BIOPSY INTERPRETATION SERIES BIOPSY INTERPRETATION OF THE GASTROINTESTINAL TRACT MUCOSA Volume 2: Neoplastic Second Edition MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd ii 11//2277//22001122 1122::3333::4466 PPMM BIOPSY INTERPRETATION SERIES Series Editor: Jonathan I. Epstein, M.D. Biopsy Interpretation of the Gastrointestinal Tract Mucosa: Neoplastic, 2/e (Vol. 2) Elizabeth A. Montgomery and Lysandra Voltaggio, 2012 Biopsy Interpretation of the Upper Aerodigestive Tract and Ear, 2/e Edward B. Stelow and Stacey E. Mills, 2012 Biopsy Interpretation of the Breast, 2/e Stuart J. Schnitt and Laura C. Collins, 2012 Biopsy Interpretation of the Lung Saul Suster and Cesar Moran, 2012 Biopsy Interpretation of the Gastrointestinal Tract Mucosa: Non-Neoplastic, 2/e (Vol. 1) Elizabeth A. Montgomery and Lysandra Voltaggio, 2011 Biopsy Interpretation of the Central Nervous System Matthew J. Schniederjan and Daniel J. Brat, 2011 Biopsy Interpretation of the Bladder, 2/e Jonathan I. Epstein, Mahul B. Amin, and Victor E. Reuter, 2010 Biopsy Interpretation of Soft Tissue Tumors Cyril Fisher, Elizabeth A. Montgomery, and Khin Thway, 2010 Biopsy Interpretation of the Thyroid Scott L. Boerner and Sylvia L. Asa, 2009 Biopsy Interpretation of the Skin A. Neil Crowson, Cynthia M. Magro, and Martin C. Mihm, 2009 Biopsy Interpretation: The Frozen Section Jerome B. Taxy, Aliya N. Husain, and Anthony G. Montag, 2009 Biopsy Interpretation of the Uterine Cervix and Corpus Anais Malpica, Michael T. Deavers, and Elizabeth D. Euscher, 2009 Biopsy Interpretation of the Liver, 2/e Stephen A. Geller and Lydia M. Petrovic, 2009 Biopsy Interpretation of the Breast Stuart J. Schnitt and Laura C. Collins, 2008 Biopsy Interpretation of the Prostate, 4/e Jonathan I. Epstein and George Netto, 2007 Biopsy Interpretation of the Upper Aerodigestive Tract and Ear Edward B. Stelow and Stacey E. Mills, 2007 Biopsy Interpretation of the Gastrointestinal Tract Mucosa Elizabeth A. Montgomery, 2005 MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd iiii 11//2277//22001122 1122::3333::4466 PPMM BIOPSY INTERPRETATION SERIES BIOPSY INTERPRETATION OF THE GASTROINTESTINAL TRACT MUCOSA Volume 2: Neoplastic Second Edition Elizabeth A. Montgomery, M.D. Department of Pathology Johns Hopkins Medical Institutions Baltimore, Maryland Lysandra Voltaggio, M.D. Department of Pathology George Washington University Hospital Washington, District of Columbia MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd iiiiii 11//2277//22001122 1122::3333::4466 PPMM Senior Executive Editor: Jonathan W. Pine, Jr. Product Manager: Marian A. Bellus Vendor manager: Alicia Jackson Senior Manufacturing Manager: Benjamin Rivera Creative Director: Doug Smock Production Service: SPi Global Copyright © 2012, 2006 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER Business Two Commerce Square 2001 Market Street Philadelphia, PA 19103 USA LWW.com All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form by any means, including photocopying, 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. Materials appearing in this book prepared by individuals as part of their offi cial duties as U.S. government employees are not covered by the above-mentioned copyright. Printed in the People’s Republic of China Library of Congress Cataloging-in-Publication Data Montgomery, Elizabeth (Elizabeth A.), 1958- Biopsy interpretation of the gastrointestinal tract mucosa. Volume 2, Neoplastic / Elizabeth A. Montgomery, Lysandra Voltaggio. — 2nd ed. p. ; cm. Neoplastic Includes bibliographical references and index. ISBN 978-1-4511-0959-7 I. Voltaggio, Lysandra. II. Title. III. Title: Neoplastic. [DNLM: 1. Gastric Mucosa—pathology. 2. Gastrointestinal Neoplasms—diagnosis. WI 301] 616.99'4307545—dc23 2012002905 Care has been taken to confi rm the accuracy of the information presented and to describe gener- ally 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 the information in a particular situation remains the professional responsibility of the practitioner. 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 current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant fl ow 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 the publication have Food and Drug Admin- istration (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 their clinical practice. To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320. International customers should call (301) 223-2300. 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. 10 9 8 7 6 5 4 3 2 1 MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd iivv 11//2277//22001122 1122::3333::4466 PPMM To my sister, Cassandra Lysandra Voltaggio To Sasha, Peter, Sean, and Jonathan Elizabeth A. Montgomery MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd vv 11//2277//22001122 1122::3333::4466 PPMM MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd vvii 11//2277//22001122 1122::3333::4466 PPMM ACKNOWLEDGMENTS The authors acknowledge their fellow pathologists, residents, and fellows for their help in identifying and collecting cases from their daily sign out and gastroenterology colleagues for supplying wonderful endoscopic pho- tos. We also want to thank Louise Bierig for her role as development edi- tor, Marian Bellus for her role as a product manager, Anoop Kumar for overseeing production, and Jonathan Pine, Senior Executive Editor, for encouraging me to undertake this project. Finally, writing a book is a time- consuming process that often takes time away from other life duties, and we thank our husbands for their patience during this endeavor. vii MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd vviiii 11//2277//22001122 1122::3333::4466 PPMM MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd