Diagnostic Histopathology of Tumors Volume 1 Part 2

687 Pages·2016·169.51 MB·English

by  Fletcher F.

DIAGNOSTIC
HISTOPATHOLOGY
OF TUMORS
DIAGNOSTIC
HISTOPATHOLOGY
OF TUMORS
Fourth Edition/Volume 1
Christopher D.M. Fletcher, MD, FRCPath
Vice Chair, Anatomic Pathology
Brigham and Women’s Hospital
Chief of Onco-Pathology
Dana-Farber Cancer Institute
Professor of Pathology
Harvard Medical School
Boston, Massachusetts
1600 John F. Kennedy Blvd.
Ste. 100
Philadelphia, PA 19103-2899
DIAGNOSTIC HISTOPATHOLOGY OF TUMORS Volume 1 PN 9996090442
FOURTH EDITION Volume 2 PN 9996090388
Two-volume set ISBN: 978-1-4377-1534-7
Copyright © 2013 by Saunders, an imprint of Elsevier Inc.
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Library of Congress Cataloging-in-Publication Data
Diagnostic histopathology of tumors / [edited by] Christopher D.M. Fletcher.—4th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4377-1534-7 (2 v. set : alk. paper)
I. Fletcher, Christopher D.M.
[DNLM: 1. Neoplasms—pathology. QZ 241]
616.994075—dc23
2012041834
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Contributors
Mahul B. Amin, MD Christopher P. Crum, MD
Professor and Chairman, Department of Pathology and Professor of Pathology, Harvard Medical School;
Laboratory Medicine, Cedars-Sinai Medical Center, Director, Division of Women’s and Perinatal
Los Angeles, California Pathology, Department of Pathology, Brigham and
Tumors and Tumor-like Conditions of the Male Genital Women’s Hospital, Boston, Massachusetts
Tract Tumors of the Female Genital Tract (Part C: Tumors of
the Placenta and Gestational Trophoblastic Disease, Part
Alberto G. Ayala, MD E: Cervix)
Deputy Chief of Pathology, Department of Pathology
and Genomic Medicine, The Methodist Hospital; John N. Eble, MD, FRCA
Professor of Pathology, Weill Medical College of Nordschow Professor of Laboratory Medicine,
Cornell University, Houston, Texas Chairman, Department of Pathology and Laboratory
Tumors and Tumor-like Conditions of the Male Genital Medicine, Indiana University School of Medicine,
Tract Indianapolis, Indiana
Tumors of the Urinary Tract
J. Eduardo Calonje, MD, DipRCPath
Director of Dermatopathology, St. John’s Institute of Ian O. Ellis, BM, BS, FRCPath
Dermatology, St. Thomas Hospital, London, United Professor of Cancer Pathology, Molecular Medical
Kingdom Sciences, University of Nottingham, Nottingham,
Vascular Tumors United Kingdom
Tumors of the Breast
Fiona Campbell, BSc, MD, FRCPath
Honorary Professor of Pathology, University of Linda Ferrell, MD
Liverpool; Consultant Gastrointestinal Pathologist, Professor, Vice Chairperson, and Director of Surgical
Department of Pathology, Royal Liverpool Pathology, Department of Pathology, University of
University Hospital, Liverpool, United Kingdom California, San Francisco, San Francisco, California
Tumors of the Esophagus and Stomach Tumors of the Liver, Biliary Tree, and Gallbladder
John K.C. Chan, MD Christopher D.M. Fletcher, MD, FRCPath
Consultant Pathologist, Department of Pathology, Vice Chair, Anatomic Pathology, Brigham and Women’s
Queen Elizabeth Hospital, Hong Kong, China Hospital; Chief of Onco-Pathology, Dana-Farber
Tumors of the Salivary Glands; Tumors of the Thyroid Cancer Institute; Professor of Pathology, Harvard
and Parathyroid Glands; Tumors of the Lymphoreticular Medical School, Boston, Massachusetts
System, Including Spleen and Thymus Introduction; Vascular Tumors; Tumors of Soft Tissue;
Peripheral Neuroectodermal Tumors
Wah Cheuk, MD
Consultant Pathologist, Department of Pathology, Jonathan A. Fletcher, MD
Queen Elizabeth Hospital, Hong Kong, China Associate Professor of Pathology, Associate Professor of
Tumors of the Salivary Glands Pediatrics, Harvard Medical School; Director, Solid
Tumor Cytogenetics, Department of Pathology,
Philip B. Clement, MD Brigham and Women’s Hospital, Boston,
Professor Emeritus, Department of Pathology and Massachusetts
Laboratory Medicine, Faculty of Medicine, Molecular Genetic Techniques in Diagnosis and Prognosis
University of British Columbia; Consultant
Pathologist, Department of Pathology and Robert Folberg, MD
Laboratory Medicine, Vancouver General Hospital, Founding Dean, Oakland University William
Vancouver, British Columbia, Canada Beaumont School of Medicine, Rochester, Michigan;
Tumors of the Peritoneum Chief Academic Officer, Beaumont Health System,
