Table Of ContentCommissioning Editor: Michael J Houston
Development Editor: Sharon Nash
Project Manager: Rory MacDonald
Design: Erik Bigland
Illustration Manager: Merlyn Harvey
Illustrator: Richard Prime
Marketing Manager(s) (UK/USA): John Canelon/Radha Mawrie
ROBBOY’S
PATHOLOGY
FEMALE
of the
REPRODUCTIVE
TRACT
SECOND EDITION
Edited by
Stanley J. Robboy Rex C. Bentley
MD FCAP MD FCAP
Professor and Vice Chairman, Department of Pathology, Associate Professor of Pathology, Department of Pathology,
Chief, Division of Diagnostic Services, Professor of Obstetrics Duke University Medical Center, Durham, NC, USA
& Gynecology, Duke University Medical Center, Durham, NC,
Peter Russell
USA MD FRCPA
Professor of Pathology, The University of Sydney and Director,
George L. Mutter
MD FCAP Department of Anatomical Pathology, Royal Prince Alfred
Associate Professor of Pathology, Harvard Medical School, Hospital, Camperdown, NSW, Australia
Department of Pathology, Brigham and Women’s Hospital,
Malcolm C. Anderson
Boston, MA, USA FRCPath FRCOG
Emeritus Consultant Histopathologist, Department of
Jaime Prat
MD PhD FRCPath Histopathology, University Hospital, Queen’s Medical Centre,
Professor and Chairman, Department of Pathology, Hospital Nottingham, UK
de la Santa Creu i Sant Pau, Autonomous University of
Barcelona, Barcelona, Spain
Notice
Medical knowledge is constantly changing. Standard safety precautions
must be followed, but as new research and clinical experience broaden
our knowledge, changes in treatment and drug therapy may become
CHURCHILL LIVINGSTONE necessary or appropriate. Readers are advised to check the most current
An imprint of Elsevier Limited. product information provided by the manufacturer of each drug to be
administered to verify the recommended dose, the method and duration
© 2009, Elsevier Limited. All rights reserved. of administration, and contraindications. It is the responsibility of the
practitioner, relying on experience and knowledge of the patient, to
First edition 2002 determine dosages and the best treatment for each individual patient.
Neither the Publisher nor the authors assume any liability for any injury
The right of Stanley J Robboy, George L Mutter, Jaime Prat, and/or damage to persons or property arising from this publication.
Rex C Bentley, Peter Russell & Malcolm C Anderson to be identifi ed The Publisher
as editors of this work has been asserted by them in accordance with the
Copyright, Designs and Patents Act 1988.
No part of this publication may be reproduced or transmitted in
any form or by any means, electronic or mechanical, including
photocopying, recording, or any information storage and retrieval
system, without permission in writing from the publisher. Permissions
may be sought directly from Elsevier’s Rights Department: phone: (+1)
215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; Working together to grow
e-mail: [email protected]. You may also complete your libraries in developing countries
request on-line via the Elsevier website at
http://www.elsevier.com/permissions. www.elsevier.com | www.bookaid.org | www.sabre.org
ISBN: 978-0-443-07477-6
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging in Publication Data
A catalog record for this book is available from the Library of Congress
The
publisher’s
policy is to use
Printed in China paper manufactured
from sustainable forests
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Contributors
Malcolm C Anderson FRCOG FRCPath John H Eichhorn MD FASCP FIAC FCAP
Emeritus Consultant Histopathologist Assistant Professor of Pathology
University Hospital Harvard Medical School;
Queen’s Medical Centre Department of Pathology
Nottingham, UK Massachusetts General Hospital
Boston, MA, USA
Jan PA Baak MD PhD FRCPath FIAC(Hon)
DrHonCausa(Antwerp) Marc Fellous MD
Professor of Pathology Faculté de Médecine Descartes
University of Bergen and Free University (Amsterdam); Institut Cochin
Department of Pathology Inserm
Stavanger University Hospital Paris, France
Stavanger, Norway
Christopher D M Fletcher MD FRCPath
Sarah M Bean MD FCAP Professor of Pathology
Assistant Professor of Pathology Harvard Medical School;
