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Farid Moinfar

Essentials of Diagnostic Breast Pathology

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Farid Moinfar

123

Essentials

of Diagnostic

Breast Pathology

A Practical Approach

With 116 Figures in 1128 Seperate Illustrations and 6 Tables

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Farid Moinfar,MD

Associate Professor of Pathology

Director, Unit of Breast & Gynecologic Pathology Department of Pathology

Medical University Graz Auenbruggerplatz 25 8036 Graz

Austria

Library of Congress Control Number: 2006932710

ISBN 978-3-540-45117-4 Springer Berlin Heidelberg New York

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcast- ing, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permissions for use must always be obtained from Springer. Violations are liable for prosecution under the German Copyright Law.

Springer is a part of Springer Science+Business Media springer.com

© Springer-Verlag Berlin Heidelberg 2007

The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protec- tive laws and regulations and therefore free for general use.

Product liability:The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature.

Editor: Gabriele Schröder, Heidelberg, Germany Desk Editor: Ellen Blasig, Heidelberg, Germany

Production: LE-TEX Jelonek, Schmidt &Vöckler GbR, Leipzig, Germany Cover design: Frido Steinen-Broo, EStudio, Calamar, Spain

Reproduction and typesetting: am-productions GmbH, Wiesloch, Germany

Printed on acid-free paper 24/3100/YL – 5 4 3 2 1 0

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This work is dedicated with great appreciation and gratitude to My dear parents, Shamsi and Ali Akbar Moinfar

My wonderful wife, Shokufeh Sodeifi-Moinfar and

All my teachers and mentors, particularly Dr. John G. Azzopardi, whose magnificent book and other papers inspired me,

and Dr. Fattaneh A. Tavassoli, a great mentor and friend.

Dedication

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Several excellent and comprehensive textbooks have been written on breast pathology [1–5]. The magnif- icent book Problems in Breast Pathology [1] written by John G. Azzopardi, and two more recent great works by Fattaneh A. Tavassoli [4] and Paul P. Rosen [3] cover almost all aspects of classic and modern breast pathology. So why should one dare to write a new book on this subject?

Over the past few years, the Department of Pathology, Medical University Graz has organized annual intensive 5-day courses on diagnostic breast pathology in order to share the experience in this field and demonstrate and discuss several common diagnostic problems, including tumor-like lesions, intraductal proliferative lesions, variants of ductal and lobular intraepithelial neoplasias, papillary neoplasms, and a variety of infiltrating breast carcinomas. During these courses, it has been my constant experience that most practicing pathologists and pathologists in training appreciate receiving a precise summary of the diagnostic criteria for each entity combined with a brief and accurate discussion of the main differential diagnoses. In dealing with a variety of breast lesions in daily practice, surgical pathologists want and need to know the essentials of diagnostic breast pathology.

So, the idea to write this book gradually evolved from these diagnostic courses, with a main focus on the essentials. This book is therefore designed as a diagnostic aid for pathologists when they encounter com- mon as well as unusual or even challenging and very difficult cases. In trying to achieve this goal, it was necessary to reduce the text but emphasize case presentations that deal with the described entities. Indeed, this book contains over 1,100 full-color illustrations demonstrating gross, histologic, cytologic, and immunohistochemical findings of common as well as challenging benign and malignant breast lesions.

I am most grateful to Dr. Fattaneh A. Tavassoli for her constructive comments, suggestions, and encour- agement throughout the preparation of this book. I am indebted to the staff pathologists at the Depart- ment of Pathology, Medical University Graz, who have supported me during the preparation of this book.

I am thankful to Drs. Helmut Denk, Manfred Ratschek and Wolfgang Öhlinger for their kind support.

I would like to acknowledge the excellent assistance and expertise of Mrs. Andrea Kaps in preparing the photomicrographs. I would like to thank the staff of the publisher, Springer, in particular Mrs. Gabriele M.

Schröder and Mrs. Ellen Blasig for their professional and efficient cooperation and consideration in the production of this book.

Once again, I would like to express my special thanks to my wife, Shokufeh Sodeifi-Moinfar, for her support and tolerance over the past three years.