Royal Oak, Michigan
Tumors of the Eye and Ocular Adnexa
vii
viii Contributors
Karuna Garg, MBBS Gunter Klöppel, MD
Assistant Professor, Department of Pathology, Professor Emeritus, Department of Pathology,
University of California, San Francisco, Technical University of Munich, Munich, Germany
San Francisco, California Tumors of the Exocrine Pancreas; Tumors of the
Tumors of the Female Genital Tract (Part A: Ovary, Endocrine Pancreas
Fallopian Tube, and Broad and Round Ligaments)
Jeffery L. Kutok, MD, PhD
David J. Grignon, MD, FRCP(C) Senior Director, Molecular Pathology, Infinity
Centennial Professor and Vice Chair for Clinical Pharmaceuticals, Inc., Cambridge, Massachusetts
Programs, Department of Pathology, Indiana Tumors of the Hematopoietic System
University School of Medicine, Indianapolis, Indiana
Tumors of the Urinary Tract Ernest E. Lack, MD
Senior Pathologist, Endocrine and Otorhinolaryngic-
Philipp U. Heitz, MD Head and Neck Pathology, Joint Pathology Center,
Emeritus Professor of Pathology, Chairman Emeritus, Silver Spring, Maryland
Department of Pathology, University of Zurich, Tumors of the Adrenal Gland; Tumors of the Autonomic
Zurich, Switzerland Nervous System, Including Paraganglia
Tumors of the Endocrine Pancreas
Gregory Y. Lauwers, MD
Jason L. Hornick, MD, PhD Professor of Pathology, Harvard Medical School; Vice
Director of Surgical Pathology, Director, Chairman, Department of Pathology, Massachusetts
Immunohistochemistry Laboratory, Brigham and General Hospital, Boston, Massachusetts
Women’s Hospital; Associate Professor of Pathology, Tumors of the Esophagus and Stomach
Harvard Medical School, Boston, Massachusetts
Tumors of the Small and Large Intestines, Including Anal Andrew H.S. Lee, MD, MRCP, FRCPath
Canal Consultant Histopathologist, Nottingham University
Hospitals, City Hospital Campus, Nottingham,
Carrie Y. Inwards, MD United Kingdom
Associate Professor of Pathology, Mayo Clinic College Tumors of the Breast
of Medicine; Department of Laboratory Medicine
and Pathology, Mayo Clinic, Rochester, Minnesota Kenneth R. Lee, MD
Tumors of the Osteoarticular System Associate Professor, Department of Pathology, Harvard
Medical School; Staff Pathologist, Department of
Julie A. Irving, MD Pathology, Brigham and Women’s Hospital, Boston,
Clinical Associate Professor, Department of Pathology Massachusetts
and Laboratory Medicine, Faculty of Medicine, Tumors of the Female Genital Tract (Part E: Cervix)
University of British Columbia; Department of
Laboratory Medicine, Pathology, and Medical Yonghee Lee, MD
Genetics, Royal Jubilee Hospital, Victoria, British Professor of Pathology, Department of Pathology, Ajou
Columbia, Canada University School of Medicine, Suwon, Korea
Tumors of the Peritoneum Tumors of the Female Genital Tract (Part C: Tumors of
the Placenta and Gestational Trophoblastic Disease)
Sanjay Kakar, MD
Professor, Department of Anatomic Pathology, Neal I. Lindeman, MD
University of California, San Francisco; Chief of Director of Molecular Diagnostics, Brigham and
Pathology, Department of Anatomic Pathology, Women’s Hospital; Associate Professor of Pathology,
Veterans Affairs Medical Center, San Francisco, Harvard Medical School, Boston, Massachusetts
California Molecular Genetic Techniques in Diagnosis and Prognosis
Tumors of the Liver, Biliary Tree, and Gallbladder
Janina A. Longtine, MD
Kyu-Rae Kim, MD, PhD Vice Chairperson, Molecular Pathology and Genetics,
Professor, Department of Pathology, Asan Medical Department of Pathology, The Mount Sinai Medical
Center, University of Ulsan College of Medicine, Center, New York, New York
Seoul, Korea Molecular Genetic Techniques in Diagnosis and Prognosis
Tumors and Tumor-like Conditions of the Male Genital
Tract M. Beatriz S. Lopes, MD, PhD
Director of Neuropathology, Professor of Pathology
David S. Klimstra, MD and Neurological Surgery, Department of Pathology,
James Ewing Alumni Chair of Pathology, Department Division of Neuropathology, University of Virginia
of Pathology, Memorial Sloan-Kettering Cancer Health System, Charlottesville, Virginia
Center, New York, New York Tumors of the Pituitary Gland; Tumors of the Central
Tumors of the Exocrine Pancreas Nervous System
Contributors ix
Joseph J. Maleszewski, MD Emad A. Rakha, MD
Assistant Professor of Pathology, Mayo Clinic College Department of Cellular Pathology, University of
