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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 ofPathology Director,Unit ofBreast & Gynecologic Pathology Department ofPathology Medical University Graz Auenbruggerplatz 25 8036 Graz Austria Library ofCongress 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 ofthe material is concerned,specifically the rights oftranslation,reprinting,reuse ofillustrations,recitation,broadcast- ing,reproduction on microfilm or in any other way,and storage in data banks.Duplication of this publication or parts thereofis permitted only under the provisions ofthe 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 ofSpringer Science+Business Media springer.com © Springer-Verlag Berlin Heidelberg 2007 The use ofgeneral descriptive names,registered names,trademarks,etc.in this publication does not imply,even in the absence ofa 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 ofany 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 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 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 ofbreast lesions in daily practice,surgical pathologists want and need to know the essentials ofdiagnostic 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 ofcommon 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 ofPathology,Medical University Graz,who have supported me during the preparation ofthis 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 staffofthe publisher,Springer,in particular Mrs.Gabriele M. Schröder and Mrs.Ellen Blasig for their professional and efficient cooperation and consideration in the production ofthis 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 ofthe breast.Churchill Livingstone,Edinburgh,1987. 3. Rosen PP.Rosen’s breast pathology,2nd edn.Lippincott Williams & Wilkins,Philadelphia,2001. 4. Tavassoli FA.Pathology ofthe breast,2nd edn.Appleton & Lange,Stamford,CT,1999. 5. Tavassoli FA, Devilee P (eds). World Health Organization classification of tumours. Pathology and genetics. Tumours ofthe 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 ofhumility,a readiness to listen to the arguments ofothers,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 ofAmerican Surgical Pathology Juan Rosai (Editor) Contents 1 The Normal Breast 5 Intraductal Proliferative Lesions 1.1 Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . 2 5.1 Usual Ductal Hyperplasia . . . . . . . . . . . . . . . . . . 68 1.2 Pregnancy and Lactation . . . . . . . . . . . . . . . . . . 2 5.2 Ductal Intraepithelial Neoplasia (DIN) . . . . . . . . . . . 70 1.3 Menopause . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 5.3 Ductal Intraepithelial Neoplasia (DIN),Flat Type . . . . 72 1.4 Immunoprofile . . . . . . . . . . . . . . . . . . . . . . . . . 3 5.4 Low-Grade Ductal Intraepithelial Neoplasia (WHO:DIN1b;Atypical Ductal Hyperplasia) . . . . . . . 74 1.5 Further Reading . . . . . . . . . . . . . . . . . . . . . . . . 3 5.5 Ductal Intraepithelial Neoplasia (WHO:DIN1c–DIN3,DCIS) . . . . . . . . . . . . . . . . . 76 2 Specimen Processing 6 Intraductal Papillary Neoplasms 2.1 Frozen Section . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.2 Core Needle Biopsy . . . . . . . . . . . . . . . . . . . . . . 9 6.1 Central Papilloma . . . . . . . . . . . . . . . . . . . . . . 124 2.3 Excisional Biopsy . . . . . . . . . . . . . . . . . . . . . . . 10 6.2 Peripheral Papilloma . . . . . . . . . . . . . . . . . . . . 124 2.4 Mastectomy . . . . . . . . . . . . . . . . . . . . . . . . . . 