Graz, Austria

November 2006 Farid Moinfar

References

1. Azzopardi JG. Problems in breast pathology. WB Saunders, London, 1979.

2. Page DL, Anderson TJ. Diagnostic histopathology of the breast. Churchill Livingstone, Edinburgh, 1987.

3. Rosen PP. Rosen’s breast pathology, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, 2001.

4. Tavassoli FA. Pathology of the breast, 2nd edn. Appleton & Lange, Stamford, CT,1999.

5. Tavassoli FA, Devilee P (eds). World Health Organization classification of tumours. Pathology and genetics.

Tumours of the breast and female genital organs. IARC Press, Lyon, 2003

Preface

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“One relies on one’s experience. But “experience” can be merely the repetition of the same error often enough… One must be willing, even anxious, to learn from one’s error. This requires a degree of humility, a readiness to listen to the arguments of others, including those of one’s juniors, and the inclination to re-examine cases in which a mistaken diagnosis has been made and to analyse the reasons for the original mistake.”

John G. Azzopardi

Problems in Breast Pathology

“Thus I learned early on the great importance of a close correlation between clinical and pathological studies. Each complements and supplements the other; it is impossible to do intelligent surgery without a thorough understanding of the pathology of disease and it is equally impossible to make an intelligent interpretation of pathology without a clear under- standing of its clinical implications.”

Arthur Purdy Stout Guiding the Surgeon’s Hand:

The History of American Surgical Pathology

Juan Rosai (Editor)

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1 The Normal Breast

1.1 Anatomy . . . 2

1.2 Pregnancy and Lactation . . . 2

1.3 Menopause . . . 3

1.4 Immunoprofile . . . 3

1.5 Further Reading . . . 3

2 Specimen Processing

2.1 Frozen Section . . . 8

2.2 Core Needle Biopsy . . . 9

2.3 Excisional Biopsy . . . 10

2.4 Mastectomy . . . 11

2.5 Axillary Lymph Nodes . . . 11

2.6 Sentinel Lymph Nodes . . . 12

2.7 Further Reading . . . 12

3 Fibrocystic Change and Duct Ectasia

3.1 Fibrocystic Change . . . 16

3.2 Duct Ectasia (Periductal Mastitis) . . . 17

4 Adenosis

4.1 Definition, Types, and Macroscopy of Adenosis . . . 28

4.2 Blunt Duct Adenosis . . . 28

4.3 Sclerosing Adenosis . . . 29

4.4 Apocrine Adenosis (Adenosis with Apocrine Metaplasia) . . . 30

4.5 Tubular Adenosis . . . 31

4.6 Adenomyoepithelial Adenosis . . . 31

4.7 Microglandular Adenosis . . . 32

4.8 Radial Scar/Complex Sclerosing Lesion . . . 32

4.9 Collagenous Spherulosis . . . 34

5 Intraductal Proliferative Lesions

5.1 Usual Ductal Hyperplasia . . . 68

5.2 Ductal Intraepithelial Neoplasia (DIN) . . . 70

5.3 Ductal Intraepithelial Neoplasia (DIN), Flat Type . . . . 72

5.4 Low-Grade Ductal Intraepithelial Neoplasia (WHO: DIN1b; Atypical Ductal Hyperplasia) . . . 74

5.5 Ductal Intraepithelial Neoplasia (WHO: DIN1c–DIN3, DCIS) . . . 76

6 Intraductal Papillary Neoplasms

6.1 Central Papilloma . . . 124

6.2 Peripheral Papilloma . . . 124

6.3 Sclerosing Papilloma . . . 125

6.4 Intraductal Papillary Carcinoma (Papillary Ductal Intraepithelial Neoplasia) . . . 125

6.5 Role of Immunohistochemistry in Diagnosing Intraductal Papillary Neoplasms . . . . 126

6.6 Additional Comments . . . 126

6.7 Further Reading . . . 127

7 Lobular Intraepithelial Neoplasia (LIN)

7.1 Synonyms . . . 156

7.2 Background . . . 156

7.3 Microscopic Features . . . 156

7.4 Additional Comments . . . 156

7.5 Further Reading . . . 157

8 Infiltrating Ductal Carcinoma (NOS Type)

8.1 Definition . . . 180

8.2 Macroscopy . . . 180

8.3 Microscopic Features . . . 180

8.4 Grading . . . 180

8.5 Additional Comments . . . 181

8.6 Further Reading . . . 181

Contents

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9 Invasive Lobular Carcinoma (ILC)