of Medicine; Senior Associate Consultant Nottingham and Nottingham University Hospitals
Pathologist, Department of Laboratory Medicine and NHS Trust, City Hospital Campus, Nottingham,
Pathology, Mayo Clinic, Rochester, Minnesota United Kingdom
Tumors of the Heart and Pericardium Tumors of the Breast
Cesar A. Moran, MD Jae Y. Ro, MD, PhD
Professor of Pathology, Section Chief, Thoracic Director of Surgical Pathology, Department of
Pathology, Department of Pathology, The University Pathology and Genomic Medicine, The Methodist
of Texas MD Anderson Cancer Center, Houston, Hospital; Professor of Pathology, Weill Medical
Texas College of Cornell University; Adjunct Professor of
Tumors of the Lung and Pleura Pathology, The University of Texas MD Anderson
Cancer Center, Houston, Texas
George L. Mutter, MD Tumors and Tumor-like Conditions of the Male Genital
Professor of Pathology, Department of Pathology, Tract
Harvard Medical School; Pathologist, Division of
Women’s and Perinatal Pathology, Department of Scott Rodig, MD, PhD
Pathology, Brigham and Women’s Hospital, Boston, Associate Professor, Department of Pathology, Harvard
Massachusetts Medical School; Associate Pathologist, Department
Tumors of the Female Genital Tract (Part B: Endometrial of Pathology, Brigham and Women’s Hospital,
Tumors) Boston, Massachusetts
Tumors of the Lymphoreticular System (Part A: Lymph
Marisa R. Nucci, MD Node; Part B: Spleen)
Associate Professor of Pathology, Harvard Medical
School; Associate Pathologist, Division of Women’s Daniel J. Santa Cruz, MD
and Perinatal Pathology, Department of Pathology, Dermatopathologist, Cutaneous Pathology, WCP
Brigham and Women’s Hospital, Boston, Laboratories, Inc., St. Louis, Missouri
Massachusetts Tumors of the Skin
Tumors of the Female Genital Tract (Part D:
Myometrium, Part E: Cervix, Part F: Vagina, Part G: Steven S. Shen, MD, PhD
Vulva) Associate Director of Surgical Pathology, Department of
Pathology and Genomic Medicine, The Methodist
André M. Oliveira, MD, PhD Hospital; Associate Professor of Pathology, Weill
Associate Professor of Pathology, Department of Medical College of Cornell University, Houston, Texas
Laboratory Medicine and Pathology, Mayo Clinic, Tumors and Tumor-like Conditions of the Male Genital
Rochester, Minnesota Tract
Tumors of the Osteoarticular System
Paul M. Speight, BDS, PhD, FRSRCPS, FRCPath
Mana M. Parast, MD, PhD Dean and Professor in Oral Pathology, School of
Assistant Professor of Pathology, Department of Clinical Dentistry, University of Sheffield, Sheffield,
Pathology, University of California, San Diego, La United Kingdom
Jolla, California Tumors of the Oral Cavity
Tumors of the Female Genital Tract (Part C: Tumors of
the Placenta and Gestational Trophoblastic Disease) Saul Suster, MD
Professor and Chairman, Department of Pathology and
Aurel Perren, MD Laboratory Medicine, Medical College of Wisconsin,
Professor of Pathology, Institute of Pathology, Milwaukee, Wisconsin
University of Bern, Bern, Switzerland Tumors of the Lung and Pleura
Tumors of the Endocrine Pancreas
Henry D. Tazelaar, MD
Sarah E. Pinder, MD Professor of Pathology, Mayo Clinic College of
Professor of Breast Pathology, Department of Cancer Medicine, Rochester, Minnesota; Chairperson,
Studies, Research Oncology, King’s College London; Department of Laboratory Medicine and Pathology,
Consultant Breast Pathologist, Department of Mayo Clinic, Scottsdale, Arizona
Histopathology, Guy’s and St. Thomas Hospitals, Tumors of the Heart and Pericardium
London, United Kingdom
Tumors of the Breast Lester D.R. Thompson, MD
Consultant Pathologist, Department of Pathology,
Southern California Permanente Medical Group,
Woodland Hills, California
Tumors of the Ear
x Contributors
Scott R. VandenBerg, MD, PhD Jacqueline Wieneke, MD
Professor, Department of Pathology, Division of Medical Officer, Pathologist, U.S. Food and Drug
Neuropathology, University of California, San Diego; Administration, Silver Spring, Maryland
Director of Neuropathology, Department of Tumors of the Adrenal Gland; Tumors of the Autonomic
Pathology, University of California, San Diego Nervous System, Including Paraganglia
Medical Center, La Jolla, California
Tumors of the Central Nervous System Robert H. Young, MD, FRCPath
Robert E. Scully Professor of Pathology, Department
Sarah N. Walsh, MD of Pathology, Harvard Medical School; Pathologist,