11 6.3 Sclerosing Papilloma . . . . . . . . . . . . . . . . . . . . 125 2.5 Axillary Lymph Nodes . . . . . . . . . . . . . . . . . . . . 11 6.4 Intraductal Papillary Carcinoma 2.6 Sentinel Lymph Nodes . . . . . . . . . . . . . . . . . . . . 12 (Papillary Ductal Intraepithelial Neoplasia) . . . . . . . 125 2.7 Further Reading . . . . . . . . . . . . . . . . . . . . . . . . 12 6.5 Role of Immunohistochemistry in Diagnosing Intraductal Papillary Neoplasms . . . . 126 3 Fibrocystic Change and Duct Ectasia 6.6 Additional Comments . . . . . . . . . . . . . . . . . . . 126 6.7 Further Reading . . . . . . . . . . . . . . . . . . . . . . . 127 3.1 Fibrocystic Change . . . . . . . . . . . . . . . . . . . . . . 16 3.2 Duct Ectasia (Periductal Mastitis) . . . . . . . . . . . . . . 17 7 Lobular Intraepithelial Neoplasia (LIN) 4 Adenosis 7.1 Synonyms . . . . . . . . . . . . . . . . . . . . . . . . . . . 156 7.2 Background . . . . . . . . . . . . . . . . . . . . . . . . . . 156 4.1 Definition,Types,and Macroscopy of Adenosis . . . . . 28 7.3 Microscopic Features . . . . . . . . . . . . . . . . . . . . 156 4.2 Blunt Duct Adenosis . . . . . . . . . . . . . . . . . . . . . 28 7.4 Additional Comments . . . . . . . . . . . . . . . . . . . 156 4.3 Sclerosing Adenosis . . . . . . . . . . . . . . . . . . . . . . 29 7.5 Further Reading . . . . . . . . . . . . . . . . . . . . . . . 157 4.4 Apocrine Adenosis (Adenosis with Apocrine Metaplasia) . . . . . . . . . . . 30 8 Infiltrating Ductal Carcinoma (NOS Type) 4.5 Tubular Adenosis . . . . . . . . . . . . . . . . . . . . . . . 31 4.6 Adenomyoepithelial Adenosis . . . . . . . . . . . . . . . 31 8.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 4.7 Microglandular Adenosis . . . . . . . . . . . . . . . . . . 32 8.2 Macroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . 180 4.8 Radial Scar/Complex Sclerosing Lesion . . . . . . . . . . 32 8.3 Microscopic Features . . . . . . . . . . . . . . . . . . . . 180 4.9 Collagenous Spherulosis . . . . . . . . . . . . . . . . . . . 34 8.4 Grading . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 8.5 Additional Comments . . . . . . . . . . . . . . . . . . . 181 8.6 Further Reading . . . . . . . . . . . . . . . . . . . . . . . 181 XII Contents 9 Invasive Lobular Carcinoma (ILC) 13 Male Breast Lesions 9.1 Macroscopy . . . . . . . . . . . . . . . . . . . . . . . . . 192 13.1 Gynecomastia . . . . . . . . . . . . . . . . . . . . . . . 366 9.2 Microscopic Features . . . . . . . . . . . . . . . . . . . 192 13.2 Papilloma . . . . . . . . . . . . . . . . . . . . . . . . . . 367 9.3 Additional Comments . . . . . . . . . . . . . . . . . . 192 13.3 Primary Male Breast Carcinoma . . . . . . . . . . . . 367 9.4 Immunohistochemistry of LIN and ILC . . . . . . . . 192 13.4 Further Reading . . . . . . . . . . . . . . . . . . . . . . 367 9.5 Grading . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 9.6 Further Reading . . . . . . . . . . . . . . . . . . . . . . 193 14 Mesenchymal Lesions/Tumors 14.1 Stromal Elastosis . . . . . . . . . . . . . . . . . . . . . . 377 10 Special Types of Breast Carcinomas 14.2 Fat Necrosis . . . . . . . . . . . . . . . . . . . . . . . . . 377 10.1 Tubular Carcinoma . . . . . . . . . . . . . . . . . . . . 223 14.3 Metaplasias . . . . . . . . . . . . . . . . . . . . . . . . . 378 10.2 Mucin-Producing Carcinomas of the Breast . . . . . 224 14.4 Pseudoangiomatous Stromal Hyperplasia . . . . . . 378 10.3 Carcinoma with Neuroendocrine Differentiation . . 226 14.5 Fibromatosis . . . . . . . . . . . . . . . . . . . . . . . . 