Table Of Content20060_FM 23/04/10 8:50 AM Page i
Breast Pathology
Diagnosis by Needle Core Biopsy
THIRD EDITION
20060_FM 23/04/10 8:50 AM Page ii
20060_FM 23/04/10 8:50 AM Page iii
Breast Pathology
Diagnosis by Needle Core Biopsy
THIRD EDITION
nnn PAUL PETER ROSEN, M.D.
Emeritus Professor of Pathology
Weill Medical College of
Cornell University
Formerly, Chief of Breast Pathology
New York Presbyterian Hospital
Cornell Center
New York, New York
nnn SYED A. HODA, M.D.
Professor of Clinical Pathology
Weill Medical College of
Cornell University
Attending Pathologist
New York Presbyterian Hospital
Cornell Center
New York, New York
20060_FM 23/04/10 8:50 AM Page iv
Senior Executive Editor:Jonathan W. Pine, Jr.
Product Manager:Marian Bellus
Vendor Manager:Bridgett Dougherty
Senior Manufacturing Manager:Benjamin Rivera
Senior Marketing Manager:Angela Panetta
Creative Director:Doug Smock
Production Service:MPS Limited, A Macmillan Company
Copyright ©2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Two Commerce Square
2001 Market Street
Philadelphia, PA 19103
©2006, 1999 Lippincott Williams & Wilkins.
All rights reserved. This book is protected by copyright. No part of this book may be
reproduced in any form or by any means, or utilized by any information storage and
retrieval system without written permission from the copyright owner, except for
brief quotations embodied in critical articles and reviews.
Printed in the People’s Republic of China.
Cover images: Top Row:Myoepithelial hyperplasia in adenosis in fat; myoepithelial
hyperplasia in adenosis in fat; myoepithelial cell nuclei are highlighted by the p63
immunostain; intraductal myoepithelial carcinoma; intraductal myoepithelial
carcinoma with diffuse nuclear reactivity for p63. Bottom Row:Florid intraductal
lobular carcinoma in situcomposed of cells with cytoplasmic mucin; florid intraductal
lobular carcinoma in situ;E-cadherin immunoreactivity is absent; granular cell tumor
surrounding a duct; intraductal papillomas with histiocytes in fibrovascular stroma.
Library of Congress Cataloging-in-Publication Data
Rosen, Paul Peter.
Breast pathology: diagnosis by needle core biopsy/Paul Peter Rosen,
Syed A. Hoda.—3rd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-60831-670-0 (alk. paper)
1. Breast—Needle biopsy. 2. Breast—Diseases—Diagnosis.
3. Breast—Histopathology. I. Hoda, Syed A. II. Title.
[DNLM: 1. Breast Neoplasms—pathology. 2. Biopsy, Needle.
3. Breast—pathology. WP 870 R813b 2010]
RG493.5.B56R67 2010
616.99’44907—dc22
2010011834
Care has been taken to confirm the accuracy of the information presented and to
describe generally accepted practices. However, the authors, editors, and publisher
are not responsible for errors or omissions or for any consequences from application
of the information in this book and make no warranty, expressed or implied, with
respect to the currency, completeness, or accuracy of the contents of the publication.
Application of this information in a particular situation remains the professional
responsibility of the practitioner; the clinical treatments described and
recommended may not be considered absolute and universal recommendations.
The authors, editors, and publisher have exerted every effort to ensure that drug
selection and dosage set forth in this text are in accordance with the current
recommendations and practice at the time of publication. However, in view of
ongoing research, changes in government regulations, and the constant flow of
information relating to drug therapy and drug reactions, the reader is urged to check
the package insert for each drug for any change in indications and dosage and for
added warnings and precautions. This is particularly important when the
recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and
Drug Administration (FDA) clearance for limited use in restricted research settings.
It is the responsibility of the health care provider to ascertain the FDA status of each
drug or device planned for use in his or her clinical practice.
Visit Lippincott Williams & Wilkins on the Internet at: LWW.COM. Lippincott
Williams & Wilkins customer service representatives are available from 8:30 am to
6 pm, EST.