Department of Pathology Professor and Director of Surgical Pathology
Duke University Medical Center Department of Pathology
Durham, NC, USA Brigham and Women’s Hospital
Boston, MA, USA
Rex C Bentley MD FCAP
Associate Professor of Pathology Peter Gearhart MD FACOG
Department of Pathology Clinical Assistant Professor of Obstetrics and Gynecology
Duke University Medical Center University of Pennsylvania;
Durham, NC, USA Department of Obstetrics & Gynecology
Penn Hospital
Annie N Y Cheung MBBS MD FRCPath (UK) FHKAM(Path) Philadelphia, PA, USA
FIAC
Professor of Pathology Arthur F Haney MD FACOG
Honorary Consultant Professor and Chairman
Department of Pathology Department of Obstetrics & Gynecology
Queen Mary Hospital University of Chicago Medical Center
The University of Hong Kong Chicago, IL, USA
Hong Kong, China
Christopher B Hubbard MD
Rajesh Dash MD FCAP Director, Pathology Informatics
Assistant Professor of Pathology Department of Pathology
Department of Pathology Duke University Medical Center
Duke University Medical Center Durham, NC, USA
Durham, NC, USA
Francis Jaubert MD
Emma M Doyle MB MRCOG FRCPath Professeur Université Descartes
Lecturer in Pathology Praticien Hospitalier APHP
School of Medicine and Medical Science Groupe Hospitalier Necker-Enfants Malades
University College Dublin Paris, France
Dublin, Ireland
Richard C Jaworski MB BS (Hons) FRCPA
Pathologist
Douglass Hanly Moir Pathology xxix
Macquarie Park, NSW, Australia
CONTRIBUTORS
James V Lacey Jr MPH PhD George L Mutter MD
Investigator Associate Professor of Pathology
Hormonal and Reproductive Epidemiology Branch Harvard Medical School;
Division of Cancer Epidemiology and Genetics Department of Pathology
National Cancer Institute Division of Women’s and Perinatal Pathology
Rockville, MD, USA Brigham and Women’s Hospital
Boston, MA, USA
Anand S Lagoo MD PhD FCAP FASCP
Associate Professor of Pathology Marisa R Nucci MD
Director, Clinical Flow Cytometry Laboratory Associate Professor of Pathology
Department of Pathology Harvard Medical School;
Duke University Medical Center Associate Pathologist
Durham, NC, USA Department of Pathology
Division of Women’s and Perinatal Pathology
Sigurd F Lax MD PhD Brigham and Women’s Hospital
Associate Professor of Pathology Boston, MA, USA
Medical University Graz;
Head of Department of Pathology Jaime Prat MD FRCPath
General Hospital Graz West Professor and Chairman
Graz, Austria Department of Pathology
Hospital de la Santa Creu i Sant Pau
John F Madden MD Autonomous University of Barcelona
Associate Professor of Pathology Barcelona, Spain
Department of Pathology
Duke University Medical Center Bradley J Quade MD PhD
Durham, NC, USA Associate Professor of Pathology
Harvard Medical School;
Anais Malpica MD Department of Pathology
Professor of Pathology and Gynecologic Oncology Division of Women’s and Perinatal Pathology
The University of Texas MD Anderson Cancer Center Brigham and Women’s Hospital
Houston, TX, USA Boston, MA, USA
Xavier Matias-Guiu MD PhD Stanley J Robboy MD FCAP
Chairman and Professor of Pathology and Molecular Professor and Vice Chairman of Pathology
Genetics Professor of Obstetrics and Gynecology
Department of Pathology and Molecular Genetics Department of Pathology
Hospital Universitari Arnau de Vilanova Duke University Medical Center
University of Lleida, IRBLLEIDA Durham, NC, USA
Lleida, Spain
Jennifer M Roberts MBBS (Hons) FRCPA
W Glenn McCluggage FRCPath Senior Gynecological Pathologist
Professor of Pathology Mayne Health Laverty Pathology
Consultant Gynecologic Pathologist North Ryde, NSW, Australia
Department of Pathology
Royal Group of Hospitals Trust Peter Russell MD FRCPA FRANZCOG (Hon)
Belfast, Antrim, UK Professor in Pathology
The University of Sydney;
Maria J Merino-Neumann MD Department of Anatomical Pathology
Chief, Division of Surgical Pathology Royal Prince Alfred Hospital
Department of Pathology Camperdown, NSW, Australia
National Cancer Institute
Bethesda, MD, USA Maria Angelica Selim MD FCAP
Associate Professor of Pathology and Medicine
Eoghan E Mooney MD FRCPath (Dermatology)
Consultant Histopathologist Director of Dermatopathology