379 10.4 Invasive Papillary Carcinoma . . . . . . . . . . . . . . 227 14.6 Myofibroblastoma . . . . . . . . . . . . . . . . . . . . 380 10.5 Invasive Micropapillary Carcinoma . . . . . . . . . . 227 14.7 Lipoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 381 10.6 Apocrine Carcinoma . . . . . . . . . . . . . . . . . . . 228 14.8 Angiolipoma . . . . . . . . . . . . . . . . . . . . . . . . 381 10.7 Secretory Carcinoma . . . . . . . . . . . . . . . . . . . 229 14.9 Granular Cell Tumor . . . . . . . . . . . . . . . . . . . . 382 10.8 Adenoid Cystic Carcinoma . . . . . . . . . . . . . . . 230 14.10 Hamartoma . . . . . . . . . . . . . . . . . . . . . . . . . 383 10.9 Acinic Cell Carcinoma . . . . . . . . . . . . . . . . . . 231 14.11 Perilobular Hemangioma . . . . . . . . . . . . . . . . 383 10.10 Sebaceous Carcinoma . . . . . . . . . . . . . . . . . . 232 14.12 Hemangioma . . . . . . . . . . . . . . . . . . . . . . . . 384 10.11 Infiltrating Cribriform Carcinoma . . . . . . . . . . . 232 14.13 Angiomatosis . . . . . . . . . . . . . . . . . . . . . . . 384 10.12 Medullary Carcinoma . . . . . . . . . . . . . . . . . . . 233 14.14 Angiosarcoma . . . . . . . . . . . . . . . . . . . . . . . 385 10.13 Metaplastic Carcinomas . . . . . . . . . . . . . . . . . 234 14.15 Leiomyosarcoma . . . . . . . . . . . . . . . . . . . . . 386 10.14 Clear Cell (Glycogen-Rich) Carcinoma . . . . . . . . . 237 14.16 Liposarcoma . . . . . . . . . . . . . . . . . . . . . . . . 387 10.15 Lipid-Rich Carcinoma (Lipid-Secreting Carcinoma) 238 14.17 Rhabdomyosarcoma . . . . . . . . . . . . . . . . . . . 387 10.16 Metastatic Carcinoma . . . . . . . . . . . . . . . . . . 238 14.18 Malignant Fibrous Histiocytoma . . . . . . . . . . . . 388 10.17 Inflammatory Carcinoma . . . . . . . . . . . . . . . . 239 14.19 Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . 389 14.20 Spindle Cell Sarcoma,Not Otherwise Specified (NOS-Type Mammary Sarcoma) . . . . . . . . . . . . 389 11 Biphasic Tumors 11.1 Fibroadenoma . . . . . . . . . . . . . . . . . . . . . . . 320 15 Myoepithelial Lesions/Neoplasms 11.2 Phylloides Tumor . . . . . . . . . . . . . . . . . . . . . 321 15.1 Background . . . . . . . . . . . . . . . . . . . . . . . . 410 15.2 Immunoprofile . . . . . . . . . . . . . . . . . . . . . . . 410 12 Diseases of the Nipple 15.3 Myoepithelial Cell Hypertrophy . . . . . . . . . . . . 410 12.1 Paget’s Disease . . . . . . . . . . . . . . . . . . . . . . . 352 15.4 Myoepitheliosis (Myoepithelial Hyperplasia) . . . . 411 12.2 Nipple Duct Adenoma . . . . . . . . . . . . . . . . . . 353 15.5 Adenomyoepithelioma . . . . . . . . . . . . . . . . . 411 12.3 (Infiltrating) Syringomatous Adenoma . . . . . . . . 354 15.6 Sarcomatoid Carcinoma with Myoepithelial Differentiation (Myoepithelial Carcinoma, Malignant Myoepithelioma) . . . . . . . . . . . . . . 412 Contents XIII 17.10 Intraductal Papillary Carcinoma . . . . . . . . . . . . 442 16 Miscellaneous Lesions 17.11 Infiltrating Ductal Carcinoma . . . . . . . . . . . . . . 442 16.1 Acute Mastitis (Puerperal Mastitis) . . . . . . . . . . . 420 17.12 Infiltrating Lobular Carcinoma . . . . . . . . . . . . . 442 16.2 Subareolar Abscess . . . . . . . . . . . . . . . . . . . . 420 17.13 Tubular Carcinoma . . . . . . . . . . . . . . . . . . . . 443 16.3 Plasma Cell Mastitis . . . . . . . . . . . . . . . . . . . . 420 17.14 Mucinous Carcinoma . . . . . . . . . . . . . . . . . . . 443 16.4 Idiopathic Granulomatous Mastitis . . . . . . . . . . 421 17.15 Medullary Carcinoma . . . . . . . . . . . . . . . . . . . 