9 8 7 6 5 4 3 2 1
20060_FM 23/04/10 8:50 AM Page v
In memory of
Flora Caspari and Paul Caspari, M.D.
Rose Rosen and Morris Rosen
and for
Mary Sue Rosen
Deborah, Madelyn, John
Jon, Karen, Jordan, Mitch
Stacy, James, Paige, Denis
In memory of
Rabia Hoda and Qamar Hoda
and for
Rana Hoda and Raza Hoda
20060_FM 30/04/10 9:41 PM Page vi
Contents
Preface to First Edition (Updated) vii 17 Adenoid Cystic Carcinoma 223
Preface to Third Edition ix
18 Secretory Carcinoma 229
Acknowledgments x
Introduction xi 19 Cystic Hypersecretory Carcinoma 233
1 Anatomy and Physiologic Morphology 1 20 Other Special Types of Invasive Duct
Carcinoma 237
2 Inflammatory and Reactive Tumors 9
21 Lobular Carcinoma In Situ and Atypical Lobular
3 Specific Infections 23
Hyperplasia 246
4 Benign Papillary Tumors 27
22 Invasive Lobular Carcinoma 263
5 Myoepithelial Neoplasms 52
23 Mesenchymal Neoplasms 274
6 Adenosis and Microglandular Adenosis 61
24 Lymphoid and Hematopoietic Tumors 303
7 Fibroepithelial Neoplasms 77
25 Metastases in the Breast from Nonmammary
8 Ductal Hyperplasia and Intraductal Carcinoma 97 Malignant Neoplasms 313
9 Invasive Duct Carcinoma 144 26 Pathologic Effects of Therapy 319
10 Tubular Carcinoma 161 27 Breast Lesions in Men and Children 329
11 Papillary Carcinoma 171 28 Pathologic Changes Associated with Needling
Procedures 340
12 Medullary Carcinoma 187
29 Specimen Processing, Pathologic Examination,
13 Carcinoma with Metaplasia 191
and Reporting 348
14 Squamous Carcinoma 202
15 Mucinous Carcinoma 205
Index 360
16 Apocrine Carcinoma 213
20060_FM 23/04/10 8:50 AM Page vii
Preface to First Edition
(Updated)
Prior to the widespread implementation of breast conser- therapy. This is a limitation of the procedure and not a
vation therapy, the role of the pathologist in breast cancer failure on the part of the pathologist or radiologist. When
care was limited to making the diagnosis from tissue ob- this situation arises, it is necessary for physicians caring
tained by surgical biopsy and documenting the extent of for the patient to consider the entire clinical situation.
the tumor after a mastectomy was performed. These two This process of reflection is often referred to as “clinical
events typically centered around a single operative proce- correlation.”
dure in which the diagnosis made with a frozen section Many mammographically detected nonpalpable lesions
was followed by a mastectomy and axillary lymph node present the pathologist with challenging diagnostic prob-
dissection. Presently, considerably more information is re- lems when excised intact and viewed in context with sur-
quired to recommend breast cancer treatment that may rounding tissues. The appearance of such lesions in the
employ more than one of the major existing therapeutic incomplete and often disrupted form of needle core biopsy
modalities: surgery, radiation, and chemotherapy. An im- samples can substantially increase the degree of difficulty.
portant part of the data used for therapeutic decisions is The major differential diagnostic problems encountered in
generated by the pathologist using routine histopathologic these specimens include:
procedures and immunohistochemistry.
