal lesion– Abscess drainage

Therapeutic excision:

– Fibroadenoma and other biopsy-proven benign lesions

– Papillary and mucocele-like lesions

– Radial scar/complex sclerosing lesion– Sentinel lymph node

2.3.1 Limitations

The various differences in the attributes of the large-core systems mean that some are not suited for all of the possible indications. The Vacora system has the most limitations because it is a single-core device that needs to be removed from the breast to retrieve each sample and cannot be used to aspirate the biopsy area.

a

b

Fig. 2.23 The EnCor system: a MRI trocar and can-ula guides and b in use for MRI-guided biopsy

Fig. 2.22 The Encor a anesthetic control display and b method of injection of anesthetic through the probe system to the biopsy site

a

b


2.3.2 Diagnostic Biopsy

When conventional automated core biopsy has either failed to target the lesion or there is a bor-derline pathological result, VAM or SLCB will usually provide the material required to either avoid unnecessary surgery for benign lesions or facilitate single-stage therapeutic surgery for malignant disease. In certain circumstances where there is a high chance of failed sampling with core biopsy, such as small clusters of suspi-cious microcalcifications and very small mass lesions, it is usually better to use VAM or SLCB as the primary sampling technique without attempting core biopsy first (Fig. 2.24a–c).

The same is true for circumstances where from the outset it is recognized that larger vol-umes of tissue will be required for diagnosis, such as suspicion of radial scar and diffuse non-

specific changes on imaging. All of the systems described here are potentially suitable for these indications, as previously described. The Intact system is not suitable for superficial lesions and the Vacora system is not ideal if more than 10–15 cores are likely to be necessary.

Similarly, the Intact and Vacora systems are not ideal for sampling complex cysts, particularly those that appear to contain a mass component. These are best biopsied by VAM devices where the probe remains in position in the breast throughout the procedure and manual vacuum can be applied. The same is true for removal of an intraductal lesion when manual vacuum is an important factor, as is the ability to move the sam-pling chamber around the area without removing the probe from the breast (Fig. 2.25a, b).

VAM systems are most widely used for stereotactic biopsy of microcalcifications iden-tified on mammography, and all of those

ba

c

Fig. 2.24 Stereotactic procedure radiograph showing a an EnCor probe in place for biopsy of calcifica-tions, b core specimens in the sample retrieval tray, and c radiography showing calcifications success-fully sampled


2

described here are suitable for this purpose. All of the upright and prone biopsy mammography systems can accommodate the VAM and Intact systems described here (Georgian-Smith et al. 2002). VAM is particularly suited for this situation, as the vacuum assistance means that sampling is directional and can be used to retrieve tissue at a distance from the actual site of the needle. For core biopsy, the needle must pass through the lesion for successful sampling, but with VAM the probe only needs to be placed close to the target area. The vacuum effect is used to pull the tissue into the sampling chamber. This is particularly useful for lesions close to the chest wall, and behind the nipple and where the cluster is more scattered. In many units now, all stereotactic biopsy procedures are carried out using VAM systems because the retrieval results are significantly better than core biopsy, and

particularly because equivocal pathology results and understaging of disease are much less fre-quent, making repeat procedures and the need for surgical biopsy much less common. Some clinicians prefer to map the samples retrieved in order to document where each sample has come from in the breast. It is not clear what the benefit of doing this is because it does not affect the subsequent management of the result and imag-ing provides the information needed if the first sets of samples do not contain sufficient mate-rial. If sample mapping is required the Vacora and Mammotome systems need to be used. For sampling lesions close to the chest wall or when using the lateral approach in women with small breasts, access to the breast requires a probe with the needle offset to avoid snagging on the biopsy table or the chest wall. The ATEC system does not have an offset needle.

Aspiration of breast abscess is preferred to surgical drainage and is usually achieved by manual suction applied through a standard nee-dle. However, VAM systems with continuous suction capability provide the means of dealing with larger and more organized breast abscesses when surgery would otherwise be required. The Vacora is not suitable for this use.

2.3.3 Therapeutic Excision

VAM and SLCB provide an alternative to surgery for the removal of known benign lesions such as fibroadenomas and focal fibrous lesions (Tennant et al. 2008). Large-core techniques are also being increasingly used instead of surgery to widely sample borderline lesions such as radial scars and papillary lesions shown on previous core biopsy to have no evidence of epithelial atypia (Rosen et al. 2002; Carder et al. 2008). The Vacora system is only suitable for removing small lesions less than 10 mm in diameter for the reasons outlined above. Similarly, the Intact system is limited by the size of its retrieval system, which has a maxi-

a

b

Fig. 2.25 Ultrasound images showing a an intraduct lesion and b an intracystic lesion, which are ideal for VAM excision


mum diameter of 20 mm. The Mammotome (7 G), ATEC (9 G), and EnCor (7 G) are all ideal for excision of large lesions. The Mammotome sys-tem takes longer to complete the task simply because each sample has to be retrieved from the sample chamber while with the other two the samples are automatically collected by their closed sampling systems. Many clinicians restrict the size of lesion they are willing to attempt to remove with VAM to around 20–30 mm. Both the EnCor and ATEC systems will retrieve more than 1 g of tissue per minute and can be readily used to excise lesions up to 50–60 mm in diameter.

There are also some reports of these tech-niques being used to sample sentinel nodes prior to surgery or primary chemotherapy treatment. However, this indication must be considered experimental at present. Similarly, SLCB and VAM should not be used for excision of known malignant lesions or borderline lesions associ-ated with a significant risk of breast cancer except in exceptional circumstances (Eby et al. 2008; Lee et al. 2008). In some patients who are not medically fit for conventional treatment (surgery and chemotherapy), SLCB and VAM can be considered. To ensure a reasonable exci-sion margin, the Intact system should be con-fined to lesions no more than 10–25 mm in diameter if a clear excision margin is to be achieved. The VAM system can be used for larger lesions but it must be recognized that the excision margins will be suspect, even if sample mapping is used.

As with all breast biopsies, ultrasound guid-ance is the preferred guidance method whenever possible. All of the systems described here can be used for ultrasound-guided biopsy. The Vacora system is usually used with a trocar. For stereotactic biopsy, this is satisfactory because the breast is fixed by compression. For ultra-sound, the trocar guide system can be less effec-tive, particularly in the large breast; since the breast is not fixed, it can be difficult to reintro-duce the needle to the same site for successive biopsies. The other VAM systems remain in the

breast throughout the biopsy procedure and are therefore easier to use in this situation. All of the systems are light enough to be easily handheld for ultrasound-guided use. The sharpness of the tri-concave tip of the Encor system means that it is more easily advanced through the breast to the target than the other systems and is more easily sited in the ideal position for ultrasound-guided VAM immediately behind the lesion (Fig. 2.21). This is particularly apparent in the dense and fibrous breast.

2.3.4 Image-Guided Biopsy Technique

Anyone familiar with the technique for image-guided fine-needle aspiration and conventional core biopsy will be able to adapt easily to the technique required for large-core biopsy because the basic principles are the same.

Particular attention must be paid to adminis-tration of sufficient local anesthetic for these large-bore procedures. Significantly larger doses are usually required than for conventional core biopsy, particularly for excision proce-dures and procedures done under ultrasound guidance. The larger size and vacuum assist-ance both mean that vessel damage is more likely with these techniques. The use of local aesthetic combined with adrenaline is preferred because this reduces the chances of hematoma and increases the time that the anesthesia is effective. Plain local anesthetic may be pre-ferred for the skin and subcutaneous tissues in older patients and those with compromised skin. For stereotactic X-ray-guided procedures, care should be taken not to inject large volumes of anesthetic since this can significantly displace the target area. The biopsy-targeting process is the same as for core biopsy with the aim of passing the probe directly through the area to be sampled and then biopsy around 360°. However, unlike core biopsy, successful sampling can be achieved if the lesion is not transfixed


2using the vacuum and directional capabilities of the VAM systems.

For ultrasound-guided sampling, the anes-thetic must be infiltrated to surround the lesion being targeted and can be used to dissect the tis-sue down to the lesion and to assist in separating the target from the deep and superficial tissues. Deep tissue anesthesia is particularly important, as for ultrasound-guided sampling the VAM probe is best positioned behind the lesion. Some also advocate the use of longer-acting local anesthetic in the deeper tissues around the target lesion to reduce postprocedure anesthesia.

All but the Vacora system allow for further injection of local anesthetic through the biopsy probe into the target area (Fig. 2.22b). This can be done as a matter of routine before the biopsy is commenced, particularly for stereotactic pro-cedures when the probe has been placed and dis-placement of the lesion is then less likely to occur. The EnCor device has a specific program for delivering local anesthetic around the area to be biopsied.

MR-guided biopsy can be achieved with all of the VAM systems described (Figs. 2.12 and 2.23b). All of the manufacturers provide MR biopsy packs that contain the necessary materi-als to carry out the procedure using most of the currently available MR biopsy coil systems (Fig. 2.23a). VAM is recommended for all MR-guided biopsies; these lesions are only vis-ible on MR and therefore the method most likely to successfully retrieve tissue from the targeted area should be used (Lee et al. 2008).

2.4 Conclusions

There are a number of well-designed devices available for vacuum biopsy and excision biopsy. These devices enable the radiologist to deliver a high level of diagnostic accuracy and

provide the means for minimally invasive ther-apeutic lesion excision of benign and border-line lesions. Accuracy approaching 99% can be achieved, thus avoiding the need for diagnostic surgical open biopsy in the vast majority of cases and providing tissue samples in quanti-ties sufficient to allow for detailed treatment planning. The choice of vacuum biopsy system will depend on workload, the image guidance methods that are used, and whether lesion exci-sion is required.

References

Bassett L, Winchester DP, Caplan RB et al (1997) Stereotactic core needle biopsy of the breast: a report of the joint task force of the American College of Surgeons and College of American Pathologists. CA Cancer J Clin 47:171

Burbank F (1993) Stereotactic breast biopsy: com-parison of 14- and 11-guage mammotome probe. Acta Cytol 37:461–471

Carder PJ, Khan T, Burrows P, Sharma N (2008) Large volume mammotome biopsy may reduce the need for diagnostic surgery in papillary lesions of the breast. J Clin Pathol 61:928–933

Eby PR, Ochsner JE, DeMartini WB, Allison KH, Peacock S, Lehman CD (2008) Is surgical exci-sion necessary for focal atypical ductal hyperpla-sia found at stereotactic vacuum-assisted biopsy. Annu Surg Oncol 15;3232–3238

Georgian-Smith D, D’Orsi C, Morris E, Clark CF, Liberty E, Lehman CD (2002) Stereotactic biopsy of the breast using an upright unit, a vacuum suction needle, and a lateral arm sup-port. AJR 178:1017–1024

Intact Medical Corporation (2008) Percutaneous contiguous electrosurgical breast biopsy devices. http://www.intactmedical.com/pdf/ML087_Rev00.pdf

Kellebrew LK, Oneson RH (2006) Comparison of the diagnostic accuracy of a vacuum-assisted percutaneous intact specimen sampling device to a vacuum-assisted core needle sampling device for breast biopsy: initial experience. Breast 12:302–308

Kettritz U et al (2003) Stereotactic vacuum-assisted breast biopsy in 2874 patients: a multicentre study. Cancer 100:245–251


Kuhl C (2007) The current status of breast MR imag-ing. Part 1. Choice of technique, image interpre-tation, diagnostic accuracy, and transfer of clinical practice. Radiology 244:356–378

Lee K-M, Kaplan JB, Murray MP, Liberman L (2008) Complete excision of the MRI target lesion at MRI-guided vacuum-assisted biopsy of breast cancer. AJR 191:1198–1202

Liberman L (2000) Percutaneous image-guided core biopsy: state of the art at the millennium. AJR 174:1191–1199

Liberman L, Bracero N, Morris E, Thornton C, Dershaw DD (2005) MRI-guided 9-guage vac-uum assisted breast biopsy: initial clinical expe-rience. AJR 185:183–193

Litherland J (2001) The role of needle biopsy in the diagnosis of breast lesions. Breast 10: 383–387

Parker SH, Burbank F (1996) A practical approach to minimally invasive breast biopsy. Radiology 200:11–20

Parker SH, Burbank F, Jackman J, Aucreman CJ, Cardenosa G, Clink TM et al (1994) Percutaneous large-core breast biopsy: a multi-institutional study. Radiology 3:359–363

Parker SH, Dennis MA, Stavros AT, Johnson KK (2006) A new breast biopsy technique. J Diagn Med Sonogr 12:113–118

Philpotts LE, Hooley RJ, Lee CH (2003) Comparison of automated versus vacuum-assisted methods for sonographically guided core biopsy of the breast. AJR 180:347–351

Rosen EL, Bentley RC, Baker JA, Soo MS (2002) Imaging-guided core needle biopsy of papillary lesions of the breast. AJR 179:1185–1192

Schueller G et al (2008) US-guided 14 gauge core needle breast biopsy: results of a validation study in 1352 cases. Radiology 248:406–413

Sie A et al (2006) Multi-center evaluation of the breast lesion excision system, a percutaneous, vacuum-assisted intact-specimen breast biopsy device. Cancer 107:945–949

Teh W, Evans AJ, Wilson ARM (1998) Editorial. Definitive non-surgical breast diagnosis: the role of the radiologist. Clin Radiol 53:81–84

Tennant SL, Evans AJ, Hamilton LJ, James J, Lee AH, Hodi Z, Ellis IO, Rakha EA, Wilson AR (2008) Vacuum-assisted excision of breast lesions of uncertain malignant potential (B3) - an alternative to surgery in selected cases. Breast 17(6):546–549

3.1 Introduction

Sonographic examination of the breast with state-of-the-art equipment has become an essen-tial part of the clinical work-up of breast lesions and a valuable adjunct to mammographic screen-ing and physical examination (Stavros et al. 1995). The technique is capable of detecting lesions not seen on mammography, allowing dif-ferentiation of cystic from solid lesions, and benign from malignant lesions. Because of the real-time capabilities and the high spatial and contrast resolution, sonography has become the optimal guidance technique for percutaneous interventional procedures and preoperative localization of nonpalpable lesions. Fine-needle aspiration (FNA) and core-needle biopsy (CNB) are long-established valuable techniques, still used in the majority of cases; vacuum-assisted biopsy (VAB) is a more recent technique with proven clinical value, which can be used under sonographic, mammographic, and magnetic imaging resonance (MRI) guidance. The pur-pose of this chapter is to describe the technique of sonographically guided Mammotome biopsy.

3.2 Equipment

In order to obtain high-quality ultrasound (US) studies, not only is sufficient experience on the part of the operator mandatory, but also high-end equipment with a dedicated high-frequency transducer. A 5-cm linear transducer is optimal (Fig. 3.1), providing a larger field of view, good visibility of needle localization and approach, and the targeted lesion; thus optimal alignment can be obtained. A transducer center frequency of around 10 MHz is optimal. Modern equip-ment and high frequencies guarantee sufficient penetration and higher resolution; the current equipment also takes advantage of a broadband frequency range. Compound scanning can give clearer visualization of the needle, because of the more perpendicular insonation of the needle usually introduced obliquely. Tissue harmonic imaging, recently available for higher frequen-cies, improves tissue contrast and reduces arti-facts, resulting in better imaging despite the use of slightly lower frequencies. Some authors report advantages of real-time 3D imaging (Fig. 3.2) in performing guided biopsy (Baez et al. 2003).

The Mammotome system, initially devel-oped by two radiologists – Parker and Burbank (Parker et al. 2001) – consists of a control unit and a holster (Fig. 3.3), on which the disposable needle is mounted. The control unit has a vacuum system with a canister that takes the

Sonographically Guided Vacuum-Assisted Breast Biopsy Using Handheld Mammotome

Luc Steyaert, Filip Van Kerkhove, and Jan W. Casselman

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Luc Steyaert ()Department of Radiobiology and Medical Imaging St-Jan General Hospital, Ruddershove 10, 8000 Bruges, Belgiume-mail: [email protected]

Renzo Brun del Re (Ed.), Minimally Invasive Breast Biopsies, Recent Results in Cancer Research 173, 43DoI: 10.1007/978-3-540-31611-4_3, © Springer-Verlag Berlin Heidelberg 2009

44 L. Steyaert et al.

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aspirated fluids or blood. The unit has a touch-screen where the different steps of the procedure can be selected and programmed, and where there the status of the needle can be checked (Fig. 3.4). The holster is connected to the control unit with electrical and mechanical connections, and with a double aspiration line. The most recent Mammotome EX equipment has micro-motors in the holster; mechanical connections are therefore no longer needed and only an elec-trical cable and vacuum lines, which are pre-mounted on the needle-connector, have to be connected (Fig. 3.5). This means a certain time gain in setting up the procedure. The presence of only one small flexible electrical cable greatly

improves the handling of the probe. The EX sys-tem (Fig. 3.6) also has faster mechanical move-ments, thereby shortening the procedure time. With the HH system (Fig. 3.7), the weight of the mechanical cables sometimes hinders the move-ment; therefore a support system that can be fixed to the table is provided.

The different movements of the needle and the aspiration are commanded by three buttons on the handheld holster, or by foot switches (Fig. 3.8); in our experience, the latter is more practi-cal since a more steady position of the US probe and biopsy needle can be obtained. The move-ment of the fingers, to command the buttons on the holster, can destabilize the position of the

Fig. 3.1 A large, preferably 5-cm-long, linear probe is best suited for interventional procedures. Modern broadband high-frequency (up to 15 MHz) trans-ducer with harmonic imaging capability. Compound

imaging is very interesting for biopsy: the different angles of insonation create sound waves more per-pendicular to the needle (yellow line), resulting in better visualization of the needle

3 Sonographically Guided Vacuum-Assisted Breast Biopsy Using Handheld Mammotome 45

probe inside the breast. The probe should be taken firmly in the hand; it can be held in differ-ent ways depending on the user’s preference or approach (Fig. 3.9).

The Mammotome probe has a double lumen; inside the first lumen, a rotating hollow cutter moves forward to cut the tissue sample that was aspirated in the biopsy window. The aspiration of tissue during cutting guarantees a good-qual-ity sample, even after multiple samples have been taken in the same area. The second lumen provides the vacuum for it, and is connected through small holes to the biopsy window. The vacuum is also controllable; we usually set it on maximum power, unless we work very close to the skin or nipple area.

A hollow rod in the center of the cutter pro-vides a second vacuum that grabs the specimen

and enables it to be transported outside where it can be picked up with tweezers (Fig. 3.10), with the needle staying in place. Thus, multiple biopsy specimens can be taken with a single insertion of the needle. The number of samples depends on the size of the lesion. The working principle of the needle is the same as the nee-dles used for stereotactic or MRI-guided pro-cedures, although the construction of the needle and holster looks slightly different. A 360° rotating possibility as for the stereotactic nee-dle is not present, and is not needed, because the rotation is made manually by the operator by turning the whole probe and holster. In addi-tion, 360° sampling is not needed because the needle is placed below the lesion, and sampling is only done in the tissue lying superficial to the needle.

Fig. 3.2 A real-time 3D scan can be helpful to have better control of the positioning of the Mammotome

needle. Example of a malignant tumor seen in three orthogonal planes simultaneously


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Fig. 3.3 Mammotome driver unit mounted on a cart a where accessories can be stored. Disconnected HH holster b with electrical and two mechanical connect-

ing cables. A flexible support arm c can be attached to the examination table and supports the weight of the cables, facilitating the use of the HH holster

Fig. 3.4 on the control monitor of the Mammotome driver unit, a representation of the position of the needle-cutter (red part) and the active aspiration (blue arrows)


The vacuum can also be used to aspirate blood in case of bleeding; bleeding is most fre-quently a slow venous bleeding, but sometimes arterial bleeding occurs, which can most often be controlled by local compression over the biopsy area and aspiration. occasionally, the thin vacuum channels inside the needle can be blocked by blood clot, small tissue fragments, and especially fat. This makes the fragments more difficult to retrieve and can make them smaller. If this is the case, the needle can be flushed through a standard luer lock connection

on one of the vacuum lines. This procedure can also be used to inject extra local anesthetic at the biopsy site. The vacuum is also helpful to elimi-nate air bubbles in the biopsy area, which dis-turb the US visibility. Air bubbles are seldom a problem since the Mammotome is a single-insertion technique, which is an advantage com-pared to other techniques that use coaxial needles and require multiple insertions.

When a tissue fragment fails to be retrieved or is smaller than expected, there is a chance that it is fragmented. In this case, we can do a “dry run,” which means that the needle is closed without cutting to try to retrieve the sample.

The procedure requires some operator experi-ence in US of the breast, as well as in performing guided biopsies. It is a freehand procedure and no guiding devices are used, which gives much more flexibility but requires more skillful han-dling from the operator. For optimal coordina-tion, it is preferable that one operator do the imaging and positioning of the needle, instead of one person manipulating the US and somebody else manipulating the Mammotome needle.

Fig. 3.5 Mammotome driver unit with new EX holster attached; note the single electrical cable (arrow) connection to the holster as well as the double vacuum line

Fig. 3.6 Detailed view of the new Mammotome EX holster for US-guided use


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In use for several years, numerous authors have described the technique, the use, and the results of their experience with this method (Parker et al. 2001; Johnson et al. 2002; Meloni et al. 2001; Wilson 2000; Steyaert and Rigauts 2003; Plantade et al. 2005).

3.3 Technique

The patient is installed in a comfortable position on a wide examination table where we can adjust the height of the table and the elevation of the head. The patient lies in the supine position, sometimes slightly turned to one side, supported by a triangular foam cushion, depending on the position of the lesion and the size of the breast. In most procedures, the patient’s arm is elevated and firmly positioned behind the head, in order to stretch the pectoral muscle and to minimize breast motion during the procedure. In some patients, this position causes compression of the subclavian artery, with thoracic outlet symptoms. Therefore, we let the patient relax the arm

between the localization and the procedure itself, which lasts only a couple of minutes depending on the numbers of samples to be taken.

We sit on the large wide examination table on the right side of the patient, in front of the US unit. The Mammotome unit is installed at the head of the table in a transverse position, with the cables and vacuum lines turned to the patient’s left side, so that the cables can bend in a large curve toward the patient (Fig. 3.11). A flexible device suspends the weight of the cables. The newer Mammotome EX has only one small electrical cable, so the weight is not a problem anymore.

The assistant is at the patient’s left side (Fig. 3.12) and will take care of the patient’s comfort and collect the samples. The assistant can pro-vide extra sterile swabs if needed.

An alternative position is to sit along the table on the side to be biopsied and to place the US unit on the opposite side in direct view (Fig. 3.13). The disadvantage of this position is that one cannot reach the US unit to make any neces-sary image adjustments.

Another way of performing a Mammotome biopsy is “the dentist’s way” (Fig. 3.14). By sit-ting at a 90°angle alongside the examination

Fig. 3.7 Mammotome HH holster with needle mounted. Three white command buttons on the upper side


table, and by adding an extra monitor on the other side of the table for the display of the US image, one can work comfortably without hav-ing to turn the head.

Two trays with sterile material are prepared, one for the operating physician (Fig. 3.15) and one for the assistant; both contain some sterile swabs, local anesthesia injection material, and sterile drape. We use a special sterile US gel. Since the procedure is short and the incision very small, no excessive precautions concerning sterility are needed. Sterile gloves, disinfection of a larger area of the breast, and the use of sterile

needles is sufficient. In our experience of more than 9 years involving over 2500 procedures, no wound infections have occurred.

The first thing to do is to examine carefully with US the lesion to be biopsied or excised and the surrounding tissue, in order to choose the best possible approach. The entry site and path-way of the needle has to be carefully planned. The entry point is usually 2–4 cm away from the lesion, to provide a good view of the needle tract, direction, and angle of insertion during the procedure. The entry point is also chosen to make a tangential approach possible, with a good view of the needle; a too steep angle gives poorer view of the needle and is more dangerous for touching or penetrating the thoracic wall (Fig. 3.16).

The best is to choose a tissue plane that is easy to penetrate for the large needle, preferably an area containing fatty tissue (Fig. 3.17). Color Doppler can be used to identify and help avoid larger vessels that could cause major bleeding in

Fig. 3.8 The different functions of the needle are commanded either by foot switches (top) or but-tons on the needle holster (bottom); the different functions are at all times clearly indicated on the monitoring screen (center)

Fig. 3.9 The new ergonomic EX holster can be manipulated in different ways according to user preferences


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Fig. 3.10 Biopsy sample pick-up on EX (top) and HH (bottom) needle

Fig. 3.11 In this room lay-out, we place the US machine on the side, as usual for diagnostic examinations; the Mammotome driver is placed at the top end of the table so that the angle of view between US screen and monitoring screen is as small as possible. The cables

are supported by a flexible arm and the Mammotome is commanded by the foot switches placed close to the US machine. operator and assistant, who collect the samples, are on either side of the patient, who is com-fortably installed on a large couch


Fig. 3.12 Schematic representation of the room lay-out seen in Fig. 3.11. operator and assistant both have a tray with sterile material

Fig. 3.13 In this lay-out, the operator sits on one side of the patient, while the US unit and a Mammotome driver are on the opposite side in direct view. In this

situation, the operator cannot command the US unit when needed (courtesy of Dr. A. Bonifacino, Rome, Italy)


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Fig. 3.14 By adding an extra monitor, placed in front of the operator at the opposite side of the examination table, the operator does not have to turn the head to look at the US unit. This lay-out is

similar to the way dentists work. Because the US unit is still within close reach, it can be manipu-lated by the operator (courtesy of Prof. R. Brun del Re, Bern, Switzerland)

Fig. 3.15 Limited amount of sterile material and local anesthetic used for the Mammotome procedure


case they are cut by the large needle (Fig. 3.18). It is more likely to find larger vessels in the medial half of the breast and in the axillary tail.

We mark the entry site and biopsy site with a skin marker (Fig. 3.19); this will facilitate the

injection of local anesthesia in the correct loca-tion and the indication of the biopsy site is used for precise application of pressure after the pro-cedure on the exact biopsy site.

Because the technique requires a small skin incision, the entry site is chosen in the least vis-ible areas or around the areola, comparable to surgical incisions. Exposed areas, mainly the upper inner quadrants, are avoided if possible, which women seem to appreciate (Fig. 3.20).

The skin is disinfected with a 70% alcohol solution; we prefer not to use staining disinfect-ants. Disinfectants containing iodide are also avoided because of the greater chance of allergic reactions. The US probe can be wrapped in a ster-ile bag, but we do not use this, since it decreases image quality and hinders manipulation of the US probe. We thoroughly disinfect the probe with an alcohol solution, which seems sufficient. The manufacturer must be contacted, since some probes are more vulnerable and alcohol disinfec-tion is not allowed on some machines and trans-ducers, because it harms the acoustic lens.

Fig. 3.16 Schematic representation of needle inser-tion; a relatively horizontal insertion from several centimeters away, tangential to the lesion, is opti-mal (green arrow). This allows better visualization of the needle and prevents hitting the thoracic wall when the needle is inserted too vertically under a steep angle (red arrow)

Fig. 3.17 Example of possible directions of needle inser-tion. Directions A and B (red arrows) are not optimal because a large amount of dense breast tissue has to be penetrated; moreover, direction A is too vertical in the

direction of the thoracic wall. Direction C (green arrow) is optimal because it crosses a fat plane in the breast, which makes needle insertion much easier and enables tangential placement of the needle below the nodule


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First, a local superficial anesthesia is admin-istrated in the area where we will insert the nee-

dle. To avoid the risk of skin necrosis, lidocaine 1% without adrenaline is injected, maximum 5 ml, with a short 22-G needle. A skin-cooling substance (e.g., ethyl chloride) can be applied prior to injection, minimizing pain. The anes-thetic is injected in real time and guided by US (Fig. 3.21).

For deeper anesthesia, 0.5% bupivacaine (with epinephrine to minimize risk of bleeding, and to keep the anesthesia longer in place – Marcaine®) is used, usually a maximum of 10 ml, with a longer 21-G IM or spinal needle. The use of adrenaline is avoided close to the skin and certainly close to the nipple because of the risk of skin necrosis, especially in older patients.

The precise application of anesthesia deeper around the lesion facilitates the insertion and accu-rate placement of the large needle. This part of the anesthesia is very important, and is used to create an approach, sometimes through dense glandular tissue, by dissecting the tissue planes (which can occasionally be painful, certainly when the injec-tion is not done slowly), and to create space to place the needle under the lesion (Fig. 3.22). The

Fig. 3.18 Color Doppler image of a lesion to be biopsied. a The direction of the needle (yellow arrow) points through a large vessel. b By chang-

ing the imaging direction (turning the probe 90°) the vessel can be easily avoided, thus preventing substantial bleeding

Fig. 3.19 Before the biopsy, we search for the exact location of the lesion to biopsy (red area) and determine the optimal insertion point (yellow area), where the skin incision will be made. Both areas are marked on the skin and this is helpful later during the procedure


Fig. 3.20 Before insertion of the large needle, we make a small skin incision of around 4 mm with an no. 11 scalpel. Although the scar is hardly visible afterward,

we try to avoid making the incision in a more visible area of the cleavage

Fig. 3.21 Because the needle is inserted below the lesion to be biopsied, a large amount of local anes-thetic is injected (green area), in this case also to make space between the lesion and the pectoral muscle (white arrows). When the lesion is close to

the skin (red arrows), an injection is made (without adrenaline) between lesion and skin. This helps to prevent aspiration of the skin during the procedure. The needle (blue arrow) is carefully and horizon-tally directed between lesion and skin


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Fig. 3.22 Example of injection underneath the lesion; note the increasing volume of the fluid collection (arrows) during injection

Fig. 3.23 Injection of local anesthetic between the lesion (yellow dotted line) and the pectoral muscle. By injecting fluid, space is created (white arrows)

to position the needle more easily. This injection has to be made slowly, since tissue dissection, espe-cially close to the pectoral muscle, can cause pain


latter is particularly important in lesions close to the pectoral muscle (Fig. 3.23). When working close to the skin or the nipple, anesthetic fluid is also injected between the lesion and the skin (Fig. 3.24), in order to avoid excessive aspira-tion of these sensitive structures during the biopsy. When removing a fibroadenoma, it is

possible to dissect the nodule from the surround-ing tissue by careful injection of fluid around it (Fig. 3.25). This facilitates the complete exci-sion and prevents the removal of unnecessary amounts of surrounding tissue.

Care should be taken not to inject air bub-bles, which cause well-known artifacts that

Fig. 3.24 Example of injection of local anesthetic between nodule and skin; needle (arrow) positioned just below the skin

Fig. 3.25 Excision of a fibroadenoma. By injecting local anesthetic around the nodule, it is possible to dissect it from the surrounding tissues; this helps

to completely remove the nodule, without too much surrounding tissue. Needle (yellow arrow) and fluid collection (white arrows) are clearly visible


3hamper visualization with US, especially in cases of microcalcifications (Fig. 3.26). Injection of local anesthetic in fatty areas can cause increased echogenicity (Fig. 3.27). This can help to outline hypoechoic nodular lesions, but can also severely hamper visualization of other lesions, especially calcifications.

During preparation, a small 4- to 5-mm skin incision is made with a no. 11 scalpel blade (Fig. 3.20). The needle is then inserted and carefully

moved forward to the desired position, under constant US monitoring. The needle is inserted in closed position - the status of the needle can be checked on the driver unit monitor - to prevent damage to the skin. When a bladed tip is used, the needle is inserted horizontally, so that the blade on the needle tip cuts more easily through the tissue planes; when in position under the lesion, we rotate 90° so that the biopsy open-ing is vertically under the area we want to biopsy

Fig. 3.26 Example of injection underneath a focus of microcalcifications (white arrows); note the increas-ing volume of the fluid collection (yellow arrows)

Fig. 3.27 Injection of local anesthetic in fatty areas can cause increased echogenicity. This can help to outline hypoechoic nodular lesions but can also

severely hamper visualization of other lesions, especially calcifications. Careful US-monitored injection is mandatory


(Fig. 3.28). It is important to align perfectly the whole length of the needle with the imaging plane, mainly for accurate evaluation of the position of the needle tip.

Before starting the sampling, the position is verified by viewing in longitudinal and trans-

verse sections. When properly positioned under the (mostly hypoechoic) lesion, we can see a bowing artifact (a nonlinear aspect of the nee-dle), caused by differences in sound speeds in normal and abnormal tissue (Figs. 3.29 and 3.30). At the level of the biopsy window, and in

Fig. 3.28 The needle is positioned smoothly: the nee-dle is inserted perpendicular to the skin, thus avoiding damage to the skin; progressively the needle is posi-tioned more horizontal and pushed gently forward; we try to place the needle tangentially under the lesion.

The oval symbol represents the needle with the bladed tip; the bladed tip is inserted horizontally for easier penetration through the tissue planes; once positioned under the lesion, the needle is turned 90° to bring the biopsy opening upwards

Fig. 3.29 The Mammotome needle is inserted beneath the lesion, thus offering a clear view of both lesion and needle. The needle is inserted in the closed posi-tion; a small denivelation (yellow arrows) can be seen

on the front and back end of the biopsy window allow-ing good positioning. Proper placement of the needle under the (hypoechoic) lesion causes a bowing artifact of the needle (red arrows)


3the closed position, we can see a small denive-lation (Fig. 3.29) at the proximal and distal ends of the biopsy opening. Furthermore, we open the biopsy window and under aspiration we

attempt to evaluate the position of the biopsy window relative to the lesion (Fig. 3.31). A per-fect alignment of the needle shows the internal holes, connecting the biopsy window with the

Fig. 3.30 Mammotome needle in place with open biopsy window; the hypoechoic nature of the nodule causes a bowing artifact of the underlying needle (due

to different sound speed), indicating the correct posi-tion of the needle. The nodule is centered in the biopsy window

Fig. 3.31 Mammotome needle in closed and open position, correctly positioned under a small focus of micro-calcifications. When opening the window and with aspiration, the lesion falls into the biopsy opening


vacuum channel (Fig. 3.32). Proper alignment of the lesion and the biopsy window in both orthogonal planes is mandatory (Fig. 3.33) to retrieve the correct tissue and to avoid cutting excessive surrounding tissue. The needle is inserted under the lesion that has to be biopsied, so that good visualisation of the lesion and the needle is provided; the biopsy window is placed upward. In some cases, a lateral placement is inevitable. The biopsy window is then oriented

more horizontally in a lateral position in rela-tion to the lesion, depending on the position of the needle relative to the lesion (Fig. 3.34). Horizontal positioning can be required to avoid skin aspiration. With the needle in the horizon-tal position (Fig. 3.35), the vacuum aspiration is directed away from the skin, and skin aspiration can be avoided. The horizontal position can be evaluated on the transverse scans because we can see the groove that runs along the length of

Fig. 3.32 Perfect alignment of the needle and lesion on longitudinal image. The needle is visible over the entire length (blue arrows), the nodule is perfectly centered over the biopsy window (red arrows); even

the tiny connecting holes (yellow arrows) to the vac-uum channel can be seen as well as the reflections of the posterior wall of the vacuum channel (green arrows), which are insonated through these tiny holes

Fig. 3.33 Longitudinal and transverse images of small superficial papilloma, with opened needle in place. on the transverse image, the needle opening can be seen (arrow)


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the needle, from the double lumen construction (Fig. 3.36).

US guidance is advantageous in that it is pos-sible to monitor the procedure in real time and have longitudinal or transverse imaging. Under

real-time guidance, samples are then taken, as much as needed, and preferably until the nodule is no longer visible under US. When removing a benign lesion, we take an extra 180° or 360° round of samples (in larger lesions) after the

Fig. 3.34 In ideal cases, the needle is placed exactly in the middle under the lesion. However, this is not always the case. In the transverse US image, it is very important to see the position of the needle, in these cases somewhat more laterally. This view

helps us to orient the optimal sampling direction. The great advantage of US is the real-time moni-toring of the procedure. The yellow lines indicate the direction in which to biopsy; no 360° sampling is needed

Fig. 3.35 With good high-resolution US equipment, the groove in the needle can be seen on transverse sec-tions, helping to orient the biopsy window. It is very

important to orient the opening horizontally when per-forming a biopsy very close to the skin to avoid aspi-ration and cutting of the skin


lesion is no longer visible on the US image, in order to leave no remaining tissue and avoid regrowth of a lesion (e.g., fibroadenoma). In most cases, and since the needle is placed below the lesion, sampling over 180° is sufficient. It is mandatory to check, in the transverse plane (rel-ative to the needle), whether there are remaining parts. Especially in larger nodules, transverse imaging is mandatory, because we can cut through the thickness of the mass and have – on longitudinal images – the false impression that the lesion has disappeared, where parts of the nodule are still present on either side of the nee-dle (Fig. 3.70). If we see no remaining tissue, any blood collection or remaining fluid is aspi-rated to clean the biopsy area.

At that time, a clip can be left to mark the biopsy site; this is not done in cases of a clearly benign lesion or previously proven (e.g., by CNB) benign histology, but the clip is placed if there is any suspicion of malignancy, to act as a guide for later surgical procedures. This makes it possible to do a hook wire localization if sur-gery is needed afterward.

The small metallic clip is difficult to see under US, but more recently developed clips with resolvable material are better seen, and can be seen several weeks after the procedure. In our experience, a US-guided hook wire localization is faster, more precise, and more comfortable for the patient than a stereotactic procedure.

In some cases, and more frequently after removal of larger lesions, a small blood-filled cavity created by the Mammotome biopsy can easily be seen on US several weeks after the biopsy. Eventual clip migration seems to be less important in US procedures compared to stere-otactic, due to absence of compression of the breast.

When the procedure is finished, the needle, with the biopsy window closed, is gently retracted. Special attention is paid so as not to damage the skin with the bladed tip of the nee-dle. The needle is checked for any remaining tis-sue fragments.

We apply immediate manual compression at the biopsy site for about 10 min to prevent hematoma. Compression time can vary among

Fig. 3.36 Due to the figure-eight cross-section of the needle, caused by the double lumen, there is a longitu-dinal groove (arrows) on each side of the needle,

which can be seen on the transverse US image, pro-viding useful indications on the orientation of the nee-dle and sample opening


3patients. The assisting nurse applies the com-pression, so the performing physician can leave the room; the total procedure time for the physi-cian is less than 30 min, and the nurse performs the pre- and postprocedure care. At these times, there is frequently a good relaxed contact between nurse and patient, which is psychologi-cally beneficial.

To finish, the skin and biopsy incision are cleaned and disinfected with alcohol. The small incision is closed with special glue (Dermabond) (Fig. 3.37); this yields good cosmetic results, less risk of infection, and needs no special attention.

A compressive bandage, exactly on the biopsy area, is applied for 1 day (Fig. 3.38). We place a swab at the exact location of the lesion and not on the biopsy entry site, and put elastic tape in a cross form, so that the optimal com-pression is exactly on at the biopsy site. No ice is used, since in our experience this results in more frequent late-stage bleeding several hours after the procedure, although the imme-diate effect on hemostasis can be beneficial. Since Dermabond is water-resistant, the patient can shower and no special wound care is needed.

Fig. 3.37 To close the small incision, we use a special glue (Dermabond, Johnson & Johnson). This leaves minimal scarring and has less risk of wound infection; it prevents bleeding and staining of the clothes. It needs no special attention and is water-resistant so patients can shower. No follow-up is needed

Fig. 3.38 A swap is fixed with a compressive cross-shaped tape (preferably elastic, unless the patient is allergic) bandage, at the exact level of the biopsy, which was marked on the skin prior to the procedure 2 cm from the insertion point (arrow), where the skin incision has been closed with Dermabond


The vast majority of patients tolerate the pro-cedure very well. No procedures had to be inter-rupted because of pain or severe bleeding. Pain at a later stage was reported only occasionally. In our series, no infection occurred. There is no need to give preventive antibiotics.

The complication rate is low, usually some superficial bruising, occasionally a small hematoma (Fig. 3.39); the literature (Simon et al. 2000)

reports less than 2%, somewhat more in the beginning of the experience. In our series, we had no serious complications requiring surgical intervention or hospitalization. In one case, we had a pseudoaneurysm (Fig. 3.40), which was controlled by compression under US guidance. When a patient reports a sudden severe pain during tissue sampling, it means that a nerve is touched, so an artery will be very close; in

Fig. 3.39 A small hematoma is sometimes present at the biopsy site, as seen here on the resection speci-men. It can help the surgeon and pathologist localize the area of interest. This type of hematoma is also

clearly seen on US and helps correctly position a hook wire. Such small hematomas are totally harmless and are not considered a complication


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that case, we avoid biopsying in this position and try to turn the needle in a different direction. To prevent pain after the procedure, we fre-quently give paracetamol or an NSAID for 2 days, although the latter may have a negative influence on coagulation, similar to salicylates.

To avoid complications and substantial hem-orrhage, it can be helpful to determine the site of arteries by using color Doppler and to inject the anesthetic with epinephrine close to the artery. Injection can also be made during the procedure via the vacuum line, where the medication is delivered on the biopsy site.

We do not routinely check the coagulation parameters; we ask to the patient if there is any history of blood coagulation disorder, and we

check for anticoagulant drugs such as sali-cylates. If this medication is being used, we usu-ally ask the patient to stop intake and postpone the procedure for 10–14 days.