9.1 Macroscopy . . . 192

9.2 Microscopic Features . . . 192

9.3 Additional Comments . . . 192

9.4 Immunohistochemistry of LIN and ILC . . . 192

9.5 Grading . . . 192

9.6 Further Reading . . . 193

10 Special Types of Breast Carcinomas

10.1 Tubular Carcinoma . . . 223

10.2 Mucin-Producing Carcinomas of the Breast . . . 224

10.3 Carcinoma with Neuroendocrine Differentiation . . 226

10.4 Invasive Papillary Carcinoma . . . 227

10.5 Invasive Micropapillary Carcinoma . . . 227

10.6 Apocrine Carcinoma . . . 228

10.7 Secretory Carcinoma . . . 229

10.8 Adenoid Cystic Carcinoma . . . 230

10.9 Acinic Cell Carcinoma . . . 231

10.10 Sebaceous Carcinoma . . . 232

10.11 Infiltrating Cribriform Carcinoma . . . 232

10.12 Medullary Carcinoma . . . 233

10.13 Metaplastic Carcinomas . . . 234

10.14 Clear Cell (Glycogen-Rich) Carcinoma . . . 237

10.15 Lipid-Rich Carcinoma (Lipid-Secreting Carcinoma) 238 10.16 Metastatic Carcinoma . . . 238

10.17 Inflammatory Carcinoma . . . 239

11 Biphasic Tumors

11.1 Fibroadenoma . . . 320

11.2 Phylloides Tumor . . . 321

12 Diseases of the Nipple

12.1 Paget’s Disease . . . 352

12.2 Nipple Duct Adenoma . . . 353

12.3 (Infiltrating) Syringomatous Adenoma . . . 354

13 Male Breast Lesions

13.1 Gynecomastia . . . 366

13.2 Papilloma . . . 367

13.3 Primary Male Breast Carcinoma . . . 367

13.4 Further Reading . . . 367

14 Mesenchymal Lesions/Tumors

14.1 Stromal Elastosis . . . 377

14.2 Fat Necrosis . . . 377

14.3 Metaplasias . . . 378

14.4 Pseudoangiomatous Stromal Hyperplasia . . . 378

14.5 Fibromatosis . . . 379

14.6 Myofibroblastoma . . . 380

14.7 Lipoma . . . 381

14.8 Angiolipoma . . . 381

14.9 Granular Cell Tumor . . . 382

14.10 Hamartoma . . . 383

14.11 Perilobular Hemangioma . . . 383

14.12 Hemangioma . . . 384

14.13 Angiomatosis . . . 384

14.14 Angiosarcoma . . . 385

14.15 Leiomyosarcoma . . . 386

14.16 Liposarcoma . . . 387

14.17 Rhabdomyosarcoma . . . 387

14.18 Malignant Fibrous Histiocytoma . . . 388

14.19 Osteosarcoma . . . 389

14.20 Spindle Cell Sarcoma, Not Otherwise Specified (NOS-Type Mammary Sarcoma) . . . 389

15 Myoepithelial Lesions/Neoplasms

15.1 Background . . . 410

15.2 Immunoprofile . . . 410

15.3 Myoepithelial Cell Hypertrophy . . . 410

15.4 Myoepitheliosis (Myoepithelial Hyperplasia) . . . . 411

15.5 Adenomyoepithelioma . . . 411

15.6 Sarcomatoid Carcinoma with Myoepithelial Differentiation (Myoepithelial Carcinoma, Malignant Myoepithelioma) . . . 412