Dermatopathologist, Cutaneous Pathology, WCP James Homer Wright Pathology Laboratories,
Laboratories, Inc., St. Louis, Missouri Massachusetts General Hospital, Boston,
Tumors of the Skin Massachusetts
Tumors of the Urinary Tract
Bruce M. Wenig, MD
Chairman, Department of Diagnostic Pathology and Charles J. Zaloudek, MD
Laboratory Medicine, Beth Israel Medical Center, St. Professor, Department of Pathology, University of
Luke’s and Roosevelt Hospitals, New York, New California, San Francisco, San Francisco, California
York; Professor of Pathology, Albert Einstein College Tumors of the Female Genital Tract (Part A: Ovary,
of Medicine, Bronx, New York; Adjunct Professor of Fallopian Tube, and Broad and Round Ligaments)
Pathology, Columbia University College of
Medicine, New York, New York
Tumors of the Upper Respiratory Tract
Preface
In the five-year interval since publication of Diagnostic in metastatic carcinomas is rarely more effective than
Histopathology of Tumors, Third Edition, conventional mor- high-quality immunohistochemistry combined with
phologic and immunohistochemical assessment has con- morphologic expertise, is more expensive and, in any
tinued to hold sway as the pre-eminent, most reliable, event, does not very often lead to clinically significant
and most cost-effective means to provide a diagnosis, change in treatment or outcome (as many of the more
prognostic assessment, and in most cases, determination treatable metastases are easily recognized by conven-
of the adequacy of excision for human tumors. Such tional means). It is troubling that many such commercial
interpretation also helps to guide therapy in many set- tests are being marketed directly to clinicians and patients,
tings. The continued utility of such “traditional” tech- who are often completely unable to distinguish snake oil
nologies and interpretive skills is somewhat reassuring in from clinically worthwhile testing. Although it is likely
the setting of the ever-widening disparities in the avail- that genomic data will ultimately prove their (progres-
ability of more expensive modern technologies, such as sively more affordable) value, until then pathologists have
molecular genetic diagnosis, gene expression profiling, a responsibility to ensure (a) that often limited patient
and genomics, not only (to a depressing degree) between tissue is used judiciously, and (b) that, in the routine (non-
the developed and still developing (or underdeveloped) trial) setting, testing of any kind has proven clinical value
areas of the world, but even among different developed that might merit action by the treating physician.
countries or regions. Remarkably, and seemingly with no evident slowing of
The role of molecular diagnosis is now very well estab- the pace, morphologic tumor classifications and methods
lished and firmly integrated in the practice of modern of prognostication continue to evolve and be ever more
surgical pathology, and is especially valuable in confirm- refined, constantly enhancing the value of high-quality
ing the presence of diagnostically important gene fusions anatomic pathology. Many of these advances have been
or mutations, in helping with therapeutic target identifi- codified in the new WHO classifications, which are cur-
cation and, not least, in enhancing diagnostic reproduc- rently being updated in a fourth edition of the “blue
ibility and tumor classification schemes. Whereas some books.” Furthermore, “new” (newly recognized) tumor
targets can be identified immunohistochemically, muta- types or subtypes of clinical or therapeutic relevance con-
tional analysis may better enable treatment selection in tinue to be characterized, both morphologically and
some contexts, especially in the setting of treatment resis- genetically, in a seemingly limitless fashion. The fourth
tance. A more complex issue, however, in some of the edition of this text has been substantially revised and
developed countries (with dangerously expanding health updated to incorporate this broad range of new informa-
care expenditure) is the interface between pathology and tion. Some chapters have been entirely rewritten, notably
genomic medicine. Expression profiling as well as whole those dealing with tumors of the small and large intes-
genome sequencing are increasingly being promulgated tines, the heart, and the ear.