Department of Pathology Department of Pathology
National Maternity Hospital Duke University Medical Center
Dublin, Ireland Durham, NC, USA
xxx
CONTRIBUTORS
Ruthy Shaco-Levy MD Mark H Stoler MD FASCP FCAP
Senior Gynecological Pathologist Professor of Pathology and Clinical Gynecology;
Department of Pathology Associate Director of Surgical Pathology and Cytopathology
Soroka Medical Center Department of Pathology
Faculty of Health Sciences University of Virginia Health System
Ben-Gurion University Charlottesville, VA, USA
Beer-Sheva, Israel
Sophia S Wang PhD
Christopher R Shea MD Investigator
Professor and Chief Division of Cancer Epidemiology and Genetics
Section of Dermatology; Environmental Epidemiology Branch
Professor of Medicine National Cancer Institute, NIH
University of Chicago Medical Center Rockville, MD, USA
Chicago, IL, USA
Richard J Zaino MD FCAP
Mark E Sherman MD Professor of Pathology
Cancer Expert Department of Pathology
Hormonal and Reproductive Epidemiology Branch Penn State University/Milton S. Hershey Medical Center
Division of Cancer Epidemiology and Genetics Hershey, PA, USA
National Cancer Institute, NIH
Rockville, MD, USA Wenxin Zheng MD FCAP
Professor of Pathology and Gynecology
Bruce Smoller MD FCAP Director of Gynecologic Pathology and Molecular Pathology
Professor and Chair Department of Pathology
Department of Pathology University of Arizona College of Medicine
University of Arkansas Medical Sciences Tucson, AZ, USA
Little Rock, AR, USA
xxxi
Foreword
It is a privilege to have the opportunity to write the foreword pathogenesis of genital tract neoplasia. The references have
for this excellent and much needed textbook. The fi eld of gyne- been carefully selected to be the most comprehensive and
cological pathology has continued to grow with new develop- current sources of further knowledge should the reader seek
ments that have changed methods of diagnosis and therapy. such.
The fi rst edition of this textbook did much to outline the under- Most importantly the text is very readable and is designed
lying principals of this fi eld and at the same time discuss both to assist the practitioner. Theoretical situations are minimized
the current state of our knowledge and practice. This second and have given way to practical explanations and methodolo-
edition carries the mission further with a wider number of gies for management of diseases that affl ict the female repro-
authors and subjects. ductive tract. The textbook will be an essential ingredient for
The text is organized in the classical manner. Beginning with the library of every physician who participates in the manage-
embrology then proceeding with organ site discussions of ment of these problems.
benign and malignant conditions. The list of authors are from
the most knowledgeable individuals in the fi eld of female repro- Philip J. DiSaia, MD
ductive tract pathology with Dr. Robboy participating in the The Dorothy J. Marsh Chair in Reproductive Biology
majority of the contributions, giving the text a smoothness not Director, Division of Gynecologic Oncology
usually seen in multi-author text books. Professor, Department of Obstetrics and Gynecology
New developments over the last decade have been carefully University of California, Irvine College of Medicine
presented. Especially where our knowledge has exploded: such Orange, California, USA
as the relationship of the human papillomavirus (HPV) and the
xxxiii
Preface
Pathology of the Female Reproductive Tract, by design, is provided pathologists with new tools to explore what until
dynamic, comprehensive and thorough, but pithy and easy to recently was considered classical pathology. Both Chapters 1
read. A decision we made when planning the 1st edition was to (embryology) and 34 (disorders of sexual development, also
give the book multi-continental fl avor. This was to acknowl- abnormal sexual development or intersex) heavily explore the
edge the reality that a common medicine is today practiced on histochemical, biochemical and genetic changes that take place
an international scale and that the standard of care is no longer over time.
