Farid Moinfar Essentials of Diagnostic Breast Pathology

Farid Moinfar Essentials of Diagnostic Breast Pathology

Farid Moinfar Essentials of Diagnostic Breast Pathology A Practical Approach With 116 Figures in 1128 Seperate Illustrations and 6 Tables 123

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, broadcasting, 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 protective 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-T E X 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

Dedication 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.

Preface Several excellent and comprehensive textbooks have been written on breast pathology [1 5]. The magnificent 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 common 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 encouragement throughout the preparation of this book. I am indebted to the staff pathologists at the Department 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

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 understanding of its clinical implications. Arthur Purdy Stout Guiding the Surgeon s Hand: The History of American Surgical Pathology Juan Rosai (Editor)

Contents 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

XII Contents 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

Contents XIII 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

Abbreviations ADH CK CNB CSL DLBCL DCIS DIN FA FISH FNA FS H&E HMW IDC IHC ILC LCIS LIN Atypical ductal hyperplasia Cytokeratin Core needle biopsy Complex sclerosing lesion Diffuse large B-cell lymphoma Ductal carcinoma in situ Ductal intraepithelial neoplasia Fibroadenoma Fluorescence in situ hybridization Fine needle aspiration Frozen section Hematoxylin and eosin High molecular weight Infiltrating ductal carcinoma Immunohistochemistry Invasive lobular carcinoma Lobular carcinoma in situ Lobular intraepithelial neoplasia LMW MALT MEC MFH MSA N/C NDA PASH PSA PT RS SA SLN SMA SMMHC TDLU UDH Low molecular weight Mucosa-associated lymphoid tissue Myoepithelial cells Malignant fibrous histiocytoma Muscle-specific actin Nucleus/cytoplasm Nipple duct adenoma Pseudoangiomatous stromal hyperplasia Prostatic specific antigen Phylloides tumor Radial scar Sclerosing adenosis Sentinel lymph node Smooth muscle actin Smooth muscle myosin, heavy chain Terminal duct-lobular unit Usual ductal hyperplasia