In case of severe arterial bleeding, one has to ensure that the bleeding has stopped before the patient is dismissed from the hospital. In a nor-mal situation, the patient leaves immediately after the procedure. We instruct the patient to compress the breast further for about 1 h, and ask them to remain calm and not use the arm for heavy work or sports, since the movements of the pectoral muscle may facilitate rebleeding. When severe bleeding occurs during the procedure, we keep the patient for 1 h and check the biopsy site with US before the patient leaves. A larger

Fig. 3.40 Postprocedure hematoma; color Doppler shows typical color swirl signal suggesting active bleeding with false aneurysm. Pathology images clearly show the relatively large transected artery. Selective compression under US monitoring successfully stopped the bleeding in this case


hematoma (>2 cm) seldom occurs (Fig. 3.41); it is usually not a problem, but can cause some swell-ing and pain. It resolves over a longer period and there is no negative long-term effect. In our expe-rience, it seldom liquefies, so we do not check it later and we do not attempt to aspirate it.

We ask the patient, if possible, to come with a friend or relative who can drive them home, and we ask the patient to compress the breast for approximatively 1 h. The position of the swab and compressive bandage can be felt easily by the patient, and this helps them to locate the site of compression. The compressive bandage must be taken off the next morning, to prevent skin irritation by the tape. The Dermabond stays over the wound like a plastic film and is water-resist-ant, so the patient can shower normally. The Dermabond needs no further attention and falls off after 2 weeks. In that period, the wound has healed correctly; no medical intervention is needed.

Steri-Strip or (resolvable) sutures can also be used, but are less practical in our view.

The indication for Mammotome biopsy is made based on all the available imaging data and is usually discussed in a multidisciplinary meeting: personal and family medical history,

age, and imaging characteristics of the lesion are discussed. Verbal and written information is provided to the patient concerning the procedure and potential periprocedural risks and complica-tions when the appointment is made. At the time of the procedure, the doctor and assisting nurse are available for questions. The patient signs an informed consent document.

Depending on the histological results, the patient is either scheduled back for a normal routine check-up (we do not perform extra con-trols in a shorter time interval) in case of benign findings, or, in case of malignant findings, is sent to the surgeon and oncological team for fur-ther treatment if necessary.

Because of the close cooperation with the pathology department, the definitive result is known within 24 to a maximum 48 h.

3.4 Indications

The main indication for the Mammotome is biopsy of clustered microcalcifications, which is usually done under stereotactic guidance

Fig. 3.41 Hematoma, 4.5 cm in diameter, after the Mammotome procedure. The total volume is around 12 cc. Usually, these hematomas do not liquify and resolve slowly, requiring no further attention


3(Brem 2001). This method has a largely proven reliability (Diebold et al. 2005; Kettritz et al. 2004) and should replace surgical open biopsy (Dhillon et al. 2006; Cangiarella et al. 2001). It is widely accepted as a standard diagnostic pro-cedure (Travade et al. 2002).

The US-guided procedure is still more a mat-ter of discussion, but should also replace surgi-cal biopsy for nodular lesions, and replace even surgery for complete removal of certain types of benign lesions. This is gradually becoming more accepted (Sebag and Rouyer 2003). Different authors have proven its increased diagnostic accuracy over FNA and CNB, especially the lower degree of histological underestimation (Philpotts et al. 2003; Liberman et al. 1999; Perez-Fuentes et al. 2001; Costantini et al. 2005; Morris et al. 2002; Cangiarella et al. 2001).

An unequivocal larger malignant nodule (Fig. 3.42) is not an indication for the Mammotome, but is routinely biopsied with CNB under US guidance with excellent results.

In our experience, the main indications are as follows.

3.4.1 Probably Benign or Indeterminate Nodular Lesions

The most frequent indications are palpable or nonpalpable nodular lesions or areas of tissue changes (ACR classification, BI-RADS 4 and 3). Most of the time, we use the classification proposed by Stavros et al. based on US criteria (American College of Radiology 1998), which classifies lesions as probably benign, indeter-minate, probably malignant, and malignant, based on morphologic criteria of the US image.

With probably benign or indeterminate masses, we always try to remove the lesion com-pletely so that there is no uncertainty on later follow-up images. To avoid the presence of remaining tissue, a precise check, after vacuum aspiration, is necessary in both transverse and longitudinal imaging planes. If possible, it can be useful to make extra biopsies around the retrieved area to ensure all tissue of the nodule is removed (March et al. 2003). The more tissue

Fig. 3.42 Typical malignant lesion on US and mammography, clear indication for CNB and not for Mammotome biopsy


we retrieve, the more reliable the histological diagnosis.

Sometimes, fibroadenomas present irregular contours, caused by fibrosis and degeneration,

and can be difficult to distinguish from malig-nant tumor (Fig. 3.43). Some fast-growing malignant tumors can have a homogeneous aspect and regular contours (Fig. 3.44). Small

Fig. 3.43 Different examples of probably benign nodu-lar lesion: slightly irregular contours and/or inhomo-geneous aspect. Mammotome biopsy and excision of

these lesions revealed a benign fibroadenomatous nature in all four cases

Fig. 3.44 Two atypical solid nodules. a oval-shaped, regular contours: probably benign characteristics on US. Biopsy revealed a poorly differentiated invasive

ductal carcinoma. b Nodule with irregular contours, probably malignant characteristics on US. Biopsy revealed a fibroadenoma


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intralesional cystic areas can be seen in fibroad-enoma, but can be caused by central necrosis in fast-growing primary or metastatic tumors (Fig. 3.45). The Mammotome offers the best possible histological sampling and can avoid unneces-sary operations.

In our experience, the psychological impact of complete removal is very important. Patients seem to be more reassured when a lesion has been removed instead of biopsied, despite the benign result. For the patient, a palpable abnor-mality is always more worrying than a nonpal-pable one.

Also in a postoperative breast, the presence of a (newly developed or previously not reported) nodule causes concern (Figs. 3.46 and 3.47); such lesions have to be considered malignant unless otherwise proven. Even after ductal

carcinoma in situ (DCIS), recurrence nearly always presents as an invasive nodule.

3.4.2 Very Small Suspicious Lesions

Lesions smaller than 5 mm, mainly small stellate lesions (Fig. 3.48), can sometimes be difficult to biopsy with standard core biopsy, as the partial volume effect of the US slice thick-ness can give the wrong impression of passing through the area. The Mammotome is only used for a malignant lesion if FNA or CNB does not seem technically possible or reliable (Fig. 3.49).

The Mammotome provides a more certain histological result, because with a few cuts

Fig. 3.45 Slightly inhomogeneous, nonpalpable, solitary mass, with sharp borders. Biopsy revealed metas-tasis of a melanoma, clearly seen on the (black) specimens


Fig. 3.46 This patient had had a tumorectomy for malignant lesion 13 years earlier. Close to the scar (white arrows), a small density was detected on mammography (right). The subsequent US exami-nation revealed a small atypical solid nodule (yel-

low arrows). Mammotome biopsy and broad excision were performed, confirming the presence of a recurrence. Five years later, the patient has no sign of recurrent disease and has had no further surgical intervention

Fig. 3.47 This patient previously had a tumorec-tomy for a malignant lesion. Close to the nipple and the scar (white arrows), a suspicious enhanc-ing nodule was detected on MRI. The subsequent US examination revealed a small, rather benign-

looking nodule (yellow arrows). Mammotome biopsy and excision were performed, confirming the presence of a benign fibroadenoma. The patient was spared a new surgical procedure by using the Mammotome


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almost the entire whole lesion is retrieved. Although this is sometimes the case, and no remaining malignant tissue is found on surgical excision, the Mammotome cannot be considered a safe therapeutic option for a malignant lesion, because of lack of orientation of the specimens and inability to provide information about safe margins.

3.4.3 Areas of Localized Attenuation

Most of the time, areas of localized attenuation are caused by areas of fibrosis in dense breast tissue, but localized acoustic attenuation can be the only sign of an invasive lobular carcinoma (Fig. 3.50). Some invasive lobular carcinomas

Fig. 3.48 Two examples of very small (2 and 3 mm) malignant lesions (invasive ductal carcinoma). Mammotome biopsy is done in these cases because there is less chance of false-negative results compared to CNB

Fig. 3.49 Small tubular carcinoma in a large fatty breast. A Mammotome biopsy is more reliable than CNB in such cases


do not present as nodules, because of the infil-tration pattern (Indian file pattern) and are therefore missed on mammography, but can nevertheless extend over a large area (Fig. 3.51). Sclerosing lymphocytic lobulitis (Fig. 3.52), as sometimes seen in diabetic patients, can also mimic infiltrating lesions. Broad sampling is recommended in these cases to provide adequate histological diagnosis. Differential diagnosis with fibrous areas in dense breast is necessary.

3.4.4 Isolated, Complex Fibrocystic Areas

In complex lesions (Figs. 3.53–3.55), only a broad histological sampling allows correct histological differentiation between fibro-cystic changes, atypia, and in situ carcinoma; in our experience, all of these tissue changes are sometimes present in the same area (Figs. 3.56 and 3.57). A solitary area in an otherwise

Fig. 3.50 Large area (arrows) where only acoustic attenuation is present; a real mass cannot be seen on US. Pathology reveals invasive lobular carcinoma.

The diffuse spreading of the tumor (Indian file pat-tern) and absence of a localized mass explains the attenuation

Fig. 3.51 Two areas of attenuation without clearly visible mass; mammography showed no detectable abnormalities. Pathology revealed extended invasive lobular carcinoma


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Fig. 3.52 Two examples of areas of strong attenuation with similar appearance: sclerosing lymphocytic lobulitis, as sometimes seen in diabetic patients, and infiltrating lobular carcinoma

Fig. 3.53 A 1-cm isolated hypoechoic area, with small cystic components, suggestive of fibrocystic changes. Lesion was detected as an enhancing area on a PET

scan done for another indication (melanoma staging). MRI showed a suspicious enhancing area. Mammotome biopsy revealed florid fibrocystic changes


normal breast parenchyma has to be consid-ered suspicious and should be biopsied or removed with the Mammotome if possible. With smaller samplings such as CNB or FNA, the risk of missing a carcinoma is much higher.

3.4.5 Papillomas

Small solitary papillomas can be accurately diagnosed with high-frequency US and color Doppler, and galactography is less often needed.

Fig. 3.55 A 2-cm area of fibrocystic changes, with some microcalcifications; pathology on Mammotome biopsy revealed high-grade DCIS

Fig. 3.54 Patient with silicon breast implant. Centrally located in the breast is a 2-cm isolated hypoechoic area with small cystic components suggestive of fibrocystic changes. Biopsy revealed areas of DCIS and microinvasive ductal carcinoma combined with fibrocystic changes


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The typical presentation is that of a small solid mass in a dilated duct or cyst, highly vascular-ized, with low-resistance flow (Figs. 3.58–3.60). It is more likely to find papilloma close to the nipple area. Nipple discharge is the most com-mon clinical sign; the fluid is most often clear or hemorrhagic. Cytology of the nipple discharge is frequently not contributive.

If there is suspicion of papilloma – which is a benign disease in the majority of cases – the lesion can be biopsied and removed using the Mammotome. However, a papilloma is a lesion with an uncertain biological behavior, and it may be difficult to differentiate from intraductal carcinoma. In addition, a benign papilloma can turn into a papillary carcinoma over time. An area of DCIS can sometimes give a similar image on US (Fig. 3.61). Removal of these lesions is therefore recommended, and surgery (microdochectomy) is difficult and requires good preoperative localization. The Mammotome is a valuable alternative and has become the first choice for solitary papillomas. In our experience and according to recent reports in the literature (Dennis et al. 2000; Govindarajulu et al. 2009), clinical manifestations also disap-pear after complete removal in nearly all cases.

The piecemeal removal of a papillary lesion can make the interpretation for the pathologist more difficult, but in our institution, experienced pathologists do not report major diagnostic problems for these cases.

3.4.6 Clusters of Microcalcifications

With better US equipment, many clusters are now visible on US (Cheung et al. 2002). When the calcifications are surrounded by hypoechoic solid tissue as in DCIS, they are easier to see (Fig. 3.62). In our series, the percentages of DCIS in US-guided procedures is higher than in stereotactic ones, which seems to indicate that the likelihood of DCIS is high (around 50% in our series) when microcalcifications are visible on US.

In difficult locations, where the stereotactic procedure is hazardous – due to lack of real-time guidance – for example, close to the nip-ple (Fig. 3.63), the skin, the pectoral muscle (Fig. 3.64), or the axillary region, US guid-ance offers a reliable and secure alternative because of the real-time monitoring (Steyaert et al. 2001; Fournier 2005). It is mandatory

Fig. 3.56 Complex, 1.5-cm isolated hypoechoic area, with small cystic components, suggestive of fibrocystic changes. A few microcalcifications were visible. Pathology revealed different histological content (Fig. 3.57)


a b

c

Fig. 3.57 Pathology slices from the complex lesion of Fig. 3.56. Mammotome biopsy showed fibrocystic changes a, DCIS b, and invasive carcinoma c in the same lesion

that the cluster be sufficiently visible, and one should take care during injection of local anesthesia that the target does not become invisible due to injection of air bubbles or because of an excessive amount of local anes-thetic. Especially in fatty breast, the injection

of local anesthesia can create areas of increased echogenicity that decreases the visibility of the calcifications. As a precaution, we try to use less anesthesia in these cases. In hypoechoic nodular lesions, however, the increased echo-genicity of the fat can improve visualization.


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Fig. 3.58 Typical aspect of an intraductal papilloma: small intraductal mass, slight ductal dilatation, and very intense vascularity on color Doppler

Fig. 3.59 Intracystic papilloma, close to the nipple; the intracystic mass is clearly vascularized on color Doppler, which clearly differentiates it from intracystic debris


The location must of course be correlated with the mammographic findings, and during the procedure, specimen radiography is neces-sary to prove the retrieval of calcifications (Figs. 3.65 and 3.66). Since microcalcifica-tions can be associated with (in situ) carcinoma,

and because in cases of malignancy remaining DCIS can still be present, despite removal of visible calcifications (Cangiarella et al. 2000), the a clip should be placed in all cases, to be able to localize the area of biopsy if further sur-gery is needed.

Fig. 3.61 Small (4-mm) intraductal mass immediately below the nipple; US image is suggestive of papil-loma. Pathology revealed DCIS

Fig. 3.60 Patient with nipple discharge: 5-mm intra-cystic papilloma was found in a dilated duct, less than 1 cm from the nipple. Breast thickness is maxi-mum 1 cm, and there is a breast implant. Because of

forward throw of the needle, CNB should be avoided. Successful Mammotome biopsy and resec-tion with 14-G needle were performed; diagnosis was confirmed and nipple discharge was cured

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Fig. 3.64 Small area of microcalcifica-tions, at posterior side of breast parenchyma. VAB was done under US guidance because of good visualization and position close to the chest wall. Pathology revealed high-grade DCIS

Fig. 3.62 A 4 × 7 mm focus of irregular microcalcifications, clearly visible on US, partially because it was surrounded by a hypoechoic area. This can be suggestive of in situ carcinoma. Benign findings on pathology report in this case

Fig. 3.63 Very small area (circled) of microcalcifications, adjacent to the nipple. US-guided Mammotome biopsy was successfully performed and revealed high-grade DCIS


Fig. 3.65 Typical longitudinal US image of DCIS: small hypoechoic band with linear central reflections (arrows), corresponding to comedo-type microcalcifications. X-ray images of corresponding Mammotome biopsy cores

Fig. 3.66 In cases of biopsy for microcalcifications, we always perform an X-ray of the cores during the procedure to confirm the presence of the calcifications. Pathology revealed DCIS in this example


33.4.7 Lesions in Difficult Locations

Compared to standard core biopsy, the absence of a forward throw of the needle reduces the risk of touching sensitive structures; we recommend the use of the Mammotome in lesions close to the nipple (Figs. 3.59 and 3.61), the thoracic wall, the skin, or the axillary region. With expe-rience, the retrieval of adequate samples of areas of microcalcifications in these difficult loca-tions (Figs. 3.62–3.64) is perfectly feasible. Also in patients with breast implants (Figs. 3.54 and 3.60), the use of the mammotome is safer than CNB. Most of these patients have only a small amount of breast tissue (the main reason for breast augmentation), and lesions are thus close to the implants. The 14-G needle is well suited for precise work on small, infracentimetric lesions in difficult areas, due to smaller samples and lower suction power.

3.4.8 Very Hard Lesions with Inconclusive Previous Biopsy or FNAC

Due to the vacuum aspiration and the rotating cutter, even in the hardest lesions where adequate

sampling with core fails, good histological results are obtained with the Mammotome. In CNB procedures the needle sometimes bends (Fig. 3.67) due to the hard tissue, resulting in inadequate sampling.

3.4.9 Inadequate FNAC or Microbiopsy Results

The literature reports false-negative results ranging between 8 and 15% for CNB, and much higher figures for FNA, certainly in microcalci-fications. This is partly due to technical reasons such as lesion location and size, and partly due to the histological type of the lesion (diffuse, ill-defined, fibrosis, inflammatory changes). The Mammotome can obtain a more confident diag-nosis because of the larger volume of tissue obtained.

3.4.10 Removal of Benign Lesions

Breast lesions, certainly when they are palpable, cause a great deal of uncertainty and anxiety to the patient. Inconclusive radiological or clinical reports aggravate these conditions, and a strong

Fig. 3.67 Very hard tumoral lesion can cause bending and deformation of the thinner core biopsy needle, which results in inadequate sampling. Use of Mammotome is more appropriate in these conditions


family history of cancer is also an aggravating factor. Because we always have to consider the attitude of the patient in the presence of a breast lesion, frequently, and many times at the patient’s request, the decision is made to surgi-cally remove a lesion that looks benign on imag-ing. The Mammotome can be a better and less expensive alternative for lesion removal in these situations (Fine et al. 2002, 2003; Carpentier et al. 2005). Recently, the FDA approved the use of the device for this purpose (Sperber 2003; Johnson et al. 2002).

Lesions up to 2.5–3 cm (Fig. 3.68) can be completely removed with minimal or no scarring (Fig. 3.69). The use of an 8-G needle is recom-mended for nodules of 1 cm or larger. The lesion must be removed as completely as possible to prevent regrowth. Therefore, careful US moni-toring of the procedure is mandatory, and the use of a transverse section is very important (Fig. 3.70). once the lesion is visibly removed on the US image, we take some extra samples in different directions to be sure that everything is removed. Visual inspection of the cores is also important to check for complete removal, since

fibroadenoma has a different, whiter appearance than glandular tissue and can be clearly distin-guished from fat (Fig. 3.71). The technique is very well tolerated by patients and is always performed on an outpatient basis.

3.4.11 Indications Discussed: Radial Scar, Large Intracystic Lesions

In radial scar, the risk of finding underlying DCIS or infiltrating ductal carcinoma (IDC) is around 18% for Mammotome biopsy. Therefore, a surgi-cal excision is still recommended by most breast specialists. However, small radial scars, without an associated nodular center on US (Fig. 3.72), are less frequently associated with malignancy (Jacobs et al. 1999) than previously thought. A radial scar smaller than 5 mm is associated in only 2.5% of cases with malignancy, whereas a lesion greater than 5 mm has a 30% risk of associated malignancy. The Mammotome can certainly help in the diagnosis, but a surgical excision is fre-quently unavoidable. In our opinion, smaller radial

Fig. 3.68 Typical aspect of a benign fibroadenoma in a 20-year-old woman who preferred removal of this lesion. This can be done perfectly with the

Mammotome using local anesthesia on an outpa-tient basis. It is a valuable alternative for surgical excision

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Fig. 3.70 US image of a 2.3-cm fibroadenoma a to be removed on request. During the procedure, the longi-tudinal scan b shows near complete removal. The transverse image c, however, shows a large part of the

lesion still present on both sides of the needle (arrow) and shows that only a transsection (dotted lines) of the lesion is done at that stage. This example under-lines the importance of the transverse image

Fig. 3.69 Same lesion as in Fig. 3.68, before and at the end of the procedure. The image on the right shows complete removal of the mass; the needle is still in place

Fig. 3.71 Piecemeal removal of a fibroad-enoma. The tissue samples on the left and right side are more yellow and contain the surrounding fat; the whiter pieces in the middle come from the fibroadenoma


scars can be removed by the Mammotome and benefit from regular follow-up. Although a Mammotome biopsy can establish a correct diag-nosis, the biggest disadvantage is that the patholo-gist misses the integrity of the lesion.

This is also the case for larger papillary intra-cystic lesions (Fig. 3.73), which are more fre-quently malignant than small papillomas (Fig. 3.74) or ductal carcinoma extending in a cyst (Fig. 3.75).

3.4.12 Other Indications

In women requesting nipple-conserving mastec-tomy for invasive or in situ disease, Mammotome biopsy can be used to determine whether leav-ing the nipple was safe. The needle is positioned beneath the nipple and biopsy specimens are taken through 360°. The histopathology of the mastectomy specimen correlates 100% with

Mammotome biopsy according to a recent study (Govindarajulu et al. 2006).

Inflammatory carcinoma, where no clear mass is visible (Fig. 3.76), can be more accu-rately diagnosed with the Mammotome than with FNA. In a number of cases, a mass cannot be found in the diseased breast and sometimes there is a clear tumor (Fig. 3.77); CNB is then possible.

3.5 Processing the Cores

The cores are immediately placed in a formalin solution for overnight fixation; this is the stand-ard routine procedure. If microcalcifications have been sampled under US guidance, it is mandatory to radiograph the cores and check for the presence of microcalcifications. This is pref-erably done with the needle still in place, so that

Fig. 3.72 Radial scar and infiltrating carcinoma can sometimes be difficult to distinguish. on US, in the presence of tumor, we frequently see a small central mass and vascularization. In this case of

radial scar, none of these signs is present, which increases the probability of fibrous scar. There is a clear stellate aspect on US (arrows) and acoustic shadow (dotted arrow)


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Fig. 3.73 Two large cysts, with intracystic masses (yellow arrow), clearly vascularized on color Doppler. Intracystic blood with sediment level and fibrinous elements (red arrows). This type of lesion

is not a good indication for Mammotome biopsy, and surgical excision is preferred in these cases. Pathology revealed intracystic benign papilloma with hemorrhage

Fig. 3.74 Typical example of an intracystic papillary carcinoma; the high-resistance flow is suggestive of malignancy. Surgical excision is preferred over

Mammotome in this case. FNAC (with aspiration of the fluid) and CNB were performed to establish preoperative diagnosis


Fig. 3.75 A larger intracystic lesion, similar to papilloma. In some areas, there is an irregular mass adjacent to the cyst, suggesting malignant tumor (arrows). Aspiration cytology of the cyst content and CNB of the mass seems more appropriate than Mammotome. The pathology report revealed high-grade DCIS and invasive tumor

further samples can be taken in the case of insuf-ficient calcifications.

In extremely rare situations, calcifications that have been retrieved from the breast are not found in the cores, because they are flushed away through the vacuum tubes into the canister (Friedman et al. 2003). This is more the case in fibrocystic disease.

The radiograph can be taken on a dedicated instrument (e.g., a Faxitron Specimen Radiography System; Faxitron X-ray Corp., Wheeling, IL,

USA) or by using a microfocus magnification view on a standard mammographic unit. In our experience, ×1.8 magnification on a full-field digital system (GE Senograph Essential GE medical systems, Milwaukee, WI, USA) gives excellent results, with the advantage of immedi-ate imaging. The image quality is largely suffi-cient to evaluate the presence of calcifications. A standard film-screen X-ray (using a microfo-cus magnification view) can also be used if no digital system is available, but it has the disad-


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vantage of requiring more time because the film must be developed.

The X-ray image of the cores not only con-firms the presence of calcifications (Figs. 3.65 and 3.66), but allows us to separate the calci-fied from the noncalcified specimens. In our experience, samples containing calcifications always show the important pathology, and in the noncalcified cores, no other relevant pathology that would alter the diagnosis and eventual treat-ment was found. Therefore, our pathologists examine 3 times more levels in the calcified specimens. We put calcified cores in a separate formalin container for this purpose.

3.6 Needle Size

Three needle sizes are currently available: 14, 11, and 8 G (Fig. 3.78). The length of the biopsy window is 23, 19, and 17 mm, respectively. The average weight of the samples is 34, 100, and 300 mg, respectively, compared to 17 mg for the standard 14-G core needle. Because of the dou-ble lumen and higher G number, the needle is much larger than a core needle, but is equally well supported (Fig. 3.79).

The standard size of the Mammotome needle is 11 G; because of the size and the double

Fig. 3.77 A large edema caused by inflammatory carcinoma. A suspicious mass was visible in this case

Fig. 3.76 A large edema caused by inflammatory carcinoma. No mass was visible in this case. Large random US-guided Mammotome biopsy gave the correct diagnosis


lumen for the vacuum, the needle is much larger than a core needle. For very small and difficultly located lesions, the 14-G needle can be used. The larger 8-G needle is mainly used for com-plete removal of larger benign lesions, where it speeds up the procedure considerably. The larger needle can also be used for lesions where the pathologist prefers to have a larger, intact speci-men, such as in cases of papilloma, radial scar, or small suspicious lymph nodes. An 8-G needle

seems to be associated with a slight increase in minor complications, mainly hematoma.

The needle has either a blunted or a bladed tip (Fig. 3.80); the bladed tip facilitates the pen-etration in the tissue by dissecting the tissue planes and this type of needle is preferred in most cases. The 14-G needle is only available with blunted tip.

Except for the 14-G needle, clips are availa-ble for every type of needle.

Fig. 3.78 Mammotome needle size comparison. Three needle sizes are available: 8, 11, and 14 G. on the larger needles, the length of the biopsy window is also greater

Fig. 3.79 X-ray image of different types of needle used in interventional breast procedures. The size of the Mammo-tome needle is much larger than the CNB, but is equally well tolerated if proper local anesthesia is applied


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3.7 Clip Placement

A small metallic clip, mounted in a flexible catheter, can be inserted through the needle (Fig. 3.81) and deployed at the site of biopsy (Fig. 3.82). The clip marks the area of biopsy for later follow-up or intervention in cases of malig-nant lesion. The clip is difficult to visualize on US, but is very clearly seen on mammography. The hook wire localization can be done under stereotactic guidance targeted on the clip. Displacement of the clip has occasionally been reported (Kruger et al. 2002), mainly in stereo-tactic procedures and more frequently in fatty breast. The newer marking devices, containing not only a metallic clip, but also an amount of resolving material, should not have this migra-tion problem.

Sometimes a small hematoma is present at the site of biopsy, which makes it easier to place a hook wire under US guidance (Fig. 3.83).

Newer clips, with resolvable material, also make a hook wire placement possible under US guidance for several weeks after the Mammo-tome procedure, because the resolvable material gives acoustic attenuation for several weeks (Fig. 3.84).

We always place a clip in cases of microcal-cifications (because in situ carcinoma is possi-ble); this is not necessary under US guidance for benign lesions. If we think there is a possibility of malignancy (microcalcifications, atypical nodules, small suspicious lesions) or in cases of papilloma, we place a clip.

3.8 US Versus Mammographic Guidance

Stereotactic guidance of the Mammotome has been a standard procedure for many years for diagnostic biopsy of clustered microcalcifica-tions. A prone table should be preferred for an optimal approach to the lesion and optimal com-fort for the patient.

US guidance is used for lesions that can be adequately visualized, mainly nodular lesions. Because of real-time control over the procedure and the more comfortable position of the patient (supine, no breast compression), US guidance is preferred where the lesion is sufficiently visible to perform the procedure safely (Maniero et al. 2002).

Abnormal densities or stellate lesions, which can be identified on US, are also preferably biopsied under US monitoring.

Fig. 3.81 Clip insertion through a guiding side-hole in the EX needle

Fig. 3.80 The Mammotome needle is available in two types, with blunted (top) and bladed (bottom) tip. The bladed tip enables easier penetration through different tissue planes


Fig. 3.82 A small catheter containing the metallic clip is inserted through the lumen of the needle (top), here on an HH needle. The clip is pushed into the tissue at the level of the biopsy window

Fig. 3.83 Small hematoma (red arrows) after Mammotome biopsy. The reflections and the acoustic shadow (white arrows), which contain resolvable pellets, are caused by the newer marking system (SenoRX). They make it possible to visualize the area of biopsy 4-6 weeks after the procedure. The hook wire can be placed under US guidance and fewer stereotactic procedures are needed

Correlation of mammographic, US, or even-tually MRI images is mandatory to identify the exact location. In some cases, we inject a very small amount (1-2 drops) of iodine contrast media into the lesion under US guidance and verify the correlation with a digital mammo-gram immediately afterward. Lesions that are

only visible on MRI can be seen in 30–40% of the cases with verification by US after MRI.

As a rule, we try to guide the Mammotome using the modality that is most comfortable for the patient (US > stereotactic mammography > MRI), with the best possible monitoring during the procedure (US > mammography > MRI),


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provided that the lesion is sufficiently visible with the chosen modality. Under US, we must be particularly sure that the lesion remains vis-ible after local anesthesia. Therefore, it is rec-ommended to put a skin marker at the exact location of the lesion before injecting ane-sthesia.

3.9 Results

We have used the mammotome for nearly 10 years and have performed over 2500 procedures, representing about 30% of our breast biopsies. The majority of the biopsies are done with the core needle, most 16 or 18 G. FNAC is rarely used for solid lesions because of the limited information.

Approximately 48% of the Mammotome procedures are done under stereotactic guid-ance, 45% under US, and 7% under MRI (this relatively high percentage is explained by the fact that we are the only center in the country that is equipped for MRI-guided procedures).

In the mammographic cases, 29% malignan-cies and 7% atypical ductal hyperplasia were found; 64% of the cases were benign, which eliminated the need for short-term follow-up. of the malignant cases, 88.7% were in situ carcino-mas, the vast majority high-grade DCIS. We only had two false-negative results in the begin-ning, mainly due to inexperience.

The US cases showed fewer malignant cases, which seems normal, because of the type of indication. We had 16% malignancies, 4% aty-pia, and 80% benign lesions. If we do not take into account the fibroadenomas removed on request (as an alternative for surgery), and if we consider papillomas as positive cases, we had 64% benign and 36% positive biopsies.

The MRI-guided procedures resulted in 32% malignant, 2% atypia, and 66% benign cases.

overall, the Mammotome is a very reliable sampling technique (Hung et al. 2001; Sebag et al. 2006) with very few complications, is relatively easy to use, and is well tolerated by the patients. The larger amount of removed tis-sue reduces the sampling error. Compared to surgical biopsy, the cost is two to three times lower, even without counting the additional

Fig. 3.84 Preoperative hook wire placement after Mammotome procedure. The correct position of the wire (arrows) is clearly visible on longitudinal (left) and transverse (right) image. A small hematoma and

the newer markers with resolvable material (causing an acoustic shadow) facilitate US-guided placement, which is faster, more precise, and better tolerated than the stereotactic-guided procedure


social cost. A major cost reduction factor is the fact that the technique is done on an outpatient basis and requires no hospitalization, not even 1-day hospitalization.

Because it is less invasive, it can be used more easily, thus reducing the cost (Bonnaerens

1997) of repetitive follow-ups or more expensive additional examinations, and above all it reduces the time between detection and diagnosis, which is very important in reassuring the patient. It can also have a prognostic impact since tumors can be diagnosed at an earlier stage; delayed diagno-sis, with the potential medicolegal impact, can also be avoided.

At present, the technique cannot be consid-ered as therapeutic in cases of malignancy.

In our hospital, the use of the Mammotome radically changed the approach to breast pathol-ogy. Lesions are detected by (full-field digital) mammography frequently combined with high-resolution US; MRI is performed only in limited cases due to more difficult access of the machines. In the presence of an abnormality, no follow-up examinations are done, but we try to provide histological proof, most of the time immediately after the diagnostic imaging. We usually have a definitive histological report within 24–48 h. This gives high patient satisfaction and reduces patient anxiety considerably. Moreover, this approach is appreciated by the clinicians.

US-guided core biopsy is the most frequently used procedure; the Mammotome is reserved for more difficult lesions and for microcalcifi-cations. Surgical open biopsy has virtually been eliminated in our hospital.

There is practically no more surgery for benign lesions. In cases of malignancy, a one-step therapeutic operation can be planned, with the patient fully informed.

Because of the high number of small lesions and in situ lesions, breast-conserving surgery and sentinel node procedures are done in a majority of cases.

All cases are discussed in a multidisciplinary team, which meets weekly.

The use of the Mammotome is in our experi-ence an important addition in our daily practice.

References

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Baez E, Huber A, Vetter M, Hackeloer BJ (2003) Minimal invasive complete excision of benign breast tumours using a three-dimensional ultra-sound-guided mammotome vacuum device. Ultrasound Obstet Gynecol 21(3):267–272

Bonnaerens J (1999) Multicenter survey in Belgium: total cost of surgical breast biopsy - non pub-lished data, used in a preparation of reimburse-ment dossier

Brem RF et al (2001)Reliability of histologic diag-nosis of breast cancer with stereotactic vacuum-assisted biopsy. Am Surg 67(4):388–392

Cangiarella J, Gross J, Symmans WF, Waisman J, Petersen B, D’Angelo D, Singer C, Axelrod D (2000) The incidence of positive margins with breast conserving therapy following mammo-tome biopsy for microcalcification. J Surg Oncol 74(4):263–266

Cangiarella J, Waisman J, Cohen JM, Chhieng D, Symmans WF, Axelrod D, Gross J (2001) Radial sclerosing lesion: correlation between mammo-tome core biopsy and surgical excision. Breast J 7(1):66–67

Carpentier E, Maruani A, Michenet P et al (2005) Les macrobiopsies échoguidées assistées par le vide peuvent-elles constituer une alternative à la chirurgie diagnostique en cas de microbiopsies non contributives. J Radiol 86:475–480

Cheung YC, Wan YL, Chen SC et al (2002) Sonographic evaluation of mammographically detected microcalcifications without a mass prior to stereotactic core needle biopsy. J Clin Ultrasound 30(6):321–326

Costantini R, Sardellone A, Marino C, Giamberardino MA, Innocenti P, Napolitano AM (2005) Vacuum-assisted core biopsy (Mammotome) for the diagnosis of non-palpable breast lesions: four-year experience in an Italian center. Tumori 91(4):351–354

Dennis MA, Parker S, Kaske TI, Stavros AT, Camp J (2000)Incidental treatment of nipple discharge caused by benign intraductal papilloma through


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diagnostic Mammotome biopsy. AJR Am J Roentgenol 174(5):1263–1268

Dhillon MS, Bradley SA England DW (2006) Mammotome biopsy: impact on preoperative diagnosis rate. Clin Radiol 61(3):276–281

Diebold T, Hahn T, Solbach C, Rody A, Balzer Jo, Hansmann ML, Marx A, Viana F, Peters J, Jacobi V, Kaufmann M, Vogl TJ (2005) Evaluation of the stereotactic 8G vacuum-assisted breast biopsy in the histologic evaluation of suspicious mammography findings (BI-RADS IV). Invest Radiol 40(7):465–471

Fine RE, Boyd BA, Whitworth PW, Kim JA, Harness JK, Burak WE (2002) Percutaneous removal of benign breast masses using a vacuum-assisted hand-held device with ultrasound guidance. Am J Surg 184(4):332–336

Fine PW, Whitworth JA Kim JK Harness BA Boyd WE Burak NN (2003) Low-risk palpable breast masses removed using a vacuum-assisted hand-held device. Am J Surg 186:362–367

Fournier D (2005) Sonographic guidance for vac-uum-assisted percutaneous biopsy of microcalci-fications of the breast. oral Presentation RSNA 2005-Chicago

Friedman PD, Sanders LM, Menendez C, Kalisher L, Petrillo G (2003) Retrieval of lost microcalci-fications during stereotactic vacuum-assisted core biopsy AJR 180:275–280

Govindarajulu S, Narreddy S, Shere MH, Ibrahim NBN, Sahu AK, Cawthorn SJ (2006) Preope-rative mammotome biopsy of ducts beneath the nipple areola complex. Eur J Surg Oncol 32(4): 410–412

Govindarajulu S, Narreddy SR, Shere MH, Ibrahim NB, Sahu AK, Cawthorn SJ (2009) Sonogra-phically guided mammotome excision of ducts in the diagnosis and management of single duct nipple discharge. Eur J Surg oncol 32:725–728

Hung WK, Lam HS, Lau Y, Chan CM, Yip AW (2001) Diagnostic accuracy of vacuum-assisted biopsy device for image-detected breast lesions. ANZ J Surg 71(8):457–460

Jacobs TW, Byrne C, Colditz G, Connolly JL, Schnitt SJ(1999) Radial scars in benign breast-biopsy specimens and the risk of breast cancer. N Engl J Med 340(6):430–436

Johnson AT, Henry-Tillman RS, Smith LF, Harshfield D, Korourian S, Brown H, Lane S, Colvert M, Klimberg VS (2002) Percutaneous excisional breast biopsy. Am J Surg 184(6):550–554; dis-cussion 554

Kettritz U, Rotter K, Schreer I, Murauer M, Schulz-Wendtland R, Peter D, Heywang-Kobrunner SH

(2004) Stereotactic vacuum-assisted breast biopsy in 2874 patients: a multicenter study. Cancer 100(2):245–251

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Meloni GB, Dessole S, Becchere MP, Soro D, Capobianco G, Ambrosini G, Nardelli GB, Canalis GC (2001) Ultrasound-guided mammo-tome vacuum biopsy for the diagnosis of impal-pable breast lesions. Ultrasound Obstet Gynecol 18(5):520–524

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Philpotts LE, Hooley RJ, Lee CH Comparison of automated versus vacuum-assisted biopsy meth-ods for sonographically guided core biopsy of the breast. AJR 2003180:347–351

Plantade R, Hammou JC, Gerard F, Chanalet I, Aubanel D, David-Bureau M, Scotto A, Fighiera M, Gueret S, Lo Monaco L (2005) Ultrasound-guided vacuum-assisted biopsy: review of 382 cases. J Radiol 86(9 Pt 1):1003–1015

Sebag P, Rouyer N (2003) Quelle est la place du mammotome sous échographie? In: Namer M, Ferrero JM (eds) Nouvelles techniques, nouv-elles thérapeutiques: nouvelles stratégies. 25e journées nationales de la société française de sénologie et de pathologie mammaire


(SFSPM). Nice, 17–19 September 2003. Springer, Paris

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4.1 Introduction

Interventional methods such as ultrasono-graphically, mammographically, or stereotacti-cally targeted/guided core vacuum biopsy or excision biopsy (Aichinger et al. 1999; Bauer et al. 1994; Burbank 1997; D’angelo et al. 1997; Ferzli et al. 1999; Heywang-Köbrunner et al. 1997, 1998; Jackman et al. 1997, 1998; Kelly et al. 1997; Krämer et al. 2002, 1998; Liberman 2000, 1998; Parker et al. 1993, 1994; Parker and Jobe 1993; Parker and Klaus 1997; Scheler et al. 2000; Schulz-Wendtland et al. 1994, 1997a, b, 1998, 2001; Sheth et al. 1999; Smathers 2000) have an established role both in complementary diagnostic investigations of the breast (clinical examination, mammog-raphy, ultrasonography), including dynamic magnetic resonance imaging (MRI), and in breast cancer screening programs (Schulz-Wendtland et al. 1997a, b). Transcutaneous biopsy procedures permit minimally invasive harvesting of breast tissue samples, enabling us to dispense with open surgical excision when histological examination demonstrates a benign focal lesion. This corresponds to the

recommendations of the European Society of Mastology (EUSOMA) (Perry 2001) and the S3 guideline “Breast Cancer Screening Program in Germany” (S3-Leitlinie 2003). Provided the criteria are strictly observed, the specificity and the negative predictive value of complementary diagnostic investigation of the breast can be improved. Moreover, compared with surgical intervention, transcutaneous biopsy techniques save money and time and incur less morbidity (Liberman 2000; Lieberman and Sama 2000; Lindfors and Rosenquist 1994). What is required, however, is an unequivocal diagnosis according to the Breast Imaging-Reporting and Data System (BI-RADS) guide-lines of the American College of Radiology (ACR) (American College of Radiology (ACR) 1998) - translated into German in a version authorized by the German Röntgen Society (ACR BI–RADS Klassifikation. 2006) – or correlating with the findings of ultrasonography (US) or magnetic resonance imaging (MRI).

4.2 Technique

The Vacora biopsy system (Bard Angiomed) comprises a handpiece (dimensions, 36 × 400 × 200 mm; weight, 400 g) in which all the functions are integrated, foremost among them vacuum and pressure generation, an electric motor, microprocessors, and a rechargeable lithium ion battery (7.2 V). The biopsy proce-dure is started by pressing a key controlled by the

The Vacora Biopsy System

R. Schulz-Wendtland

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R. Schulz-WendtlandGynecological Imaging, Institute of Radiology University of Erlangen–Nürnberg Universitätsstrasse 21–23 91056 Erlangen, Germanye-mail: [email protected]. uni-erlangen.de


98 R. Schulz-Wendtland

4microprocessors. The disposable biopsy needle used in the Vacora biopsy system consists of two hollow cannulas, one inside the other, and a vacuum–pressure piston system. The needle diameter is 11 G (3.5 mm). After local anesthe-sia and, if indicated, a stab incision, the coaxial introducer sheath guides the biopsy needle to the desired location. The high pressure gener-ated by the system facilitates removal of the tissue cylinder from the sampling window and cleanses the vacuum cannula after each sample is harvested. Consistency of biopsy quality is thus assured even after removal of multiple samples. The biopsied tissue is not drilled out; rather, homogeneous, unfragmented cylinders are obtained (Schulz-Wendtland et al. 2003a, b). The European Guidelines for Quality Assurance (Pathology) (Sloane et al. 1997) are observed when sending the samples for histological examination. In the event of a discrepancy between the findings of complementary diag-nostic techniques and core histology, intraop-erative histology is required (Figs. 4.1–4.4).