as providing additional information of critical clinical As always, any and all errors or omissions are entirely
importance—yet, at this point in time, the value of such the responsibility of the editor, and I remain deeply
testing has only rarely been demonstrated and validated, indebted to the contributors for the unfailingly high
for example in prognostication for invasive carcinoma of quality of the material that they provide, as well as the
the breast (Oncotype Dx and Mammaprint assays)—while enthusiasm with which they do so. Finally, I should like
most other such testing remains unvalidated, analytically to warmly acknowledge, with considerable gratitude, the
or clinically, and of unproven clinical value. In particular, hard work and unfailing support of my outstanding sec-
there are no good data confirming that identification of retary, Kathleen Radzikowski, and also of the “key
a potentially targetable mutation in a tumor type in which players” at Elsevier—Bill Schmitt, Katie DeFrancesco,
the role of that specific gene has never been demon- and Louise King.
strated represents anything more than a sophisticated
(and expensive) shot in the dark. Similarly, gene expres- Christopher D.M. Fletcher
sion profiling as a means of identifying the primary site Boston, 2012
xi
C H A P T E R 8
Tumors of the Esophagus
and Stomach
Fiona Campbell • Gregory Y. Lauwers
CHAPTER OUTLINE
ESOPHAGUS 378 STOMACH 392
Epithelial Tumors 378 Epithelial Tumors 392
Nonepithelial Tumors 389 Nonepithelial Tumors 409
Tumor-like Lesions 391 Tumor-like Lesions 417
discussion) and usually occurs as a manifestation of
ESOPHAGUS
raised dysplasia in columnar (Barrett) esophagus.8
Multiple adenomatous polyps with synchronous adeno-
EPITHELIAL TUMORS
carcinoma have been reported.9 Recently described
rare adenoma variants include a pyloric gland type10 and
Squamous Cell Papilloma
gastric foveolar type,11 the latter complicated by intramu-
and Papillomatosis
cosal adenocarcinoma.
Clinical Features
Submucosal Adenoma
Squamous cell papilloma may occur anywhere in the
esophagus but is found most commonly in the lower A few cases of submucosal adenoma of the esophagus,
third as a single, well-demarcated sessile intraluminal arising from submucosal mucous glands or ducts,12
tumor, usually less than 1.5 cm in size.1 A giant form has including pleomorphic adenomas comparable with those
been described.2 Multiple lesions,3 sometimes in associa- arising in salivary gland (see Chapter 7),13 have been
tion with Goltz syndrome (focal dermal hypoplasia), may described.
also occur.4 The etiology of these lesions is not clear;
some are related to chronic irritation3 and others to Epithelial Dysplasia
human papillomavirus (HPV) infection.5,6 (Intraepithelial Neoplasia)
Epithelial dysplasia, arising in squamous or columnar
Histologic Appearances
epithelium, is considered as a precancerous lesion and is
Histologically, squamous papilloma has a papillary archi- characterized by cellular atypia, abnormal differentiation,
tecture with a core of vascular connective tissue covered and disorganized architecture. All of these features are
by hyperplastic, normally maturing, squamous epithe- more prominent in severe or high-grade dysplasia and,
lium (Fig. 8-1). Papilloma virus–associated changes may conversely, are less pronounced in mild or low-grade
be seen, including koilocytosis and multinucleation. dysplasia. Because high-grade dysplasia may be histologi-
cally indistinguishable from intraepithelial or in situ car-
cinoma, the term intraepithelial neoplasia is often used
Differential Diagnosis
synonymously with dysplasia.
In biopsy material, squamous papilloma must be differ-
entiated from well-differentiated verrucous squamous Squamous Cell Dysplasia
cell carcinoma (see later discussion). Rare cases of squa-
mous cell carcinoma arising in association with squamous In the esophagus, squamous cell dysplasia, morphologi-
papillomatosis are seen.7 cally indistinguishable from its counterpart in other squa-
mous mucosae such as the uterine cervix, often precedes
Adenoma (Polypoid Dysplasia) or coexists with invasive squamous cell carcinoma. Careful
histologic examination of esophagectomy specimens for
Adenoma is a rare polypoid tumor, which is indistin- nonirradiated squamous carcinoma discloses squamous
guishable histologically from gastric adenoma (see later dysplastic lesions of all grades (mild, moderate, or severe)
378