n reactive changes vs. recurrent carcinoma after lumpectomy
The complex multifactorial description of breast patho -
n benign sclerosing lesions (radial scar ) vs. infiltrating
logy now considered to be standard practice has expanded
carcinoma
the diagnostic report from a brief one- or two-line state-
n papilloma vs. papillary carcinoma
ment, such as “Infiltrating duct carcinoma, grade II; nega-
n fibroadenoma vs. cystosarcoma
tive lymph nodes” to a catalogue of data one or more pages
n atypical duct hyperplasia vs. intraductal carcinoma (DCIS)
in length, often including many statements indicating the
n DCIS vs. DCIS with (micro)invasion
absence as well as the presence of features regarded as rele-
n spindle cell tumors (metaplastic carcinoma vs. sarcoma)
vant to therapeutic decisions and to prognosis. A partial
n vascular lesions (angioma vs. angiosarcoma)
list of this information includes classification of the carci-
noma, histologic grade, nuclear grade, tumor size, and Although self-evident, it is important to understand that
statements about vascular invasion, the proportion of the the diagnosis made with a needle core biopsy specimen
in situ component in invasive lesions, subtype of in situ can only be based on the samples available to the patholo-
carcinoma, multifocality, and proximity of carcinoma to gist and that these samples are not always representative of
margins of excision. Immunohistochemistry is used to all of the pathologic findings in a given case. Conse-
characterize distribution of estrogen and progesterone re- quently, carcinoma may be found in up to 50% of surgical
ceptors, as well as other biomarkers and oncogene expres- biopsies after a needle core biopsy diagnosis of atypical hy-
sion which are part of pathology reports. Proliferative perplasia, and microinvasion may be present in about 20%
activity may be estimated by the pathologist using im- of surgical excisions after a needle core diagnosis of intra-
munohistochemistry. ductal carcinoma. Three principles offer guidance in the
Other advances have added to the complexity of the use of the needle core biopsy procedure for the diagnosis
pathologist’s role in breast cancer treatment. Primary and treatment of breast lesions:
among these is the widespread use of needle core biopsy
n Anything can turn up.
procedures, especially for the diagnosis of nonpalpable
n What you see is what you have and it may not be all
mammographically detected lesions. Stereotactic needle
there is.
core biopsy is an extremely valuable tool in planning
n What you have may be all there is.
breast conservation therapy because it can establish the
diagnosis of nonpalpable lesions before operative surgi- The emergence of the needle core biopsy procedure as a
cal intervention. Needle core biopsy procedures often major diagnostic tool epitomizes the growing complexity of
yield diagnostic samples, but in a significant number of the interaction of radiologists, surgeons, and pathologists in
cases the material obtained offers ambiguous findings the diagnosis and management of mammary diseases, espe-
that do not provide a specific diagnosis on which to base cially in the era of breast conservation therapy. Specialization
20060_FM 23/04/10 8:50 AM Page viii
viii Preface to First Edition (Updated)
in medicine has created circumstances in which the specialist diagnosis, does not permit inclusion of contributions from
physician is increasingly dependent on the assistance of col- other important members of the team, including surgeons,
leagues who have acquired complementary expertise. This radiotherapists, and medical oncologists who depend on
evolving situation has contributed to the team approach to these diagnoses to implement therapy.
disease management reflected in this volume. The inten-
tional limited scope of this presentation, which focuses on Paul Peter Rosen, M.D.
20060_FM 23/04/10 8:50 AM Page ix
Preface to Third Edition
This third edition of Breast Pathology Diagnosis by Needle ences and text that appeared in the second edition to limit
Core Biopsy builds upon the two preceding volumes. A the book to a manageable size. As a consequence, we are
substantial number of images have been added, and a few no longer able to include chapters on the clinical aspects of
images have been replaced. New and updated information imaging and needle core biopsy techniques that appeared
is provided on laboratory procedures for processing needle in prior editions.
core biopsy samples, the use of immunohistochemistry This edition has been thoroughly reviewed, rewritten,
and molecular studies in the diagnosis of breast lesions, and subjected to rigorous scrutiny by the publisher’s excel-
and differential diagnosis. The advantages and limitations lent staff at various stages in the production process. The
of needle core biopsy sampling are emphasized through- choice of illustrations and references, the selection of data
out the text. New topics include basal-like and triple nega- cited, and the conclusions expressed reflect the authors’ ex-
tive carcinoma. perience and opinions.
As new information, references, and illustrations have
been added, it has become necessary to omit selected refer- Paul Peter Rosen, M.D.