The Vacora biopsy system can be used under US or stereotactic guidance or can be directed by MRI, e.g., the Mammotome biopsy system (Ethicon Endo-Surgery, Breast Care). With US, the Vacora biopsy system is better than the Mammotome vacuum biopsy system, because all the functions, including generation of vac-uum and high pressure, are integrated into a handpiece, avoiding the need for tubing con-nected to a vacuum device. Under stereotactic direction, however, the Mammotome vacuum biopsy system is superior, because the Vacora biopsy system has to be completely withdrawn from the indwelling coaxial needle after every cut to remove the tissue cylinder; this is not nec-essary with the Mammotome system. Thus both systems, Vacora with integrated functions and Mammotome with external vacuum generation, have their advantages. The same is true for MRI-guided interventions. With the Vacora biopsy system, a Micromark clip (Biopsys Medical)

can be introduced at the biopsy site at any time through the indwelling coaxial needle, marking the site for future diagnostic imag-ing procedures. The newly developed resorb-able gel clips (Gel Mark Ultra, SenoRx) can be used in the same way (Schulz-Wendtland et al. 2002).

4.3 Indications and Contraindications

4.3.1 US-Guided Transcutaneous Vacuum Biopsy

4.3.1.1 Indications

The indications for US-guided transcutaneous vacuum biopsy (Vacora) are:

1. Histological investigation of suspicious US-differentiated focal findings (size, 1 cm, correlating with BI-RADS grade 4 on mammography)

2. Preoperative confirmation of carcinoma in suspicious US-detected focal lesions (size, 1 cm, correlating with BI-RADS grade 5 on mammography)

The consensus recommendations of the German Society of Senology (DGS) for indication and performance of vacuum biopsy of the breast under US guidance (Krainick-Strobel et al. 2005) should still be followed:

1. Status after core biopsy in the case of per-sisting suspicion of carcinoma (BI-RADS 4/5, disagreement between diagnostic imag-ing and histology)

2. Suspicious lesions (BI-RADS 4/5) around 5 mm in diameter

3. Intraductal/intracystic vegetations (e.g., iso-lated papillomas)

4 The Vacora Biopsy System 99

Fig. 4.1 Vacora vacuum biopsy system (Bard Angiomed)

Fig. 4.2 Suspicion of T1N0MX breast cancer (arrow). Histology after primarily US-targeted core biopsy (CNB): mastopathy


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Fig. 4.4 Suspicion of T1N0MX breast cancer (focus in Fig. 4.2). The needle of the vacuum biopsy sys-tem (LCNB) is in the lesion (arrow). Fifty percent decrease in lesion size on US. Histology after

US-guided vacuum biopsy (LCNB): invasive duc-tal breast cancer. Histology after subsequent breast-sparing therapy: 0.5-cm invasive ductal breast cancer

Fig. 4.3 Suspicion of T1N0MX breast cancer (focus in Fig. 4.2). Following primarily US-targeted core biopsy (CNB) and negative histology, US-guided vacuum biopsy was carried out (LCNB): needle in the caudal portion of the lesion (arrow)

4. Resection of clearly benign but symptomatic lesions (e.g., symptomatic fibroadenomas or recurrent symptomatic cysts)

4.3.1.2 Contraindications

Severe coagulation disorders and allergies to local anesthetics are absolute contraindications.


4.3.2 Stereotactic Vacuum Biopsy

4.3.2.1 Indications

The indications for stereotactically guided vacuum biopsy (Vacora) in light of the possibility of a sam-pling error for foci less than 5 mm are as follows:

1. Histological investigation of suspicious foci differentiated only on mammography (BI-RADS 4/5)

2. Preoperative confirmation of carcinoma in suspicious foci detected only on mammogra-phy (BI-RADS 4/5)

3. Histological investigation followed by a mammographic differential diagnosis of mastopathy, DCIS (suspicious microcalcifi-cations) (BI-RADS 4 and BI-RADS 5)


Severe coagulation disorders and allergies to local anesthetics are absolute contraindications.

4.3.3 MRI-Guided Vacuum Biopsy

4.3.3.1 Indications

The indications for MRI-guided transcutaneous vacuum biopsy (Vacora) are:

1. Histological investigation of suspicious foci differentiated only on MRI (>5 mm, correlating with BI-RADS grade 4 on mammography)

2. Preoperative confirmation of carcinoma in suspicious foci detected only on MRI (>5 mm, correlating with BI-RADS grade 5 on mammography)


The presence of a cardiac pacemaker or other metallic device in the patient’s body is a contraindication.

4.4 Side Effects

Slight pain, bleeding, and vasovagal reactions can be expected.

Pain is minimized by application of a local anesthetic. Good cutaneous anesthesia is most important; the parenchyma is much less sensi-tive to pain than the skin.

Cutaneous bleeding can, as a rule, be caused by stab incisions. The development of a more extensive hematoma is counteracted by specific wide compression (for 10–15 min or 30 min, application of a compression bandage).

Vasovagal reactions in the course of stereo-tactic-mammographic interventions are observed more frequently in sitting than in supine patients. They can be avoided by performing the proce-dure in appropriate surroundings and by per-sonal care of the patient.

4.5 Results

Sensitivity and specificity of up to 100% for US-, MRI-, and stereotactically guided biopsy with the Vacora biopsy system have been reported in the literature (Bauer et al. 1994; Parker et al. 1993, 1994; Parker and Jobe 1993; Parker and Klaus 1997; Scheler et al. 2000; Schulz-Wendtland et al. 1997a, b, 1998, 2001, 2003a, b, 2005; Sittek et al. 2005; Hauth et al. 2005).


44.6 Limitations

The Vacora biopsy system has the same limita-tions as the Mammotome biopsy system.

4.7 Practical Hints

The Vacora biopsy system is of equal value as the Mammotome vacuum biopsy system. The integration of vacuum generation into the hand-piece is an advantage on US, but on stereotacti-cally guided biopsy it is disadvantageous in that the Vacora system has to be completely removed from the coaxial needle every time a new tissue cylinder is obtained. The same is true for MRI-guided biopsy.

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Schulz-Wendtland R, Krämer S, Lang N, Bautz W (1998) Ultrasonic guided microbiopsy in mam-mary diagnosis: indications, technique and results. Anticancer Res 18:2145–2146

Schulz-Wendtland R, Aichinger U, Krämer S, Lang N, Bautz W (2001) Mammographisch/stereo-taktisch gezielte Vakuum- /Exzisionsbiopsie. Radiologe 41:379–384

Schulz-Wendtland R, Heywang-Köbrunner SH, Aichinger U, Krämer S, Wenkel E, Bautz W (2002) Verbessert die Clipmarkierung im Rahmen der sonographischen oder stereotaktischen Brustbiopsie die Verlaufsbeobachtung kleiner Mammaläsionen und Lokalisation von Tumoren nach Chemotherapie? RöFo 174:620–624

Schulz-Wendtland R, Aichinger U, Krämer S, Tartsch M, Kuchari, Magener H, Bautz W (2003a) Sonographisch gezielte Stanzbiopsie: Wieviele Biopsiezylinder sind notwendig? RöFo 175:94–98

Schulz-Wendtland R, Kramer S, Bautz W (2003b) First experiences with a new vac-uum-assisted device for breast biopsy. RöFo 175(11):1496–1499

Schulz-Wendtland R, Wenkel E, Imhoff K, Bani M, Bock K, Degenhardt F, Bautz W (2005) Interventional methods in diagnostics of the breast – a new vacuum biopsy system for the breast in routine clinical practice. Ultraschall Med 26(5):411–414

Sittek H, Wieser A, Kessler M, Britsch S, Vick C, Untch M, Reiser M (2005) Sonographically guided, minimally invasive biopsy of uncertain mammary lesions. Clinical experience with a new biopsy system. Radiologe 45(3):269–277

S3-Leitlinie (2003) W. Zuckschwerdt Verlag München. Brustkrebsfrüherkennungs programm in Deutschland. der AWMF

Sloane JP, Böcker W, Holland R et al (1997) Leitlinien für die Pathologie - Anhang zu den Europäischen Leitlinien für die Qualitätssicherung beim Mammographie-Screening. Pathologe 18:71–88

Sheth D, Wesen CA, Schroder D, Boccaccio JE (1999) The advanced breast biopsy instrumenta-tion (ABBI) experience at a community hospital. Am Surg 65:729–730

Smathers RL (2000) Advanced breast biopsy instru-mentation device: Percentages of lesion and sur-rounding tissue removed. AJR 175:801–803

5.1 Introduction

There are different stereotactic systems with dif-ferent tables for breast biopsy available around the world. In three of the six described methods or tables, the patients are in the prone position, whereas the other techniques use the upright system.

– The Giotto system: the Mammobed in com-bination with a digital mammography unit

– The MultiCare Platinum system: the Lorad table from Hologic

– The Fischer table– Breast biopsy with upright stereotactic image

guidance by Siemens– The GE system: Diamond with Delta 32– The StereoLoc II system from Hologic

5.1.1 Prone Position Techniques

The patient lies prone on the stereotactic table with the breast suspended through a hole in the table (Fig. 5.5). The breast is then placed in compression. Images are then obtained using

digital X-rays. These X-rays use much less radi-ation than traditional mammograms. Images are taken at two 15–24° angles from the center. The images are viewed on a computer monitor, and the physician can identify the lesion in three dimensions. The computer can then help guide a biopsy needle to the exact coordinates of the lesion.

The breast tissue can be removed in different ways with the use of devices and systems from different companies. First the ABBI procedure was promoted and successfully performed in many centers in the United States, around the world, and also in Switzerland (Marti et al. 2001; Kochli 2000; Senn Bahls et al. 2006). This device removes a larger core of tissue (5-20mm). In this fashion, the entire lesion can sometimes be removed with an accurate diag-nosis. The procedure has been developed with the use of the so-called Lorad table. However, with the development of the Mammotome system, the ABBI procedure became less popu-lar. The major advantage of the Mammotome procedure is that there is virtually no scar. In the meantime, many other devices and systems have been proposed for use on different tables in the prone position as well as in the upright position or for hand-free use. However, the Mammotome system from Johnson & Johnson is now widely used around the world and was further improved technically in 2006.

Available Stereotactic Systems for Breast Biopsy

Ossi R. Köchli

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Ossi R. KöchliBreast Center Zürich-Bethanien, Toblerstrasse 51, 8044 Zürich, Switzerlande-mail: [email protected]


106 O.R. Köchli

55.1.1.1 The Giotto System: The Mammobed in Combination with a Digital Mammography Unit

The Giotto system is a prone biopsy system for digital stereotactic biopsy that offers extraordi-nary precision, digital image quality (with 50×50 mm CCD and resolution up to 20 lp/mm), and ease of use. The Biopsy Digit device has totally automated functions and is able to use all devices for core biopsy (single-use and otherwise), biopsy with suction (compatibility with the Mammotome certified by Johnson & Johnson), needles for cytology and markers. The ±0.5-mm accuracy makes the Biopsy Digit one of the most precise biopsy systems. The needle guide is moved with motor-driven movements in three directions and is moved automatically into position by the computer. The tube’s ±24° rota-tion movement is also motor-driven and checked by the computer and automatically operates

the three collimations (when the automatic colli-mator is present). The needle guide can also be moved manually using a remote control with 0.1-mm steps in three directions. The prone position is ideal for breast biopsy: there are unquestionable advantages for the patient and operators, and above all for the diagnostic qual-ity of the result.

However, one of the greatest advantages of the Giotto System is the possibility of perform-ing mammographies in a routine setting with the same system and equipment. Nevertheless, the option of performing stereotactic biopsies by adding only the Mammobed with the patient in the prone position is advantageous (Fig. 5.1). The time needed to change from mammogra-phy mode to biopsy mode is less the 10min (Fig. 5.2). It is clear that this setting is much more cost-effective than a stand-alone table with a mammography unit that is used for biopsy only.

Fig. 5.1 Traditional mammography set-up without biopsy from Giotto

5 Available Stereotactic Systems for Breast Biopsy 107

Because the Mammobed has wheels, the patient’s position can be changed easily and no lateral arm for biopsy is needed. Almost every lesion can be reached after correct positioning of the patient’s breast in the digital unit of the mammography unit. However, there are also limitations. In patients with small breasts, it can be impossible to perform the procedure because of the risk of perforating the breast on the other side. Sometimes using an acryl glass plate can help, but as with other stereotactic systems and tables, breasts that are too small with little volume are not suitable for stereotac-tic biopsies. Moreover, lesions that are too close to the skin surface are not candidates for this type of surgery. This is also true for other systems.

In the Zurich Bethanien Breast Centre, we have performed more than 150 stereotactic breast biopsies, most of them with the Mammotome. In only one case did we experience a technical

failure due to a mechanical problem with the table. otherwise, we were able to perform all the procedures with no problems. All referred cases could be biopsied. Although in some cases a minor hematoma occurred, we had no cases requiring open surgery due to bleeding or infection. Also, in cases with lesions showing microcalcifications very close to the pectoral muscle, we could perform the biopsy because the Mammobed allowed us to turn the patient’s breast until we could reach the lesion. In the Giotto System, no lateral arm is needed. However, it is crucial to mention that careful patient selection is needed to obtain such good results. As mentioned above, lesions in the skin or very close to the skin, for example, are never candidates for stereotactic biopsy. In less than 5% of all biopsies, we had to use the “arm through the hole” method to be able to reach the lesion (Fig. 5.3). Using the Giotto Mammobed, this is not a problem.

Fig. 5.2 The Mammobed attached to the stereotactic unit from Giotto

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5.1.1.2 The MultiCare Platinum System: The Lorad Table from Hologic

MultiCare Platinum’s exclusive contoured table with centered aperture optimizes efficiency. With the patient lying prone in either direction, the C-arm can be positioned at any angle through 180°, providing true 360° access (Fig. 5.4). The flexible positioning capability ensures easy access with the shortest skin-to-lesion distance, guaran-teeing direct access to inferior lesions. Approach angles can be varied with minimal to no move-ment of the patient, ensuring fast, efficient com-pletion of procedures (Lifrange et al. 2002). The system has a number of unique features.

An adjustable breast tray compensates for variable breast thickness, which reduces lesion shift in stereo views for image clarity. The image receptor moves in tandem with the X-ray tube, which allows the receptor X-ray beam to remain perpendicular, eliminating image distortion gen-

erally associated with increased parallax. An air gap provided between the image receptor and the breast, along with stainless steel compression paddles, improves image quality by minimizing the amount of scatter radiation reaching the image receptor. The system’s intuitive Cartesian coordi-nate system ensures accurate targeting (±1mm). As with other systems, the digital spot mammog-raphy method determines the precise position of the lesion in the x-, y-, and z-planes.

In summary, the Lorad table offers safety and comfort for the patient. The surgeon has a free operation platform and handling the table is relatively easy because of the orthogonal stere-otactic system. There is an universal support of all biopsy systems, e.g., ATEC, the automated tissue excision collection breast biopsy system from Suros Surgical Systems, or the Mammotome from Johnson & Johnson, as well as other devices. Another advantage of the Lorad table is that it can be positioned close to the wall in a rather small operating room.

Fig. 5.3 A patient from the Zurich Bethanien Breast Center with the “arm through the hole” method for a lesion very close to the pectoral muscle


5.1.1.3 The Fischer Table

The Fischer Company proposes two products for stereotactic breast biopsy. The MammoTest and the MammoTest Select (Fig. 5.5). The first product comes with a standard camera and the other comes with a special camera, called Elite, with a higher-resolution monitor. However, the prone position table was the same for both prod-ucts. The special features of the Fischer table are a 28-cm aperture allowing the patient to put her arm through the hole, 270° rotation with an additional lateral arm (+90°), a true target on scout capability, an electromagnetic floating table top, and an open tube for the surgeon’s comfort. Another exclusive feature of the MammoTest is angled targeting using polar coordinates. Because the needle is set at an angle, it provides superior access. The polar-coordinate approach of MammoTest allows for greater access to all areas of the breast, includ-ing hard-to-reach lesions high in the axillary region (Fig. 5.6). In addition, angled targeting

eliminates inference during the scout view, yielding true target on scout capability.

In September 2005, the Hologic company announced that it had completed the acquisition of Fischer Imaging Corporation’s intellectual property relating to its mammography business and products, including the rights to their SenoScan digital mammography and MammoTest stereo-tactic breast biopsy systems. This is the reason why the Fischer table is no longer made and Hologic is now marketing the MultiCare Platinum System, the so-called Lorad table only. It can be anticipated that in the future a new product will be marketed with all the advantages of both systems.

5.1.2 Upright Systems

Breast biopsy using upright stereotactic mam-mography requires the patient to sit upright in a chair or to lie on her side (lateral recumbent position). Perhaps the most difficult part of a

Fig. 5.4 The Lorad table from Hologic

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Fig. 5.6 ongoing procedure with the Fischer table (MammoTest) and the Mammotome using polar coordinates

Fig. 5.5 The Fischer table with a patient in the prone position


biopsy with upright stereotactic image guidance for many patients is the need to sit upright with-out moving during the biopsy. Therefore, upright stereotactic mammography may not be a viable option for some elderly, anxious, or physically impaired persons. However, upright stereotactic mammography may be an appropriate method for patients who would find it difficult to climb up onto the prone table (Meloni et al. 2002).

5.1.2.1 Breast Biopsy with Upright Stereotactic Image Guidance by Siemens: The Opdima System

The opdima digital biopsy and spot imaging system combines good image quality with opti-mized clinical workflow and is compatible with the Mammomat 1000, 3000 Nova, and Novation systems. opdima is designed to perform efficient stereotactic needle and core biopsies as well as localization procedures in the upright position. With a detector resolution of 20lp/mm-1, opdima provides very high resolution. When

Podima is used with the Mammomat, the result is a versatile, multitasking system that can per-form image acquisition, work-up, and digital biopsy. As with other systems, the breast biopsy path is imaged from two slightly angled direc-tions to help guide the needle using an upright stereotactic mammography system. The patient’s breast is slightly compressed and held in posi-tion throughout the procedure. Several stereo-tactic pairs of X-ray images are made. Small samples of tissue are then removed from the breast using a hollow core needle or vacuum-assisted biopsy device that is precisely guided to the correct location using X-ray imaging and computer coordinates (Fig. 5.7).

What are the advantages of the opdima sys-tem? Because there is no need for a special table, the whole system is not very expensive. The cost of using the upright-type unit is much lower than that of the prone-type unit because the latter is extremely expensive, as mentioned above, and a film-based method rather than a digital image method is usable in the upright-type unit. Furthermore, no extra room is needed.

Fig. 5.7 Patient in the upright position at the Sonnenhof Breast Center in Bern, Switzerland

112 O.R. Köchli

5The upright-type unit also has advantages over the prone-type unit in terms of the ability to biopsy lesions of extremely lateral location and cost.

What are the disadvantages of this system? Lesions that are close to the thoracic wall cannot be reached. Furthermore, patients have more vasovagal reactions, they look directly at the needle and the blood, and the lying down proce-dure, when possible, is not always well accepted by patients.

5.1.2.2 Breast Biopsy with Upright Stereotactic Image Guidance by GE: Delta 32

The lightweight Delta camera units are simple and fast to implement. No external wiring or connections are needed, but the units connect to Diamond by simply placing the camera in its position. No time-consuming calibration or sys-tem warm-up is needed. Stereotactic work is given a new dimension with the Delta 32 TACT option for 3D digital mammography. The stere-otactic biopsy device Delta 32 can be upgraded to TACT 3D imaging functionality. The Diamond breast care platform with Delta 32 TACT is a good diagnostic breast imaging system for dig-ital stereotactic biopsy as well as diagnostic dig-ital spot and 3D imaging. Delta 32 allows a free choice of projection angle within ±185° to mini-mize the distance from the skin to the lesion. The stereotactic angles can be freely selected by the user between ±15° to optimize the biopsy accuracy and the volume of view. The special compression system with manual fine-tuning informs the user about applied force and com-pression thickness, while the motorized and automated movement of the needle guide makes stereotactic examinations accurate and conven-ient. However, as mentioned in Sect. 5.1.2, there are limitations for all upright systems. This is the reason why many breast centers around the world choose a system with a prone position.

5.1.2.3 The Stereoloc II Upright Breast Biopsy System from Hologic

The StereoLoc II is an upright breast biopsy system compatible with the Lorad M-IV. Trans-forming from screening mammography to stereotactic diagnostic imaging is fast and easy with the StereoLoc II system. However, there is no prone position possible, as seen in the Giotto system, with the use of the Mammobed. Therefore, the prone position table from Lorad, the MultiCare Platinum, has been favored by many centers (see 5.1.1).

5.2 Cost of the Systems

In general, the cost of the prone-position sys-tems is much higher than those using an upright-position system. The Giotto system uses a relatively inexpensive Mammobed that can be positioned underneath the digital biopsy unit and is therefore the most cost-effective. The Lorad table is “a biopsy-only table” or system and is therefore much more expensive.

5.3 Cost of the Procedures

Many health insurance providers cover the cost of a breast biopsy. However, women should always check with their health insurance compa-nies before undergoing any medical procedure to determine whether the cost of the biopsy and related costs will be covered (and at what rate). Women should also check to see if special refer-rals are necessary, since many health mainte-nance plans require these prior to any specialist consultations or procedures. In Switzerland, for example, a stereotactic biopsy is covered by the


general insurance. See also the chapter by Brun del Re.

References

Kochli oR (2000) Developments in minimally inva-sive breast surgery – overview and our own expe-rience: new diagnostic and therapeutic challenges in breast cancer. Gynakol Geburtshilfliche Rundsch 40:3–12

Lifrange E, Dondelinger RF, Quatresooz P, Vandevorst G, Colin C (2002) Stereotactic breast biopsy with an 8-gauge, directional, vacuum-assisted probe: initial experience. Eur Radiol:2180–2187

Marti WR, Zuber M, oertli D, Weber WP, Muller D, Kochli oR, Langer I, Harder F (2001) Advanced breast biopsy instrumentation for the evaluation of impalpable lesions: a reliable diagnostic tool with little therapeutic potential. Eur J Surg 167:15–18

Meloni GB, Becchere MP, Soro D, Feo CF, Profili S, Dettori G, Trignano M, Navara G, Canalis GC (2002) Percutaneous vacuum-assisted core breast biopsy with upright stereotactic equipment. Indications, limitations and results. Acta Radiol 43:575–578

Senn Bahls, E, Dupont Lampert V, oelschlegel C, Senn HJ (2006) Multitarget stereotactic core-needle breast biopsy (MSBB) – an effective and safe diagnostic intervention for non-palpable breast lesions: A large prospective single institu-tion study. Breast 17:222–229

6.1 Introduction: Role of MR Mammography

During the last decade, MR mammography has been successfully tested as an adjunct imaging modality to mammography and ultrasound of the breast. Lesions that cannot be detected in mammography and ultrasound are shown with high sensitivity and in realistic extent but spe-cificity is still poor. However, the high sensitiv-ity of MR alone is not satisfactory if histology cannot be obtained. Therefore MR mammogra-phy should only be performed if there is the opportunity to verify findings in histology in a selected small group of patients in which the lesions cannot be biopsied otherwise or follow-up appears not indicated. MR mammography should therefore only be offered by institutions that can offer MR biopsy or that are in close contact with a site that can offer this type of biopsy.

Prior to any thought about MR biopsy, the diagnostic MR examination on which the indica-tion is based should be checked for quality. This includes perfect timing (5th to 12th day after the beginning of menstruation), cessation of hor-mone replacement therapy 4–6 weeks prior to the

exam, and the choice of established contrast media with appropriate dosage. Mammography, ultrasound, and MR exams (preferably in digital format and not simply print-outs) should be avail-able, checked, and correlated, and focused ultra-sound should be tried with the intent for biopsy prior to MR indication.

For adequate performance of MR mammog-raphy, the following important points should be kept in mind:

– The appointment should be timed with respect to the menstruation cycle and hor-mone replacement therapy.

– A dedicated bilateral breast coil is manda-tory for MR mammography.

– Established extracellular paramagnetic con-trast media should be administered in the recommended dose. Blood pool agents are not yet established.

– Spatial and temporal resolution should be sufficient.

– Timing is essential: a T1-weighted sequence should be available before and at two or more time points after intravenous contrast administration.

– Only an experienced radiologist using the ACR MR BI-RADS lexicon should report MR exams.

– MR biopsy should be available not necessar-ily on site but in a center with close contact.

Typical established indications for MR mam-mography comprise the following:

MRI-Guided Minimally Invasive Breast Procedures

Harald Marcel Bonel

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Harald Marcel BonelInstitute for Diagnostic, Pediatric and Interventional Radiology, Inselspital, University of Bern, Freiburg strasse 10, 3010 Bern, Switzerlande-mail: [email protected]

Renzo Brun del Re (Ed.), Minimally Invasive Breast Biopsies, Recent Results in Cancer Research 173, 115Doi: 10.1007/978-3-540-31611-4_6, © Springer-Verlag Berlin Heidelberg 2009

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6– Problem solving in case of inconclusive

findings in conventional imaging;– Screening of the contralateral breast in

women with histological evidence of unilat-eral breast cancer;

– Differentiation between a solitary lesion, multifocal or multicentric cancer and detec-tion of concomitant DCIS;

– Evaluation of the breasts in case of an unknown primary carcinoma, e.g., axillary lymph node metastasis;

– Evaluation of therapy response in patients with neoadjuvant chemotherapy;

– Screening of women with a lifetime risk of 20% or more to develop breast cancer, including mutation carriers such as BCRA1 and BCRA2.

6.1.1 Indications

Contrast-enhanced MRi can provide important additional information when performed in cer-tain indications. When suspicious lesions are identified on MR mammography and cannot be reproduced using other imaging modalities, a decision must be made as to its management, because further diagnostic work-up is indicated.

one possibility is the short-term follow-up of such findings. This could result in potentially higher costs and a possible delay in the start of treatment of a malignant lesion. Even though reliable data is not yet available suggesting a poorer outcome when this method is used, sim-ply the potential of a poorer outcome and the psychological effect of having to wait implies for both the patient and referring physician that this is only one option.

Another option is to use MR-compatible equipment for preoperative localization. This option requires less MR-compatible equipment and can be highly effective if used wisely. However, a disadvantage is that all lumpectomies would require an intubation narcosis. Still, in case

of biopsies with anatomic limitations, such as localization close to the axilla or thoracic wall, wire markers with or without additional blue staining can be the preferred option.

Minimally invasive percutaneous biopsies became available by MR-compatible equipment. Because there is not yet any real-time imaging available in a quality and ease comparable to ultrasound-guided biopsies and MR-compatible equipment is usually only partially MR- compatible, MR-guided biopsies require much thought and planning, and the staff demands extra training to effectively perform such biopsies. Furthermore, the difficulty in handling and the investment in the materials suggest a certain number of interventions to be done by the MR teams, which is another obstacle to the wide-spread use of this method.

Because of the special MR-compatible devices and the long time needed for the inter-vention, MR-guided interventions are costly. MR is definitely not an appropriate method to check for biopsy-suspicious calcifications, a stereotactic approach should be used. it is also reasonable to recheck suspect findings found only on MRi with ultrasound (second-look ultrasound): the real-time images and the flexi-bility of using almost all available interventional devices are invaluable advantages. if the lesion can be detected using ultrasound, an interven-tion using ultrasound is preferable. Marking clips, which are seen in all imaging modalities, are available and reassure in future follow-up examinations that the right lesion has been biopsied.

Prior to the intervention, all recent imaging materials should be available. in the setting of a busy MR suite, MR scans read from CD-RoMs are too time-consuming to be studied at the last minute and this hinders work flow. We usually prepare all necessary materials the day before, check function of essential tools such as the vacuum biopsy device, and discuss access and procedure as a team including physicians and technologists. Success of the biopsy is not

6 MRI-Guided Minimally Invasive Breast Procedures 117

necessarily dependent on the size of the lesion; small lesions can also be biopsied with great suc-cess. However, risk of malignancy and positive predictive value increase with the size of the lesion, and a follow-up should be considered as a reasonable alternative in lesions measuring 3mm or less. Smaller lesions, however, can potentially be completely removed by vacuum biopsy.

Fine-needle biopsies should not be per-formed. Cytology in case of malignancy is not as valuable as histology, and histology remains the only reasonable choice. only true cut biop-sies, which are ideally repeated several times and use suction (vacuum core biopsies) should used. Prior to any biopsy in a patient, we recom-mend becoming familiar with the biopsy systems to be used. A training session using phantoms, e.g., vitamin capsules injected through incisions in a piece of ham, are an easy training ground and provides familiarity with materials and handling.

6.1.2 Technique and Practical Tips

it is very reasonable to contact the producer of MR-compatible materials prior to acquisition to make sure which parts of the equipment are MR-compatible. Frequently, mechanical parts are not compatible, but only the coaxial guid-ance can remain in the patient and scanner dur-ing image acquisition. Battery-operated systems should be recharged prior to any intervention, because batteries lose their power faster in strong magnetic fields.

Properly positioning the patient is essential. Palpable lesions should be marked by a vitamin or nitroglycerine capsule fixed to the skin with a band-aid. in case of nonpalpable lesions, appro-priate measurements in a simulated body posi-tion (e.g., distance to the nipple) and marks on the skin in the likely position require suitable positioning in the compression device. Because of the soft tissue composition of the breast, the

suspected area can and always should be brought as close as possible to the guidance system prior to the first scan. Slight rotation of the breast can shorten the access through normal breast tissue; in a few cases multiple lesions can be aligned and biopsied using the same access over a coax-ial system. in cases of large but heterogeneous lesions, this procedure is particularly advanta-geous. Lesions that are lateral and/or close to the thoracic wall can be reached more easily if the opposite side of the body is lifted. MRi-compatible localization systems usually include a table on which the patient lies in the prone position, and a measurement coil, which is included or very close to the opening, which gives access to the breast (Fig. 6.1 ). The patient’s position is usually a little higher above the scan-ner table, and some patients do not fit in the interventional setting that has filled the gantry tightly in the diagnostic scan. Reducing the cushions is only a short-term option: many patients are less likely to endure the interven-tional session in this case. The opening for the opposite breast must be closed if a medial access is needed. it is a good idea to spend sufficient time making the patient comfortable with cush-ions; however, patient movement must be lim-ited because any change in position after the first diagnostic scan will make the intervention more difficult if not impossible, especially if the lesion shows a rapid wash-out of contrast media. if possible, the arms should be brought caudally to limit patient movement while providing improved access to the positioning device. Note that with different compressions of the diagnos-tic vs. the interventional scan, the position of the lesion can also differ greatly; therefore a thorough analysis of the first diagnostic images should not be spared. To serve for all possible localiza-tions and potentially reduce damage to healthy tissues, the positioning device should allow medial, lateral, and cranial access to the breast.

Whether a grid or a tripod-based system is used is a matter of preference and tradition (Figure 6.5). The grid is more frequently used in

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North America and has its advantages in terms of comprehension of the localization and han-dling. However, its flexibility is limited, because angulations are not possible. This can be a limi-tation, especially in biopsies that are located not in the center of the breast but, for example, close to the thoracic wall and toward the axilla. Here, systems that allow angulation are of clear advan-tage. Post and pillar devices allow not only a large range of motion but also angulation (Fig. 6.2). Angulation, however, is more difficult. Angles have to be calculated in addition to dis-tances; therefore, a mechanical system allowing angulation should be supported by an intuitive software module that calculates angles and posi-tions (Figure 6.6). A hands-free approach can also be very effective in large lesions but is not recommended in small lesions. The hands-free approach requires a great deal of practice but has no limitations in the hands of an experienced radiologist.

We appreciate having lateral and cranial access to the breast. This often reduces the length of the path needed through healthy breast to reach the region to be biopsied and/or marked.

Prior to the first diagnostic scan, a fiducial mark visible on MR images must be placed in the grid or on the post and pillar arrangement. Different designs are available, some have to be filled with fluid prior to use. The tip of this marker becomes the reference for all future scans. Familiarity with the length and tip of the fiducial mark is again essential for planning. if the region of interest can be anticipated, the marker should be brought to the region of the intervention planned as close as possible prior to the first scan. This is the proper time for the first disinfection.

Rarely lesions only visible in MR are already seen in precontrast sequences. if multiple lesions are to be biopsied, select the lesion first that

Fig. 6.1 Patient lying on the biopsy coil and table. For all diagnostic scans and interventions, the patient lies in the prone position. Measurements in MR therefore usually differ from ultrasound or mammography. The biopsy coil leaves more space between the MR stretcher and the patient. in this

illustration, a grid biopsy system is shown under-neath the patient. if the arms are at the side and not above the head, immobilization is better and there is less stress on the shoulder joint. in addition, access is better from the side (DynaCAD, courtesy of invivo inc.)


a

b

Fig. 6.2 Post and pillar system used for localization. The patient’s head is positioned to the right on the pillow. The post (PP) is strong enough to support even heavier mechanical parts such as the Mammotome (Ethicon inc.). For systems that are not as heavy, a smaller post with a telescopic prolongation is availa-ble. The long screw at the post is used for an up-and-down movement; the post can be moved cranial and caudal and fixed in any position (scale in the zoomed b). The flexible breast coil c is different from a diag-nostic coil, in that the phased array segments are only attached to the table. This is not a technical drawback but can be an advantage for lesions located close to

the thoracic wall and is advantageous because access is not limited. However, the coil profile is different and also delivers a slightly but notably different image quality. The medial (M) and lateral (L) compression plates can be moved freely and locked for the inter-vention. The lateral compression plate has horizontal bars that allow access to the skin. The whole com-pression system including the post can be turned 90° to allow interventions through cranial access. The fiducial mark (asterisk) is shown on the right side of the post, ideal for a lesion located cranially. This posi-tioning system is completely reusable and can be sterilized (Noras MRi Products inc.)

120 H.M. Bonel

6shows in precontrast images and do your contrast dynamics later. The first diagnostic scan there-fore usually includes contrast dynamics to show the features of suspected malignancy only with the same image quality as the diagnostic scan that usually precedes the intervention. Based on these images, the position of the marker is corrected to the localization on the skin, which is closest to the lesion. it is certainly possible to calculate the positions mentally; however, intuitive and effec-tive software modules are available that reduce the time needed for positioning. Software support for calculating the adjustments is a clear advan-tage not only with respect to the patient lying in an uncomfortable position, but also in terms of scanner time. once the marker has been adjusted, the area can be disinfected.

Before the intervention can start, we recom-mend verifying the correct position of the marker to the skin with a repetition of the MR scan. if another adjustment of the marker is nec-essary, we recommend repeating this scan again. once the position of the marker is correct, we measure the distance from the tip to the center of the lesion. Check the path and potential risks such as pneumothorax or damage to a major blood vessel. However, the risk of a complica-tion is usually low.

if the lesion is to be marked, a skin incision is usually not mandatory but still might ease the propulsion of the device depending on the wire or marker set being used. This is especially true in soft breasts in which the skin is widely deformed by the skin puncture. if there is sub-stantial deformation of the skin and/or the cal-iber of the biopsy unit is large, we recommend making an incision, because frequently the nee-dle deviates from its ideal path and even a minor deviation could mean a missed target, especially if the needle has to be propelled for a long dis-tance. Propel the needle to the desired depth in the breast, if necessary hold the skin by small surgical hooks or tweezers (which must be also be MR-compatible). Ceramic needles have the advantage of MR-compatibility and only small signal erasure; however, the surface in some models is rougher than metal and the cutting tip requires practice. Therefore, a long-incision biopsy is a good way to start forward feed of a ceramic needle (Fig. 6.3). The lesions are pushed farther with rougher needles and are more dif-ficult to find than if they are visible on subtrac-tion images only. one method to achieve a comprehensive subtraction image again is to push the needle another 1–2cm in the breast and pull back to the ideal position: this way the

Fig. 6.3 This is a MR-compatible ceramic needle (Mammotome, Ethicon inc.). it can remain in the MR scanner to check the lesion. The tip of the cutting knife (CK) is very sharp, but a skin incision with a scalpel remains necessary. The opening allows checking both the localization of the chamber and application of

local anesthesia if the patient is in pain. The needle has a rougher surface compared to metal needles. For easier detection in the MR scanner, an internal coating of the needle gives a high signal, whereas the ceramic parts of the needle remain black in the MR image. Note the black tip of the needle in Fig. 6.10d


Fig. 6.4 Cutting chamber of the mammotome (Ethicon inc.) vacuum can be applied in the chamber, which sucks tissue to the chamber. A rotating knife comes from the right and cuts a biopsy, which can be saved without removing the system. The white bar on the right indicates the length from the tip to the distal end

of the biopsy chamber, the mammotome is ideally pushed about 7 mm beyond the location of the lesion and cuts the lesion from the side. Therefore, distal of the lesion there must be enough distance to the skin for the “dead end” of the mammotome tip. Cutting the skin on the opposite side must be avoided

lesion is drawn back to its original position. However, the distance to the opposite skin, which must not be perforated, must be observed, and the damage to the breast is more than neces-sary, so we rarely use this technique.

if you are using a completely MR-compatible wire or coaxial system you should check the position of the needle tip now. Frequently, the lesion is pushed to the side, and sometimes, especially if the coaxial system or wire is propelled central to the lesion, the lesion is pushed to the other side and the needle must be advanced farther. The coaxial needle usually allows verification of the position of the cutting chamber close to the lesion to be biopsied (Fig. 6.7e). Still, the position of the coaxial nee-dle could be adjusted. if the patient is reposi-tioned in the gantry, be aware of the biopsy material and avoid contamination or dislocation by the lateral wall of the gantry. Software tools are marketed to calculate the position of the lesion and the fiducial marker more quickly and easily. in our experience, mental calculation is usually faster, but the software tools are reliable and enable us to check our calculation with ease; if angulation is necessary, the appropriate software definitely safes time.

if the lesion is to be marked, the hooks of the wire can now be used to anchor the wire in the breast. Methylene blue can be used in addition

and injected in the needle used for application. As an alternative, a deposition of markers is possible if the patient travels far to the surgery, but this should be avoided, because the potential number of errors increases compared to a wire mark (Fig. 6.8). A final scan verifies the posi-tion and should serve to describe the position of the marker with regard to the lesions to be biop-sied. We recommend using a guidewire that can be drawn back to the needle and be corrected, because release of the wire can push the lesion farther from the coaxial system. After wire marks, we immediately call the surgeon who is going to operate on the patient to reduce com-munication errors with regard to the position of the wire in the tumor.

An 11-G system or even an 8-G system is recommended for biopsies. in our experience, the patient usually does not feel a difference between smaller and larger diameters, this is why we usually use larger diameters for faster biopsies. Some patients experience pain during the biopsy removal. We have good pain relief results after application of local anesthesia to the biopsy site using the coaxial system. We rec-ommend taking multiple biopsies and checking their appearance and immediately putting the biopsies in formalin in a labeled container. Using a vacuum-assisted 11-G system, we usually take 20 samples and rotate after each

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Fig. 6.5 Post and pillar vs. grid. The post and pillar system a has the greatest flexibility and can be moved smoothly and exactly to any position in the blue square. However, the needle holder can be angulated, and lesions outside of the frame can be biopsied as well. Markers in the frame and a fiducial mark in the needle holder allow optimal adjustment of the sys-tem to reach virtually all the lesions depicted. The

grid system is the most comprehensive and allows biopsy of all lesions in the blue square that can be reached by simple feed forward rectangular to the fixation plate. its simplicity is appealing, but the grid can be limiting in some patients. This system is par-tially disposable. (Screenshots of the original soft-ware: invivo DynaCAD, Courtesy of invivo inc., reprinted with permission.)


Fig. 6.6 Localization software. Modern software modules are specified to the dimensions of the localization hardware. in this example, the target area is indicated by cross hairs in the sagittal and axial planes. The software instantly indicates the optimal position of the post and pillar system.

After adjustments, the lesion is exactly hit by sim-ple advancement, if the breast does not deform and the lesion does not move. otherwise, readjust-ments might be necessary. (Screen shots of the original software: Courtesy of invivo inc., reprinted with permission.)

biopsy; for an 8-G system, usually ten samples are sufficient. if different sites are biopsied in one session, different containers for each site biopsied are mandatory. if the repeated biopsies do not yield sufficient tissue, it might be necessary to increase vacuum suction to pull more tissue in the cutting chamber (Figs. 6.7 and 6.9). in our experience, battery-operated vacuum biopsy devices are much easier to handle. However, they cannot create enough low pressure to yield sufficient material in these cases. A MR-compatible marker should be placed at the location of the biopsy. These markers are usually metallic and made of tiny titanium cages and are easily detected in mammography. Some are also coated with material that can be detected on ultrasound, such as collagen. However, the detectability wanes after a few months. it is nec-

essary to practice releasing the marker in the coaxial system to prevent dislocation of the marker when the coaxial tube is removed. Spontaneous dislocation, however, is rare. in case of subcutaneous lesions, we usually try to release the marker a little further from the skin to avoid palpability.

After biopsy, a postprocedure scan is recom-mended to verify the site(s) sampled. in addi-tion, hematoma size can be estimated prior to compression. Finally, the position of a metallic marker in relation to the biopsy site can be char-acterized for future follow-up examinations. Spontaneous dislocation of the marker is model-dependent and rare. However, the application system should be turned 180° prior to removal in order to avoid removal of the application sys-tem and marker at the same time.