443 16.5 Lymphocytic Mastitis (Diabetic Mastopathy) . . . . 421 17.16 Apocrine Carcinoma . . . . . . . . . . . . . . . . . . . 443 16.6 Eosinophilic Mastitis . . . . . . . . . . . . . . . . . . . 422 17.17 Adenoid Cystic Carcinoma . . . . . . . . . . . . . . . 443 16.7 Silicone Mastitis and Diseases Associated 17.18 Metaplastic (Sarcomatoid) Carcinoma . . . . . . . . 444 with Cosmetic Augmentation . . . . . . . . . . . . . 422 17.19 Phylloides (Phyllodes) Tumor . . . . . . . . . . . . . . 444 16.8 Further Reading . . . . . . . . . . . . . . . . . . . . . . 422 17.20 Further Reading . . . . . . . . . . . . . . . . . . . . . . 444 16.9 Pathologic Effects of Adjuvant Radiotherapy . . . . . . . . . . . . . . . . 423 18 Immunohistochemistry (Selected Topics) 16.10 Pathologic Effects of (Neo)adjuvant Chemotherapy . . . . . . . . . . . 423 18.1 Role of Immunohistochemistry 16.11 Malignant Lymphoma . . . . . . . . . . . . . . . . . . 424 in Diagnostic Breast Pathology . . . . . . . . . . . . . 472 16.12 Diffuse Large B-cell Lymphoma . . . . . . . . . . . . 424 18.2 Immunohistochemistry 16.13 Burkitt’s Lymphoma . . . . . . . . . . . . . . . . . . . 425 in the Differential Diagnosis 16.14 Extranodal Marginal-Zone B-cell Lymphoma of Epithelial Lesions:Myoepithelial Cells . . . . . . . 472 of MALT Type . . . . . . . . . . . . . . . . . . . . . . . . 425 18.3 Carcinomas with Myoepithelial Differentiation 16.15 Follicular Lymphoma . . . . . . . . . . . . . . . . . . . 425 Versus Primary Sarcoma . . . . . . . . . . . . . . . . . 473 18.4 Microinvasive Carcinoma . . . . . . . . . . . . . . . . 473 18.5 Cell Population in Intraductal Proliferative Lesions: 17 Cytopathology of Benign Homogeneous Versus Heterogeneous and Malignant Lesions (Selected Topics) Cell Population (Neoplasia Versus Hyperplasia) . . . 473 18.6 Paget’s Disease . . . . . . . . . . . . . . . . . . . . . . . 474 17.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . 440 18.7 Distinction Between DIN (DCIS) and LIN (LCIS) . . . 474 17.2 Fibrocystic Change . . . . . . . . . . . . . . . . . . . . 440 18.8 Systemic Metastasis of Breast Carcinoma . . . . . . 474 17.3 Proliferative Breast Diseases Without Atypia (Adenosis,Ductal Hyperplasia) . . . . . . . . . . . . . 440 18.9 Micrometastatic Disease in Axillary Lymph Nodes (Including Sentinel Nodes) . . . . . . . . . . . . . . . 474 17.4 Proliferative Breast Lesions with Atypia . . . . . . . . 441 18.10 Immunohistochemistry for Prognostic 17.5 Lactating Adenoma and Lactating Changes . . . . . 441 or Predictive Factors in Breast Carcinoma: 17.6 Fibroadenoma . . . . . . . . . . . . . . . . . . . . . . . 441 Hormone Receptors . . . . . . . . . . . . . . . . . . . 475 17.7 Intraductal Papilloma . . . . . . . . . . . . . . . . . . . 441 18.11 HER2/neu Overexpression . . . . . . . . . . . . . . . . 475 17.8 Ductal Intraepithelial Neoplasia 18.12 Further Reading . . . . . . . . . . . . . . . . . . . . . . 475 (Ductal Carcinoma In Situ) . . . . . . . . . . . . . . . . 441 17.9 Lobular Intraepithelial Neoplasia . . . . . . . . . . . 442 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . 493

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This abundantly illustrated reference work focuses on the essential information needed by pathologists in order to interpret breast lesions (tumors) appropriately. Particular attention is paid to the diagnostic criteria with systematic analysis of differential diagnoses. Value and limitations of imm
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