local, but global. The many advances discussed throughout the A goal of this book, although never explicitly stated in the
book emanate from many different countries. In this newest fi rst edition, is that all of the concepts and fi ndings presented
edition, 41 authors have been invited to participate, again could be used today in everyday practice. The book was not
representing many of the leading institutions throughout the written to discuss theory, but rather what could be put into
world. As with the 1st edition, we have tried to make the text practice today. Hence, many pearls are included that we use in
appear seamless as if prepared by a single author, yet retaining our daily practices. Further, a new chapter (Chapter 36) was
the fl avor and indeed the differences that a multitude of authors added that systematically details the many immunohistoche-
and editors bring when viewing the same area. The positive mical markers useful in gynecologic pathology. We hope this
response from our readers has reaffi rmed the value of this proves a useful reference.
approach. If there is one area in which the editors have strayed into the
To add further functionality, the authors have drawn upon future, it regards the importance of both synoptic reporting and
their extensive personal experience, queries of trainees and coding, both of which make the reports rendered useful to the
junior colleagues, and discussions with senior colleagues to clinicians and managers of the electronic record in which the
identify those problems and questions which are commonly reports appear. Since publication of the fi rst edition of this
encountered in practice. Unanswerable questions, today’s puz- book, the College of American Pathologists (CAP) has entered
zling conundrums and provocations stimulate those insights into two key agreements that are having a major impact on all
that will become tomorrow’s advances. In both incorporating of medicine. The College has authorized the American College
and fi ltering the ever increasing recent literature, the authors of Surgeons (ACS) to utilize CAP derived standardized data
have consciously presented only those theories and explana- elements and synoptic report formats. In turn, the American
tions that we have considered hold merit. College of Surgeons now requires that for an institutional tumor
Several aspects of the second edition are new. By involving registry to be ACS certifi ed, all pathology reports must incor-
many new authors, perspectives on presentation for individual porate pathology reporting elements deemed critical by the
organs by necessity have differed. In some instances, this is CAP. Synoptic reports ensure that all relevant information is
because medicine has evolved. Emerging new concepts about included in the diagnosis rendered, allowing for better treatment
the pathogenesis of endometrial carcinoma have led to an of patients and easier comparison of fi ndings across institutions.
entire new body of work on separating those lesions that are The elements of synoptic reporting are covered in Appendix C.
precancerous, now called endometrial intraepithelial neoplasia, The second major event occurred in 2005 when the coding
from those that have histologic appearances of hyperplasia, system the CAP developed (SNOMED, or Systematized
but are biologically benign (Chapter 15). Knowledge has also Nomenclature of Medicine) which also incorporated the United
exploded in our understanding of the relation between human Kingdom’s Clinical Terms Version 3) was adopted by the US
papilloma virus (HPV) and the pathogenesis of cervical neo- National Library of Medicine as the major language of health-
plasia, with new understanding about the biology of those care. The importance of this language and its role as a critical
precancerous lesions that themselves might regress spontane- element of electronic healthcare is described in Appendix D.
ously (Chapters 7 and 8). We see the beginning of major insights To keep the volume current and manageable for the reader,
being made in endometrial cancer and ovarian cancer. To the the authors have emphasized inclusion of references published
extent possible, these insights are incorporated into this edition, since 2000. To the extent feasible, earlier articles have been
although we anticipate a plethora of new fi ndings in the next pruned as they are now general knowledge and easily accessible
decade. The development of reliable immunohistochemical from various databases. Further, current review articles have
techniques, some borrowing from molecular diagnostics, have been given preference rather than the original older articles. xxxv
PREFACE
The review articles often provide new insights and advances We truly hope that within the year, your book will be ragged
not present in the original. and ravaged from use.
Finally, during the intense multiyear endeavor required to
prepare both the prior and this edition, your editors have Stanley J. Robboy
enjoyed a buoyant spirit and have tried to portray this in the George L. Mutter
various chapters. Except where deemed outrageous by either Jaime Prat
the editors from Elsevier or our wives, we have left several Rex C. Bentley
purposeful elements of humor embedded in the text. Like the Peter Russell
children’s series, “Where’s Elmo”, we challenge the reader to Malcolm C. Anderson
fi nd these inclusions.
xxxvi
Dedication
To our wives — Marion, Patty, Serena, Genie, Gail & Chris-
tine — the loves of our lives.
xxxvii