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Fig. 6.7 (continued) again well depicted, but relatively close to the skin caudal of the breast. The mammo-tome was used for this biopsy. The verification scan (ceramic knife indicating the position, e shows that the cutting part of the needle is still cranial to the

lesion, whereas the tip is already close to the caudal skin. The ceramic knife therefore could not be advanced farther caudally. The histologic findings were suggestive of nonrepresentative tissue, and the biopsy had to be repeated


Fig. 6.8 Clip localization of a suspicious lesion in the right breast of a 47-year-old patient with sus-pected multicentric cancer in the left breast. The patient was an outside referral to be operated by her favorite surgeon and opted for a clip marker instead of a wire for comfort during transfer. A closer radiologic site performing biopsies was not available. Subtraction images of the first diagnos-tic scan a and the second diagnostic scan (b, observe the small indentations of the bars from the

lateral compression device) immediately before the procedure show a reproducible morphology and position of the suspicious lesion. A coaxial system was used, which shows the needle in the proper position c and the satisfactory deposition of the marker d. Both sides were operated in one ses-sion. A multicentric carcinoma of the left side was diagnosed, an ablation was performed. on the right side, histology found a lobular neoplasia with adenosis

Fig. 6.7 Suspicious lesion in a 53-year-old patient. influence of compression in a focus localized close to the skin. T1-weighted images are shown on the left (1 min after intravenous injection of paramagnetic contrast), subtraction images on the right for easier

identification of the focus. The diagnostic scan is shown in a–d. The original diagnostic scan a and b used slight mediolateral compression. For the biopsy, because of the close localization to the skin, a craniocaudal compression was used. The lesion is

Butterfly band-aids usually suffice for care for the skin at the incision; the incision is usu-ally too small to be sewed. Manual compression of the breast and cooling using cold packs is essential for hematoma reduction. Usually 10-20min suffice to stop bleeding. However, in individual cases compression up to 1h is neces-sary. Nevertheless, back-up of a breast surgeon to control heavy bleeding is wise, although very rarely necessary in our experience. A good sup-port bra relieves some pain and we recommend

informing the patient to have a comfortable and supporting bra for the day of intervention.

So far we recommend follow-up of all patients by mammography, ultrasonography, and MR mammography at suitable intervals depending on detectability of the lesion prior to biopsy, the results, and the usual risks. Follow-up exams, how-ever, do not make much sense in the first 6 weeks after the procedure, because granulation tissue-makes interpretation more difficult and decreases specificity of the exam.

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6.1.3 Limitations

Depending on the hardware used, lesions close to the thoracic wall or near the axilla might be difficult or impossible to reach. The risk of pneumothorax is commonly exaggerated but must be kept in mind. Angulation of the biopsy unit or localization of the biopsy chamber, which is commonly not localized at the tip but slightly

more proximal, can limit the opportunity for biopsy. in these cases, however, preoperative localization with a marking wire is probably the best option. While straightforward cases can be biopsied in 30min or less, especially in tech-nically difficult cases with multiple sites, the intervention can be prolonged and cause discom-fort for the patient. Bilateral biopsies in one session can be done in the uncomplaining valiant case, but two separate sessions are recommended.

Fig. 6.9 Complete removal of a suspicious lesion in a 37-year-old patient using vacuum-assisted biopsy. in the subtraction images, the suspected lesion can be appreciated in a reproducible morphology and posi-tion despite the change in direction of compression from the first a to the second diagnostic scan just before the intervention b. After adjustments, the fidu-

cial marker can be seen in the proper position in the last scan prior to intervention c. The scan done for verification right after the intervention shows a large hematoma at the location where the lesion was removed. The images indicate complete removal of the lesion d. The follow-up exam 6 months later remained negative and showed no signs of recurrence


a b

c d e

Fig. 6.10 Complete removal of a Bi-RADS iV lesion in a 41-year-old patient. The lesion is depicted with early enhancement and a smooth delineation in the diagnostic scan a. The coil used for intervention depicts more noise but still the lesion can be clearly seen. Because of movement in this patient, the sub-traction images could not be used. Using the ceramic needle of the vacuum biopsy device, the lesion is pushed from the center more medially c. This makes

additional corrections necessary, and again the lesion moved a little bit farther but was centered in the biopsy chamber d. The verification scan e shows the location of the biopsy indicated by the ceramic needle after the removal of the biopsy device. As a result of tissue removal, the biopsy cavity can be clearly visualized on the postprocedure scan. The follow-up exam remained negative with no signs of regrowth, scarring was distinct

Patient movement prior to the final verification scan limits its accuracy and promotes false-negative results.

Compared to stereotactic biopsies, a major drawback is the fact that samples retrieved by MR biopsy cannot be compared to in vivo MR findings. Sample radiographs have been

used with moderate success. Therefore, a marker is more important and has greater sig-nificance. Also, MR follow-up is of greater value not only for quality control of the biopsy, but also because it can be reasoned that local recurrence could be detected only with MR imaging.

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66.2 Conclusion

MR-assisted vacuum biopsy closes a gap that was a nuisance in the last two decades: high sensitivity and low specificity with unsolvable lesions. MR-guided vacuum biopsy can now solve cases that are otherwise inconclusive. Modern technologies allow easier handling, but an experienced team with a long tradition and several biopsies per week is still needed to perform such biopsies with sufficient expertise. All results from vacuum-assisted MR-guided biopsies of the breast must be seen as critical in terms of indication, MR presentation, and histo-logical result. Marks compatible for MR and for conventional mammography facilitate the follow-up exams that are frequently necessary to conclude certain cases. on-site quality man-agement should be backed up by superregional quality criteria concerning both MR mammog-raphy and MR-assisted biopsy to assure patient benefit and cost control.

References

MR MammographyFrei KA, Kinkel K, Bonel HM, Lu Y, Esserman

LJ, Hylton NM (2000) MR imaging of the breast in patients with positive margins after lumpectomy: influence of the time interval between lumpectomy and MR imaging. AJR 175:1577–1584

Libermann L, Morris EA, Dershew DD, Abramson AF, Tan LK (2003) Ductal enhance-ment on MR imaging of the breast. AJR 181:519–525

Liberman L, Mason G, Morris EA, Dershaw DD (2006) Does size matter? Positive predictive value of MRi detected breast lesions as a func-tion of lesion size. AJR 186:426–430

Mann RM, Kuhl CK, Kinkel K, Boetes C (2008) Breast MRi: guidelines from the European Society of Breast imaging. Eur Radiol 18(7):1307–18

Morakkabati-Spitz N, Leutner C, Schild H, Traeber F, Kuhl C (2005) Diagnostic usefulness of segmental and linear enhancement in dynamic breast MRi. Eur Radiol 15:2010–1017

Wire localizationErguvan-Dogan B, Whitman GJ, Nguyen VA,

Dryden MJ, Stafford RJ, Hazle J, McAlee KR, Phelps MJ, ice MF, Kuerer HM, Middleton LP (2007) Specimen radiography in confirmation of MRi-guided needle localization and surgical excision of breast lesions. AJR 187:339–344

Javid SH, Carlson JW, Garber JE, Birdwell RL, Lester S, Lipsitz S, Golshan M (2007) Breast MRi wire-guided excisional biopsy: specimen size as compared to mammogram wire-guided excisional biopsy and implications for use. Ann Surg Oncol 13(12):3352–3358

Lampe D, Hefler L, Alberich T, Sittek H, Perlet C, Prat X, Taourel P, Amaya B, Koelbl H, Heywang-Kobrunner SH (2002) The clinical value of preoperative wire localization of breast lesions by magnetic resonance imaging – a multicenter study. Breast Cancer Res Treat 75:175–179

Van den Bosch MAAJ, Daniel BL, Pal S, Nowels KW, Birdwell RL, Jeffrey SS, ikeda DM (2006) MRi-guided needle localization of suspicious breast lesions: results of a freehand technique. Eur Radiol 16:1811–1817

Vacuum biopsyCauser PA, Piron CA, Jong RA, Curpen BN, Luginbuhl

CA, Glazier JE, Warner E, Hill K, Muldoon J, Taylor G, Wong JW, Plewes DB (2006) MR imaging – guided breast localisation system with medial or lateral access. Radiology 240(2):369–379

Heywang-Köbrunner SH, Sinnatamby R, Lebeau A, Lebrecht A, Britton PD, Schreer i (2009) interdisciplinary consensus on the uses and tech-niques of MR-guided vacuum-assisted breast biopsy (VAB): Results of a European Consensus meeting. European Journal of Radiology, in press.

Kellerhoff K, Schlossbauer T, Herzog P, Reiser M (2008) MR-gestützte interventionen in der Mammadiagnostik. Radiologe 38:367–374

Perlet C, Heywang-Kobrunner SH, Heinig A, Sittek H, Casselman J, Anderson i, Taourel P (2006) Magnetic resonance-guided vacuum-assisted breast biopsy. Cancer 106:982–990

7.1 Introduction

Breast cancer is the most common malignancy diagnosed in women in Germany and is the leading cause of cancer death. Recently, it was demonstrated that mammography screening can reduce mortality from breast cancer by 21% (Nystrom et al. 2002).

The vast majority of breast cancers originate in the epithelial lining of the ductal system of the breast. Invasive breast cancer is believed to result from progressive molecular and morpho-logic changes including the phenotypic appear-ance of cellular atypia.

In the last few years there has been an increase in intraductal carcinoma from approxi-mately 4 to 20% (Bässler 1998). Ductal carci-noma in situ (DCIS) is assumed to be a precursor lesion that continually progresses to invasive breast cancer. It is generally accepted that early detection of DCIS remains a problem, because only approximately 40-60% can be diagnosed using clinical symptoms and/or mammography (Bässler 1998). Even if DCIS can be visualized by mammography, the extent of the disease is often underestimated, because microcalcifications

do not necessarily reflect the complete tumor size (Faverly et al. 2001). Consequently, approx-imately 30% of the patients will have to undergo a second operation and/or radiotherapy due to incomplete resection (Vicini et al. 2001). There is considerable interest in alternative screening methods for this group of women, such as breast magnetic resonance imaging. Several intraduc-tal approaches including nipple aspiration, ductal lavage, and ductoscopy are currently being evaluated as new methods for obtaining minimally invasive access to ductal cells. Subsequent cytological and/or molecular analy-sis of these cells may allow individual breast cancer risk assessment or even permit early diagnosis of cancer.

7.2 Methods for Sampling Intraductal Breast Cells

Nipple aspiration is the least invasive of the methods for sampling the intraductal environ-ment. Following massage of the breast, suction is applied to the nipple using a modified breast pump, and in most women small samples of nipple aspirate fluid (NAF) will appear on the nipple surface, which can be collected in cap-illary tubes. The sample from one breast is generally pooled because of the small volumes of NAF produced.

Nipple aspiration may not yield fluid in all women, with investigators reporting success rates of approximately 40-80%. Sufficient cells

Ductoscopy of Intraductal Neoplasia of the Breast

Michael Hünerbein, Matthias Raubach, Kirang Dai, and Peter M. Schlag

7

Michael Hünerbein ()

Department of Surgery and Surgigal Oncology, Charité Universitätsmedizin Berlin, Campus Berlin Buch and Helios Hospital, 13122 Berlin-Buch, Germanye-mail: [email protected]


130 M. Hünerbein et al.

7for morphologic characterization are only found in approximately 50% of the patients (Sharma et al. 2004; Wrensch et al. 2001, 1993). Although some studies have demonstrated occasional detection of malignant cells, the most signifi-cant limitation of nipple aspirate cytology is the low percentage of cancer cells in the specimen, even in patients with known breast cancer.

Ductal lavage is a minimally invasive proce-dure in which a microcatheter is inserted into the nipple duct orifice to a maximum depth of 1.5 cm. Nipple aspiration is used to find fluid-producing ducts, because these are the most likely to be successfully cannulated. Normal saline is injected through the catheter in the duc-tal system and lavage is performed by withdraw-ing the fluid afterwards. Although more invasive than nipple aspiration, ductal lavage has the advantage of collecting duct-specific samples. Ductal lavage has been reported to produce cytologic specimens of higher quality with more epithelial cells and cell clusters than NAF sam-ples (Dooley et al. 2001). However, in a recent study ductal lavage was performed in 38 patients with NAF and revealed markedly atypical or malignant cells in only 13% of the patients and mildly or markedly atypical cells in 42% of the patients (Khan et al. 2004).

Ductoscopy is an emerging technique that promises a targeted approach to the diagnosis of intraductal disease. Ductoscopy allows direct visualization of the ductal system and targeted aspiration of lavage fluid for cytologic analysis (Love and Barsky 1996). In most studies, fiberoptic ductoscopy has been used to evalu-ate the etiology of spontaneous nipple discharge (okazaki et al. 1991; Shen et al. 2000). Data from these studies suggest that ductoscopy can be considered a safe and efficient alterna-tive to ductography. Cannulation of the dis-charging duct is successful in most patients (Table 7.1) with high lesion localization rates (Table 7.2).

7.2.1 Technique of Ductoscopy

Ductoscopy is usually performed using fiberop-tic instruments with a diameter of 0.7-1 mm. The flexible fiberscope is introduced through a cannula with a side port for injection of air or saline solution (Fig. 7.1). In contrast to others, we use a rigid 0.7-mm gradient index microen-doscope (Volpi AG, Schlieren, Switzerland), which provides better resolution and brightness

Table 7.1 Success rates of nipple duct cannulation for ductoscopy

Author Year n Cannulation (%)

okazaki 1991 46 90Dooley 2002 27 96Dietz 2002 119 88Hünerbein 2006 114 92

Table 7.2 Sensitivity of ductoscopy and galactography in the detection of intraductal lesions in women with nipple discharge

Author Year n Duc. Gal.

Yamamoto 2001 65 97% 89%Dietz 2002 70 90% 76%Hünerbein 2006 38 96% 89%

7 Ductoscopy of Intraductal Neoplasia of the Breast 131

(Dooley et al. 2004; Hünerbein et al. 2003; Shen et al. 2001). Unlike conventional fiberop-tic instruments, this all-fiber microendoscope consists of fused gradient index lenses. The optic is attached to a high-resolution 0.5-in. CCD PAL color camera head (Fig. 7.2). This technique, in combination with a 24-W metal halide light source (Intralux Vision, Volpi AG, Schlieren, Switzerland) provides high light intensity and excellent image resolution (Fig. 7.3). For ductoscopy, the microendoscope is introduced

through a 0.9-mm needle with a lateral port for air insufflation.

After disinfection, an anesthetic cream (lido-caine) is applied to the nipple. A 0.025-in. guidewire is inserted in the duct and the orifice is dilated grad-ually by 17-, 18-, and 20-G angiocatheters over the guidewire. Then the ductoscope is introduced into the lactiferous sinus and the ductal system is dis-tended by insufflation of air. All accessible branches of the duct are explored. The appearance, number, and localization of intraductal lesions can be

Fig. 7.1 Flexible fiberoptic ductoscope with insertion cannula and side port for air insufflation

Fig. 7.2 Rigid gradient index ductoscope with CCD camera handle


7

documented on video. Papillary lesions, ductal obstruction, red patches, and microcalcifications are considered ductal abnormalities.

7.2.2 Ductoscopic Biopsy

We have developed a special biopsy device for vacuum-assisted ductoscopic biopsy. The nee-dle has a lateral oval opening located 3 mm from the distal tip (Fig. 7.4). The surface of the opening is designed as a cutting blade to cut off tissue samples from lesions that protrude into the lumen. Usually, the tip of the ductoscope ends at the tip of the cannula, thus sealing the biopsy chamber. When a neoplastic lesion is found, the ductoscope is withdrawn 4 mm to open the biopsy chamber. Under visual guid-ance, the lesion can now be maneuvered into the biopsy chamber. Retrieval of the instrument while suction is applied allows a tissue sample to be obtained. The size of the biopsy samples is approximately 1 mm and the diagnostic quality is generally good.

7.2.3 Ductoscopy in Women with Nipple Discharge

Several studies demonstrate that ductoscopy can identify intraductal lesions in a high proportion of women with nipple discharge (Matsunaga et al. 2001; Yamamoto et al. 2001). In a com-parative study on 119 patients, a higher localiza-tion rate was obtained with ductoscopy than with preoperative ductography (90% vs. 76%). In this study, direct intraoperative visualization was used for ductoscopy-directed duct excision, which yielded a high rate of intraductal neopla-sia (88%) (Dietz et al. 2002). In our experience, the sensitivity of ductoscopy and galactography in the detection of intraductal lesion was compa-rable (96% vs. 89%). It must be emphasized that a negative ductoscopy result cannot exclude dis-tal lesions. on the other hand, it remains diffi-cult to make a tissue-specific diagnosis with galactography and it cannot be used for intraop-erative real-time guidance of duct excisions.

There is some evidence that ductoscopy can contribute to more accurate resection of intra-ductal lesions. In a group of 117 women with nipple discharge, ductoscopy-guided surgical

a b

Fig. 7.3 Ductoscopic aspect of a normal duct a and intraductal neoplasia b


excision resulted in a higher detection rate of ductal neoplasia than conventional surgery (18.6% vs. 8.5%) (Moncrief et al. 2005). Although visualization of a luminal lesion cor-related with proliferative disease, reliable dis-tinction between benign and neoplastic lesions was not possible based on the endoscopic appearance. of 49 lesions labeled papilloma at the time of ductoscopy, eight cases (17%) were found to involve more serious disease pathologi-cally. We have developed a ductoscopic biopsy technique that allows precise tissue sampling from intraductal lesions under ductoscopic guid-ance (Hünerbein 2004). Essentially, the ductoscope

is introduced through a needle with a lateral biopsy window at the tip, allowing one to per-form vacuum-assisted biopsies (Kim et al. 2004). Intraductal lesions were discovered in approximately 80% of the women with nipple discharge, and ductoscopic biopsy was success-ful in more than 95% of the cases. The size of the biopsy specimens was approximately 1 mm and the quality of the samples was adequate for histopathologic analysis and immunohistochem-istry. Histopathology showed benign papilloma in most patients (85%), but there were also two cases of DCIS and two cases of invasive cancer (Hünerbein et al. 2006a). Matsunaga et al. also reported promising results of ductoscopic biopsy in women with nipple discharge and papilloma-tous lesions (Matsunaga et al. 2004). Intraductal biopsy yielded diagnostic material in approxi-mately 90% of the patients. These data and our results suggest that ductoscopy can identify pap-illary lesions in a significant number of patients with pathologic nipple discharge, which can then be characterized by intraductal biopsy. Preoperative diagnosis of atypia in a papilloma may have surgical implications.

7.2.4 Ductoscopy in Breast Cancer

Carcinoma in situ or an intraductal component associated with an invasive carcinoma is an important surgical problem. Local recurrence is observed in up to 31% of the patients with an extensive intraductal component but only in 11% of patients without this intraductal involve-ment (Harris 1996). Intraoperative margin assessment has been used to reduce the re-exci-sion rates in patients with DCIS treated with breast-conserving surgery (Chagpar et al. 2003). Ductoscopy may help the surgeon identify sus-picious intraductal lesions not visualized by preoperative radiologic imaging methods.

our data suggest that intraoperative ductoscopy can identify otherwise unrecognized extensive

Fig. 7.4 Technique of intraductal vacuum-assisted biopsy


7intraductal neoplasia in some patients who are at risk for incomplete resection. In 50 women with the preoperative diagnosis of breast cancer, ductos-copy identified additional intraductal lesions in 50% of the patients (Hünerbein et al. 2006b). Three types of lesions, i.e., red patches, ductal obstruc-tion, and microcalcifications, were associated with intraluminal proliferative disease. Although endo-scopic appearance alone may not allow a tissue-specific diagnosis, there was a good correlation between the presence of red patches or microcalci-fications and DCIS. It can be assumed that ductos-copy is more likely to detect ductal abnormalities in patients with multifocal disease or extensive intraductal spread. There were abnormal ductos-copy findings in more than 80% of patients with extensive intraductal disease in the resection speci-men. Patients with a normal ductal appearance had a substantially lower risk for extensive intraductal disease (16%).

Intraoperative ductoscopy may be particu-larly useful in patients with mammographic microcalcifications or patients at high risk for intraductal carcinoma and high-density breast parenchyma. Clinical factors that are associ-ated with ductal carcinoma include a family history of breast cancer, previous breast biopsy, nulliparity, and BRCA1 or BRCA2 mutations (Claus et al. 2005; Trentham-Dietz et al. 2000). Evidence suggests that the identi-fication of ducts with intraductal pathology can be improved by breast massage, nipple fluid aspiration, and cannulation of fluid-pro-ducing target ducts. Using this technique, Dooley et al. were able to navigate the ducto-scope to within 1 cm of the target lesion in 97% of women with breast cancer in their study (Dooley 2003). Ductoscopy identified intraductal pathology outside the anticipated lumpectomy margin in 41% of the patients. According to the additional information pro-vided by ductoscopy, more extensive resec-tions were performed in these patients, and the positive margin rate decreased from 23 to 5%. It was concluded that ductoscopy can

detect more cancerous and precancerous disease than anticipated by routine preopera-tive mammography.

7.3 Summary

Ductoscopy is an emerging technology that may improve evaluation of intraductal neoplasia in women with nipple discharge or those undergo-ing surgery for breast cancer. Ductoscopy can identify most lesions in patients with nipple discharge and may be used for guidance of ductal resection. In patients with breast cancer, ductoscopy holds promise to improve the detection of additional intraductal components, especially in women with extensive disease. Intraductal biopsy is a new minimally invasive technique for tissue sampling of intraductal neoplasia. Clearly, ductoscopy with ductoscopic biopsy is not suitable for screening early breast cancer because of the invasive nature of the procedure and the inability to examine all ducts. Further prospective studies will be required to clarify the exact role of ductoscopy with ducto-scopic biopsy for the evaluation of intraductal neoplasia.

References

Bässler R (1998) Histopathologie und aktuelle Klassifikationen des Mammakarzinoms. Onkologe 4:878–895

Chagpar A, Yen T, Sahin A, Hunt KK, Whitman GJ, Ames FC, Ross MI, Meric-Bernstam F, Babiera GV, Singletary SE, Kuerer HM (2003) Intraoperative margin assessment reduces reex-cision rates in patients with ductal carcinoma in situ treated with breast-conserving surgery. Am J Surg 186:371–377

Claus EB, Petruzella S, Matloff E, Carter D (2005) Prevalence of BRCA1 and BRCA2 mutations in


women diagnosed with ductal carcinoma in situ. JAMA 293:964–969

Dietz JR, Crowe JP, Grundfest S, Arrigain S, Kim JA (2002) Directed duct excision by using mam-mary ductoscopy in patients with pathologic nip-ple discharge. Surgery 132:582–587

Dooley WC (2003) Routine operative breast endoscopy during lumpectomy. Ann Surg Oncol 10:38–42

Dooley WC, Ljung BM, Veronesi U, Cazzaniga M, Elledge RM, o’Shaughnessy JA, Kuerer HM, Hung DT, Khan SA, Phillips RF, Ganz PA, Euhus DM, Esserman LJ, Haffty BG, King BL, Kelley MC, Anderson MM, Schmit PJ, Clark RR, Kass FC, Anderson Bo, Troyan SL, Arias RD, Quiring JN, Love SM, Page DL, King EB (2001) Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst 93:1624–1632

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8.1 Introduction

Over the last decade, minimally invasive biopsies, such as core-needle biopsies (CNB), have gained wide acceptance for the preoperative diagnosis of breast disease. Due to frequent fragmentation of the tissue and lack of architec-tural orientation, diagnosis based on this type of biopsy poses many problems for pathologists.

Minimally invasive biopsy (MIB) in most cases allows for the decision of whether patients need to undergo additional surgical procedures including excision biopsy or even mastectomy. Pathologists establish the final diagnosis. Pathological examination is therefore one of the most crucial steps in the management of patients with breast disease. The decision process is mainly based on an accurate pathologic assess-ment, which also takes into account an apprecia-tion of the differing biologic implications of the diverse entities observed. It must be kept in mind that many histopathological parameters have profound prognostic and predictive impact. In general, there is a difference between the pathological findings in biopsies from mammo-graphically detected and readily symptomatic lesions. In MIBs from screen detection there is a

diagnostic shift from frankly malignant to bor-derline and preinvasive lesions, which poses additional difficulties for accurate assessment. These lesions include premalignant breast dis-ease such as columnar cell lesions, intraductal hyperplasia with or without atypia, lobular neo-plasia, and ductal carcinoma in situ (DCIS). For example, recent studies have shown that colum-nar cell lesion with atypia (flat epithelial atypia) is often associated with DCIS and invasive car-cinoma. Likewise, lobular neoplasia in needle core biopsies was followed by DCIS and inva-sive carcinoma in excisional specimens in as many as 25% of the cases. Papillary lesions of the breast have an association with invasive carcinoma, and excision biopsy is mandatory.

8.2 Pathology of Breast Disease in Minimally Invasive Biopsies

MIBs are performed on areas with radiologic architectural abnormalities or microcalcifications. When microcalcifications are the main feature, they must be sought in the histological slides. One histological clue of not readily discernible calcifications is the artificial tissue disruption on H&E stain (Fig. 8.1). Special stains such as Kossa are helpful and will highlight calcifications as black lumps (Fig. 8.2). Importantly, it must be kept in mind that calcifications must have a minimal size to be detectable on mammography, i.e., at least 100–150 mm.

Pathology of Breast Tissue Obtained in Minimally Invasive Biopsy Procedures

Gad Singer and Sylvia Stadlmann

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Gad Singer ()Chefarzt des Instituts für Pathologie, Kantonsspital Baden, 5404 Baden, Switzerlande-mail: [email protected]


138 G. Singer and S. Stadlmann

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8.3 Benign Epithelial Lesions

8.3.1 Periductal Mastitis

Periductal mastitis involves larger and intermedi-ate-size ducts, generally in the subareolar location. Periductal mastitis refers to distended ducts

(duct ectasia) lined by normal or reactive epithe-lium, filled with amorphous, eosinophilic material and/or foam cells, with severe periductal chronic inflammation (Fig. 8.3). Inflammation may lead to periductal fibrosis, which can result in duct oblit-eration. This phenomenon may also occur in high-grade DCIS and obscures the actually malignant lesion (formerly referred to as “healing” of DCIS).

8.3.2 Fibrocystic Change

Fibrocystic change refers to numerous macro-scopically visible cysts that show a rounded shape, lack stromal elastin, and display frequent apocrine metaplasia (Fig. 8.4). Apocrine meta-plasia can be papillary and subclassified into simple, complex (with small papillae), and highly complex (with interconnecting bridges). Apocrine cells are characterized by prominent nuclear pleomorphism. Cytological changes must be severe to consider these lesions as atyp-ical. Minimal changes such as fibrosis, slightly enlarged ducts, and minor degrees of blunt duct adenosis are normal findings.

Fig. 8.1 Microcalcifications. Artificial disruption of tissue

Fig. 8.2 Kossa stain. Calcifications are highlighted (brown reaction)

8 Pathology of Breast Tissue Obtained in Minimally Invasive Biopsy Procedures 139

8.3.3 Sclerosing Adenosis

Sclerosing adenosis is characterized by myoepi-thelial and stromal hyperplasia, but preserved two-cell layers. The most important diagnostic clue on H&E sections is a retained organoid architecture, which in most cases can also be appreciated in MIB (Fig. 8.5), although it may be difficult to differentiate it from malignant lesions. Adenosis may display an infiltrative pattern, even with involvement of peripheral nerves and blood vessels, a feature not to be

misinterpreted as malignancy. Calcification may be present and, if of relevant size, may explain radiologic findings.

Nodular sclerosing adenosis or tumor adeno-sis refers to lesions that can form mammograph-ically and macroscopic tumorous lesions, which can be mistaken for invasive carcinomas. This is especially the case if the epithelial lining of ade-nosis is changed by apocrine metaplasia with increased nuclear pleomorphism. DCIS might also involve sclerosing adenosis. Severe nuclear atypia must therefore be excluded and is always suspicious.

The tubular structures of sclerosing lesions contain a rim of myoepithelial cells with characteristic clear cytoplasms. Occasionally, myoepithelia can be very inconspicuous. The main differential diagnosis to sclerosing adenosis in MIBs is tubular carcinoma. Since carcinomas lack any myoepithelial layer, com-bined immunohistochemical stains with anti-bodies against p63, smooth muscle myosin heavy chain, and calponin are very useful for the confirmation of a benign lesion. There are some architectural clues that point to tubular carcinomas. In contrast to sclerosing lesions, tubular carcinomas infiltrate more haphazardly and then lack the main characteristic stellate features of sclerosing lesions, although these

Fig. 8.3 Periductal mastitis. Dilated glands with periductal chronic inflammation and focal accu-mulation of foam cells

Fig. 8.4 Apocrine metaplasia in an area with fibrocystic changes

Fig. 8.5 Sclerosing adenosis. Organoid lobular pro-liferation, including epithelial lined glands, myoep-ithelium, and stromal cells


8architectural features are in most cases not always obvious in MIBs. Invasion of fat around or through normal glandular structures is suggestine for malignancy.

8.3.4 Columnar Cell Lesions

Columnar cell lesions of the breast comprise a spectrum of changes ranging from columnar cell change, columnar cell hyperplasia, and columnar cell hyperplasia with atypia (flat epi-thelial atypia). Under screening conditions, the detection of microcalcifications has led to the recognition of these entities.

Columnar cell change is characterized by extended lobules, often containing calcified lumps within the secretion (Fig. 8.6). The lob-ules are lined by a single layer of epithelial cells with increased luminal-directed cytoplasm and so-called apical snouts. More extensive multi-layering (more than two layers) of the epithelial cells is classified as columnar cell hyperplasia. Rarely, single-layered or hyperplastic columnar cell changes show mild cytological atypia, including enlargement of nuclei, hyperchroma-sia, and prominent nucleoli, and the lesion then is termed flat epithelial atypia (Fig. 8.7). If more extensive architectural changes such as micro-papillary structures and/or cribriform areas are present, these lesions are classified as atypical proliferations of the ductal type (this corre-sponds to either atypical ductal hyperplasia (ADH) or low-grade DCIS in larger biopsies). Severe nuclear atypia is not part of the spectrum of flat epithelial atypia and should be classified as high-grade DCIS, even if it presents as flat.

Many epithelial proliferations may be asso-ciated with columnar cell lesions, including lobular neoplasia (LN), ADH, low-grade DCIS, and invasive carcinoma, in the majority of the cases of the tubular type. Flat epithelial atypia is therefore a low-grade neoplasia or an indica-tor lesion for malignant disease. This view is

supported by the lack of stain for basal cytok-eratins and in most instances the homogeneous immunoreactivity for the estrogen receptor (ER). The association with malignancy is the most important message for the clinician.

8.3.5 Usual-Type Epithelial Hyperplasia

Usual-type epithelial hyperplasia (UDH) is composed of a mixed cell population including epithelial cells, basal myoepithelial cells, and

Fig. 8.6 Columnar cell change. Dilated lobules lined by a single layer of cells with apical snouts

Fig. 8.7 Flat epithelial atypia. Distended acini lined by atypical cells with apical snouts and prominent nucleoli


metaplastic apocrine cells (up to four cell layers thick). Florid forms are sometimes observed. UDH is characterized by a syncytial, streaming growth pattern of nonuniform cells with oval-oid nuclei, irregular and slit-like, peripheral lumina, and rare mitotic activity (Fig. 8.8). Marked nuclear atypia is lacking. Immunohistochemical stains for ductal epithelia (CK18/19) and basal epithelial cytokeratins (CK5/6) are very helpful in identifying the heterogenous cell population diagnostic for UDH. The immunohistochemical staining for CK5/6 shows a characteristic mosaic pattern of basal keratins (Fig. 8.9).

This contrasts with the majority of atypical ductal lesions, which lack staining for basal cytokeratins. In addition, epithelial cells in UDH are often ER-negative.

The diagnosis of ADH should not be made in MIB. In larger specimens, the diagnosis of ADH is characterized by a monomorphic intraductal proliferation of epithelial cells with hyperchro-matic nuclei. ADH can be diagnosed if the fea-tures are not sufficient to make a clear diagnosis of DCIS. Any lesion with high-grade cytology qualifies as high-grade DCIS, independent of size. In most cases, ADH shows a cribriform (sieve-like), sometimes micropapillary or solid growth pattern. On immunohistochemical examination, the cells in ADH are CK18/19+, CK5/6−, and ER+. In contrast to UDH, the sec-ondary lumina within the neoplastic cell popula-tion have a punched-out appearance and are more regular and rounded. In order to fit into the category of ADH, the maximal lesion size is 2–3 mm. Newer pathogenetic theories challenge the older view that UDH might progress to ADH. Chromosomal abnormalities are not observed in UDH, but are frequent in ADH. Both lesions develop independently, and untreated ADH clearly progresses to low-grade DCIS. Both UDH and ADH may be associated with mam-mographic abnormalities such as architectural distortion, with or without microcal cifications.

8.3.6 Lobular Neoplasia

Historical terms such as atypical lobular hyper-plasia (ALH) and lobular carcinoma in situ (LCIS) should be merged together under the diagnosis of lobular neoplasia (LN). This is based on molecular studies which show that the two entities are basically the extension range of the same neoplastic proliferation, which tradi-tionally have been separated on the basis of quantitative features related to the extent of lobular involvement. LN is characterized by

Fig. 8.8 Usual epithelial hyperplasia (UDH). Mixed population of cells displaying a streaming pattern. The luminal spaces are irregular

Fig. 8.9 C5/6 staining in UDH. Typical mosaic staining pattern


8

proliferation of small round or cuboidal incon-spicuous cells within the terminal duct lobular units (Fig. 8.10). The cells have a high nuclear-to-cytoplasmic ratio and might contain signet-ring-type intracytoplasmic mucin vacuoles, resulting in the morphology of so-called target cells. The neoplastic cells often display a paget-oid infiltration into neighboring larger ducts.

The pleomorphic subtype of LCIS is charac-terized by larger, polymorphous cells. The loss of E-cadherin immunoreactivity, a transmem-brane glycoprotein crucial for the formation of intercellular junctions, is a characteristic feature of LN and can used for diagnosis. It must be kept in mind that LN may not be a correlate for a radiological finding. Therefore, biopsy must be repeated or a wider excision is warranted. In large specimens, very mild forms of LN can be frequently found in association with benign fibrocystic change, involution, or normal breast tissue and, as sole lesions, can probably be ignored. In contrast, in MIB specimens the extent of LN cannot be assessed with certainty. LN is regarded as a marker for increased risk of breast cancer. Importantly, this risk applies to both breasts. However, recent studies indicate that LCIS is a precursor lesion for invasive can-

cer, but with less pronounced molecular abnor-malities than DCIS and therefore with slower progression. This could explain why LN is regarded as a risk factor and not as an obligate precursor to invasive carcinoma. Regarding LN in MIBs, 25% of cases might be associated with DCIS or invasive cancer, therefore warranting excisional biopsy.

8.4 Fibroepithelial Lesions

8.4.1 Fibroadenoma

Fibroadenoma is a benign lesion composed of an epithelial and a stromal component with a so-called pericanalicular and/or intracanalicular growth pattern (Fig. 8.11). The epithelial rim is mainly double-layered. Metaplastic or hyper-plastic changes may be observed. Epithelial pre-dominant fibroadenomas, so-called tubular adenomas, may occur.

The stroma is composed of spindle cells, but occasionally contains fat, smooth muscle, or even bone. Myxoid changes may be pronounced and large myxoid lesions are sometimes associ-ated with Carney’s syndrome. Aging phenomena include sclerosing hyalinization accompanied by calcifications, which are visible on mam-mography. Areas with atypical hyperplasia or in situ carcinoma should be sought. LN within a fibroadenoma is more frequent than DCIS. These neoplastic changes do not occur more often than in normal breast tissue. In MIBs, usu-ally only parts of a fibroadenoma are encoun-tered and rarely the entire lesion.

Fibroadenomatoid hyperplasia refers to coa-lescent areas of fibroadenomatous changes and might not be the lesion that has been detected by the clinician, because these lesions are usually not palpable.

Fig. 8.10 Lobular neoplasia. Proliferation of small round or cuboidal inconspicuous cells within the terminal duct lobular units


8.4.2 Phyllodes Tumor

Phyllodes tumor (PD) must be distinguished from fibroadenoma on MIB. This distinction is very important because of the different impli-cations of this diagnosis. The diagnosis of PD must be followed by immediate excisional biopsy, because of the biologic behavior of PD. The low-grade variant of PD can be very difficult to discern from fibroadenomas. PD is usually more cellular, but higher cellularity can also be observed in fibroadenomas from younger women. Typical features such as leaf-like projections into cystic spaces, stromal overgrowth with a pronounced periepithelial rim, and bipolar fibroblasts may help in establishing the correct diagnosis, but are not readily visible in MIBs. In contrast, malignant phyllodes tumors are easily identified by their sarcomatous stroma with abundant pleomorphic nuclei and mitotic figures (Fig. 8.12).

8.4.3 Benign Papillary Lesions

The accurate diagnosis of papillary lesions is one of the most challenging tasks in the pathology

of MIB. An intraductal papilloma is a lesion with an arborescent, fibrovascular core, covered by two cell layers, which are composed of an inner myoepithelial and an outer epithelial layer (Fig. 8.13). Fibrosis, hemorrhage, and hemosi-derin sometimes produce a pseudoinfiltrative pattern and even lead to relocation of tumor for-mations into vascular spaces, which would prompt the incorrect diagnosis of malignancy.

UDH frequently occurs in papillary lesions. Apocrine and squamous metaplasia are some-times observed. ADH and DCIS, the latter

Fig. 8.11 Fibroadenoma. Intracanalicular growth pattern Fig. 8.12 High-grade malignant phyllodes tumor. Pronounced stroma cellularity, highly atypical cells, and high mitotic rate

Fig. 8.13 Intraductal papilloma. The fibrovascular core is covered by layers of two different cell types (myoepithelial and epithelial)


8usually of the low-grade type, may also be detected within the lesion, which is then termed atypical papilloma. These lesions must be dis-tinguished from encysted intraductal papillary carcinoma, which is usually associated with fine papillary cores. The myoepithelial layer in benign lesions may be highlighted using the appropriate immunohistochemical stains as pre-viously described, although myoepithelia are not a guarantee of a benign lesion, as papillary car-cinomas might also posses a discontinuous layer of myoepithelial cells.

Immunohistochemical staining with CK5/6 may be helpful to establish the diagnosis of malignancy, as papillary carcinomas usually turn out to be negative for this cytokeratin, while benign lesions show a mosaic staining pattern. Since a malignant lesion cannot be ruled out, the consequence of diagnosing any papillary lesion on MIB is full excision and thorough sampling.

8.5 Malignant Noninvasive Lesions

DCIS is defined as a proliferation of malignant epithelial cells that arise from the terminal duct lobular units and spread within the ductal and lobular structures. In contrast to invasive carci-noma, it does not show a destruction of the basal membrane with subsequent invasion of the stroma. Features that favor DCIS are the slightly larger cell size, readily visible cell membranes and nucleoli, cytoplasmic basophilia, variation in cellular arrangement and size, greater cellular cohesion, and lack of intracytoplasmic lumina. The architectural features are identical to those described for ADH. Low-grade DCIS is defined as a monomorphic neoplastic proliferation of small cells, with a nuclear size of less than two red blood cells (RBCs), with rounded nuclei and inconspicuous nucleoli (Fig. 8.14). The cells frequently show a cribriform or micropapillary growth pattern; a solid growth pattern can

also occur. The intercellular lumina in the areas with cribriform growth are rounded and evenly spaced.

Papillary DCIS (or noninvasive papillary carcinoma) is characterized by low-grade mono-morphic tumor cells on papillary fronds (Fig. 8.15) that usually do not possess myoepithelia (see benign papillary lesions). High nuclear grade is associated with clinically more aggres-sive disease. Grading is performed by compar-ing the nuclei with RBC size. High-grade DCIS (Fig. 8.16) is defined as a nuclear size of more than three RBCs. The nuclei show a marked

Fig. 8.14 Low-grade DCIS with small regular cells and a cribriform growth pattern

Fig. 8.15 Papillary carcinoma in situ. Tumor cells on papillary fronds that lack myoepithelia


polymorphism and prominent nucleoli. Central necrosis is identified as eosinophilic mass with cell debris. This type of necrosis has been termed comedo necrosis. The necrosis tends to be calci-fied, which results in mammographically detect-able calcifications.

Other forms of high-grade DCIS include the cribriform and micropapillary subtypes.

Microinvasion, which is defined as infiltration of no more than 1 mm in diameter is observed in most cases of high-grade DCIS but is a rare phe-nomenon in MIBs. Although very rare, it could provide important information to the clinician, in particular it helps to decide whether a sentinel lymph node examination would be appropriate.

Negative immunohistochemical stains for myoepithelial markers may help in the differen-tial diagnosis to lobular involvement by DCIS, which may be mistaken for microinvasive carci-noma and show a preserved myoepithelial layer.

8.6 Invasive Carcinoma

Invasive ductal carcinomas (Fig. 8.17) exhibit great variation in appearance and are the most common carcinomas, accounting for up to 75%

of all breast carcinomas. Some authors even prefer to refer to it as no special type or no specific type.

Less common variants of invasive breast carcinoma include infiltrating lobular carcinoma, which is composed of small regular cells identical to lobular neoplasia. The cells infiltrate as single rows (Indian file pattern) or target-oid patterns around normal ducts (Fig. 8.18). Pleomorphic lobular carcinoma is a variant with a more unfavorable prognosis.

Tubular carcinomas are a highly well-differentiated variant of ductal carcinoma, which consists of round-to-ovoid and/or angulated tubules composed of a single cell layer (Fig. 8.19). The cells are small, without marked poly-morphism of nuclei. Occasionally, cytoplasmic apical snouts are observed, given the close connection of this subtype to flat epithelial atypia, which is also often observed in its vici-nity. Over 90% of the tumor must exhibit this growth pattern in order to qualify as tubular carcinoma. Reliable classification on MIBs is not possible. Remarkably, tubular carcinomas might no longer be found in the subsequent resec tion specimen because usually they are small.

