Farid Moinfar
Essentials of Diagnostic Breast Pathology
Farid Moinfar
123
Essentials
of Diagnostic
Breast Pathology
A Practical Approach
With 116 Figures in 1128 Seperate Illustrations and 6 Tables
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
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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
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Printed on acid-free paper 24/3100/YL – 5 4 3 2 1 0
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
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
“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)
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 . . . 82.2 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 . . . 163.2 Duct Ectasia (Periductal Mastitis) . . . 17
4 Adenosis
4.1 Definition, Types, and Macroscopy of Adenosis . . . 284.2 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 . . . 685.2 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 . . . 1246.2 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 . . . 1567.2 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 . . . 1808.2 Macroscopy . . . 180
8.3 Microscopic Features . . . 180
8.4 Grading . . . 180
8.5 Additional Comments . . . 181
8.6 Further Reading . . . 181
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 . . . 22310.2 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 . . . 32011.2 Phylloides Tumor . . . 321
12 Diseases of the Nipple
12.1 Paget’s Disease . . . 35212.2 Nipple Duct Adenoma . . . 353
12.3 (Infiltrating) Syringomatous Adenoma . . . 354
13 Male Breast Lesions
13.1 Gynecomastia . . . 36613.2 Papilloma . . . 367
13.3 Primary Male Breast Carcinoma . . . 367
13.4 Further Reading . . . 367
14 Mesenchymal Lesions/Tumors
14.1 Stromal Elastosis . . . 37714.2 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 . . . 41015.2 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
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 . . . 44017.2 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 . . . 47218.2 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
. . . 493XIII Contents
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