XII Contents

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16 Miscellaneous Lesions

16.1 Acute Mastitis (Puerperal Mastitis) . . . 420

16.2 Subareolar Abscess . . . 420

16.3 Plasma Cell Mastitis . . . 420

16.4 Idiopathic Granulomatous Mastitis . . . 421

16.5 Lymphocytic Mastitis (Diabetic Mastopathy) . . . . 421

16.6 Eosinophilic Mastitis . . . 422

16.7 Silicone Mastitis and Diseases Associated with Cosmetic Augmentation . . . 422

16.8 Further Reading . . . 422

16.9 Pathologic Effects of Adjuvant Radiotherapy . . . 423

16.10 Pathologic Effects of (Neo)adjuvant Chemotherapy . . . 423

16.11 Malignant Lymphoma . . . 424

16.12 Diffuse Large B-cell Lymphoma . . . 424

16.13 Burkitt’s Lymphoma . . . 425

16.14 Extranodal Marginal-Zone B-cell Lymphoma of MALT Type . . . 425

16.15 Follicular Lymphoma . . . 425

17 Cytopathology of Benign and Malignant Lesions (Selected Topics)

17.1 Introduction . . . 440

17.2 Fibrocystic Change . . . 440

17.3 Proliferative Breast Diseases Without Atypia (Adenosis, Ductal Hyperplasia) . . . 440

17.4 Proliferative Breast Lesions with Atypia . . . 441

17.5 Lactating Adenoma and Lactating Changes . . . 441

17.6 Fibroadenoma . . . 441

17.7 Intraductal Papilloma . . . 441

17.8 Ductal Intraepithelial Neoplasia (Ductal Carcinoma In Situ) . . . 441

17.9 Lobular Intraepithelial Neoplasia . . . 442

17.10 Intraductal Papillary Carcinoma . . . 442

17.11 Infiltrating Ductal Carcinoma . . . 442

17.12 Infiltrating Lobular Carcinoma . . . 442

17.13 Tubular Carcinoma . . . 443

17.14 Mucinous Carcinoma . . . 443

17.15 Medullary Carcinoma . . . 443

17.16 Apocrine Carcinoma . . . 443

17.17 Adenoid Cystic Carcinoma . . . 443

17.18 Metaplastic (Sarcomatoid) Carcinoma . . . 444

17.19 Phylloides (Phyllodes) Tumor . . . 444

17.20 Further Reading . . . 444

18 Immunohistochemistry (Selected Topics)

18.1 Role of Immunohistochemistry in Diagnostic Breast Pathology . . . 472

18.2 Immunohistochemistry in the Differential Diagnosis of Epithelial Lesions: Myoepithelial Cells . . . 472

18.3 Carcinomas with Myoepithelial Differentiation Versus Primary Sarcoma . . . 473

18.4 Microinvasive Carcinoma . . . 473

18.5 Cell Population in Intraductal Proliferative Lesions: Homogeneous Versus Heterogeneous Cell Population (Neoplasia Versus Hyperplasia) . . . 473

18.6 Paget’s Disease . . . 474

18.7 Distinction Between DIN (DCIS) and LIN (LCIS) . . . 474

18.8 Systemic Metastasis of Breast Carcinoma . . . 474

18.9 Micrometastatic Disease in Axillary Lymph Nodes (Including Sentinel Nodes) . . . 474

18.10 Immunohistochemistry for Prognostic or Predictive Factors in Breast Carcinoma: Hormone Receptors . . . 475

18.11 HER2/neu Overexpression . . . 475

18.12 Further Reading . . . 475

Subject Index

. . . 493

XIII Contents

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ADH Atypical ductal hyperplasia

CK Cytokeratin

CNB Core needle biopsy CSL Complex sclerosing lesion DLBCL Diffuse large B-cell lymphoma DCIS Ductal carcinoma in situ DIN Ductal intraepithelial neoplasia

FA Fibroadenoma

FISH Fluorescence in situ hybridization FNA Fine needle aspiration

FS Frozen section

H&E Hematoxylin and eosin HMW High molecular weight IDC Infiltrating ductal carcinoma IHC Immunohistochemistry ILC Invasive lobular carcinoma LCIS Lobular carcinoma in situ LIN Lobular intraepithelial neoplasia

LMW Low molecular weight

MALT Mucosa-associated lymphoid tissue MEC Myoepithelial cells

MFH Malignant fibrous histiocytoma MSA Muscle-specific actin

N/C Nucleus/cytoplasm NDA Nipple duct adenoma

PASH Pseudoangiomatous stromal hyperplasia PSA Prostatic specific antigen

PT Phylloides tumor

RS Radial scar

SA Sclerosing adenosis SLN Sentinel lymph node SMA Smooth muscle actin

SMMHC Smooth muscle myosin, heavy chain TDLU Terminal duct-lobular unit

UDH Usual ductal hyperplasia

Abbreviations

Riferimenti

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