Medullary and atypical medullary carcinomas are subtypes of ductal carcinomas characterized by syncytial interconnecting proliferations of

Fig. 8.16 High-grade DCIS with large pleomorphic cells arranged in solid formations. There is a cen-tral comedo-type necrosis with microcalcification

Fig. 8.17 Invasive ductal carcinoma. Tumor is com-posed of infiltrating glands made up of atypical cells


8

grade 3 carcinomas with large vesicular nuclei and prominent nucleoli. The tumor is admixed with large numbers of lymphoid cells.

Since the border of the carcinoma must be well defined, a diagnosis on MIB specimens cannot be made with certainty. Patients with BRCA1 gene mutations more frequently show tumors with medullary features.

So-called mucinous carcinomas show clus-ters of uniform small cells in lakes of extracel-lular mucin. A definite diagnosis of pure mucinous carcinomas in MIBs is not feasible. Stromal mucin in MIBs is frequently associated

with malignancy, even if no malignant features are initially observed. Excision of the lesion might be warranted.

Other breast carcinomas include variants such as infiltrating papillary, apocrine, and meta-plastic carcinomas. A very aggressive variant has been recognized and termed invasive micro-papillary carcinoma (Fig. 8.20). This tumor is associated with widespread metastases at initial presentation and has a poor prognosis. The micropapillary pattern in carcinomas diagnosed in MIBs might therefore suggest more aggres-sive surgical procedures.

8.7 Grading of Breast Carcinoma

Grading of breast carcinoma is based on scores for tubule formation, nuclear pleomorphism, and mitoses. Mitoses are counted per ten high-power fields. Each part is scored from 1 to 3. The scores are added and this gives the overall histological grade, as follows:

Total score of 3, 4, or 5 = Grade 1Total score of 6 or 7 = Grade 2Total score of 8 or 9 = Grade 3

Fig. 8.18 Invasive lobular carcinoma. Infiltration of small cells in rows (Indian file pattern)

Fig. 8.19 Tubular carcinoma. Characteristically highly differentiated, sometimes angulated infil-trating glands

Fig. 8.20 Invasive micropapillary carcinoma. The tumor is composed of micropapillae with charac-teristic surrounding retraction artifacts


It is advisable that grading be performed on all histological subtypes of breast carcinoma, even in MIBs. Terms such as “well differenti-ated” or “poorly differentiated” in the absence of a numerical score should be avoided.

The presence of vascular invasion is consid-ered an adverse independent prognostic feature and was introduced into the risk categories defined in the St. Gallen Consensus Conference for therapy in breast cancer in 2005. It is there-fore important to state whether or not it is present. Because it is difficult to distinguish between lymphatic and blood channels, the term vascular invasion is preferable. A clearly identifiable rim of endothelium should be present. Immunostaining using vascular markers such as CD31, CD34, or D2-40, a marker for lymphatic endothelium, could be used as an adjunct for diagnosis.

8.8 Predictive Factors in MIBS

We have gained a great deal of expertise in the examination of predictive factors for therapy such as ER, PR, and HER-2/neu by using immunohistochemistry and fluorescence in situ hybridization (FISH). It has been shown that the examination of these factors is feasible in MIBs and representative for the whole tumor.

References

Burstein HJ, Polyak K, Wong JS, Lester SC, Kaelin CM (2004) Ductal carcinoma in situ of the breast. N Engl J Med 350:1430–1441

Leake R, Barnes D, Pinder S et al (2000) Immuno-histochemical detection of steroid receptors in breast cancer: a working protocol. J Clin Pathol 53:634–635

Otterbach F, Bankfalvi A, Bergner S, Decker T, Krech R, Boecker W (2000) Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast. Histopathology 37:232–240

Page DL, Ellis IO, Elston CW (1995) Histologic grading of breast cancer. Let’s do it. Am J Clin Pathol 103:123–124

Rampaul RS, Pinder SE, Gullick WJ et al (2002) HER-2 in breast cancer: methods of detec-tion, clinical significance and future prospects for treatment. Crit Rev Oncol Hematol 43: 231–244

Schnitt SJ, Vincent-Salomon A (2003) Columnar cell lesions of the breast. Adv Anat Pathol 10: 113–124

Shelley Hwang E, Nyante SJ, Yi Chen Y, Moore D, DeVries S, Korkola JE, Esserman LJ, Waldman FM (2004) Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma. Cancer 100:2562–2572

Shin SJ, Rosen PP (2002) Excisional biopsy should be performed if lobular carcinoma in situ is seen on needle core biopsy. Arch Pathol Lab Med 126:697–701

9.1 Technical Failures

The term technical failure may describe either the physical inability to retrieve tissue in a radiologic lesion or the inability to retrieve a tissue sample that explains the features of the radiologic lesion, which is also called a dis-crepancy or noncorrelation between imaging and histology. While the first is easily identi-fied during the biopsy procedure due to lack of tissue or inability to target the lesion, the latter requires correlation of the features of the lesion on imaging with histology. Examples are missing calcifications on histology in cases of a biopsy of a cluster of microcalcifi-cations. Another example of a discrepancy is the histologic diagnosis of fatty tissue after an ultrasound-guided core biopsy of suspected fibroadenoma. A reason for such a discrep-ancy may be the slipping away of the fibroad-enoma during core-needle biopsy. Hence, the discrepancy of the histology result is due to a technical failure of the biopsy instrumenta-tion, e.g., the inability to penetrate the lesion and sample tissue.

Imaging–histology discordance occurs in 3.1% of stereotactic or ultrasound-guided breast biopsies (Liberman et al. 2000). Repeat biopsy performed in 45 discordant lesions

revealed carcinoma in 24.4%. Hence, repeat biopsy or open excision of such lesions has to be recommended.

The repeat biopsy of a lesion with a discord-ant histology should be performed using a large-volume biopsy device, since complete excision rather than sampling of a mammographic target is associated with lower frequencies of discord-ance (Liberman et al. 2002).

If the above-mentioned technical failures and high-risk lesions are taken into account, sterotactic breast biopsy has a lower false-negative rate (0.1%–0.7%) than open breast biopsy (Table 9.1). The false-negative rate of open breast biopsy with needle localization was 2.3% in 23 studies involving 9,101 patients (Fehr et al. 2002).

9.2 Underestimation of Breast Pathology on Minimally Invasive Breast Biopsy Specimens

There are distinct breast pathologies on mini-mally invasive breast biopsy specimens that carry the inherent risk of being underestimated (see Table 9.2). In other words, the histological diagnosis of the re-excision specimen is more malignant than that of the minimally invasive breast biopsy specimen.

Invasive cancer within a ductal carcinoma in situ (DCIS) is often not recognized with mini-mally invasive breast biopsy due to sampling

Limitations of Minimally Invasive Breast Biopsy

Mathias K. Fehr

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M.K. FehrDepartment of Obstetrics and Gynecology, Cantonal Hospital, Frauenfeld, Switzerland e-mail: [email protected]


150 M.K. Fehr

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error in large DCIS. The rate of underestimation seems to depend on the radiologic size of the lesion as well as on the amount of tissue sampled by the breast biopsy device. In the series reported by Pandelidis et al. (2003), 15% (5/76) of DCIS less than 1.5 cm in diameter on mammography turned out to have invasive components, whereas the underestimation rate was 60% (6/19) in lesions greater than 1.5 cm. Similarly, in the series reported by Brem et al. (2001), only 2% (1/48) of DCIS with a mammographic size below

3 cm were underestimated compared to 31% (4/13) measuring more than 3 cm (p = 0.006).

In any case, re-excision of the biopsy site is recommended, not only to avoid underestimation but also to obtain clear margins (Table 9.3).

In ultrasound-guided minimally invasive breast biopsy, underestimation of DCIS also occurs. However, there are few data on ultrasound-guided minimally invasive breast biopsy of DCIS, since these lesions are rarely detected on ultrasound (Table 9.4).

Table 9.2 Incidence of high risk histologies in minimally invasive breast biopsy specimen

Histological diagnosis on biopsy specimen

Incidence of this diagnosis on 880 stereotactic breast biopsies Possible final diagnosis on re-excision

Atypical ductal hyperplasia 4.5% DCIS, invasive cancerDCIS 13% Invasive cancerLobular neoplasia 2% Invasive cancerPapillary lesions 0.16% Intracystic papillary carcinomaRadial scar 0.6% Tubular carcinoma, adjacent invasive cancer

Table 9.1 occurrence of breast cancer following minimally invasive breast biopsy with benign histol-ogy and no discordance (false-negative rate)

Author n Average follow-upBreast cancers during follow-up

Core biopsy stereotactic n %Jackman et al. (1999) 295 55 months (6–85) 2 0.7%Meyer et al. (1999) 855 >12 months 0 0%Burns et al. (2000) 400 33 months (24–48) 5 1.25%Liberman et al. (1997) 154 >6 months 0 0%Lee et al. (1999) 298 33 months (5–65) 2 0.7%Dahlstrom and Jain (2001) 109 2.4–7.5 years 2 1.8%Brenner et al. (2001) 475 >12 months 6 1.3%Total 2,586 17 0.7%

Vacuum-assisted core biopsyKlem et al. (1999) 202 >3 months 1 0.5%Heywang et al. (1998) 129 >6 months 0 0%Liberman et al. (2000) 82 13 months (6–24) 0 0%Kettritz et al. (2004) 1,438 25 months (6–67) 1 0.05%Total 1,851 2 0.1%

Large-volume core biopsy (ABBI, SiteSelect)Schwartzberg et al. (2000) 104 6–24 months 0 0%University Hospital Zurich 74 6–24 months 0 0%

9 Limitations of Minimally Invasive Breast Biopsy 151

Table 9.3 Underestimation of DCIS on stereotactic breast biopsy using different biopsy systems

AuthorCore biopsy 14 G

Mammotome 14 G

Mammotome 11 G

Mammotome 8 G

Large-volume ABBI SiteSelect

Burbank (1997) 9/55 0/32Nguyen et al. (1996) 4/26Acheson et al. (1997) 10/54Jackman et al. (2001)

76/373 38/348 69/605

Mendez et al. (2001) 21/77Libermann et al. (1995–1999)

3/16 5/49

Darling et al. (2000) 14/67 8/47 18/175Fuhrman et al. (1998)

30/84

Won et al. (1999) 7/20 3/20Cho et al. (2005) 5/10 7/17Pandelidis et al. (2003)

12/91

Meyer et al. (1999) 1/28Brem et al. (2001) 4/38 1/23Schwartzberg et al. (2000)

0/14

Damascelli et al. (1998)

0/11

Matthews and Williams (1999)

2/6

Sheth et al. (1999) 1/12Yang et al. (2000) 0/6Kettritz et al. (2004)

49/422 (12%)

University Hospital Zurich

9/30 8/38 2/32

All 179/782 46/427 128/1,053 9/61 5/81% Under-estimated 22% 11% 12% 15% 6%

Table 9.4 Underestimation of DCIS on ultrasound-guided minimally invasive breast biopsy

Core biopsy 14 G Mammotome 11 G Mammotome 8 G

Cho et al. (2005) 5/10 (50%) 7/17 (41%)University Hospital Zurich

3/4 (75%)

Atypical ductal hyperplasia (ADH) may present as clustered microcalcifications on mam-mography. There is currently no general agree-ment on whether quantitative criteria should be applied to separate ADH from low-grade DCIS.

Some define the upper limit of ADH as one or more completely involved duct cross-sections measuring 2 mm or less in aggregate, while others require that the characteristic cytology and architecture be completely present in two

152 M.K. Fehr

9

spaces (Tavassoli et al. 2003). In any case, the distinction between ADH and DCIS depends on the amount of tissue available for diagnosis (Table 9.5).

It should be noted that even with large-vol-ume biopsy instrumentation underestimation of ADH still occurs in around 20% of cases. Therefore, re-excision of the diseased duct in a segmental fashion is recommended.

Again, there is also underestimation of ADH in ultrasound-guided minimally invasive breast biopsy. However, there are few data on this,

since ADH is rarely detected on ultrasound (Table 9.6).

It seems advisable that a mammographic lesion should not only be sampled by the mini-mally invasive biopsy system but also excised. This means that a larger mammographic lesion should be sampled by a large-volume biopsy system. Since the ABBI and SiteSelect devices are no longer available, the 8-G Mammotome needle or multiple biopsy sites seem to be preferable in larger lesions. However, even if the mammographic lesions are completely excised

Table 9.5 Underestimation of ADH on stereotactic breast biopsy using different biopsy systems


Mammotome 14 G

Mammotome 11 G

Mammotome 8 G ABBI SiteSelect

Burbank (1997) 8/18 0/8Philpotts et al. (1999/2000)

6/30 10/41

Cho et al. (2005) 7/12 1/5Jackman and Marzoni (1997–2002)

26/54 13/74 22/104

Joshi et al. (2001) 3/8 0/15Burak et al. (2000) 5/40Libermann et al. (2002)

12/49

Darling et al. (2000)

11/25 11/28 16/86

Reynolds (2000) 15/98Adrales et al. (2000)

9/62

Brem et al. (1999) 4/16Meyer et al. (1999) 10/18 9/24 1/9Rao et al. (2002) 11/31Pandelidis et al. (2003)

6/37

Arpino et al. (2004)

9/41

Kettritz et al. (2004)

32/141 (24%)

Schwartzberg et al. (2000)

0/1

University Hospital Zurich

6/15 3/18 2/5

All 60/165 33/149 127/634 3/18 2/6% Underestimated 36% 22% 20% 17% 30%


by the biopsy system, 10–17% of ADH or DCIS are underestimated (Table 9.7).

Lobular neoplasia is also a high-risk lesion that is often underestimated. Re-excision of the biopsy site is recommended following 14-G core biopsy since missed invasive cancers have been reported. Following vacuum-assisted core biopsy, the recommendation of re-excision is debated when the entire lesion has been removed on postbiopsy imaging.

overall, DCIS or invasive cancer was found in 22% (36/162) of re-excision specimens fol-lowing the diagnosis of lobular neoplasia on minimally invasive breast biopsy. Even if the mammographic lesion was completely excised by minimally invasive breast biopsy, two of seven cases showed DCIS or invasive cancer on the re-excision specimen (Elsheikh and Silverman 2005). Hence, it seems prudent to advise open re-excision if lobular neoplasia is diagnosed on the minimally invasive breast biopsy specimen, although data are scarce. opponents of re-excision argue that lobular neo-plasia is more an indicator lesion than a true, localized cancer precursor. However, the accu-

racy of this diagnosis based on a minimally invasive breast biopsy seems to be unreliable.

There is abundant evidence that atypical papillary lesions, consisting of papillomas with atypia suggestive of papillary carcinoma or atypical ductal hyperplasia, are associated with a significant risk of carcinoma and need to be excised. This risk ranges from 29 to 92% depending on the extent of atypical cells present on minimally invasive breast biopsy specimens (Renshaw et al. 2004).

on the other hand, biopsy of papillary lesions without atypia using the vacuum-assisted core biopsy device yielded no instance of underestima-tion in 23 cases (Philpotts et al. 2000; Mercado et al. 2001). Even when using 14- or 11-G core biopsy, no carcinomas were found at open excision in 18 cases when histology of the core biopsy showed no or minimal atypia (Renshaw et al. 2004). Hence, most authors do not proceed to re-excision if the entire sonographic or radiologic lesion was removed and the papillary lesion does not show atypia.

Whether sampling of papillary lesions using a core biopsy is sufficient for a reliable diagnosis is hotly debated. Some authors recommend

Table 9.6 Underestimation of ADH on ultrasound-guided minimally invasive breast biopsy

Core biopsy 14 G Mammotome 11 G Mammotome 8 G

Cho et al. (2005) 7/12 1/5University Hospital Zurich 2/2 0/2All 58% 43%

Table 9.7 Underestimation rates in DCIS and ADH according to the completeness of the removal of the mammographic lesion following stereotactic breast biopsy

Completely excised lesion Sampled lesion

DCISLiberman et al. (2002) 4/59 (6.8%) 12/60 (20%)University Hospital Zurich 6/38 (16%) 12/66 (18%)All 10/97 (10%) 24/126 (19%)ADHLiberman et al. (2002) 6/32 (19%) 5/16 (31%)University Hospital Zurich 2/15 (13%) 4/17 (24%)All 8/47 (17%) 9/33 (27%)

154 M.K. Fehr

9re-excision since six cancers were found in 29 papillary lesions diagnosed by 14-G core-needle biopsy (21%) (Philpotts et al. 2000; Liberman et al. 1999). on the other hand, others do not rec-ommend excision following core biopsy of pap-illomas without atypia, since no carcinomas were found at open excision in 18 cases (Renshaw et al. 2004). However, data are scarce and not very reas-suring (see Tables 9.8 and 9.9).

A radial scar is a benign lesion that on imag-ing resembles invasive carcinoma because the lobular architecture is distorted by the scleros-ing process. A high incidence of atypical hyper-

plasia and carcinoma has been reported in complex sclerosing lesions detected by mammography, particularly in larger lesions. Furthermore, the differentiation from a tubular carcinoma may be difficult if only little tissue is available. In nine cases diagnosed using 14-G core-needle biopsy, two cancers were found at re-excision (Philpotts et al. 2000; Jackman et al. 1999). Using vacuum-assisted core biopsy devices, such underestima-tion does not seem to occur (Philpotts et al. 2000). Hence, re-excision is not mandatory if the entire lesion has been removed on imaging (Table 9.10).

Table 9.8 Underestimation of lobular neoplasia on stereotactic breast biopsy specimens using different biopsy systems


Mammotome 14 G

Mammotome 11 G Mammotome 8 G

Elsheikh and Silverman (2005)

1/3 8/30

Dmytrasz et al. (2003)

3/7

Burak et al. (2000) 1/6Philpotts et al. (2000) 1/4Arpino et al. ( 2004) 3/21Irfan and Brem (2002)

1/7

Lechner et al. (1999) 18/84 (biopsy system not specified)

Table 9.9 Underestimation of papillary lesions without atypia by minimally invasive breast biopsy

Author Biopsy technique Number re-excisedUnderestimated cancers and DCIS

Mercado et al. (2001) 11-G mammotome 6 1Liberman et al. (1999) 14-G and 11-G core 4 0Philpotts et al. (2000) 14-G core and 11-G

mammotome6 1

Ioffe et al. (2000) Unknown 8 2Rajendiran et al. (2001) Unknown 27 2Renshaw et al. (2004) 14-G and 11-G core 18 0Carder et al. (2005) 14-G core 16 0Mercado et al. (2006) 14-G core 36 2 DCIS, 8 ADHValdes et al. (2006) 11-G mammotome 33 4Valdes et al. (2006) 14-G core 17 6


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10.1 Introduction

Breast cancer is the leading malignant disease in women in the Western world. It affects 9–12% of women during their lifetime (Heywang-Köbrunner and Schreer 2003). In the United States breast cancer causes more than 43,000 deaths per year, in the countries of the European Union more than 74,000 (Eurostat Datenbank Newcronos, unpublished data). Early detection and effective treatment of breast cancer are the major factors contributing to the decline in the mortality rate.

At present, mammography is the gold standard for the detection of breast cancer. Despite recent technical advances, mammography may miss as many as 10–25% of carcinomas, particularly in radiographically dense breasts. Furthermore, the high rate of false-positive mammograms (60–70%) results in a correspondingly high rate of biopsies that impose a heavy psychological burden on women and a heavy financial cost on the health-care system (Heywang-Köbrunner and Schreer 2003; Elmore et al. 1998).

Various additional modalities such as ultra-sound (US) or magnetic resonance imaging (MRI) have been introduced to adjunctively either increase

cancer detection or to improve discrimination between malignant and benign lesions. Despite complementary use of these imaging modalities, breast cancer is missed in a considerable number of cases (Heywang-Köbrunner and Schreer 2003; Elmore et al. 1998). Over time, substantial insight into the pathophysiology of breast carcinomas and other breast diseases has been gained. This knowl-edge should be included in breast imaging strate-gies of the future. Researchers expect to gain more, and particularly more precise and specific, information about breast lesions in the future, leading to earlier diagnosis of breast cancer and a more precise discrimination between benign and malignant tumors.

This chapter focuses on recent advances of breast imaging modalities spanning the spectrum from US to MRI, to positron emission tomogra-phy (PET), to optical imaging, and finally to elec-trical impedance scanning. Special emphasis is given to techniques that allow insights into a cel-lular and subcellular level. Thus, breast cancer can be detected at its molecular onset before ana-tomic changes become apparent.

10.2 Ultrasound

In 1954, Howry and colleagues first described a cirrhotic breast cancer with a B-imaging technique. In 1972, Kossoff and Jellins influenced

Advances in Breast Imaging: A Dilemma or Progress?

Daniel Flöry, Michael W. Fuchsjaeger, Christian F. Weisman, and Thomas H. Helbich

10

T.H. Helbich Department of Radiology, General Hospital Vienna (AKH) Waehringer Guertel 18-20, 1090 Vienna Austriae-mail: [email protected]


160 D. Flöry et al.

10the development of US gray-scale imaging of the breast with the Octoson scanner. Kobayashi and Wagai presented clinical studies reporting diagnostic criteria to differentiate benign from malignant breast lesions. During the next few years, the technical development efforts were concentrated on high-frequency linear trans-ducers. In the early 1980s, the first electronic focusation of a 5-MHz linear transducer was available. Companies learned to master high-frequency US technology, from 5 to 7.5 MHz. In the early 1990s, the transducer design with 128 active US elements changed to 192 elements. Current breast US systems with broad-band high-frequency transducers, e.g., 6–16 MHz, with full digital data management and high resolution combined with transmitter and receiver focusing are the basis for the high level of breast US imaging. An additional technical development resulted in low blood-flow velocity detection with the color Doppler, power Doppler, or high-definition flow-imaging technique. The progress in two-dimensional (2D) high-frequency US transducer technology combined with com-pound imaging is the basis for high-quality three-dimensional (3D) volume US for breast imaging (Rizzatto 2001; Weismann 2000). Four-dimensional (4D) US offers almost real-time 3D-rendered image information. In breast US technology, 3D/4D US is the most advanced development providing additional aspects to conventional 2D sonography: completely new superior diagnostic information such as the ability to study a breast mass and the surround-ing tissue in three orthogonal planes or to obtain new information about the 3D vessel architec-ture using glass body rendering.

The technical progress of conventional 2D breast sonography makes US the most important complementary imaging tool to mammography for diagnostic reasons. Under breast screening conditions, additional US used as a second screening test proved to be worthwhile (Kolb et al. 2002; Buchberger et al. 2000; Leconte et al. 2003). The grading of the breast parenchyma

density in mammography is classified by the American College of Radiology (ACR) into four categories. The sensitivity of mammography in cases of dense breast parenchyma declines from 98% in ACR grade 1 to 47.8% in ACR grade 4 density. Using US as a second-line screening test, the sensitivity in ACR grade 4 breasts for US is 76%. In the studies of Kolb and colleagues combining mammography and US information under screening conditions, the overall sensitiv-ity in ACR grade 3 and 4 mammography breast densities is increased up to 97% (Kolb et al. 2002). Comparable results have been published by Buchberger et al. (2000) and Leconte and colleagues (Leconte et al. 2003).

A dilemma of complementary US breast imaging lies in the fact that a number of benign breast lesions can be found in addition to mam-mography, the reason for further follow-up investigations or biopsies. Kolb et al. reported a 34.1% PPV (positive predictive value) for mam-mography and 25.4% for the combination of mammography and US (Kolb et al. 2002). As a consequence, breast lesions visible with US have to be assessed by diagnostic criteria con-cerning shape, orientation, margin, surrounding echogenicity, echogenicity of the lesion, sound transmission, and vascularity in order to improve the specificity and the predictive values. US BI-RADS published by the ACR (American College of Radiology 2003) and the US BI-RADS-adapted version of the German, Austrian, and Swiss Ultrasound Societies aim to assess and classify the lesion (Madjar et al. 2006). 3D breast US in combination with com-puter-aided analysis has the potential to help dif-ferentiate benign and malignant breast lesions. The studies of Moon et al. showed accuracy to be 87%, sensitivity 85%, specificity 88%, PPV 83%, and a negative predictive value (NPV) of 90% (Moon et al. 2005).

In Sect. 10.2.1, the recent progress, espe-cially in 3D and 4D breast US imaging, is dis-cussed and an algorithm is presented on how to use advanced US technology in daily diagnostic

10 Advances in Breast Imaging: A Dilemma or Progress? 161

routine work without facing the dilemma of los-ing time and control of the technical options. The 2D panoramic view technique (XTD View) is highlighted.

10.2.1 Multiplanar Display Mode

Multiplanar representation uses the 3D US information from the three planes (the A-, B-, and C-plane) that cut the voxels that are orthog-onal to each other (Weismann 2005). The A-plane shows the original scan plane during typical 2D US investigation and volume acqui-sition. The B-plane is orthogonal to A and C and offers the typical rectangular US informa-tion of 2D scanning, for example, the sagittal or transversal plane. The completely new diag-nostic information is obtained by the coronal plane (C-plane), which is orthogonal to A and B. Furthermore, the system allows navigation through the entire acquired volume, conduct-ing parallel interactive movements through the image slices. In all three planes, a colored dot indicating an identical voxel can be directed in every activated plane into the volume of inter-est (VOI). Synchronous parallel image move-ment in the corresponding orthogonal planes can be observed and shows the rectangular VOI reformatted. A dynamic analysis of the 3D-acquired US information of an anatomical detail is available and is easier to understand, for example, complex collecting duct branching.

10.2.2 Niche Mode View

The 3D US data are represented as a “cut-open” view of, for example, the interior view of a tumorous lesion and its surrounding tis-sue (Weismann 2005). This mode also impres-sively demonstrates the relationship of the

converging subareolar collecting ductal sys-tem and the mamilla. After 3D US data acqui-sition, the entire nipple area and the retromammilar region are offered in one vol-ume. An optimal time-gain adjustment com-bined with contrast resolution imaging (CRI) is necessary to reduce shadowing behind the nipple area for full diagnostic information of the ductal system.

10.2.3 Surface Mode

The surface mode provides the assessment of the surface rendering structures (Weismann 2005). A good result of surface rendering can be obtained by studying the inner structures of a cyst or an intraductal papilloma outlined by echo-poor fluid. The gray values of the surface are identical with the gray values of the original scan. Impressive surface information of a more complex 3D lesion morphology can be obtained (Fig. 10.1).

10.2.4 Transparency Mode

The acquired US volume data provide a 3D rendering using transparency mode and fad-ing, for example, between a maximum or min-imum mode adjustment (Weismann 2005). This mode gives reliable information of duc-tal anatomy and pathology, e.g., intraductal papilloma. Additionally, an animated study distinctly illustrates ductal branching or intra-ductal pathological structures and gives infor-mation of their spatial relationships. The transparency mode makes a biopsy needle inside the acquired 3D US data set visible. Combined with an animated rotation of the transparent rendered tissue block, the position of the needle in relation to the lesion can be evaluated.


10

10.2.5 Static 3D Volume Contrast Imaging

Static volume contrast imaging (VCI) makes it possible to study a static 3D data set with a preselected slice thickness (1–10 mm) at the same time in all three planes with different ren-dering algorithms. The benefit of this technique is to enhance the contrast between the lesion and the background structures with the aim of opti-mizing the contours in order to make accurate measurements and correct differential criteria analysis.

10.2.6 4D Volume Contrast Imaging

VCI is a real-time 4D US technique offering thick-slice rendering (6- to 10-mm slice thick-ness) or thin-slice rendering (2- to 4-mm slice thickness) (Weismann 2005). The rendering algorithm is a combination of surface and transparency mode. The Voluson 730 technol-ogy (GE Medical Systems Kretz-Ultrasound) offers VCI in the typical 2D US accessible

planes as well as in the coronal plane. The advantage of the VCI technique compared with conventional 2D US is the contrast-enhanced representation of almost isoechogenic lesions compared to the background. As a conse-quence, VCI provides an accurate measurement and safe needle guidance into, for instance, an echo-poor fibroadenoma surrounded by echo-poor fatty tissue. VCI-C is the preferred tech-nique for studying a lesion and the surrounding tissue under 4D related sonopalpation and dynamic 4D investigation. As a consequence, VCI-C is able to differentiate between spicula-tion of the breast mass and a US artifact, caused by shadowing, arising from the borderline between a fatty tissue lobule of mid-echogenic-ity and the hyperechogenic fibroglandular con-stituents mimicking spiculation. Sonopalpation means to compress and decompress the breast tissue with the finger and to monitor the move-ments between the different tissue layers with VCI-C. Dynamic 4D US studies present the imaging information, coming up from a circu-lar movement of the transducer under the C-plane aspect of the lesion and the surround-ing breast tissue.

Fig. 10.1 Multiplanar display mode with the volume of interest (VOI) positioned in a 2.8-cm liponecrotic cyst with C-plane surface rendering of the echogenic fat constituents (→) inside the cyst outlined by fluid


10.2.7 Inversion Mode

Echo-poor breast lesions are suitable for render-ing with the inversion mode technology. The VOI has to cover the entire lesion (Weismann 2005). The inversion rendering mode shows the lesion in a 50% mixed surface smooth and 50% gradient light algorithm as a white colored 3D model. The low threshold level has to be customized, on the one hand to suppress the echogenic constituents in the VOI, on the other hand to present the echo-poor lesion in a 3D-surface algorithm. The addi-tional echo-poor structures, not related to the lesion, can be removed by the electronic scalpel. To understand which structures are not related to the lesion, the entire rendered VOI has to be rotated around the y- and/or the x-axis. The inver-sion mode is a tool with quick access to the 3D morphology of the investigated breast mass. The shape of a lesion is an important diagnostic crite-rion with which to differentiate between benign and malignant breast tumors.

10.2.8 Volume Calculation

The basic principle of volume calculation (VoCal) is to combine geometric surface information with the volume data set of a lesion. On the condition that the lesion is circumscribed with clear con-tours, the VoCal software enables automated or manual volume calculation. The surface geometry is defined by rotation of an image plane around a fixed axis. The surface geometry can be visualized as a colored surface, a wire mesh model, or a ren-dered gray-scale surface (Fig. 10.2).

10.2.9 Tomographic Ultrasound Imaging

Tomographic ultrasound imaging (TUI) presents the diagnostic information of a static 3D data set in a 2D documentation, thermoprint or laser-print, comparable with CT or MR scans. A topo-gram gives the exact spatial position of the slices

Fig. 10.2 VoCal analysis of a 6.7-ml fibroadenoma: a wire mesh model, b original gray-scale values, and c skin model of the fibroadenoma


10obtained from the 3D data set and the custom-ized distance between the different slices. TUI primarily offers comprehensive diagnostic infor-mation of the 3D extent of a lesion on the basis of a 2D display. To optimize information trans-fer, TUI makes it possible to slice and document the lesion in all three planes (Fig. 10.3).

10.2.10 Glass Body Rendering

Glass body rendering is a special transparency mode, which makes the gray-scale data trans-parent and displays the color data of 3D high-definition flow (HD-Flow), 3D power Doppler, and 3D color Doppler in a surface mode (see next section below). This mode offers the basis for a detailed study of the 3D vascular supply of the lesion and the surrounding breast tissue.

10.2.11 Power Doppler, Color Doppler, and High-Definition Flow

Breast cancer tends to produce angiogenic fac-tors that influence blood vessel growth into the tumor. Neovascularization can be found inside the tumor and in the peritumoral tissue. There are reports in the literature on investigations concerning the evaluation of the quantity of blood flow, the vascularization pattern inside and outside of the tumor, and the imaging infor-mation related to contrast enhancers. The vascu-lar assessment aims to help differentiate between benign and malignant breast tumors and to give information on the degree of neovascularization, which correlates with the biological behavior of the tumor. The vascularization of a breast lesion can be investigated using 2D and 3D techniques with power Doppler (amplitude-based color

Fig. 10.3 A-plane topogram a of a 0.7-cm infiltrating ductal carcinoma (IDC) with the lines indicating the slice positions; the slices from –3 to 4 represent the cross-sections through the IDC with 0.8-mm slice distances


Doppler sonography) and frequency-based color Doppler sonography, which presents coded colors related to the median frequency shift combined with the option of spectral Doppler analysis. High-definition flow (HD-flow) is a color Doppler technique offering slow flow detection comparable to power Doppler (less than 1 cm min−1) and additionally gives infor-mation on the blood flow direction.

The color-coded methods can present the neovascularization of a carcinoma with an irreg-ular vascular pattern, artery–venous shunts, and missing vessel autoregulation in contrast to nor-mal breast tissue vessels. This is the background for many studies with 2D US and computer-assisted quantitative color Doppler analysis aiming at differentiating malignant and benign breast lesions. The morphological pattern of tumor vessels and tumor-feeding vessels has been studied by 2D and 3D US (madjar et al. 2006). Madjar and Jellins described the contrast enhancement flow from the periphery to the center of malignant as well as benign tumors. In their study, the carcinomas showed this pattern to be more pronounced, with the malignant neo-vascularization revealed as having a distinct radiating pattern and a vascular corona, equiva-lent to the growth zone of the tumor, visible in the echo-dense rim seen on B-mode US. Stuhrmann and colleagues studied the vasculari-zation of breast tumors and found that the mor-phological pattern and the course of the vessels were the parameters that offered the best differ-entiation between benign and malignant breast lesions (sensitivity, 95%; specificity, 83%).

The analysis of the 3D vascular architecture is an approach for 3D HD-Flow, 3D power Doppler, and 3D color Doppler studies. 3D power Doppler imaging provides the analysis of blood flow and 3D vascularization patterns of the entire tumorous lesion without the limitation of scanning only 2D planes, including the poten-tial problem that the most representative slice might not be scanned. 3D HD-Flow adds the blood flow direction to the 3D vascular architecture.

Glass body rendering offers the basis for a detailed study of the 3D vascular supply of the lesion and the surrounding breast tissue struc-tures. In combination with glass body rendering, the vascular architecture in relationship to the tumor extent and the surrounding breast tissue can be investigated. Suppressing the gray-scale parameters, a 3D angiogram will be obtained.

3D power Doppler volume information rep-resents an effective tool for evaluating the color histogram and the spatial distribution of the ves-sels inside and outside of the malignant or benign tumor. 3D reconstructions of the color volume data are suitable for studying the 3D vessel distribution and the potential irregulari-ties in vessel shape. The color histogram gives information on the vascularization index (VI), the flow index (FI), and the vascularization-flow index (VFI) inside a user-defined volume of interest (VOI). The VI gives information in per-cent (%) on the amount of color values (vessels) in that VOI. The VI is calculated by dividing the color values by the total voxels minus the back-ground voxels of the selected VOI. The dimen-sionless FI measures the mean blood flow intensity. The figure ranges from 0 to 100. The FI is calculated as the ratio of weighted color values (weighted by their amplitudes) to the number of the color values. The VFI gives com-bined information on vascularization and mean blood flow intensity. The VFI is also dimension-less and ranges from 0 to 100. It is calculated by dividing the weighted color values (weighted by their amplitudes) by the total voxels minus the background voxels.

10.2.12 Extended View Documentation

Extended (XTD)-View is a 2D US technique that estimates the probe movement by analyzing subsequent images. Based on the computed movement, all images of a sequence can be mapped into a common reference system, thus


10generating a compound panoramic image. This technique offers the basis for a precise docu-mentation of a lesion in the breast with one image. In the radial scan direction (duct paral-lel), the transducer will be moved without com-pressing the tissue from a mid-lesion position directly on a radial path toward the mid-nipple position. The shortest distance between the lesion and the nipple will be measured. The shortest distance measurement between skin surface and lesion follows to clarify the position of the lesion in depth. The breast pictogram tells whether it is the right or left breast. The position of the radial transducer path toward the lesion is documented by the transducer icon in the breast pictogram using the clock for description. Another target of the XTD-View documentation is to produce an image to study the structure (homogeneous vs. inhomogeneous) and the den-sity of the breast tissue (fibroglandular tissue vs. fatty tissue). For this purpose, from each breast quadrant an XTD-View image from the periph-ery to the nipple will be obtained and docu-mented by using the breast pictogram.

Algorithm on how to use 2D/3D and 4D US progress in breast imaging

(1) Lesion detection

High-quality 2D US is the basis for detecting a breast lesion complementary to mammography or as a first-line imaging tool (Kolb et al. 2002).

(2) Static 3D US multidimensional lesion analysis

After the acquisition of the diagnostic baseline static 3D volume US data set of the lesion and the surrounding tissue, the lesion will be studied in the multiplanar display mode. In the A- or B-plane, the lesion will be rotated around the y-axis. The lesion shape, orientation, margin, surrounding echogenicity, echogenicity of the lesion, and acoustic transmission are studied. In the C-plane of the multiplanar display mode, the lesion will be analyzed for signs of com-pression or a star/retraction pattern (Fig. 10.1)

(Rotten et al. 1999). If the contrast between lesion and surrounding tissue is poor, 3D static VCI can enhance the contrast. Compared with 2D imaging, a static 3D US volume offers much more comprehensive information for a second reading.

(3) Static 3D US lesion measurements and lesion volume calculation

From the same baseline diagnostic 3D volume US data set described in point 2, the longest axis in all three perpendicular planes is evaluated. No measurement failure obtained by 2D oblique cross-sections of the lesion can influence the 3D long axis measurements. Afterward, the volume of the lesion is calculated by VoCal. For follow-up, the long axis measurements and the lesion volume information in milliliters are available.

(4) Documentation of the lesion

The most comprehensive documentation of the lesion can be obtained with tomographic ultrasound imaging (TUI). This type of docu-mentation uses the baseline diagnostic 3D US volume.

(5) Complementary 4D US of the lesion

Only if something related to the lesion criteria remains unclear does complementary 4D US follow the baseline diagnostic static 3D US vol-ume analysis.

(6) Vascular study of the lesion and surround-ing tissue

An HD-Flow, power Doppler, or color Doppler 3D US volume data set is acquired. The vascu-larity of the lesion and the surrounding tissue as well as the 3D vascular architecture of the feed-ing vessels are studied using glass body rendering.

(7) Documentation of the lesion vascularity

TUI or glass body rendering of the 3D HD-Flow US data set of point 6 can be used for documentation.


(8) XTD-View documentation

XTD-View is a tool for precise documentation of the lesion in the breast with one image. In the radial scan direction (duct parallel), the shortest distance between the lesion and nipple (lesion–nipple distance) will be measured followed by the shortest distance measurement between lesion and skin (lesion–skin distance). The breast pictogram tells whether it is the right or left breast. The position of the radial transducer path toward the lesion is documented by the trans-ducer icon in the breast pictogram using the clock for description.

10.2.13 Conclusion

Not to become overrun with recent advances in breast US imaging, one must be familiar with new technical equipment on the market. An optimized and clear algorithm for using most modern US technologies helps maximize the ratio between time input and diagnostic output. The progress of 2D and 3D US presenting the vascular supply and vascular architecture of a breast lesion makes these techniques important diagnostic tools offering additional means for differentiating benign from malignant breast lesions. According to the above-mentioned top-ics, advanced 2D, 3D, and 4D US technologies are a clear progress fit for daily diagnostic prac-tice that provides perfect documentation of breast anatomy and breast pathology.

10.3 Magnetic Resonance Imaging

Since its introduction in the mid-1980s, con-trast-enhanced MRI of the breast has been linked to the use of gadopentetate. Numerous studies dealing with gadopentetate-enhanced MRI of

the breast have been published to date. From this large body of evidence, we have learned that contrast-enhanced MRI of the breast has an excellent sensitivity, approaching nearly 100% in invasive breast carcinomas (Helbich 2000). In general, carcinomas tend to enhance faster and wash out earlier than benign tissues. However, there are exceptions to this pattern. Certain car-cinomas, particularly lobular cancer and carci-noma in situ, may enhance slowly or not at all. On the other hand, some enhancement may be observed in benign lesions such as fibroadeno-mas. Thus, the specificity of MRI of the breast has been rather variable, ranging from 37 to 97% (Helbich 2000). Despite the use of several criteria in the classification of MRI-detected lesions (MRI lexicon) and the interpretation of contrast-enhancement kinetics, the method is still subject to improvements. Some new devel-opments have been made recently, which focused mainly on the development of high field strength systems for breast imaging and contrast agents such as macromolecular and tumor-specific contrast agents. Some of these new advances will be summarized in the following sections.

10.3.1 1.5-Tesla Systems and Gadopentetate

Today, MRI of the breast is most commonly used as a problem-solving method in cases with equivocal findings in mammography and US or in cases with scarring after radiation therapy or breast-conserving surgery (Helbich 2000). In addition, MRI is considered the gold standard in the preoperative evaluation of multicentric and contralateral breast carcinomas. The role of MRI in the screening of patients who are at high risk for breast cancer (BRCA1 and BRCA2 gene car-riers) is currently under investigation, but seems to have a major impact. Despite its frequent use, there is still no standardized and generally accepted protocol for MRI of the breast. However, there is some agreement among


10researchers about a suitable protocol. T1-weighted 2- and 3D gradient-echo tech-niques with and without fat subtraction are most often recommended for dynamic breast MRI over 6–10 min following bolus injection of gadolinium-based contrast agents at a dose of 0.1–0.2 mmol per kg body weight. In addition to T1-weighted sequences, a T2-weighted sequence should be performed to demonstrate cysts or cystic lesions. Use of a system with a field strength of 1.5 T and a dedicated breast coil are mandatory for optimal results. To ensure a com-plete characterization of detected lesion, both the morphological appearance and the enhance-ment kinetics should be studied. To standardize the terminology of morphological findings at MRI of the breast, a BI-RADS lexicon has been developed, analogous to the BI-RADS lexicon for mammography and US.