vviiiiii 11//2277//22001122 1122::3333::4466 PPMM INTRODUCTION TO GASTROINTESTINAL TRACT BIOPSY INTERPRETATION GENERAL FEATURES OF GI BIOPSY INTERPRETATION Probably the key principle of gastrointestinal (GI) biopsy interpretation is that the GI tract has a limited repertoire of responses to a host of injuries, and diagnosing the type of injury in any given biopsy often requires cor- relation with clinical and endoscopic information. On the other hand, nor- mal biopsies may be obtained from symptomatic patients, and pathologists should not succumb to the temptation of reporting “infl ammation,” which serves little purpose since infl ammatory cells are a normal constituent of the lamina propria. Other patients may be very ill from diseases that are mural or extraintestinal, and mucosal biopsies offer little information to the treating physician. However, some systemic diseases include GI tract mani- festations that can be identifi ed if a consistent, systematic approach is used. When dealing with mucosal biopsies of the GI tract, it should also be noted that the vast majority of specimens display the mucosa and, rarely, a small amount of submucosa. This is especially signifi cant when dealing with lesions that are usually limited to the submucosa and beyond (e.g., lipomas, infl ammatory fi broid polyps). Both pathologists and clinicians should be aware that lack of histologic fi ndings does not preclude underly- ing pathology. Of course, mucosal biopsies should not include muscularis propria. When they do, it is a good practice to contact the endoscopist and discuss the possibility of endoscopic perforation. OVERVIEW COMMENTS ON THE GI TRACT Before a discussion of mucosal biopsies can ensue, it is worthwhile to review the overall microscopic anatomy of the GI tract in general. The innermost layer of the GI tract is the mucosa, consisting of three components: 1. Epithelium (with protective, secretory, or absorptive properties). 2. Lamina propria. This is a loose connective tissue zone support- ing the avascular epithelium. In the esophagus, stomach, and small bowel, it is rich in lymphatics, whereas it is less so in the lower tract. This is of clinical signifi cance in evaluating carcinomas because they can attain lymphatic access with minimal invasion in the upper tract. In the esophagus and stomach, there are few immune cells (lymphoid and plasma cells) in the lamina propria. Some observers regard the ix MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd iixx 11//2277//22001122 1122::3333::4466 PPMM x INTRODUCTION TO GASTROINTESTINAL TRACT BIOPSY INTERPRETATION presence of plasma cells, no matter how few, as an abnormal fi nd- ing in gastric biopsies. It is our practice to report infl ammation in this site only when there is obvious expansion of the lamina propria (increased dot density) at low power. In the small bowel and colon, lamina propria lymphocytes and plasma cells are more abundant. Neutrophils do not belong in either the lamina propria or the epithe- lium. Eosinophils are a normal lamina propria constituent and can be particularly prominent in the right colon in the healthy patient. Mucosal biopsies from all sites must be assessed for prominence in the normal infl ammatory components, which is usually identifi ed at low power as an abnormal expansion of the lamina propria. 3. Muscularis mucosae. This is a slim double layer of smooth muscle separating the mucosa from the submucosa. It has an inner circular and outer longitudinal arrangement, and, in this respect, it can be regarded as a miniaturized muscularis propria. In the normal state, colonic crypts extend down to the superior aspect of the muscularis mucosae. Crypt shortening (usually with basal plasmacytosis) is an indicator of chronic injury. The mucosa is wholly distinct in the various regions of the GI tract. Note that the muscularis mucosae is considered a component of the mucosa for the purposes of staging invasive carcinomas. The submucosa is composed of connective tissue and houses Meissner nerve plexus as well as large caliber vessels. The muscularis propria is the main wall of the GI tract and is composed of an inner circular and outer longitudinal layer of smooth muscle. Between these layers is Auerbach nerve plexus. The outermost component is either adventitia or serosa. The former lacks a mesothelial membrane lining. Parasympathetic ganglion cells are found in the nerve plexi (both Meissner and Auerbach), but the submucosal Meissner plexi contain neu- ronal cell bodies of the intrinsic sympathetic nerve system that function on the local area of the gut. These are the neurons that have chemoreceptors and mechanoreceptors. They synapse on both other ganglion cells and muscle or secretory cells. Ganglion cells are not a normal component of the mucosa and, when identifi ed, are indicative of chronic injury. The pathologist should be aware of several points in the GI tract that lack a serosa, which is an issue mostly in staging tumors in resection specimens rather than in interpreting biopsies. Most are aware of the lack of serosal tissue in the esophagus, but several retroperitoneal portions of the colorectum share this feature. The posterior surfaces of the ascending and descending colon lack a peritoneal covering and are in direct contact with the retroperitoneum. In contrast, the anterior and lateral surfaces of the ascending and descending colon are covered by a visceral peritoneum (serosa). The transverse colon is entirely intraperitoneal and is supported on a long mesentery that is attached to the pancreas. The descending colon becomes the sigmoid colon at the origin of the mesosigmoid, and MMoonnttggoommeerryy VVooll IIII__FFMM..iinndddd xx 11//2277//22001122 1122::3333::4466 PPMM