10.3.2 3.0-Tesla Systems

The development of MRI systems with a field strength greater than 1.5 T has led to research on the use of these systems for MRI of the breast. There are several requirements for obtaining T1-weighted gradient-echo (GE) sequences, which are most commonly used for breast MRI. Firstly, GE sequences must be acquired with a high enough spatial resolution to delineate mor-phologic details of small, enhancing lesions. Secondly, acquisition time has to be short enough to achieve optimal arterial phase con-trast to allow optimal kinetic analysis of enhanc-ing lesions. These requirements can be best met by using high-field MRI systems. Because of these time constraints and for reasons related to the signal-to-noise ratio (SNR), the maximum achievable spatial resolution at 1.5 T is limited. New image acquisition techniques, such as par-allel imaging with sensitivity encoding (SENSE), may be used to reduce acquisition times. At 1.5 T, however, high matrix imaging with parallel

imaging usually results in an inappropriately low SNR. Higher field strengths provide a higher SNR, which can be translated into higher spatial and temporal resolution and therefore into improved image quality. However, the opti-mal balance between temporal and spatial reso-lution still remains undetermined.

Besides its advantages, it is evident that breast MRI at higher field strengths raises a number of difficulties and problems. Stronger susceptibility effects, longer T1 relaxation times, shorter in-phase echo times, and higher radiof-requency (RF) deposition complicate or even impede image aquisition. In addition, homoge-neous signal intensity for a large field of view is more difficult to achieve with higher field strength. For breast imaging, this may interfere with the clinical demand to image both breasts simultaneously. All types of motion (breathing, pulsation, and considerable or subtle motion) can result in substantially stronger artifacts at higher field strengths than at 1.5 T.

Despite these potential obstacles, the pre-liminary results obtained with 3-T systems are encouraging. In a study by Kuhl et al., where the authors compared breast MRI results at 1.5 and 3 T in the same patients, differential diagnosis of enhancing lesions was possible with a higher diagnostic confidence at 3.0 T than with 1.5 T (Kuhl et al. 2006).

Altogether these results indicate that the 3-T system will most likely expand the possibilities of breast MRI significantly and that 3-T systems will be a future requisite for optimal breast MRI. In addition, high-field systems offer the possi-bility for functional MRI techniques such as MRI spectroscopy or perfusion-weighted MRI (please see Chaps. 10.3.5).

10.3.3 Macromolecular Contrast Agents

In addition to the developments in high-field MRI systems, new contrast agents hold great


promise for improved breast MRI in the future (Daldrup-Link and Brasch 2003).

A major limiting characteristic of the small molecular gadolinium chelates (such as gado-pentetate), which are today used for breast MRI, is that they extravasate nonselectively from the blood in the interstitium of both normal and pathological tissues in the breast. In breast carci-nomas, angiogenic factors induce the growth of a dense microvasculature. These cancerous ves-sels show a higher microvascular permeability and ease the extravasation of contrast media. Thus, rapid enhancement can be observed in breast carcinomas. Macromolecular contrast media (MMCM) are defined as contrast agents with a molecular weight greater than 10 kDa. They are designed to be sufficiently large that they do not extravasate across the normal endothelium, but they diffuse across the abnor-mal endothelium in pathological lesions (e.g., in breast carcinomas). Thus, the intention is to dif-ferentiate breast lesions according to their microvascular permeability (Daldrup-Link and Brasch 2003).

The prototype of MCMM is albumin-(Gd-DTPA)35, and a multitude of substances are cur-rently under clinical investigation. Experimental studies with albumin (Gd-DTPA)35 show that the microvascular permeability for this MCMM is significantly elevated in malignant carcinomas, whereas almost no measurable permeability was observed in benign fibroadenomas. However, its prolonged elimination and its immunologic potential impede the clinical use of this con-trast agent.

Another group of MCMMs, which are more appropriate in their physiological behavior, are superparamagnetic iron oxide particles (SPIOS). A larger subset of SPIOS are already approved for clinical use when imaging the reticuloendothe-lial system, such as the spleen and the liver. These agents, however, have been shown to be unsuit-able for breast imaging because they are cleared from the blood too rapidly. A smaller subset of SPIOS, called ultrasmall superparamagnetic

iron oxide particles (USPIOS), have a prolonged intravascular half-life and have been shown to have the potential to define macromolecular hyperpermeability encountered in most malig-nant tumor vessels. Four components, including feruglose (Clariscan), ferumoxtran (Sinerem, Combidex), and ferumoxtran-10 (Resovist S), are currently being investigated in clinical or preclinical studies.

A first multicenter clinical trial of Feruglose-enhanced MRI revealed a positive predictive value between 78 and 91%, depending on the characteristics of the lesions studied. In contrast, no enhancement was observed in normal and mastopathic breast tissue (Daldrup-Link et al. 2003).

Other types of MCMM are macromolecular gadolinium chelates. This group of contrast agents is based on gadolinium, which is bound in chelate molecules to obtain probes of a defined molecular weight. Because it has been shown that specificity of MCMM to define microvascular permeability increases with the molecular weight of the probe, whereas sensitiv-ity decreases with molecular weight, a certain dichotomy exists on what should be considered as the probe’s ideal molecular weight. However, the molecular weight of probes is generally limited to approximately 50 kDa, which is the maximum molecular weight that still allows renal elimination. To date, several different groups of probes have been investigated. One group is the mid-size gadolinium probes, which have a molecular weight of less than 30 kDa. Several different substances from this group have already been tested in clinical studies. One of them is Vistarem (Guerbet, France), which has already shown promising results in vivo. Compared to gadopentetate, different enhancement patterns were observed for this probe. Invasive carcinomas showed a minor initial enhancement, followed by a slowly increasing enhancement over time. No wash-out could be observed, but all carcinomas examined showed pronounced rim enhancement. The reason


10for this enhancement pattern may be a continuous transendothelial diffusion of the MCMM into the tumor interstitium over time. Preliminary clinical experiments also exist with several simi-lar substances. Taken together, the data that are available to date indicate that these mid-size gadolinium-based probes may be useful for MR mammography.

Another approach to the research on gadolin-ium-based contrast agents is the small-molecu-lar-weight gadolinium chelates that reversibly bind to plasma proteins to a certain extent. These compounds may offer an answer to the above-mentioned dichotomy: the nonbound fraction of the probes, which are small molecules, provides sensitivity. In contrast, the protein-bound frac-tion (large molecules) provides specificity. One probe from this group, Gd-BOPTA (Multi Hance, Bracco, Italy) is still approved for sev-eral applications in gastrointestinal imaging. This probe binds to serum albumin with a rela-tively weak affinity. Preliminary experiments in breast imaging have demonstrated a rapid enhancement of breast carcinomas after bolus injection of Gd-BOPTA, whereas benign lesions show a delayed uptake. However, the albumin-bound fraction of Gd-BOPTA leads to an increased T1 relaxivity of the contrast agent, which improves breast cancer detection and the delineation of vessels in the breast tissue. Thus, Gd-BOPTA may also be suitable for breast imaging, although its definite value needs to be assessed in larger studies (Daldrup-Link and Brasch 2003).

10.3.4 Tumor-Specific Contrast Agents

A further step in contrast media research involves the development of contrast agents that selec-tively target molecular and cellular processes. Researchers expect to gain more from these sub-stances, particularly more precise and specific information on breast lesions. The goal is to achieve a noninvasive tissue differentiation by the

selective imaging of tissue features that are char-acteristic of a specific disease. For example, most cells of breast carcinomas offer antigens or recep-tors at their cell surface that are characteristic of a tumor entity and can therefore be used for imag-ing. In addition, this imaging strategy can also be used to obtain valuable prognostic information, for example, on the hormonal stage of breast car-cinomas. However, most of this research is still preclinical, but preliminary results show great promise for future applications.

A concept that has been extensively studied in the past is the imaging of the transferrin receptor (Hogemann-Savellano et al. 2003). The transfer-rin receptor is a cell-surface internalizing recep-tor that is frequently overexpressed on breast cancer cells relative to surrounding tissues. Several studies have correlated expression of the transferrin receptor to tumor grade and metastatic potential, and it has been suggested that receptor levels may be helpful in grading tumors and determining prognosis. In an experimental set-ting, ligands for the transferrin receptor have recently been conjugated to magnetic iron oxide nanoparticles (MIONs). When this ligand–MION complex binds to the transferring receptor, the receptor selectively shuttles the MIONs into the cell. As a result of the intracellular MION accu-mulation, substantial changes in T2 signal inten-sity can be observed (Fig. 10.4a–c).

An alternative approach, which does not require internalization of the contrast agent, relies on the labeling of extracellular cell-sur-face receptors with a targeted contrast agent. The contrast agent is conjugated to a mono-clonal antibody that binds to the receptor with high affinity.

A receptor that has been found to be suitable for this concept is the her2/neu tyrosine kinase receptor, which is frequently overexpressed in tumor cells. Analogous to the technique men-tioned above, MIONs have been coupled to anti-bodies against the her2/neu receptor. Again, all receptor-positive cell lines, but not the controls, showed substantial changes in T (Kuhl et al. 2006) signal intensity at 1.5 T (Funovics et al. 2004).


10.3.5 Functional Breast Imaging Techniques (Spectroscopy, Diffusion-Weighted Imaging)

The concept of functional breast imaging is to image the functional parameters of breast carci-nomas. Two approaches that have been studied recently are MR spectroscopy (MRS) and diffu-sion-weighted MRI.

MRS is a technique that may provide infor-mation on cellular metabolism. It is based on the observation that neoplastic breast tissue con-tains elevated levels of total choline-containing compounds (tCho), which have methyl protons that resonate at a chemical shift of 3.2 ppm. The precise mechanisms by which neoplastic tissue exhibits elevated levels of tCho are not fully understood. It has been proposed that the increased level of phosphocholine, the primary metabolite responsible for the tCho peak in neo-

plastic tissue, is a result of the increased synthe-sis of membranes by replicating cells. With the use of special MR sequences, it is possible to detect the resonance at 3.2 ppm, which appears to be a characteristic choline peak in the spec-trum. However, performing in vivo MRS of the breast can be technically challenging because spectral artifacts may arise. Despite these obsta-cles, MRS is increasingly being studied as a potential adjunct to breast MRI since it can be included in a regular breast imaging protocol.

Several studies conducted at 1.5 T have shown that in vivo MRS can be used to distin-guish between benign and malignant tissues. These studies, which were conducted under the hypothesis that tCho is only detectable in malig-nancies, used only a qualitative tCho assess-ment. A meta-analysis of five studies showed that malignancies could be identified with 83% sensitivity and 85% specificity.

Fig. 10.4 a–c In vivo MRI of a single mouse with ETR-positive (left arrowhead) and ETR-negative (right arrowhead) flank tumors (courtesy of A. Moore, Charlestown, USA). a T1-weighted coronal SE image: ETR-positive and ETR-negative tumors have similar signal intensities. b T2-weighted gradient-echo image after administration of Tf-MION: A sub-

stantial difference is seen between ETR-negative and ETR-positive tumors. The ETR-positive tumor accu-mulates the superparamagnetic probe, which decreases signal intensity. c Composite image of a T1-weighted spin-echo image obtained for anatomic detail with superimposed R2 changes after Tf-MION administration, as a color map


10In similar studies conducted at 4 T, the

increased sensitivity also allows detection of tCho in benign lesions and normal subjects. Thus, quantification of the tCho peak would be necessary, with the expectation that tCho levels are higher in malignancies than in benign lesions or normal tissues. Two groups have reported quantification of tCho levels using external phantom referencing methods. These studies demonstrated the feasibility of quantitative breast MRS, but they were limited to small patient groups.

Additionally, several groups have reported the use of MRS to follow the effects of chemo-therapy since it is assumed that the choline peak diminishes with tumor regression.

However, all studies that are available today suggest that MRS is a promising technique, but further work is needed to evaluate possibilities for clinical use. Especially with the clinical use of stronger field MR scanners and better coils, the sensitivity of MRS may be improved further.

Another functional imaging technique is dif-fusion-weighted breast MRI (DW-MRI). DW-MRI provides image contrast through measurement of the diffusion properties of water within tissues. Application of diffusion sensitizing gra-dients to the MR pulse sequence senses the dis-placement of water molecular over distances of 1–20 mm. Malignant lesions have a higher cel-lular density and a resulting reduced extracellu-lar space, which restricts water motion compared to benign lesions, thus diffusion properties of water molecules are altered. To date, DW- MRI has been described to be useful mainly in the field of neuroradiology, but there are ongoing efforts to use this technique for the differentiation of breast lesions. Combining images obtained with different amounts of diffusion weighting provides an apparent diffusion coefficient (ADC) map. In several studies (Woodhams et al. 2005), it was found that the mean ADC value of the malignant lesions was statistically lower than that of the benign lesions and normal breast tissues. Similar to MRS, it was shown that the

use of sensitivity encoding parallel imaging (SENSE) on high-field MRI scanners is espe-cially useful for DW- MRI since artifacts are reduced and a higher confidence with respect to ADC changes is achieved. Thus, it is expected that DW- MRI will further improve with these new MRI systems.

10.4 Positron Emission Tomography

Positron emission tomography (PET) scanning using 18F-DG tracers has gained widespread acceptance for the diagnosis, staging, and man-agement of a variety of malignancies, including breast cancer (Kumar and Alavi 2004). Similar to other imaging modalities, research has been conducted on molecular imaging with PET. As with the approaches that have been described above for optical imaging, a multitude of new PET tracers are currently under development, which are aimed at targeting molecular and cel-lular processes.

10.4.1 Imaging of Cellular Proliferation and Apoptosis

While PET imaging using 18F-DG relies mainly on glucose metabolism, there has been a con-tinual search for tracers that more specifically monitor tumor growth and, perhaps more impor-tantly, cancer cell death in order to develop an imaging modality that can follow treatment response accurately.

One approach in PET research is to develop tracers that are capable of assessing tumor cell proliferation. It has been shown that this is pos-sible with radio-labeled thymidine compounds.

Thymidine is incorporated into DNA and therefore thymidine uptake and retention in the tumor serves as a specific marker of cell prolifera-tion. The thymidine analog 18-F-fluorothymidine


(18F-T) has already been successfully used for imaging tumoral proliferation in breast carcino-mas in several studies. A recently published study by a German group led by Smyczek-Gargya et al. compared 18F-DG and 18F-T in breast carcino-mas. They found 18F-T uptake in 13 of 14 breast carcinomas and in seven of eight axillary lymph node metastases. A tumor-to-background ratio of 18F-T was similar to 18F-DG (Smyczek-Gargya et al. 2004).

Apart from imaging cell proliferation, a tech-nique to image cell death (apoptosis) would be useful for many clinical applications, particu-larly to follow the effects of adjunct chemother-apy and radiotherapy. A common problem with mammography and US in follow-up examina-tions during chemotherapy is the fact that the amount of tumor cell death caused by chemo-therapy cannot be efficiently quantified with these imaging modalities. A quantitative meas-urement of tumor cell death immediately fol-lowing chemotherapy is needed to help validate both new agents and to optimize administration of existing therapies. The most widely studied agent for the in vivo study of apoptosis is annexin V, which can be radiolabeled with many nuclides, including 18F (Yagle et al. 2005). Annexin V is a 36-kDa protein that binds to phosphatidylserine lipids in the cell membrane with high affinity. Because one of the earliest measurable events in apoptosis is the eversion of phosphatidylserine from the inner membrane leaflet to the outer cell surface, annexin V has proven useful for detecting the earliest stages of apoptosis in numerous experimental studies. However, this technique has not yet been evalu-ated in breast carcinomas. Thus, its role for breast imaging is not foreseeable at this time.

10.4.2 Receptor Imaging

Analogous to optical imaging, PET can be used to assess surface receptors on cells of breast

carcinomas, including estrogen, progesterone, and her2/neu. Determining the presence of estrogen and her2/neu receptors in malignant breast tumors is an important step in the initial work-up of breast cancer because it is a major determinant in therapeutic strategy and is an indicator of prognosis. One of the most fertile new areas of PET research involves the develop-ment of specialized PET tracers that allow in vivo quantification of these receptors.

To assess the estrogen receptor (Funovics et al. 2004), F-fluoroestradiol (FES)-PET can be used (Linden et al. 2006). This tracer has been shown to correlate with estrogen receptor (ER) expression and to be capable of predicting response to tamoxifen.

Very similar to the estrogen receptor, the 185-kDa transmembrane glycoprotein human epider-mal growth factor receptor 2 (HER-2) is frequently overexpressed in breast cancers. Overexpression correlates with poor patient prognosis, and visu-alization of HER-2 expression might provide valuable diagnostic information influencing patient management. To data, several studies describe synthesized ligands to HER-2 that were radiolabeled with iodine nuclides in experimental studies (Robinson et al. 2005).

10.5 Optical Imaging

The term optical imaging comprises imaging tech-niques that use the light of different wavelengths for medical imaging. Light in the near infrared (NIR) part of the spectrum is typically selected for these techniques because it can penetrate to depths of several centimeters of soft tissue, e.g., the breast. Light thereby offers wavelength-dependent inter-actions with tissue that yield unique contrast mechanisms for imaging; scattering, absorption, and fluorescence of intrinsic and extrinsic tissue elements. Optical imaging research has been in progress for several decades, but the technique has


10consistently been hampered by technical problems. In recent years, considerable advances have been made in the laser technique, photon detection, and reconstruction algorithms, significantly improving optical imaging techniques.

10.5.1 Imaging of Hemoglobin

Intrinsically, the main light absorbers of the breast in the NIR window are hemoglobin (oxy-hemoglobin and deoxyhemoglobin). Imaging of the absorption coefficient at appropriately selected wavelengths can quantify the concen-trations of water and oxyhemoglobin and deoxy-hemoglobin of breast tumors, and obtain measures of hemoglobin concentration. These features are associated with angiogenesis and hypoxia, which are two correlates of breast malignancy. Angiogenesis and hypoxia in breast carcinoma leads to the formation of new vessels, and optical imaging is able to visualize the resulting increased perfusion of the malignant tissue. Over the last few years, numerous systems based on measurements of hemo-globin absorption have been described in the literature, with a multitude of different technical approaches. The spectrum ranges from mono-wavelength systems that acquire images in the parallel plate geometry to multi-wavelength tomographic systems. Two systems that are now on the market are the CTLM device (IDSI, Ft. Lauderdale, FL, USA) and the Soft Scan System (ART, Advanced Research Technologies, Saint Laurent, CA, USA). The CTLM device has undergone clinical evaluation at our institution in the last few years (Floery et al. 2005).

10.5.2 CTLM Device

The CTLM (CT laser mammography) device is a tomographic system that transilluminates the

breast with an NIR laser light, very similar to regular X-ray CT. CTLM uses a laser wave-length of 808 nm, which exactly matches the crossover point of the absorption curves of both oxy- and deoxyhemoglobin. Thus, CTLM visu-alizes both forms of hemoglobin within the tissue and creates a “hemoglobin angiogram” of the breast. Tissues that are well-perfused and have high tissue hemoglobin concentrations show increased absorption of laser light. Less perfused tissues, in contrast, show moderate or no absorption.

With the ability to gain insight into tissue perfusion, CTLM provides additional informa-tion to characterize breast lesions that may be complementary to the structural information from mammography and US. Thus, a more precise discrimination between benign and malignant is possible, adding CTLM as a third modality to other imaging techniques. Consequently, it is expected that the currently high rate of biopsies with a negative result, caused by the limited specificity of mammography and US, may be reduced. Presently, CTLM is recommended as an add-on modality, which means that the CTLM images are read in conjunction with mammog-raphy and US (Fig. 10.5a and b).

Patients benefit from the absence of any radiation risk with this technique. Consequently, CTLM appears especially suitable for the exam-ination of younger patients or patients with numerous repeat examinations where additional radiation exposure of the breast is undesirable (e.g., BRCA gene carriers who are at high risk for breast cancer or patients who are in surveil-lance after a carcinoma). The use of CTLM as a singular modality is not recommended at this time. However, the technique also appears valu-able in screening programs, but further research remains necessary.

The CTLM device has already been clini-cally evaluated by several groups, including our own department. Taken together, the data that are presently available demonstrate that CTLM is sensitive in delineating invasive breast


carcinomas (sensitivity from 47 to 85%). In our group, we found a sensitivity of 73% in 420 patients. Receiver-operating curve (ROC) anal-ysis demonstrated that a more precise discrim-ination between benign and malignant lesions was possible with CTLM. However, we still observed carcinomas that were occult with the present CTLM system: mainly noninvasive and lobular carcinomas and high-grade inva-sive ductal carcinomas. However, a good deal of these false-negative lesions are entities that are known to have little angiogenic activity, maybe too few to be detected with the present CTLM system. Improvements in the system itself and the use of optical contrast agents may lead to improved sensitivity in the future.

10.5.3 Optical Imaging of Extrinsic Contrast Agents

Similar to other clinical imaging modalities, con-trast agents can enhance the potential applications of optical imaging in the future. Optical contrast agents are fluorochromes, which are excited by a specific wavelength and consequently emit light of a characteristically higher wavelength.

Indocyanine green (ICG) is a fluorescing dye that is already FDA-approved. It is an intravascular contrast agent that may extravasate through ves-sels of high permeability, such as cancerous ves-sels, and accumulates in breast carcinomas. Therefore, ICG imaging of the breast mainly probes permeability and vascularization and is especially suitable to enhance hemoglobin absorp-tion imaging. Preliminary results with this tech-nique were presented by Ntziachristos et al., who correlated ICG-enhanced optical imaging with gadolinium-enhanced MRI in the same patients. The group found that the ICG-enhanced images revealed good congruence with the Gd-enhanced MR images (Ntziachristos et al. 2000).

A new advance that holds great promise for breast cancer research is the recent development of “smart” optical probes for optical molecular imaging in the NIR range. Smart optical contrast agents are nonfluorescing in their basic form and are activated by tumor-associated enzymes (such as cathepsins and matrix metalloproteinases) or target-specific tumor receptors. Thus, they are able to identify their molecular targets in vivo. These agents are quenched in the absence of the targeted enzymatic activity, yielding highly spe-cific fluorescence signals. Many studies have

Fig. 10.5 a, b Images obtained from a 44-year-old female patient. a Mammography shows an indis-tinct mass with pleomorphic microcalcifications, classified as BI-RADS IVc. b CTLM in 3D MIP reconstruction: At the corresponding location,

CTLM shows a volume of increased absorption (large arrows) with a round shape. Histologic diagnosis of the lesion revealed invasive ductal carcinoma. Also shown: normal vessels seen from different views (arrowheads)

a b


10been conducted using different agents and differ-ent enzymes as activators. In a recent study, a long circulating synthetic graft copolymer bear-ing NIR fluorochromes positioned on cleavable substrate sequences were synthesized (Tung et al. 2000). In its native state, the reporter probe was essentially nonfluorescent at 700 nm, but became brightly fluorescent when the latter were released by cathepsin D. In a similar setting, Bremer et al. used a cathepsin-sensing fluores-cent probe in murine breast cancer. Correlation with MRI was obtained in all cases. In this set-ting, all tumor nodules could be identified by optical imaging (Bremer et al. 2005).

An alternative approach that has been pro-posed by several groups is to target specific cell-surface receptors by using fluorochromes that are conjugated to ligands for this receptor. One possible molecular target for this technique is the EGF (epidermal growth factor) receptor. The EGF receptor and its ligands are frequently overexpressed in breast carcinomas; this is asso-ciated with increased metastatic potential and poor prognosis. Recently, successful imaging of the EGF receptor in human breast tumor xenografts using NIR-fluorophore-labeled EGF ligands was proposed by Ke et al. (2003).

10.6 Electrical Impedance Scanning

Electrical impedance scanning (EIS) is a new adjunctive, noninvasive, radiation-free imaging modality. EIS is based on the principle of detecting differences in electrical conductivity between malignant and nonmalignant tissue (Fricke and Morse 1926). Malignant tumors show substantially lower electrical impedance values than surrounding normal tissue. With EIS electrical conductivity (the ability to trans-mit current), the reciprocal value of electrical impedance and capacity (the ability to store charge) can be quantified.

In 1926, Fricke and Morse were the first to describe different electrical capacitances of excised malignant and healthy breast tissue (Fricke and Morse 1926). From then on, electrophysiologi-cal differences of malignant and healthy tissue have been repeatedly investigated by different groups. In 1996, Jossinet et al. demonstrated that healthy tissue is characterized by moderate differences in its impedance (Jossinet1996). In contrast, various breast tumors (fibroadenomas as well as malignant tumors) showed extremely decreased impedances and consequently higher conductivities. In vitro studies demonstrated 20- to 40-fold higher values for conductivity and capacity in malignant tissue compared to normal tissue (Surowiec et al. 1988). This is attributable to changes in cellular water content and the amount of extracellular fluid, destroyed cellular membranes, and tight junctions with consequently reduced membrane potentials. Furthermore, malignant cells show a different alignment and orientation as well as a higher packing density than normal cells (Jossinet 1998). Most benign lesions showed electrical properties of normal tissue, thus leading to the possibility of differentiating benign from malig-nant lesions.

This knowledge stimulated the further development of this noninvasive technology resulting in two diagnostic tools: electrical impedance tomography (EIT) and electrical impedance mapping (EIM = EIS). With EIT, a large number of impedance measurements are made from electrodes placed on the body sur-face. The data gathered are processed and a computer reconstruction calculates 2D or 3D images of the distribution of the conductivity within the body (Zou and Guo 2003). The first EIM-based machine was built in the late 1980s and reported in (Piperno et al.1990). Within a few years, improvements of the technology established the acceptance of EIS. In 1999, TransScan TS2000 (Mirabel Medical, Austin, TX, USA) was approved by the FDA as an adjunctive modality to mammography for the


use of differentiation of breast lesions (Figs. 10.6a–c and 10.7a, b).

10.6.1 Targeted EIS with TransScan TS2000

Targeted EIS is used for lesions as an adjunct to mammography (MG), ultrasound (US), and MRI to differentiate benign and malignant lesions.

The Measurement Procedure

The EIS examination is performed with the patient recumbent, similar to the position gener-ally used during US examination, with the ipsilateral arm raised above her head, to flatten the breast as much as possible, allowing perfect contact of the flat surface of the scan probe with the skin surface just above the lesion. Special attention has to be paid to superficial skin

a b

c

Fig. 10.6 A 48-year-old woman with fibrocystic changes of the right breast. a Mammography shows an ill-defined mass, BI-RADS category IV (arrows). b US demonstrates a hypoechoic, ill-

defined 10-mm lesion; BI-RADS IV. c EIS was negative; LOS III (black arrow delineates indicator bar displaying the LOS III result on the EIS screen)


10

lesions (scratches, irritations, nevi, scars) because these might produce high-conductivity artifacts with false-positive results. Optimal electrical coupling is achieved by the use of a US gel. A low-level imperceptible electrical cur-rent (£5 mA) is then transmitted via a handheld metal cylinder (source electrode) to the trans-ducer (target electrode) on the skin surface of the breast. The first recording made is of the nipple sector of the breast containing the suspi-cious lesion, as a reference scan for the software. After recording the nipple sector, several record-ings of the area containing the suspicious lesion are obtained.

TransScan TS2000 records a 2D gray-scale image (map) encoding electrical capacitance

and conductivity differences measured over seven frequencies (100–5,000 Hz) producing a real-time image (displayed at 200 Hz) of electri-cal impedance in the breast. In a TransScan TS2000 image, the nipple is bright white, reflecting the high conductance of ductal tissue; the surrounding normal breast tissue is displayed in varying shades of gray. Other regions of high capacitance and conductivity (often associated with the presence of a carcinoma) appear as white spots on the display unit. However, the final assessment of the suspicious lesion is achieved using a postprocessing algorithm (soft-ware version 2.67), taking into account a spec-tral analysis of the ipsilateral nipple recording, the critical frequency at 5,000 Hz, the ratio of

a

b

Fig. 10.7 A 55-year-old woman with mucinous car-cinoma of the left breast. a Mammography shows a partially ill-defined mass; BI-RADS category IV

(arrow). US was normal. b EIS was positive; LOS IV (black arrow delineates indicator bar display-ing the LOS IV result on the EIS screen)


capacitance to conductivity at 5,000 Hz, the presence of a high-conductivity focal spot, and the woman’s age. This algorithm calculates the level of suspicion (LOS) for each recorded lesion on a five-grade scale in analogy to the BI-RADS system (I = no finding, II = benign, III = probably benign, IV = suggestive of malig-nancy, V = highly suggestive of malignancy). The LOS of every single lesion is displayed on the monitor in addition to the gray-scale image at 200 Hz. The examination time is approxi-mately 5 min. To precisely find and scan the area of interest, a US correlation of nonpalpable lesions is mandatory.

Scientific Evaluation

In the last few years, several studies have been published on EIS for differentiation of suspi-cious breast lesions, although with different study designs and different but promising results (Malich et al. 2001; Fuchsjäger et al. 2002). In these single-center studies, sensi-tivities ranged from 69 to 88% and specifici-ties from 66 to 82%. A European multicenter trial on 484 women with 545 lesions showed a sensitivity of 82.5% and a specificity of 58.9% (Fuchsjäger et al. 2005). Results were better for small lesions, microcalcifications, and invasive cancers.

In contrast to other imaging modalities, size does not seem to be a limitation, since cancers with a diameter of 3 mm have now been described. On the other hand, the results have been worse for larger lesions (³10 mm) in vari-ous publications (Malich et al. 2001; Fuchsjäger et al. 2002). Potential reasons are discussed in the literature (Fuchsjäger et al. 2003).

EIS recently demonstrated a high adjunctive diagnostic potential in BI-RADS category IV lesions with an NPV of 96.1% (Fuchsjäger et al. 2003). If this trend is confirmed in future evalu-ations, a negative EIS result in these lesions could be a firm indication to manage them as BI-RADS category III and refer patients for

6-month short-interval follow-up, rather than performing a biopsy. Patient morbidity and eco-nomic costs, as well as the hazards of a false-positive mammography interpretation, could be minimized.

10.6.2 Screening EIS with T-Scan 2000ED

Based on electrical impedance scanning (EIS), the T-Scan 2000ED is used in conjunction with clinical breast examination (CBE) in an age-group (£45 years) for which other screening methods are less effective or limited.

The Measurement Procedure

In contrast to the targeted procedure, measure-ments are made over all sectors of the breast, including the nipple, following a pre-set compu-ter-guided sequence that is displayed on the monitor in real time together with measured impedance maps or images at 1,100 Hz. The recording sequence starts at the nipple sector and follows a series of measurements around the breast, starting in the upper, outer sector and proceeding from lateral to medial areas (sectors). The computerized system directs the examiner sequentially to the next sector to be measured. Measurements are taken in a mirrored-image-type scanning pattern (clockwise on the left and counter-clockwise on the right breast); a total of nine locations (sectors) are measured (nipple, plus eight surrounding sec-tors) on each breast. No examiner interpretation is needed. Capacitance and conductivity meas-ured over a greater frequency range from 100 Hz to 1 GHz. A postprocessing algorithm automatically characterizes breast tissue as screen-positive (suspicious; red indicator bar) or screen negative (within the normal range; green indicator bar). The complete procedure takes an average of 8 min. Women with a screen-positive EIS should be reassured that this by no means


10indicates that they have cancer, rather that they have a reading outside the normal range of tissue impedance. In women with screen-positive EIS, a regular imaging evaluation (MG, US) must fol-low. By the time this book appears in print, First devices were recently approved by the FDA.

Scientific Evaluation

A first multicenter trial has shown 95% specifi-city and 38% sensitivity for a screening popula-tion of 1,550 women below the age of 45 (Stojadinovic et al. 2005). The authors concluded that EIS may have an important role as a screen-ing tool for identifying young women who should be followed up more closely with advanced imaging technologies for early detection of breast cancer. However, the value of screening EIS has yet to be determined with upcoming scientific studies. As in MRI, the hormonal status may influence the EIS results significantly; therefore EIS should be per-formed in the f irst half of the menstrual cycle (Perlet et al. 2000).

10.7 Conclusion

Overall, EIS is currently an established adjunctive imaging modality in special breast lesions (BI-RADS IV, lesions smaller than 10 mm). If fur-ther studies demonstrate its value as a screening modality, EIS might be used as a first-line imaging method in young women in the near future.

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11.1 Introduction

Only in a few European countries (Switzerland, France, Poland, Belgium, and some local projects in Germany) are minimally invasive breast biopsies (MIBB) reimbursed by health insurance. Public health authorities ask for detailed estimates and calculation of costs as well as laborious, expensive evaluation procedures as the basis for decision making before obliging insurance to provide reim-bursement. In Europe, which services insurance companies are required to pay is generally a mat-ter of public policy. However, the following delib-erations apply equally to direct negotiations with private or governmental insurers elsewhere.

Minimally invasive breast biopsies are at the endpoint of a diagnostic algorithm before histo-logical examination. The starting point is mam-mography (and especially in younger women, ultrasound), which is done

– As a screening procedure– For individual precaution– Because of clinical findings or in women at

risk (symptomatic mammography, risk mammography)

The following sections analyze the generally accepted factors and data to be considered when predicting the numbers and cost of minimally invasive breast biopsy in a given region or coun-try. These include the frequency and circum-stances of mammography, the recall rate for abnormal findings on mammography, and the type and distribution of the different follow-up investigations and biopsy procedures performed to clarify these abnormal findings.

The distribution of the different biopsy pro-cedures is altered by new procedures being developed and by the pattern of reimbursement on the part of the health insurance entities.

11.2 Frequency of Mammography

The frequency of mammography in a region or a country depends substantially on:

– Whether a breast screening program exists– Starting at what age and which time intervall

screening is performed– The participation rate in the screening program– The prevalence and incidence of breast cancer

There are national screening programs in the UK, France, The Netherlands, and Sweden, and regional screening programs exist in Belgium, Germany, Italy, Ireland, Portugal, Spain, and Switzerland.

Cost–Benefit Analyses

Renzo Brun del Re, Regula E. Bürki and Swiss Study group MIBB of the Swiss Society of Senology

11

Renzo Brun del Re () Ärztlicher Leiter Spezialabteilung für Brusterkran kungen, Lindenhofspital Bern, Aarhergergasse 30, 3011 Bern, Switzerlande-mail: [email protected]


184 R. Brun del Re and R.E. Bürki

11The participation rate in screening programs

varies greatly between 25 and 85% of eligible women per year. First-round attendance and reat-tendance tend to increase over time (Tornberg et al. 2005; Chiarelli et al. 2006; Bulliard et al. 2005; Jean et al. 2005).

11.3 Recall Rate

After the number of women who have a mam-mogram, the second main cost determinant is the quantity of follow-up investigations for sus-pect or unclear findings at mammography.

The recall rate is the rate at which mammo-graphically screened women are recalled for additional assessment.

The portion of women who are recalled varies greatly – between 1 and 15% – depending on country and program (Yankaskas et al. 2001; Farria and Monsees 2004; Vejborg et al. 2002; Gur et al. 2005; Otten et al. 2005). The recall rate is twice as high in the United States (12.5–14.4%) than in the United Kingdom (7.6%), with similar cancer detection rates (Smith-Bindman et al. 2003).

The definition of recall rate varies in the lit-erature (Yankaskas et al. 2001) and the addi-tional investigations are differentiated. But basically one can distinguish between other imaging methods (repeated mammographies with targeted and enhanced pictures, sonogra-phy, or MRI) and fine-needle aspiration biopsy, core biopsy, and vacuum-assisted biopsy.

The recall rate after mammographies within and outside of screening programs must be differentiated.

11.3.1 Recall Rate in Screening Programs

Generally, the portion of unclear and suspect findings is smaller in mammography screening

programs than outside of screening programs, for different reasons:

– Since screening addresses all women (thus, without previous risk evaluation), fewer sus-pect findings result than with risk mammographies.

– Screening programs are subject to quality requirements: technical evaluation/monitoring of the devices, double-reading, etc. contrib-ute a great deal to better, i.e., less uncertain results.

– Accumulated experience with longer programs leads to substantially safer results.

In countries that introduced mammography screening at the beginning of the 1990s, the recall rate is very low. In Finland for example, it is only 2.9% (Dean et al. 1999). In The Netherlands, only 1.5% of the women who have a mammogram for the first time, and less than 0.89% with further mammography, are recalled for further evaluation (Otten et al. 2005; Holland et al. 2007). Most countries do not reach such “dream rates.” In France, the recall rate in 1997 was 7.8% in the first and 4.5% in the second round (Seradour et al. 1997). In the Canadian screening programs, the recall rates were 9.5% for initial screening and 4.6% for subsequent screening (Paquette et al. 2000). In the German mammography study, the number of the addi-tional investigations was about 4.1%, and the number of recommendations for biopsies was 1%. As mentioned before, the studies do not indicate clearly whether the reported recall rates are for further imaging or for further biopsies or both.

11.3.2 Recall Rate Outside of Screening Programs

There is no statistical information on this sub-ject. With symptomatic mammographies, one must assume that suspicious findings, which have to be clarified, will be discovered more

11 Cost–Benefit Analyses 185

frequently. A yardstick could be the breast can-cer risk. In women with a familial risk, the per-sonal risk is four times higher than in risk-free women. But one cannot reliably conclude from this that they need four times more follow-up investigations. On the one hand, they will have more frequently scheduled examinations than the group without specific risk; on the other hand, the repetition effect will reduce the neces-sity for further investigations. Moreover, a sub-stantial portion of risk mammographies take place in younger women (under 50 years), who have a lower incidence of breast cancer com-pared to older women, so that suspicious find-ings are expected to be rarer.

Considering all these factors, a recall rate for mammographies outside screening programs of about 6% can be estimated (Baur et al. 2001).

11.4 Distribution of Further Investigations

With suspicious and unclear findings, further noninvasive imaging procedures may be per-formed, such as repeat mammography, spot-mam-mography, sonography, and MRI. Development in this area is proceeding fast, so that more effec-tive application of these modalities can be expected in the future. The other method for further clari-fication is surgical biopsy.

In an Italian study with invited and self-referred attendees for screening, the biopsy rate was 12.6% vs. 17%. This means that out of 100,000 women screened, 1,200 vs. 1,700 had to undergo a biopsy (Bucchi et al. 2003). It is unclear what the biopsy rate is in a symptomatic population. The actual number of biopsies is underestimated, however, partly because often several biopsies are necessary (e.g., open biopsy must follow if the preceding conventional core biopsy did not provide a clear diagnosis or the results were concordant with mammographic findings).

11.4.1 Open (Surgical) Biopsy

Since the new minimally invasive procedures should substitute open biopsy in as many cases as possible, their number is particularly important compared to the number of conventional, open, biopsies. However, very few data are available in the literature concerning the relative frequency of the different biopsy procedures. There are comments that (too) many open biopsies are still being performed. A Dutch statistic (1999) reports that with nonpalpable findings an open biopsy is performed in well over half of the cases. Since mammography in screening pro-grams predominantly discovers nonpalpable lesions, these results can supply an approximate value. Various other investigations showed that in approximately 60% of cases an open biopsy is performed. Liberman Sama. (2000) estimate that 76-85% of open biopsies for diagnostic rea-sons could be avoided and replaced by mini-mally invasive breast biopsies (MIBB).

11.4.2 Substitution of Open Biopsies

Whether the percentage of open biopsies will be reduced in favor of MIBBs depends on whether MIBBs are reimbursed. In view of the obvious advantages of MIBB, market penetration might take place rapidly after a short delay, once MIBBs are reimbursed in a given country. In the Swiss Evaluation Study 2002–2007, it was shown that open biopsies had decreased by 42% since MIBBs were being reimbursed (Figs. 11.1 and 11.2) according to the SGS study group (Brun del Re and Study Group of the Swiss Society for Senology 2007).

The tendency to replace open surgery by MIBBs could also be shown in the United Kingdom where the rate of open biopsies dropped from 6.5% in 1999 to 3.5% in 2004. In the meantime, procedures such as fine-needle


11

aspiration cytology (FNAC) and core biopsies increased from 27 to 35.5%.

11.4.3 Substitution of Other Diagnostic Procedures

FNAC is well established for palpable and mam-mographically and/or sonographically clearly recognizable lesions. However, with a positive cytological result (cancer cells), FNAC cannot differentiate between an invasive cancer and an in situ carcinoma. With discordant mammo-graphic or sonographic findings and a negative cytological result, further clarification is man-datory. In the German Guidelines (Stufe-3-Leitlinien 2003), FNACs are only recommended for lesions with a prospective “specific” cytol-ogy (fibroadenomas, fat necrosis, and lymph nodes). There is little reason to assume that care-ful and fast fine-needle aspiration, where it is indicated, will be replaced by the new proce-

dures. However, as long as MIBBs are not reim-bursed, fine-needle aspiration will continue to be performed even in unsuitable cases.

Conventional core biopsies are also relatively economical procedures. Nevertheless, here too further clarifications are mandatory for negative histological results discordant with the mammo-graphic and/or sonographic findings. There will probably be a trend to apply the safer procedures from the beginning, once the costs are reimbursed.

Generally, the different procedures are not simply interchangeable (perhaps with the excep-tion of the conventional core biopsy and FNAC) but are assigned to certain indications. In addi-tion, it can be assumed that there will be uncer-tainties as to the best diagnostic procedure to be employed, which will lead to the application of different procedures based on trial and error. This is the area where the more reliable new MIBBs could substitute other procedures. On the one hand, some of the “cheaper” old procedures will

Decrease of open biopsies2002-2006 Switzerland (AFS Statistic)

100 8670 66 58

%

020406080

100

2002 2003 2004 2005 2006

Fig. 11.1 Decrease in open biopsies

Fig. 11.2 Increase in minimally invasive biopsies in Switzerland (total biopsies 8,272) (Extrapolation1)

Increase of minimal-invasiv biopsies2002-2006 (Swiss Evaluation Study)

100 100

138154

183

%

0

50

100

150

200

2002* 2003 2004 2005 2006


be replaced with MIBBs, although they would have provided at least partially valid results. On the other hand, through the early application of the new MIBBs, many open biopsies can be avoided and thus costs saved.

The expectation is that after acceptance of reimbursement, a certain not completely cost-neutral shift to the new MIBBs will take place.

11.5 Trends and Scenarios

The number of both mammographies and follow-up investigations will increase. Among other fac-tors, this is a result of changing demographics with increasing numbers of women reaching the at-risk age.

The number of open breast biopsies and the average annual increase or decrease of these biopsies can serve as the basis for the projected

growth of MIBB. The increase and decrease that are caused by demographic changes will have to be subtracted from that number.

11.6 Comparison of Costs

Several authors compared the costs for MIBBs and surgical biopsies (Burkhardt and Sunshine 1999; Buijs-van der Woude et al. 2001; Liberman and Sama 2000; Golub et al. 2004; Brun del Re and Study Group of the Swiss Society for Senology 2007) (Table 11.1).

Burkhardt et al. compared open vs. core breast biopsy by means of three cost calculations (input resources, actual payment, billing charges.) Based on input resources, open biopsies are three times as expensive as stereotactic core biopsies (U.S. $698 vs. $243) and also based on actual payment (U.S. $2398 vs. $799). Theoretically, by

Table 11.1 List of relevant studies

Study Study design Methods Cost effectiveness

Burkhardt and Sunshine (1999)

Open, comparative Open biopsy, core vacuum-assisted biopsy

Open biopsy 2.5–3 times more expensive than MIBB. Theoretically it would be possible to save $1.6 milliards by replacing open biopsy by MIBB in the US

Liberman et al. (2000)

Retrospective, comparative

Open biopsy, vacuum-assisted biopsy

Using MIBB 73% of open biopsies can be avoided. MIBB showed 20% cost reduction compared to open biopsies

Buijs-van der Woude et al. (2001)

Open, hypothetical, comparative

Open biopsy, MIBB

Open biopsy twice as expensive as MIBB if MIBB is centralized

Golub et al. (2004)

Retrospective, comparative

Open biopsy, core biopsy

The costs of treatment of a women with breast cancer is 45% more expensive if the diagnosis is made by open biopsy in stead of MIBB

Brun del Re et al. (2007)

Prospective, open, hypothetical

Open biopsy, MIBB

The costs of 8,270 interventions by MIBB including secondary surgery are 37.7% compared to the costs of hypothetical 8,270 open biopsies with secondary surgery (in Switzerland most open biopsies are done under general anesthesia and during hospitalization)


11replacing open biopsies with minimally invasive procedures, $1.6 billion could be saved per year in the United States.

Buijs et al. compared the hypothetical costs of stereotactic vacuum-assisted biopsy in decentral-ized use of 114 hospitals and centralized use of ten hospitals with the cost of open biopsy in The Netherlands. Open biopsies cost an average of €1,184. With decentralized use of MIBB, the cost per procedure would be €1,186 and with central-ized use €572. This leads to the conclusion that centralization would be more cost-effective.

Golub et al. examined the economic conse-quences in relation to the degree of radiologic sus-picion and the degree of abnormality. The cost for the operative treatment of a carcinoma was clearly higher when the diagnosis had been made with an open biopsy. With a mastectomy, the costs amounted to U.S. $2,775 vs. $1,849, if the diagno-sis had been made by core biopsy. With a lumpec-tomy, the cost was U.S. $2,112 vs. $1,365. The main reason was that 84% of open biopsies had to be reoperated. When the diagnosis had been con-firmed beforehand with a core biopsy, reoperation was necessary in only 33% of cases.

To compare open biopsy and MIBBs, a spe-cial algorithm was developed (Brun del Re 2001) (Fig. 11.3:1-6).

If a nonpalpable lesion is found by mam-mography and/or ultrasound that must be inves-tigated by histology, tissue has to be removed.

This can be done by open surgery or mini-mally invasive biopsy (1).

If histology reveals a benign lesion, and the lesion is completely removed, the investigation is completed. In all these cases (100%) a second intervention in terms of open surgery is unnecessary (2).

In cases where a symptomatic or growing fibroadenoma or a new fibroadenoma in women over 35 years or with atypia in cytology was completely removed by MIBB, the procedure was therapeutic and diagnostic, in contrast to premalignant and malignant lesions, where the minimally invasive procedures are only diagnos-tic and never therapeutic.

If after an open biopsy the lesion is revealed to be an atypical hyperplasia or a carcinoma in situ and if the margins are free, a second inter-vention is unnecessary (3), but this is only the case in 30–40%. According to the literature, 50–70% of in situ carcinomas and atypical duc-tal hyperplasia (ADH) are not excised with free margins by open surgery (Velanovich et al. 1999). This requires a second intervention, even after open surgery (4). Better results would only be possible if in all open surgery cases the exci-sion would be extended, since the surgeon does not know whether the lesion being operated is benign or malignant. But this also would mean that in 70% of cases, that is all cases with benign lesions, too much tissue would be removed. On the other hand, it has been shown that in cases where the surgeon knew, for example, after an MIBB, that a carcinoma in situ or invasive can-cer was being operated, the excision was more often with free margins (6).

After minimally invasive biopsies, a second intervention by means of open surgery is manda-tory in all cases of malignancy, but open surgery as the first intervention can be avoided (5).

If an invasive cancer is diagnosed, a second intervention in both procedures (at least a senti-nel lymphadenectomy) is indicated (6).

Frozen Sections

Most pathologists advise against frozen section in nonpalpable lesions for the following reasons:

– Loss of tissue by the frozen technique.– The final diagnosis is only possible after

paraffin section.

If the diagnosis of invasive cancer can be con-firmed by MIBB, frozen section can be avoided, the surgical time can be shortened, and the patient can decide before surgery which type of intervention she wants, including the option of sentinel lymph node biopsy (SLNB).


11.6.1 Costs and Savings

The following data are needed for cost calculations:– Direct costs, including personnel costs,

infrastructure costs, material costs, as well as capital costs

– Indirect costs, i.e., costs due to disability during the intervention, hospitalization, and recovery.

Simply from the point of view of the number of staff involved in open surgery and MIBB, the difference is striking (Fig. 11.4).

As an example, a detailed cost calculation (in euros) of all MIBBs performed in Switzerland during the period from 1 July 2002 to 31 December 2006 is presented (Table 11.2).

If all 8,270 interventions would have been done by open surgery, the costs including the necessary secondary interventions due to lack of free margins would have been more than €51.8 million. The costs for the 8,270 MIBBs, includ-ing the necessary secondary interventions, were €19.5 million. The savings during the 42-month evaluation period was €32.2, i.e., €9.2 million per year (Fig. 11.5).

Fig. 11.3 Algorithm of open biopsies and MIBBs

non-palpable mammographic or sonographic lesion

Minimally-invasive BiopsyOpen Biopsy

atypical hyperplasiaca-in-situ not with free

margins(50 -70% of cases)

benignatypical hyperplasiaca-in-situ

First Intervention

Re-excision Tumorectomy, Wedge Resection

Mastectomy Axillary Lymphadenectomy

benign

Second Interventioninvasive cancer

invasive cancer

1

2 2

4 5

6 6

3

1

atypicalhyperplasia

or ca-in-situwith freemargins


11

11.7 Decision Makers Have Changed

In the past, doctors were used to conducting sci-entific discussions on a medical level.

In today’s procedures, involving sophisti-cated devices and instruments, it is no longer the doctors who decide which product is to be produced. Companies make that decision. Mergers in the context of a global economy or marketing decisions can mean that products suddenly disappear from the market. Even if doctors are absolutely confident that a given product is the best, they have no influence over industry management decisions, nor do they have the financial means to maintain produc-

tion. The investments made in acquiring certain instruments for one’s practice or hospital are lost. ABBI disappeared from the market in 2003, SiteSelect from 2004 to 2006, and the Fischer Biopsy Table in 2005.

Yet doctors as well as industry have to learn that it is politics that in the end decides which medical procedures will be reimbursed and which not. Minimally invasive biopsies that are only reimbursed for in-patient procedures and not in an ambulatory setting as in some European countries (i.e., Belgium and Austria) flies in the face of logic.

Many people talk about evidence-based medicine, but nobody is talking about evidence-based politics.

Fig. 11.4 Staff needed for open surgery and minimally invasive biopsy

© R. Brun del Re

Nurse

Anesthesia Nurse

Anesthesiologist

Orderly

2-3 Persons

Surgeon / AssistentSurgical Nurse

Open surgery

RadiologistTechnician

Breast RadiologistTechnician

9 Persons

Minimally Invasive Biopsy

Surgeon(Surgical Nurse)


Table 11.2 Cost calculation

Direct costs incl. patho (€)

Indirect costs (€)

No. cases

Total costs of each procedure (€)

Calculation of savings (hypothetical, all biopsies with free margins) (€)

Calculation of savings (realistic) (€)

Primary open biopsies

Costs if all interventions would have been done by open biopsy

5,273 318 8,270 46,239,847 46,239,847 46,239,847

Secondary necessary open surgery after primary open biopsy because of not free margins in cases with atypical hyperplasia and carcinoma in situ (in 60% of the cases)

5,273 318 1,002 5,602,458 0 5,602,458

Cost of primary and secondary open procedures

46,239,847 51,842,305

Primary MIBBABBI 1,320 106 3 4,277SiteSelect 1,320 106 121 172,499MammotomeStereotactic on biopsy table 1,213 106 4,600 6,069,783Stereotactic, upright system 1,213 106 304 401,134Handheld 986 106 1,464 1,598,806VacoraStereotactic on biopsy table 1,123 106 960 1,179,523Stereotactic, upright system 880 106 129 127,192Ultrasound-guided 888 106 221 219,728Sterotactic core biopsy on biopsy table

868 106 468 456,089

Cost of all MIBBs 8,270 10,229,032 10,229,032 10,229,032

Secondary necessary open surgery after MIBB because of danger of underestimation in cases with atypical hyperplasia

5,273 318 506 2,829,041 2,829,041 2,829,041

Secondary necessary open surgery after MIMB because of not clear margins in cases with carcinoma in situ

5,273 318 1,164 6,507,912 6,507,912 6,507,912

Cost of secondary open surgery after MIBB

1,670 9,336,953 9,336,953 9,336,953

Savings per MIBB 26,673,861 32,276,319Savings per MIBB per year 9,221,806


11

11.8 Conclusions

The advantages of minimally invasive biopsy methods are clear:– Reliability:

• Preciselocalization(±1mm).• Representativetissueissecurelyremoved.

– These methods are tissue-friendly: up to30-80%lesstissueisneeded.

– The cosmetic result of the procedure isexcellentwithoutmakinganyconcessionstosafety.

– Hospitalizationcanbeavoided.– Thepatientdoesnotneedgeneralanesthesia.– Thecomplicationrateisextremelylow.– Patientsareabsentfromworkfor1or2days

only.

As always, there are winners and losers. The most important player on the winning side is the patient, who benefits from a less invasive proce-dure that gives high-quality results, followed by the health insurance system, which saves money, and industry, which will be selling single-use devices.

On the losing side are the doctors and the hospitals by earning much less with an MIBB compared to an open surgical intervention (Table 11.3).

In this day and age the question should not be: “Why is a minimally invasive biopsy per-formed?” Rather the question should be: “Why is a minimally invasive biopsy not performed instead of an open biopsy?”

References

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Table 11.3 Winners and losers

Winners Losers

Patients + + + Doctors Less income

Insurance Less expenses

Hospitals Less income

Industry More revenues

Fig. 11.5 Comparison of costs of open biopsies vs. MIBBs

Comparison of costs: open biopsy /minimal invasiv biopsy8270 interventions (2002-2006)

46.239847

10.229032

5.602458

9.336953

32.276319

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intervention

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11

1 Study Group “Evaluation of Minimal-Invasive Breast Biopsies” of the Swiss Society for Senology (ordered by postal code)1000 Imagerie du Flon, D. Lepori1004 Clinique de la Source, Avenue Vinet 30, Lausanne, L. Chapuis, B. Burri, Anderegg1011 CHUV - Centre Hospitalier Universitaire Vaudois, RAD Radiologie Diagnostique, Rue du Bugnon 46, 1011 Lausanne Schnyder, J-Y. Meuwly1201 Imagerie médicale, 18 place Cornavin, 1201 Genève, J. Battikha1204 Clinique des Grangettes, Radiologie, Chemin des Grangettes 7,1224 Chênes-Bougeries, K. Kinkel1204 Institut ImageRive, 1 rue de Rive, Genève GE, J.-Ch. Piguet, G.de Geer, B.Ody, Ph. Braudé, Couson1205 Centre D’Imagerie Médicale, rue Jean Violette 5, Genève, V. Cerny, Sarbach, Kahn1206 Clinique Générale Beaulieu, Radiologie, Chemin du Beau-Soleil 20, GenèveP. Rouge, M. Kiener, M Quinodoz1211 Hôpital universitaire de Genève, G. Vlastos Genève1272 Clinique Genolier, J.-P. Verdon1700 Hôpital Cantonal, Clinique de Gynécologie et Obstétrique, Fribourg; D. Stucki, J. Buss1950 Institut de Radiologie de Sion, Rue du Scex 2, Sion, D. Fournier3011 R. Brun del Re, Aarbergergasse 30, Bern3012 Klinik Engeried, Radiologie, Riedweg 15, Bern, P. Cerny, M. Sonnenschein, P. Ruijs, O. Zeller3012 Lindenhofspital Senologie Bremgartenstrasse 117 Bern, S. Gasser Sojcic, M. Dumont dos Santos, J.-L- Ducommun, M. Hauser, R. Brun del Re, K. Thomi3012 Praxis Medidonna, Sonnenhofklinik-Engeriedspital, Bern, G. Berclaz3012 Frauenklinik, Inselspital, Effingerstrasse 102, Bern, Ch. Meyer, K. Leuch4020 Bethesda-Spital, Gellertstrasse 144, Basel W. Hedtler, F. Haberthür, H. Ladewig, D. Müller4031 Kantonsspital Basel, Chirurgische Poliklinik, Gynäkologische Klinik, Basel, D. Oertli, W.R. Marti, C. Viehl, E. Wight, R. Zanetti, S. Schmid, D. Wruk, R. Blum, A Gairing4101 Kantonsspital Bruderholz, Frauenklinik, Bruderholz, S. Heinzl, U. Uehlinger, D. Hänggi, E. Godi4102 Praxisklinik, Hauptsstrasse 11, Binningen D. Musfeld4632 Praxis P. Scott Baslerstr. 2, Trimbach5000 Kantonsspital Aarau, Senologie, Buchserstrasse 5, Aarau, H. Haueisen, D. Sarlos

5405 Kantonsspital Baden, Radiologisches Institut, Dättwil, Kubik-Huch, Dr M. Kaufmann, R. Löw, E. Wegmann, M. Unterweger6000 Kantonsspital Luzern, Zentrum für Mammadia-gnostik, Frauenklinik – Röntgeninstitut,Luzern, B. Allgayer, M. Bleichenbacher, Schönhofen, F. Kremer, C. Kurtz6006 Klinik St. Anna, Senologie, St.-Anna-Strasse 32, Luzern Th. Vollmar, J. Schneitter6210 Kantonales Spital Sursee-Wolhusen, Dr. E. Infanger, E. Vlajkovic6330 Zentrum für Radiologie, Rigistrasse 1, Cham, M. Livers, J. Wurm6500 Centro senologico della svizzera italiana ORBV, Bellinzona L. Bronz, E Cauzza6924 Sorengo Senologiezentrum der Clinica Sant’Anna, G. Kampmann, Foderà7000 Senologiezentrum, Frauenklinik Fontana, Kantonsspital Graubünden, Lürlibadstrasse 118, Chur, R. A. Steiner7502 Spital Oberengadin, Samedan, Ch. Winkler8008 Brustzentrum Zürich, Ch. Rageth, E. Saurenmann, E. Sarasin Ricklin, Otto, B. Scholl, C. Brachler8044 BrustCentrum Zürich-Bethanien, O. Köchli, Th. Vollrath, A. Landolt8091 Universitätsspital, Frauenklinik, Rämistrasse 100, Zürich, D. Fink, M. Fehr, C. Hutzli, J. Pok, St. von Orelli8180 Spital Bülach, Gynäkologie/Radiologie, Spital-strasse 24, Bülach, M. Kaufmann, P. Beer, R. Kunz8208 Kantonssspital Schaffhausen, Schaffhausen, P.M. Fehr, M. Eberhard8401 Kantonsspital Winterthur, Frauenklinik, Winter-thur, Th. Hess, M. Berghorn8500 Kantonsspital Frauenfeld, Radiologisches Institut, Frauenfeld, S. Duewell, M Bürge8610 Spital Uster, Uster, Ch. Honegger, K. Dreiskämper8620 GZO Spital Wetzikon, Spitalstrasse 60, Wetzikon, J. Schneider, J. Ostapiuk8805 Brust-Team Zürich, R. Stoffel, P. Villars, R. Baumgartner8853 Spital Lachen, Frauenklinik/Radiologie Lachen, D. Burger, H. Schönhofen9006 Zentrum für Tumordiagnostik und Prävention, Rorschacherstrasse 150, St. Gallen, H.J. Senn, V. Dupont Lambert, B. Thürlimann (Kaspi SG),M. Bamert (Kaspi SG)9472 Kantonales Spital Grabs, Spitalstrasse, Grabs, F. Limacher, J. Heyder

12.1 Evidence for the Clinical Relevance of Minimally Invasive Breast Biopsy

With image-guided percutaneous needle biopsy, different procedures are available today to remove tissue samples without surgery. By guid-ing tissue removal stereotactically with X-ray, ultrasound, or magnetic resonance imaging (MRI), even nonpalpable lesions can be accu-rately biopsied. None of these methods requires hospitalization and all of them can be carried out with the patient under local anesthesia. Which method is used in an individual case depends on the type of lesion detected.

There are acknowledged guidelines regard-ing indications and technique for the different procedures as well various treatises on the effi-cacy and effectiveness of minimally invasive breast biopsies.

12.1.1 Older Systematic Reviews

There are numerous review articles on mini-mally invasive breast biopsy procedures (Reynolds 2000; Fehr et al. 2002). They generally

rely on older studies than more recent analysis (Table 12.1). As biopsy procedures are con-stantly being refined, we considered only studies from the last 10 years.

12.2 Literature Search Methods

12.2.1 Evidence on Performance

The primary literature search was done with PaperChase (PaperChase, One Garrison Drive, Bedford, MA 01730, USA) in MEDLINE and OLDMEDLINE (National Library of Medicine, USA) (see Fig. 12.1). We considered the time between 1997 and 17 March 2007 (last update). Additionally, we searched the relevant databanks of DIMDI (Deutsches Institut für Medizinische Dokumentation und Information; German Institute for Medical Documentation and Information) (see Table 12.2). The search and selection criteria were based on those of Hoorntje et al. (2003).

There were no randomized comparative stud-ies identified. Since the indications for biopsy vary, we can assume that the patients examined with different biopsy methods also vary.

Studies from 1997 to 2007 were included in the analysis if they met the following criteria:

Systematic Review and Meta-analysis of Recent Data

Renzo Brun del Re , Regula E. Bürki and Study Group MIBB of the Swiss Society of Senology

12

Renzo Brun del Re ()Ärztlicher Leiter Spezialabteilung fürBrusterkrankungen, Lindenhofspital Bern, Aarbergergasse 30, 3011, Bern, Switzerlande-mail: [email protected]



12

Table 12.1 Incidence of carcinomas after successful stereotactic biopsy with benign histology (histology explains mammogram finding) Fehr et al. (2002, Table 5)

Authors n cases Mean follow-up

Incidence of carcinomas during follow-up

n %

Jackman et al. (1999) 295 55 Months (6–85) 2 0.7Meyer et al. (1999) 855 >12 Months 0Burns et al. (2000) 400 33 Months (24–48) 5 1.25Liberman et al. (1997) 154 >16 Months 0Lee et al. (1999) 298 33 Months (5–65) 2 0.7Dahlstrom and Jain (2001) 109 2.4-7.5 Years 2 1.8Brenner et al. (2001) 475 >12 Months 6 1.3Total 2,586 17 0.7Klem et al. (1999) 202 >3 Months 1 0.5Heywang-Kobrunner et al. (1998)

129 >6 Months 0 0

Liberman et al. (2000) 82 13 Months (6–24) 0 0Total 413 1 0.2

Fig. 12.1 Algorithm of literature search (main search in MEDLINE and search criteria)

L) *ON D&K 735

M) SENSITIVITY 52202N) SENSITIVITY AND SPE... 161246O) *SUM MN 207765P) *ON L&O 153

Q) 1997...2007 5708859R) *ON P&Q 133

S: PAIN 120,747T: HEMORRHAGE 60,348U: HEMATOMA 18,243V: VASOVAGAL 527W: HYPOTENSION 17,536X: SYNCOPE, VASOVAGAL 1,085Y: SUM VWX 18,595Z: COMPLICATION 19,0961A: INTRAOPERATIVE COMPLICATIONS 18,3491B: POSTOPERATIVE COMPLICATIONS 220,4821C: SUM Z1A1B 248,9161D: SUM TUVWXZ1A1B 334,1071E: ON L&1D 18

R & 1E 155

+ Manual& references ……… 207

E) BIOPSY 117507 F) CORE 14653 G) VACUUM 4795 H) *ON E&F 1027 I) *ON E&G 209 J) MAMMOTOME K) *SUM HIJ 1226

A) BREAST 143217 B) BREAST NEOPLASMS 144992 C) MAMMAE 11602 D) *SUM ABC 199811

12 Systematic Review and Meta-analysis of Recent Data 197

• Ameanofatleast100patients(exclusionofpreselected subgroups).

• 14-Gcorebiopsiesor11-Gvacuum-assistedbiopsies.

• Diagnosisconfirmedbysurgery,openbiopsy(gold standard) or follow-up.

• Thefindingscouldbecategorizedintofourmaingroups:benign,elevatedrisk/risklesion(ADH, etc.), ductal carcinoma in situ, andinvasivecarcinoma.Twelve studies met these criteria in the 14-G

core biopsy group. There were three additional studies that met the criteria for the most part but not entirely.

In the 11-G vacuum-assisted biopsy group, 15 studies were identified that met the criteria.

Two studies with open biopsies and subse-quent follow-up served as reference. The full texts of all 32 articles were analyzed.

In addition, the data of the multicenter evaluation study for minimally invasive breast biopsies of the Swiss Study Group under the aegis of the Swiss Society of Senology were added (Brun del Re et al. 2007). In this open, prospective, nonrandomized study with 41 participating centers, 8,270 lesions were biop-sied (three ABBI, 121 SiteSelect, 6,368 Mammotome, 1,320 Vacora, and 467 other) (Brun del Re et al. 2006).

12.2.2 Evidence on Risks and Safety

As stated above, the primary literature search was conducted with PaperChase in the refer-ences of MEDLINE and OLDMEDLINE for the time period of 1997 to 17 March 2007 (last update). In addition, a full test search of the 201 abstracts and full texts was conducted for que-ries relevant to risk (compare Fig. 12.2). Quantitative data were collected whenever avail-able. The full text search concentrated on “seri-ous” and “unexpected” events. Unfortunately, there were few studies with a systematic capture of adverse events according to a standardized procedure, making quantitative conclusions difficult.

12.2.3 Presentation and Analysis of the Data

We had to be able to assign the findings to one of the four main categories: benign, elevated risk/risk lesion (ADH, etc.), ductal carcinoma in situ, or invasive carcinoma. The algorithm of Burbank and Parker (1998) was used, as in other similar analyses (see Tables 12.3 and 12.4).

Table 12.2 Queried databanks at DIMDI (Deut-sches Institut für Medizinische Dokumentation und Information)

AZ72 etBZ01 BundeGLOBAL HealthBE00 BetansanzeigerCC00 CCMedCDAR94 NHS-CRD-DARECR00 CCRISEM00 EMBASEEM74 EMBASEGA03 GmsGE79 GeroLitGM03 GMS meetingsHG05 Hogrefe-Verlagsdatenbank und

VolltexteHN69 HECLINETHS00 HSDBINAHTA NHS-CRD-HTAKL97 Kluwer-VerlagsdatenbankKP05 Krause and Pachernegg

VerlagsdatenbankKR03 Karger-VerlagsdatenbankMK77 MEDIKATNHSEED NHS-EEDSM78 SOMEDSP97 Springer-VerlagsdatenbankSPPP Springer-Verlagsdatenbank

PrePrintTV01 Thieme-Verlagsdatenbank


12

12.2.3.1 Comments on the Key Variables Used

Negative and Positive Predictive Value The neg-ative predictive value is the proportion of patients with negative test results who are cor-

rectly diagnosed as being healthy. The positive predictive value is the proportion of patients with positive test results who are correctly diag-nosed as having the disease.

From a clinical point of view, the negative predictive value is more unequivocal and more

Table 12.3 Algorithm from Burbank and Parker

Two-step surgical histology

IBC DCIS ADH Benign

One

-ste

p bi

opsy

hi

stol

ogy IBC A A A A

DCIS U A A AADH U U A ABenign M M A A

Algorithm for histological comparison of vacuum-assisted large-core breast biopsy (VALCBB) and surgical pathology. One-step biopsy histology = VALCBB histology; two-step surgical histology = surgical histologyIBC invasive breast carcinoma, DCIS ductal carcinoma in situ, ADH atypical ductal hyperplasia, A agreement, U underestimate, M miss

Fig. 12.2 Fourteen-G core biopsies: frequency of reclassification from benign to carcinoma. Results in % and 95% CI as difference from the mean value of all studies

"False" benign; Difference to mean value of 3.1%

Benign to Invasive Ca. + Duct.Ca.in situ

% &

95

& V

I

−6.0%

−4.0%

−2.0%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

de W

aal e

t al 2

006

Kos

lkel

a et

al.

2005

Dill

on e

t al.

2005

Faj

ardo

et

War

d et

al.,

200

0

Jack

man

et a

l.,19

99M

eyer

et a

ll.,

1999

Ver

kooi

jen

et a

l.20

02B

uchb

erge

r et

Dah

lstr

om J

E, J

Ain

S.,

2001

Mak

oske

et a

l.,

Han

et a

l.,20

03K

irshe

nbau

m e

tal

., 20

03

Cry

stal

et a

l. 20

05

Cho

et

al.,

2005


important for the evaluation of the performance of different biopsy methods. In principle, a nega-tive result will not lead to further evaluation and therefore has to have a high degree of certainty.

The picture is complicated in our case by gray-zone findings such as elevated risk (i.e., atypical hyperplasia) and inconsistent results, which lead to further tests. Approximately one-third of all cases will eventually have a malignancy. Therefore two-thirds of all patients will end up with a benign final diagnosis. But their diagnostic procedures will likely be identical to those of a positive find-ing. To circumvent this issue in the current analy-sis, the information was divided into three categories and treated separately.

Diagnosis: Benign. We analyzed the risk of a false-negative finding in terms of missing a duc-tal carcinoma in situ or invasive carcinoma and the degree of the predictive value (certainty not to be reclassified later to a higher category). This conceptually corresponds to “SnNout” (mnemonic for when a sign, test, or symptom has a high sensitivity, a negative result rules out the diagnosis.)

Diagnosis: Elevated Risk, Uncertain/Risk Lesions (ADH, etc.). We analyzed the risk of a false-negative

finding in terms of a ductal carcinoma in situ or inva-sive carcinoma not identified by the biopsy.

Diagnosis: Carcinoma (Ductal Carcinoma In Situ or Invasive Carcinoma). In addition to the descriptive term of the prevalence, we ana-lyzed the sensitivity, i.e., the certainty that no ductal carcinoma in situ or invasive carcinoma was missed (subclassification into the some-times listed early and late misses was waived) (Table 12.5).

Table 12.5 shows the calculation model used for the key variables based on a summary of the selected studies according to Burbank and Parker’s algorithm.

Most authors present their results excluding inadequate samples and usually without infor-mation regarding the number of exclusions.

12.2.3.2 Comments on Data Analysis

The studies meeting the inclusion criteria are sum-marized in a table listing the relevant data accord-ing to the Cochrane recommendations for systematic reviews (Higgins and Green 2005). Statistical cal-culations were carried out with WinSTAT Version

Table 12.4 Method of summarizing the selected studies according to the algorithm of Burbank and Parker

Final diagnosis

BenignRisk lesions (ADH, etc.)

Ductal carcinoma in situ

Invasive carcinoma S

Bio

psy

Benign B BR BiS Bca B + BR + BiS + Bca

Risk lesions (ADH etc.)

R RiS Rca R + RiS + Rca

Ductal ca in situ iS Ca iS + CaInvasive carcinoma

Ca Ca

S B BR + R BiS + RiS + iS Bca + Rca + Ca + Ca

Total

Abbreviations are arbitrarily selected symbols for calculation (Table 12.5)B = benign; BR = Biopsy benign-final diagnosis risk lesion; BiS = Biopsy benign-final diagnosis Ca in situ; Bca = Biopsy benign-diagnosis invasive carcinoma; R = Risk lesion; Ris = Biopsy risk lesion-final diagnosis carcinoma in situ; Rca = Biopsy risk lesion-final diagnosis invasive carcinoma; iS = Ductal carcinoma in situ; Ca = invasive carcinoma


12

2001.1 for Excel. Ordinal data are listed in percent and 95% confidence interval (95% CI) (Kirkwood 1988). Significance was calculated as a double-sided p; significant differences are p £ 0.05 (p < 0.1 counts as a trend). Mean values were compared with the Student’s t-test; nominal and ordinal data were compared with the appropriate c2-test.

12.3 Presentation and Analysis of the Data

12.3.1 Evidence Used

12.3.1.1 Open Biopsies as the Gold Standard

Tables 12.6 and 12.7 summarize the studies with open NLBB biopsies (needle localization breast biopsy), which were included as the reference value. These two studies compare the biopsy result with that obtained in the subsequent sur-gery or in the follow-up period. Listed are the study (first author, year, study location), study design, a brief description of the operative spec-ifications, the number of biopsies, the number

of biopsies with benign findings and follow-up, the time of follow-up (months, mean value, and range), and the number of carcinomas found during follow-up among patients who originally had biopsies with benign findings, in absolute numbers and in percentage.

12.3.1.2 Fourteen-G Core Biopsies and 11-G Vacuum-Assisted Biopsies

Tables 12.8–12.11 summarize the studies with 14-G core biopsies and those with 11-G vac-uum-assisted biopsies. All studies compared the biopsy result with the result obtained in the subsequent surgery or in the follow-up period. Listed are the study (first author, year, study location), study design, a brief description of the operative specifications, the number of biopsies, the number of biopsies with benign findings and follow-up, the time of follow-up (months, mean value, and range), and the number of carcinomas found during follow-up among patients who originally had biopsies with benign findings, in absolute numbers and in percentages. Studies with incomplete data are listed separately.

Table 12.5 Calculation model of key variables

Risk false negative Risk false negative in ADH

Sensitivity* Cancer prevalence

“Benign”: predictive value (negative)

Ratio benign to invasive Ca. + DCIS

Ratio risk lesion (ADH etc.) to DCIS or invasiv. Ca.

Sensitivity (Ca n in biopsies/n detected)

Prevalence Ca and DCIS

Ratio benign to benign+benign but finally risk lesion+benign but finaly ductal carcinoma in situ+benign but finally invasive carcinoma

(BiS + Bca)/(B + BR + BiS + Bca)

(RiS + Rca)/(R + RiS + Rca)

(iS + Ca + Ca)/(Bca + Rca + Ca + Ca + BiS + RiS + iS)

(iS + Ca + Ca)/TOTAL

(B)/(B + BR + BiS + Bca)

* Without reclassification from in situ to invasiveAbbreviations see Table 12.4


Tabl

e 12.

6 S

umm

ary

of c

ompa

rati

ve s

tudi

es i

nclu

ded

wit

h op

en n

eedl

e lo

cali

zed

brea

st b

iops

ies

(NL

BB

)

Stud

yaM

etho

dC

ount

ryB

iops

ies

(n)

Ben

ign

+

follo

w-u

p (n

)Fo

llow

-up

(mon

ths)

Var

iati

onIn

cide

nce

Inci

denc

e of

ca

rcin

oma

as %

of

beni

gnC

omm

ent

Rie

dl e

t al.

(200

5)S

tere

otac

tica

lly

need

le-g

uide

d,

open

bre

ast

biop

sy N

LB

B

Aus

tria

b1,

018

442

4724

–86

51.

1M

issi

ng f

ollo

w-u

p da

ta

of 1

08 p

atie

nts

not

cons

ider

ed

Ver

kooi

jen

et

al.

(200

0)S

tere

otac

tica

lly

need

le-g

uide

d,

open

bre

ast

biop

sy N

LB

B

The

N

ethe

rlan

dsc

199

199

60.5

–6

3.0

Sen

sitiv

ity

(car

cino

ma

n bi

opsy

/n to

tal)

of

NL

BB

was

99%

aft

er 2

ye

ars

of f

ollo

w-u

p, b

ut

only

96%

aft

er 5

yea

rsa S

tudy

des

ign:

ret

rosp

ectiv

e, c

ompa

rativ

e w

ith

surg

ery

and

foll

ow-u

pb D

epar

tmen

ts o

f R

adio

logy

, Gyn

ecol

ogy,

Sur

gery

and

Cli

nica

l Pat

holo

gy, M

edic

al U

nive

rsit

y V

ienn

a, V

ienn

a, A

ustr

iac U

nive

rsit

y M

edic

al C

ente

r U

trec

ht, T

he N

ethe

rlan

ds

Tabl

e 12.

7 S

umm

ary

of d

ata

of in

clud

ed c

ompa

rati

ve s

tudi

es w

ith

open

nee

dle

loca

lize

d br

east

bio

psie

s (N

LB

B)

Stud

ies

(n)

Bio

psie

s (n

)

Ben

ign

+

follo

w-u

p (n

)Fo

llow

-up

(mon

ths)

Var

iati

onIn

cide

nce

of

carc

inom

as%

Inc

iden

ce

carc

inom

as95

% C

I

21,

217

745

4424

-86

111.

50.

8–2.

2


12

Tabl

e 12.

8 S

umm

ary

of s

tudi

es in

clud

ed w

ith

14-G

cor

e bi

opsi

es c

ompa

red

to r

esul

t at o

pera

tion

and

dur

ing

foll

ow-u

p (s

tudi

es w

ith

inco

mpl

ete

info

rmat

ion

in i

tali

cs)

Stud

ySt

udy

desi

gnT

echn

ique

Bio

psie

s (n

)

Ben

ign

+

cont

rols

(n

)

Car

cino

mas

du

ring

fo

llow

-up

of

orig

inal

ly

beni

gn

find

ings

(n)

Ca

(n)

duri

ng

follo

w-u

p in

% o

f or

igin

al

beni

gn

find

ings

Com

men

tM

ean

Ran

ge

Cho

et a

l. (2

005)

a

Ope

n co

mpa

ra-

tive

wit

h G

11,

not r

ando

miz

ed

US

-gui

ded,

Pro

-Mag

2.

256

142

89.

21–

2816

3.7

0

Dil

lon

et a

l. (2

005)

b

Ope

nU

S, c

lini

cal o

r st

ereo

tact

ic g

uida

nce

2,42

7c77

224

3–67

858.

4N

o fo

llow

-up

= 9

2;

foll

ow-u

p <

3 m

onth

s =

144

, el

imin

ated

Cry

stal

et a

l. (2

005)

c

Ope

n, f

ollo

w-u

p >

2 ye

ars

US

-gui

ded,

Mon

opty

715

404

3927

–60

123.

00

Faja

rdo

et a

l. (2

004)

d

Ope

n, r

and-

omiz

ed

ster

eota

ctic

vs.

so

nogr

aphi

c gu

idan

ce

Ult

raso

und

(US

CB

) or

st

ereo

tact

ic (

SC

B)

guid

ance

; 14-

G g

uns

or v

acuu

m-a

ssis

ted

14-

or 1

1-G

dev

ices

1,68

11,

214

276–

5518

1.5

Pre

dom

inan

tly

14-G

dev

ices

use

d;

resu

lts

pool

ed

Han

et a

l. (2

003)

e

Ope

nU

S-

and

ster

eota

ctic

co

re-n

eedl

e bi

opsy

, B

iopt

y gu

n

201

138

15.5

6–48

118.

072

Pat

ient

s, n

o di

rect

follo

w-u

ps

avai

labl

e; e

xclu

ded

from

ana

lysi

s. M

ean

age

only

47

year

s

Kir

shen

baum

et

al.

(200

3)f

Ope

n, s

tere

otac

-ti

c gu

idan

ceS

tere

otac

tic

core

ne

edle

bio

psy;

di

spos

able

14-

G

need

le (

Bar

d)

282

141

253–

842

1.4

Las

t 23

biop

sies

w

ith M

amm

otom

e.

No

follo

w-u

p in

114

pa

tient

s ex

clud

ed

from

ana

lysi

s

Follo

w-u

p (m

onth

s)


(con

tinu

ed)

Ver

kooi

jen

et

al.

(200

2)g

Ope

nS

tere

otac

tic

14-G

ne

edle

bio

psy

863

352

15.5

6–48

205.

7In

suff

icie

nt

mat

eria

l = 1

3

Buc

hber

ger

et a

l. (2

002)

h

Ope

nU

S-g

uide

d 14

-gau

ge

need

le b

iops

y P

RO

-MA

G

594

356

18>

183

0.8

No

mea

n va

lue/

stan

dard

dev

iati

on

Mak

oske

et

al.

(200

0)i

Ope

nU

S-g

uide

d 14

-gau

ge

need

le b

iops

y P

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551

377

20.4

K.A

.0

0.0

14 B

iops

ies

wit

h M

amm

otom

e; 3

10

pati

ents

wit

hout

fo

llow

-up

War

d et

al.

(200

0)j

Ope

nS

tere

otac

tic

core

bi

opsy

117

8116

4–36

11.

20

Jack

man

et

al.

(199

9)k

Ope

nS

tere

otac

tic

core

bi

opsy

, 14-

G n

eedl

e (A

CN

1,4

16)

482

307

556–

852

0.7

0

Mey

er e

t al.

(199

9)l

Ope

nS

tere

otac

tic

core

bi

opsy

, 14-

G n

eedl

e (A

CN

1,4

16)

1,36

085

512

K.A

.5

0.6

30%

Wit

hout

fo

llow

-up

>1

year

Kos

kela

et a

l. (2

005)

m

Ope

nSt

ereo

tact

ic c

ore

biop

sy, 1

4-G

nee

dle

(Bio

pty)

197

115

246–

394

3.5

All

car

cino

mas

du

ring

furt

her

eval

uati

on n

ot

duri

ng fo

llow

-up

de W

aal e

t al.

(200

6)n

Ope

nU

S-gu

ided

, cor

e bi

opsy

, 14-

G n

eedl

e59

932

136

K.A

.5

1.6

Youn

g pa

tien

ts

51.0

± 1

0 ye

ars

Dah

lstr

om

and

Jain

(2

001)

o

Ope

nSt

ereo

tact

ic-g

uide

d,

core

bio

psy,

14-

G

need

le

301

230

K.A

.29

–90

73.

4F

ive

case

s w

ith

re-b

iops

y (d

iscr

epan

cy o

f re

sult

s) a

nd tw

o du

ring

foll

ow-u

p


121,

279

ultr

asou

nd-g

uide

d co

res,

739

cli

nica

lly g

uide

d co

res,

and

409

ste

reot

acti

c-gu

ided

cor

es.

a (C

ompa

rat v

s. 1

1 G

): S

eoul

Nat

iona

l Uni

vers

ity

b Uni

vers

ity

Hos

pita

l, D

ubli

n, I

rela

nd.

c (n

lesi

ons)

: Uni

vers

ity

of th

e N

egev

, Isr

ael

d Uni

vers

ity

of I

owa

Hos

pita

l and

Cli

nics

, Iow

a C

ity,

IA

, US

Ae S

ungk

yunk

wan

Uni

vers

ity

Sch

ool o

f M

edic

ine,

Suw

on, K

orea

f Mas

onic

Med

ical

Cen

ter,

Chi

cago

, IL

, US

Ag U

nive

rsit

y M

edic

al C

ente

r U

trec

ht, T

he N

ethe

rlan

dsh U

niv.

-Kli

nik

für

Rad

iodi

agno

stik

, Inn

sbru

ck, A

ustr

iai S

t. L

uke’

s H

ospi

tal,

Bet

hleh

em, P

enns

ylva

nia,

PA

, US

Aj S

t Jos

ephs

Hea

lthc

are

Cen

tre,

Lon

don,

ON

, Can

ada

k Sta

nfor

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nive

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edic

al C

ente

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tanf

ord,

CA

, US

Al B

righ

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nd W

omen

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ospi

tal,

Bos

ton,

MA

, US

Am K

uopi

o U

nive

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tal,

Kuo

pio,

Fin

land

n Gem

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rust

zent

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Dac

hau

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Inst

itut

für

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holo

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Mün

chen

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enha

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man

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nive

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Can

berr

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ospi

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Can

berr

a, A

ustr

alia

Tabl

e 12.

8 (c

onti

nued

)

Tabl

e 12.

9 S

umm

ary

of 1

4-G

cor

e bi

opsy

dat

a (s

tudi

es w

ith

inco

mpl

ete

info

rmat

ion

in i

tali

cs)

Stud

y de

sign

Bio

psie

s (n

)B

enig

n +

fol

low

-up

(n)

Follo

w-u

p (m

onth

s)R

ange

Car

cino

mas

% C

arci

nom

as95

% C

I

Det

aile

d da

ta9,

420

5,48

719

.81-

8517

03.

12.

7-3.

5

No

deta

iled

dat

a1,

511

840

35.8

6-39

212.

51.

7-3.

3

Tota

l10

,931

6,32

721

.91-

8519

13.

02.

7-3.

3


Tabl

e 12.

10 S

umm

ary

of s

tudi

es i

nclu

ded

wit

h 11

-G v

acuu

m-a

ssis

ted

biop

sies

com

pare

d to

res

ults

at

oper

atio

n or

dur

ing

foll

ow-u

p

Stud

ySt

udy

desi

gnM

etho

dB

iops

ies

(n)

Ben

ign

+

follo

w-u

p (n

)C

arci

nom

as

occu

rred

Car

cino

ma

as

% o

f or

igin

al

beni

gn

find

ings

Mea

nR

ange

Cas

sano

et a

l. (2

007)

a

Ope

nU

S-g

uide

d,

vacu

um a

ssis

ted

385

300

3628

-42

20.

7

Cho

et a

l. (2

005)

b (C

ompa

rativ

e vs

. 14

G)

Ope

n, c

ompa

red

wit

h 14

-G, n

ot

rand

omiz

ed

US

-gui

ded,

M

amm

otom

e41

610

08.

81-

253

0.9

Ket

trit

z et

al.

(200

4)c,

d

Ope

nU

S g

uide

d,

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opty

2,24

61,

462

256-

671

0.1

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osch

itz

et a

l. (2

004)

e

Ope

nS

tere

otac

tic

vacu

um-a

ssis

ted

100

5333

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3.8

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brog

etti

et a

l. (2

003)

f

Ret

rosp

ectiv

e,

isol

ated

mic

roca

lcif

i-ca

tion

s, c

ompa

riso

n w

ith

surg

ery

and

foll

ow-u

p

Ste

reot

acti

c va

cuum

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iste

d23

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.A.

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bold

et a

l. (2

003)

g

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n; B

I-R

AD

S I

VS

tere

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tic

vacu

um-a

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mot

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210

140

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.?

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00.

0

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gman

n et

al.

(200

3)h

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vacu

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ssis

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164

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8

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l. (2

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i

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(200

2 b)

j

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wit

h su

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reot

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c va

cuum

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d M

amm

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318

100

K.A

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0

Follo

w-u

p (m

onth

s)


12

Sit

tek

et a

l. (2

002)

k

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n pr

ospe

ctiv

e up

-rig

ht v

s. ly

ing

posi

tion

(n

= 3

09)

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c va

cuum

-ass

iste

d M

amm

otom

e

328

215

K.A

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120

0.0

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vade

et a

l. (2

002)

l

Ope

nS

tere

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tic

vacu

um-a

ssis

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mot

ome

252

157

113-

190

0.0

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giar

ella

et a

l. (2

001)

m

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nS

tere

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tic

vacu

um-a

ssis

ted

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mot

ome

9976

20.5

6-36

00.

0

Lai

et a

l. (2

001)

nR

etro

spec

tive

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reot

acti

c va

cuum

-ass

iste

d47

331

5K

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6-24

20.

6

Bec

k et

al.

(200

0)o

Ope

n, p

rosp

ectiv

eS

tere

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tic

vacu

um-a

ssis

ted

Mam

mot

ome

482

364

K.A

.6-

240

0.0

a Eur

opea

n In

stit

ute

of O

ncol

ogy,

Mil

an, I

taly

and

Hos

pita

l de

Cli

nica

s, C

urit

iba,

Par

ana,

Bra

zil

b (C

ompa

rativ

e vs

. 14-

G):

Seo

ul N

atio

nal U

nive

rsit

y, K

orea

, c HE

LIO

S K

lini

kum

Ber

lin,

and

Mar

tin-

Lut

her-

Uni

vers

ität

Hal

le, a

nd K

lini

kum

Deg

gend

orf,

Fri

edri

ch-

Ale

xand

er-U

nive

rsit

ät E

rlan

gen-

Nür

nber

g, N

urem

berg

, Ger

man

y, d N

ot in

clud

ed 6

28 b

enig

n w

itho

ut f

ollo

w-u

p, e U

nive

rsit

y of

Vie

nna

Med

ical

Sch

ool a

nd L

udw

ig

Bol

tzm

ann

Inst

itut

e fo

r C

lini

cal a

nd E

xper

imen

tal R

adio

logy

Res

earc

h, V

ienn

a, A

ustr

ia, f U

nive

rsit

a de

gli S

tudi

Fir

enze

, Flo

renc

e, I

taly

, g Ins

titu

t fur

Dia

gnos

tisc

he u

nd

Inte

rven

tion

elle

Rad

iolo

gie

Kli

niku

m d

er J

.W.G

.-U

nive

rsit

ät F

rank

furt

/Mai

n, F

rank

furt

, Ger

man

y, h A

btei

lung

Rad

iolo

gisc

he D

iagn

osti

k U

nive

rsit

atsk

lini

kum

T

übin

gen,

Tüb

inge

n, G

erm

any,

i Hos

pita

l Vir

gen

del C

amin

o, P

ampl

ona,

Spa

in, j U

nive

rsit

y of

Vie

nna

Med

ical

Sch

ool,

Vie

nna,

Aus

tria

, k Kli

niku

m G

roßh

ader

n de

r U

nive

rsit

ät M

ünch

en, M

unic

h, G

erm

any,

l Cen

tre

de s

énol

ogie

, Cle

rmon

t-Fe

rran

d, F

ranc

e, m

New

Yor

k U

nive

rsit

y M

edic

al C

ente

r an

d B

eth

Isra

el M

edic

al C

ente

r, S

aint

V

ince

nt’s

Com

preh

ensi

ve C

ance

r C

ente

r, N

ew Y

ork,

NY

, US

A, n F

ooth

ills

Med

ical

Cen

tre,

Cal

gary

, Can

ada,

o D. D

iagn

. Rad

iol.,

Uni

vers

ität

Hal

le, H

alle

, Ger

man

y


Table 12.11 Summary of 11-G vacuum-assisted biopsy data

Studies (n)

Biopsies (n)

Benign + follow-up (n)

Follow-up (months)a

Range Carcinomas occurred

Carcinomas occurred (%)

95% CI

15 6,069 3,965 19.6 3-36 33 0.8 0.6-1.1

a No data. Mean in seven studies

12.3.2 Results

12.3.2.1 0pen Biopsy as Gold Standard

In the pooled data of the two studies used here as reference; 1.5% of the patients were diagnosed with a new carcinoma in the follow-up period. In retrospect, these were then classified as erro-neous diagnosis. It seems significant, however, that in the study by Verkooijen et al. (2000) the sensitivity of the NLBB after 2 years was 99%, but dropped to 96% after 5 years (98.5 and 97.7% for the studies pooled here).

The results of the open procedures are sum-marized in Tables 12.12–12.14.

12.3.2.2 Fourteen-G Core Biopsy

There are no randomized studies comparing 14-G core biopsy with other procedures. All identified studies are nonblinded and descriptive.

The total pool consists of 10,886 patients: 6,327 of these patients with a benign finding were followed up for an average of 22 (range, 1-85) months. Within this interval, 191 patients devel-oped a carcinoma (3.0%; 95% CI, 2.7–3.3%).

If one includes only the 12 studies with com-plete information according to the selected Burbank and Parker criteria, the pool consists of 9,375 patients: 5,487 of these patients with a benign finding were followed up. Within this inter-val, 170 patients developed a carcinoma (3.1%;

95% CI, 2.6–3.9%). With an elevated risk (5.4% of patients, predominantly atypical hyperplasias), the probability of a malignant diagnosis was 33.3% (95% CI, 29.2–41.2%). Detailed information on absolute frequency, frequency of reclassification from benign or elevated risk to carcinoma, as well as sensitivity, prevalence, and predictive value of a benign biopsy finding (pool of 12 studies) is listed in Tables 12.15–12.17 and Fig. 12.2.

The study by Dillon et al. (2005) is an outlier on account of its many false-negative cases, although it included 1,279 ultrasound-guided, 739 clinically guided, and 409 stereotactic biop-sies. The false-negative results were 1.7, 13, and 8.9%, respectively.

Cho et al. (2005) carried out a nonblinded, nonrandomized comparative study. With an average follow-up of only 9 months (range, 1–28), the false-negative findings were probably underestimated. Moreover, they used predomi-nantly 11-G vacuum-assisted biopsies for calci-fications, which further diminishes the comparative significance of this study.

Han et al. (2003) also indicated that in their study the false-negative findings were highest at the beginning of the learning curve.

12.3.2.3 Eleven-G Vacuum-Assisted Core Biopsy

The total pool consists of 6,062 patients: 3,965 patients had benign findings and were followed up for an average of 19.6months (range, 3–36). Within this interval, 33 patients developed a car-cinoma (0.8%; 95% CI, 0.6–1.1%).

12

Table 12.12 Open procedures: biopsy result vs. definitive result (operation, follow-up); pool of two studies

Summery

Final diagnosis


Ductal carci-noma in situ

Invasive carcinoma Total

Bio

psie

s

Benign 728 6 0 11 745Risk lesions (ADH, etc.) No data No data No data No dataDuctal carcinoma in situ No data No data No dataInvasive carcinoma 472 472Total 728 6 0 483 1,217

Table 12.13 Open procedures: biopsy result vs. definitive result in % (operation, follow-up); pool of two studies

Summary in %

Final diagnosis




Bio

psie

s

Benign 59.8% 0.5% 0.0% 0.9% 61.2%Risk lesions (ADH, etc.) No data No data No data No dataDuctal carcinoma in situ No data No data No dataInvasive carcinoma 38.8% 38.8%Total 59.8% 0.5% 0.0% 39.7% 100.0%Corrected −1.4% 0.5% 0.0% 0.9%

Table 12.14 Open procedures: results in %, frequency of reclassification from benign or elevated risk (ADH) to carcinoma; sensitivity, prevalence, and predictive value of a benign finding; pool of two studies

Open procedures

Reclassification

Sensitivity (carcinoma: n biopsies/total n)a

Prevalence carcinoma + in situ

Benign: negative predictive value

Benign to carcinoma or ductal carcinoma in situ; 95% CI

Risk lesion to carcinoma in situ or invasive carcinoma

Riedl et al. (2005) 0.9% 0.1-1.9% No data 99.0% 46.4% 98.0%Verkooijen et al. (2000)

3.0% 0.6-5.9% No data No data No data 97.0%

Summary 1.5% 0.6-2.6% No data 97.7% 38.8% 97.7%a Without reclassification from in situ to invasive

Table 12.15 Fourteen-G core biopsies: biopsy result vs. definitive result (operation, follow-up); pool of 12 studies

Summary

Definitive diagnosis




Bio

psie

s Benign 5,257 60 33 137 5,487Risk lesion (ADH, etc.) 31 307 73 96 507Ductal carcinoma in situ 544 127 671Invasive carcinoma 2,710 2,710Total 5,288 367 650 3,070 9,375

Table 12.16 Fourteen-G core biopsies: biopsy result vs. definitive result in % (operation, follow-up); pool of 12 studies

Summery in %


Benign Risk lesions (ADH, etc.)



Bio

psie

s

Benign (%) 56.1% 0.6% 0.4% 1.5% 58.5%Risk lesion (ADH, etc.) (%) 0.3% 3.3% 0.8% 1.0% 5.4%Ductal carcinoma in situ (%) 5.8% 1.4% 7.2%Invasive carcinoma (%) 28.9% 28.9%Total (%) 56.4% 3.9% 6.9% 32.7% 100.0%Corrected (%) −2.1% −1.5% −0.2% 3.8%

Table 12.17 14-G core biopsies: results in %, frequency of reclassification from “benign” or “elevated risk” (ADH) to “carcinoma”; sensitivity, prevalence, and predictive value of a benign finding; pool of 12 studies

14 G

Occurred carcinomas

Sensitivity (carcinoma n biopsies/n total)a


Benign: negative predic-tive value

Benign to invasive carcinoma or ductal carci-noma in situ

Risk lesions (ADH etc.) to ductal carcinoma in situ or invasive carcinoma

% 95% CI % 95% CI % % %

Cho et al. (2005) 3.7 1.9-6.1 5.3 −4.8 to 16.0

87.0 20.3 96.3

Dillon et al. (2005) 8.4 6.7-11.2 37.2 30.3 to 48.4

88.7 50.6 89.4

Dahlstrom and Jain (2001)

3.0 0.8-5.8 0.0 0-0 88.9 18.6 97.0

Fajardo et al. (2004) 1.5 0.8-2.4 42.1 29.3-60.4

90.7 24.4 96.7

Han et al. (2003) 8.0 3.5-13.7 14.3 −4 to 35.9

77.2 22.4 90.6

Kirshenbaum et al. (2003)

1.4 −0.5 to 3.7

26.1 8.1-48.4 93.4 40.8 97.9

Verkooijen et al. (2002)

5.7 3.3-8.9 23.1 6.9-43.2 94.9 55.9 90.6

Buchberger et al. (2002)

0.8 −0.1 to 2 75.0 45-115.5 96.2 38.2 99.2

Makoske et al. (2000)

0.0 0-0 26.3 12.3-44.3

92.9 24.0 100.0

Ward et al. (2000) 1.2 −1.2 to 4 0.0 0-0 96.4 24.1 98.8Jackman et al. (1999)

0.7 −0.2 to 1.7

55.2 37.1-80.6

88.7 29.6 99.3

Meyer et al. (1999) 0.6 0.1-1.2 30.7 21-44.3 92.8 30.4 99.4Koskela et al. (2005) 3.5 0.1-7.5 No data No data 95.3 41.6 96.5deWaal et al. (2006) 1.6 1.6-1.7 No data No data 98.2 46.4 98.4Crystal et al. (2005) 3.0 1.3-5.1 No data No data 96.3 43.5 97.0Pooled, complete data

3.1 2.6-3.9 33.3 29.2-41.2

90.9 36.1 95.8

Pooled, all studies 3.0 3-3.3 91.8 37.2 96.0a Without reclassification from in situ to invasive


12

Table 12.18 Eleven-G vacuum-assisted biopsies: biopsy result vs. definitive result (operation, follow-up); pool of 15 studies

11-G VAB


BenignRisk lesion (ADH, etc.)



Bio

psie

s

Benign 3,930 2 15 18 3,965Risk lesion (ADH, etc.) 1 282 40 23 346Ductal carcinoma in situ 897 117 1,014Invasive carcinoma 737 737Total 3,931 284 952 895 6,062

Table 12.19 Eleven-G vacuum-assisted biopsies: biopsy result vs. definitive result in % (operation, follow-up); pool of 15 studies

11-G VAB in %


Benign Risk lesion (ADH, etc.)



Bio

psie

s

Benign (%) 64.8% 0.0% 0.2% 0.3% 65.4%Risk lesion (ADH, etc.) (%) 0.0% 4.7% 0.7% 0.4% 5.7%Ductal carcinoma in situ (%) 14.8% 1.9% 16.7%Invasive carcinoma (%) 12.2% 12.2%Total (%) 64.8% 4.7% 15.7% 14.8% 100.0%Corrected (%) −0.6% −1.0% −1.0% 2.6%

With an elevated risk finding (5.7% of patients, predominantly atypical hyperplasias), the probability of a malignant diagnosis was 18.2% (95% CI, 14.1–24.5%). Detailed infor-mation on absolute frequency, frequency of reclassification from benign or elevated risk to carcinoma, as well as sensitivity, prevalence, and predictive value of a benign biopsy finding (pool of 12 studies) is listed in Tables 12.18–12.21 and Fig. 12.3.

The studies by Ambrogetti et al. (2003) and by Pfarl et al. (2002b) are outliers on account of their many false-negative cases compared to the mean value of the other studies. The study reported by Ambrogetti et al. was a retrospective analysis of cases with radiologically isolated calcifications. The study by Pfarl et al. (2000a) is also instructive. Here the false-negative find-

ings were clearly higher for radiologists with fewer than 15 stereotactically guided biopsies compared to their more experienced colleagues (10.0% vs. 0.6%; p = 0.002).

The study by Sebag et al. (2006) does not fit into the chosen Burbank and Parker criteria and is mentioned here only briefly. The authors found 471 benign lesions and 179 malignancies. Three carcinomas (0.64%) were later reclassified to the “probably benign lesion” category. In five cases, the 11-G VAB underestimated the pathology. Two cases of atypical ductal hyperplasia were found to be ductal carcinomas in situ (DCIS) at the definitive surgery and three cases of DCIS were found to be invasive carcinomas. The authors noted that in their series a surgical proce-dure was avoided for 71% of the women. There were no malignancies found during follow-up.


Table 12.20 Eleven-G VAB core biopsies: results in %, frequency of reclassification from benign or elevated risk (ADH) to carcinoma; sensitivity, prevalence, and predictive value of a benign finding; pool of 15 studies

11-G VAB

Occurred carcinomas Sensitivity (carci-noma: n biopsies/n total)a


Benign: negative predic-tive value

Benign to invasive carcinoma or ductal carcinoma in situ

Risk lesions (ADH, etc.) to ductal carcinoma in situ or invasive carcinoma

% 95% VI % 95% VI % % %

Cassano et al. (2007)

0.7 −0.3 to 1.7

0.0 0–0 97.4 19.7 99.3

Cho et al. (2005) (comparative vs. 14-G)

0.9 −0.1 to 2.1

20.0 −0.2 to 44.3

91.5 15.6 99.1

Kettritz et al. (2004)

0.1 −0.1 to 0.2

20.1 13.9–29 95.0 27.8 99.9

Lomoschitz et al. (2004)

3.8 −1.4 to 9.8

50.0 1–108.9 91.5 43.0 96.2

Ambrogetti et al. (2003)

7.8 4-12.8 22.7 5.2–44.3 88.2 41.2 91.7

Diebold et al. (2003)

0.0 0-0 0.0 0-0 100.0 28.6 100.0

Siegmann et al. (2003)

0.8 −0.8 to 2.7

28.6 −4.9 to 68.2

92.3 22.0 99.2

Apesteguia et al. (2002)

0.0 0–0 7.1 −6.3 to 22.7

97.9 35.4 100.0

Meloni et al. (2002)

0.0 0–0 40.0 −2.9 to 91.2

94.3 32.4 100.0

Pfarl et al. (2002a, b)

7.0 2–13.2 35.3 12.6–63.8

93.9 63.2 92.0

Sittek et al. (2002)

0.0 0–0 8.7 −2.8 to 22.2

97.8 27.4 100.0

Travade et al. (2002)

0.0 0–0 13.8 1.2–29 94.3 26.2 100.0

Cangiarella et al. (2001)

0.0 0–0 20.0 −4.8 to 49.3

84.6 13.1 100.0

Lai et al. (2001) 0.6 −0.2 to 1.7

16.7 −4.4 to 41.5

97.3 30.9 99.4

Beck et al. (2000) 0.0 0, 0 0.0 0-0 100.0 21.8 100.0

Summary 11-G VAB

0.8 0.5–1.2 18.2 14.1, 24.5

94.8 28.9 99.1

a Without reclassification from in situ to invasive


12

Table 12.21 Complications and undesired side effects of NLBB in two safety studies

Patients (n)

With compli-cations

Insufficient tissue

Circulatory collapsea

Infection, abscess

Hema-toma Seroma

Wound dehis-cence

Rappaport et al. (1991)

144 27 4 4 4

Kaelin et al. (1995)

301 24 6 3 12 0

Total 445 51 10 4 7 12 1 2

Total (%) 100 11.46 2.25 0.90 1.57 2.70 0.22 0.45

NLBB needle localization breast biopsiesa With hospitalization

12.4 Safety of MIBB

12.4.1 Open Biopsy as Gold Standard

The studies listed under “Evidence on Performance” (12.2.1) give no information regarding risks and safety. However, two older studies that specifically evaluated this aspect may serve as a useful guide (see Table 12.21). Even if we subtract the cases with insufficient tissue, there were complications in approximately 9.2% of patients who had a NLBB (needle local-ization breast biopsy).

12.4.2 Fourteen-G Core Biopsies and 11-G Vacuum-Assisted Biopsies

As the summary of complications and undesira-ble side effects in studies with 14-G core biop-sies shows, termination of the procedure due to technical issues is relatively rare (~4.5%) (see Tables 12.22 and 12.23). The same is true for ter-mination because of undesired effects (~0.27%). The following undesired effects are mentioned in descending frequency: pain, vasovagal reactions, and hemorrhage (see Table 12.23).

As the summary of complications and unde-sired effects in studies with 11-G vacuum-assisted core biopsies shows, termination of the procedure due to technical issues is also rela-tively rare (~1.7%) and less frequent than with 14-G core biopsies (see Tables 12.24 and 12.25). This also holds true for termination because of undesired effects, although it is somewhat more frequent than in the studies with 14-G core biop-sies. The following two main undesired effects are mentioned: pain and vasovagal reactions, although hematomas (4.7%), hemorrhage (1.2%), and pain (1.1%) are reported quite fre-quently in this population. In addition, 79% of patients report a subcutaneous hematoma (see Sect. 12.5 for quality of life (HRQoL)).

Pfarl et al. (2002a, b) reported comparable results, although without a significant differ-ence between 11 and 14 G. In 560 patients biopsied using the Mammotome, Beck et al. (2000) described only one relevant hematoma requiring surgical evacuation and only one case of scar formation documented mammographi-cally. In 297 cases, Lai et al. (2001) observed 3.9% relevant (“non-minor”, i.e., “significant and major”) complications during, and 3.6% after the procedure, only two of which required treatment (a vasovagal-induced seizure and a migraine). In a head-to-head comparison, Burbank (1997) reported a 1.1% complication


rate in 14 G and 1.4% in 11 G Mammotome biopsies.

In the Swiss study (Brun del Re et al. 2007), no complications were reported in 7,380 of 7,835 interventions. The complication rate including technical reasons was 5.6%. In only 2‰ did the intervention have to be terminated. In 394 cases, hematomas were found. In 378 cases, the patients were only followed up. Surgical interventions were unavoidable in 16 cases. In one case, the biopsy could not be per-formed after insertion of the needle due to arte-rial bleeding. In one case, a granulomatous infection was observed. In eight cases, vasova-gal reactions were reported; the intervention had to be terminated in only one case with a biopsy procedure in the upright position. In two cases,

the microcalcifications could not be identified in the digital picture. In two cases, the breast was too small. In one case, the tumor was too hard. In five cases, the patient complained of pain. A laceration of the skin was reported three times as a result of difficult positioning. One patient complained of severe neck pain during the intervention. In four cases, technical prob-lems with the biopsy table and in four cases problems with the clip were reported. Migration of its clip was observed three times. In nine cases, the lesion could not be biopsied because of its location in the breast. One patient declined the intervention after positioning. The interven-tion was terminated twice without a reason pro-vided. In five cases, the complications were not specified. In one case, a hematoma caused by

Fig. 12.3 Eleven-G VA-core biopsies: frequency of reclassification from benign to carcinoma. Results in % and 95% CI as difference from the mean value of all studies

Benign to invasive Ca. + Duct.Ca.in situ

"False" benign; Difference to mean value of 0.8 %

% &

95%

VI

Cas

sano

et a

l., 2

007

Cho

et a

l., 2

005

(Com

para

t vs.

14G

)

Ket

tritz

et a

l. 20

04

Lom

osch

itz e

t al.,

200

4

Am

brog

etti

et a

l., 2

003

Die

bold

et a

l., 2

003

Sie

gman

n et

al.,

200

3

Ape

steg

uia

et a

l., 2

002

Mel

onie

et a

l., 2

002

Pfa

frl e

t al.,

200

2

Sitt

ek e

t al 2

002

Tra

veda

et a

l., 2

001

Can

giar

ella

et a

l., 2

001

Lai e

t al.,

200

1

Bec

k et

al.,

200

0

−4.0%

−2.0%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

12

Tabl

e 12.

22 C

ompl

icat

ions

and

und

esir

ed s

ide

effe

cts

in s

tudi

es w

ith

14-G

cor

e bi

opsy

(on

ly s

tudi

es l

isti

ng d

ata)

Safe

ty, n

pa

tien

ts

Ter

min

atio

n of

pro

ce-

dure

due

to

tech

nica

l pr

oble

ms

Ter

min

atio

n du

e to

und

esir

ed e

ffec

tsU

ndes

ired

eff

ects

Com

men

tn

nn

nn

n

Faja

rdo

et a

l. (2

004)

2,40

315

7H

emor

rhag

e3

Ane

sthe

sia

(all

ergy

)2

Pain

9O

ther

re

ason

s9

Kir

shen

baum

et

al.

(200

3)49

2V

asov

agal

re

acti

on5

Hem

orrh

age

4O

ne c

ase

hem

orrh

age

reop

erat

ed

Ver

kooi

jen

et

al.

(200

2)95

211

3W

ith-

dr

awna

24In

suff

icie

nt

mat

eria

l = 1

3

Buc

hber

ger

et

al.

(200

2)58

9H

emor

rhag

e1

One

cas

e he

mor

rhag

e re

oper

ated

b

Mak

oske

et

al.

(200

0)88

722

War

d et

al.

(200

0)12

19

Vas

ovag

al

reac

tion

Mey

er e

t al.

(199

9)1,

643

Infe

ctio

n1

Pne

umo-

thor

ax1

No

seri

ous

side

eff

ects

Kos

kela

et

al.

(200

5)19

71

Infe

ctio

nsn

= ?

Hem

atom

an

= ?

a Agr

eem

ent f

or th

e st

udy

wit

hdra

wn*

* S

erio

us


Table 12.23 Summary of complications and undesired side effects in studies with 14-G core biopsy

Termination

Safety, n patients

Technical problems n (%) Undesired effects: n (%) Other reasons n (%)

Hemorrhage 4 (0.05%) Vasovagal reactions

5 (0.07%) Withdrawna 42 (0.58%)

7,284 329 (4.50%) Pain 9 (0.12%) Anesthesia (allergy)

2 (0.03%)

Undesired effects: othersHemorrhage 4 (0.05%) Infection 1 (0.01%) Pneumothorax 1 (0.01%)

a Agreement for the study withdrawn

the overly enthusiastic reception by her dog when the patient arrived home was reported. In 11 cases, “complications other than bleeding” were not further specified.

12.4.3 Conclusions on the Safety of MIBB

Despite the lack of a unified or at least compa-rable data gathering method on complications and undesirable side effects, adverse events seem to be significantly less frequent with 14-G core biopsies and with 11-G vacuum-assisted core biopsies than with open biopsies. There does not appear to be a clinically relevant differ-ence between 14-G core biopsies and 11-G vac-uum-assisted core biopsies.

12.5 Quality of Life (HRQoL)

In the COBRA study (core biopsy after radio-logical localization) Verkooijnen et al. (2002) compared the quality of life of patients before and after an open (n = 27, not COBRA participants) or a 14-G core biopsy (n = 826). The EuroQol and the Survey Short-Form-36 (SF-36) quality of life questionnaires were used. The two groups were comparable in terms of demographic variables and biopsy results. Four days after the procedure, the mean EuroQol

score was significantly worse in the open biopsy group than the 14-G core biopsy group (61 vs. 71, p < 0.001). A similar difference was observed with the VAS (visual analog scale), although it did not reach statistical significance. The differences in favor of the core biopsy in terms of pain and physical functioning in the SF-36 scale were particularly pronounced (see Fig. 12.4 and Table 12.26).

Huber et al. (2003) examined patient satis-faction immediately after an 11-G core biopsy and 6 months later. Fifteen of the 91 patients had complaints during the procedure and the major-ity had a subcutaneous hematoma (79%). During the biopsy, 73 patients (83%) felt “very good”; four patients considered the procedure uncom-fortable; three patients felt pain despite local anesthesia, and eight (9%) felt afraid. Six patients felt constrained during the first few days after the procedure and one patient indi-cated that she was not satisfied with the cos-metic result. None of the patients reported a retrospective preference for surgical biopsy rather than an 11-G vacuum-assisted biopsy.

In an evaluation of stereotactic vacuum-assisted biopsies in terms of biopsy success, histological accuracy, patient acceptance, and optimization of BI-RADS-correlated indication, Siegmann et al. (2003) reported that 98.5% of patients (130/132) would choose vacuum-assisted biopsy again.

For a review of the psychological impact of core biopsies, see the study by Barreau et al. (2005).


12

Tabl

e 12.

24 C

ompl

icat

ions

and

und

esir

ed s

ide

effe

cts

in s

tudi

es w

ith

11-G

vac

uum

-ass

iste

d co

re b

iops

ies

(onl

y st

udie

s li

stin

g da

ta)

Ter

min

atio

n du

e to

te

chni

cal

prob

lem

s

Ter

min

atio

n du

e to

und

esir

ed e

ffec

tsU

ndes

ired

eff

ects

Com

men

tn

nn

nn

n

Cas

sano

et

al.

(200

7)40

419

Cli

p m

ispl

aced

6H

emat

oma

6H

emor

rhag

e22

00

No

late

un

desi

red

effe

cts

Ket

trit

z

et a

l. (2

004)

2,87

4V

asov

agal

re

acti

on5

Con

vuls

ions

(a

fter

bio

psy)

1H

emat

oma

25H

emor

rhag

e,

ongo

ing

4In

fect

ion

5H

emat

oma:

op

erat

ed 3

+

hosp

ital

ized

for

1

nigh

t: 1

he

mor

rhag

e 3

oper

ated

Die

bold

et

al.

(200

3)22

113

Hem

orrh

age

1H

emor

rhag

e6

Hyp

oten

sion

4C

onvu

lsio

n +

hy

pert

ensi

onS

iegm

ann

et

al. (

2003

)16

6H

emat

oma

5H

emor

rhag

e10

Hyp

oten

sion

1N

o pa

in in

63

.3%

; sev

ere

pain

in 1

.8%

Ape

steg

uia

et a

l. (2

002)

132

Hem

orrh

age

3H

emat

oma

Hem

orrh

age

3pa

in2

Mel

oni

et a

l. (2

002)

129

27H

emor

rhag

e1

Vas

ovag

al

reac

tion

5H

emat

oma

2

Sit

tek

et a

l. (2

002)

333

4N

oH

emat

oma

217

Vas

ovag

al

reac

tion

18Pa

in, s

ever

e9

Pun

ctur

e of

the

hem

atom

a n

=

12T

rava

de

et a

l. (2

002)

252

No

Hem

atom

a8

Hem

orrh

age

4Pa

in50

Pun

ctur

e of

the

hem

atom

a n

=

3. P

ain

duri

ng

biop

sy =

20;

af

ter

biop

sy =

30

Can

giar

ella

et

al.

(200

1)13

9N

o re

leva

nt

com

plic

atio

nsB

eck

et a

l. (2

000)

609

Hem

atom

a1

00

Sub

stan

tial

sc

arri

ng1

Ope

rate

d, n

= 1


Table 12.25 Summary of complications and undesired side effects in studies with 11-G vacuum-assisted core biopsy

Termination

Safety, n patients

Technical problems, n (%) Undesired effects, n (%)

5,577 63 (1.13%) Hemorrhage 11 (0.2%) Vasovagal reaction

10 (0.18%)

Convulsions (after biopsy)

1 (0.02%)

Undesired effects: others, n (%)Hematoma 264 (4.73%) Hemorrhage 67 (1.2%) Hypotension 5 (0.09%)Pain 61 (1.09%) Infection 5 (0.09%) Substantial

scarring1 (0.02%)

Convulsion in presence of hypertension

1 (0.02%)

Fig. 12.4 Quality of life (SF-36) after an open breast biopsy and a 14-G core biopsy, 4 days after the procedure

SF-36, rating after biopsy

0 10 20 30 40 50 60 70 80 90 100

Mean score

Needle biopsy group open breast biopsy

Physical performance , p < 0.001

Social performance , p= 0.04

Physical functioning , p= 0.001

Emotional functioning , NS

Vitality, NS

General health , NS

Pain , p= 0.006

Mental functioning , NS

12.6 Summary and Discussion of the MIBB Data Presented

Evaluation of the performance of minimally invasive biopsies is complicated by the lack of

standardized and randomized study protocols. On the other hand, this should increase the exter-nal validity of the available data. They should be sufficiently relevant for daily practice because they include approximately 18,000 biopsies that were validated by subsequent surgery or for the most part by follow-up of several years.


12

The performance profile of minimally inva-sive biopsies compared to open biopsies is excellent, with the 11-G vacuum-assisted biopsy seemingly superior to the 14-G core biopsy (see Table 12.27). However, there are no head-to-head comparisons of the various procedures and there are multiple external factors that could generate a bias in favor of one or the other biopsy technique. As a case in point, virtually no study reports on the selection or assignment cri-teria for a given procedure. It is striking that the prevalence of carcinomas is lower in the 11-G VAB studies, which one would expect to find in a lower rate of erroneous diagnoses. The experi-

ence of the surgeon or radiologist will also influ-ence the performance of a given technique.

Ciatto et al. (2007) published a large retro-spective analysis of approximately 4,000 mini-mally invasive biopsies (January 1996-March 2005). The sensitivity results are very similar to the analysis presented here (see Tables 12.28 and 12.29). The authors show - as already documented by Liberman et al. (2001) – how significant the experience of the physician is for the accuracy of the biopsy. As in the series presented here, the incidence of insufficient tissue was slightly more frequent in the 14-G core biopsies than with the 11-G VAB. The probability of the reassignment

Table 12.26 Quality of life (SF-36) before and 4 days after an open breast biopsy and a 14-G core biopsy

Before After

Needle biopsy

Open biopsy p

Needle biopsy

Open biopsy p

Physical performance 86.7 77.1 NS 85.3 66.3 p < 0.001Social performance 78.3 75 NS 78.3 65.5 p = 0.04Physical functioning 96.7 75 p = 0.003 81.9 48 p = 0.001Emotional functioning 65.5 65.2 NS 54.4 53.3 NSVitality 69.8 66.8 NS 65.4 58.3 NSGeneral health 63.7 68.6 NS 65.9 68.8 NSPain 93.1 87.8 NS 86.9 70.6 p = 0.006Mental functioning 68.6 65.8 NS 66.2 62.8 NS

Table 12.27 Pooled data in %: frequency of reassignment from benign or elevated risk (ADH) to carcinoma; sensitivity, prevalence and predictive value of a benign biopsy finding

Reassignment Sensitivity (carcinoma n biopsies/n total)a

Prevalence carcinoma and in situ

Benign: negative predictive value

Benign to invasive carcinoma + carcinoma in situ

Risk lesion (ADH etc.) to carcinoma in situ or invasive carcinoma

% 95% CI % 95% CI % % %

Open biopsiesb 1.5 0.6–2.6 No data 97.7 38.8 97.7Open biopsiesc 0.9 0.2–1.8 No data 98.5 38.8 98.314-G, pooled 3.1 2.6–3.9 33.3 29.2–41.2 90.9 36.1 95.811-G VAB, pooled 0.8 0.5–1.2 18.2 14.1–24.5 94.8 28.9 99.1a Without reassignment from in situ to invasiveb Follow-up 44 months (range, 24-86 months)c Follow-up 34.3 months (range, 24-86 months)


Table 12.28 Specificity and sensitivity in the series of Ciatto et al.a

Sensitivity (95% CI) (n) Specificity (95% CI) (n)

14-G CB 92.10% (87.6-96.6) (128/139) 93.10% (90.2-96.0) (271/291)11-G VAB 96.20% (94.5-97.9) (461/479) 86.90% (83.8-90.1) (373/429)Total 95.30% (93.6-97.0) (589/618) 89.40% (87.2-91.7) (644/720)a Ciatto et al., Table 5: Comparison of the accuracy of stereotactic automated CB (14) and VAB (11 G) for isolated microcalcifications

Table 12.29 Insufficient biopsy materiala obtained as a function of operator experience, imaging method, and biopsy method in the Ciatto et al. seriesb

Patients treated by one physician (n)

% (n) Significance

0–100 2.76 (4/145) p = 0.0004101–500 0.86 (7/805)>500 0.39 (12/3,074)Image guidance methodUltrasound 0.67 (13/1,950) p = 0.56Stereotactic 0.48 (10/2,087)Biopsy method11-G VAB 0.29 (4/1,391) p = 0.13Automated 14-G 0.72 (19/2,646)a Material not sufficient for a reportb Table 2: inadequacy rate of core needle biopsy as a function of operator, cumulative case load, guidence method and core method

of an elevated-risk (ADH) finding to a ductal car-cinoma in situ or an invasive carcinoma was 27.7% (95% CI, 24.5–30.9%) in the same series of patients (Houssami et al. 2007). This issue was also thoroughly discussed by Mahoney et al. (2006) and Dillon et al. (2005), but has little bearing on the overall analysis of the perform-ance of minimally invasive biopsies.

Hoorntje et al. (2003) analyzed 22 published studies of minimally invasive biopsies. The percentage of false-negative diagnoses with an elevated-risk finding (ADH, etc.) was 16% (95% CI, 12–20%) with an 11-G VAB. Also, the in situ carcinomas had to be staged up to an invasive carcinoma in 11% (95% CI, 9–12%) of cases. The numbers were clearly higher for the 14-G core biopsies, i.e., 40% (95% CI, 26–56%) and 15% (95% CI 8–26%), respectively.

Golub et al. (2004) demonstrated the cost effectiveness of the 14-G core biopsy in the U.S. healthcare system with prospective data (14 G in 1,121 patients vs. open biopsy in 501 patients between 1996 and 1998). In the sensitivity anal-ysis, the core biopsy was the least expensive option in 95.4% of the Monte Carlo simulations. Liberman and Sama (2000) showed the cost effectiveness of 11-G vacuum-assisted core biopsies with prospective data on 200 patients in the U.S. healthcare system.

The fine-needle biopsy, which was not dis-cussed here, is clearly inferior to the minimally invasive biopsies. However, both procedures can be combined to their advantage. The 11-G VAB Mammotome biopsy has replaced the more invasive ABBI (Advanced Breast Biopsy Instrumentation) procedure, with equal effectiveness.


1212.7 Conclusions

As is evident from the summary in Figs. 12.5–12.7, an open procedure can be avoided with a minimally invasive biopsy in almost two-thirds of patients with breast symptoms or findings requiring further work-up. The performance of minimally invasive biopsies is comparable with that of the open procedure. The numbers needed to treat (NNT) to avoid an open procedure is therefore around 1.5, while the more difficult to estimate numbers needed to harm (NNH) (aban-doning the procedure for technical reasons/insufficient tissue, termination of procedure due to complications) lies at around 20–50 patients.

The probability that an elevated-risk find-ing (ADH, etc.) will have to be reclassified during the course of the further work-up as an in situ or an invasive carcinoma is relatively high (in approximately one-third of cases), although it only concerns about 5–6% of the biopsied patients. A large part of the newer lit-erature studied the improvement of the diag-nostic certainty in this subcategory. As the summary of the data in Table 12.30 shows, these clearly favor the minimally invasive biopsies.

There are also several expert opinions published on the efficacy and effectiveness of minimally invasive breast biopsies, which - though not discussed here – all reach similar conclusions (AETMIS 2006).

Fig. 12.5 Fourteen-G core biopsies, summary of the data in %, biopsy finding vs. definitive diagnosis; pool of 12 studies

14-G VABdone

Termination5.2%

Benign58.5 %

Risk lesion(ADH)5.4 %

CA in situ7.2 %

invasive Ca28.9 %

Benign56.1 %


CA in situ0.4 %

invasive Ca

1.5 %


CA in situ0.8 %

invasive Ca1.0 %


Fig. 12.6 Average cost estimate of 14-G core biopsies with the information from Fig. 12.5; pool of 12 studies

14-G VABdone

Termination 5.2%

Benign58.5 %


CA in situ7.2 %

invasive Ca28.9 %

Benign56.1 %


CA in situ0.4 %

invasive Ca1.5 %


CA in situ0.8 %

invasive Ca1.0 %

Assumption: open biopsy costs 100, MIMB costs 30 monetary units

Result:Σ MIMB = 51.46

1.intervention100%X30=30

2. intervention5.2%X30=1.56





Fig. 12.7 Eleven-G vacuum-assisted core biopsies, summary of the data in %, biopsy finding vs. defini-tive diagnosis; pool of 15 studies

11-G VABdone

Termination1.52%

Benign65.4 %


CA in situ16.7%

invasive Ca12.2%

Benign64.8 %


CA in situ0.2 %

invasive Ca0.3 %


CA in situ0.7 %

invasive Ca0.4 %


12

Table 12.30 Summary of the data on diagnostic certainty and quality of life

Open, NLBB 14-G Core biopsy 11-G VAB

Technical termination/insufficient material 2.25% 0.7–4.5% 0.29–1.7%Termination, undesired effects 9.20% 0.27% 0.49%Undesired effects 0.07–1.1% 1.4–7%SF-36 scale, 4 days after biopsy, meanPhysical performancea 66.3 85.3 No statementPaina 70.6 86.9 No statementRetrospective questioningPreference open biopsy No statement No statement 0/91Willing to repeat No statement No statement 130/132a Highly significant; score higher = better

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