Ebook Gastrointestinal pathology and its clinical implications (2nd edition): Part 1

tahir99 - UnitedVRG
vip.persianss.ir

G

ta
vi hir
p. 9
pe 9
rs - U
ia n
ns ite
s. dV
ir R


Lewin, Weinstein, and Riddell’s

Gastrointestinal
Pathology and Its
Clinical Implications
Second Edition
VOLUME I

tahir99 - UnitedVRG
vip.persianss.ir
Riddell_FM_Vol-1.indd 1

2/14/2014 6:44:05 PM

G
ta
vi hir
p. 9
pe 9
rs - U
ia n
ns ite
s. dV
ir R
tahir99 - UnitedVRG
vip.persianss.ir
Riddell_FM_Vol-1.indd 2

2/14/2014 6:44:05 PM


Lewin, Weinstein, and Riddell’s

ta
vi hir
p. 9
pe 9
rs - U
ia n
ns ite
s. dV
ir R

G

Gastrointestinal
Pathology and Its
Clinical Implications
Second Edition
VOLUME I

Robert Riddell, MD, FRCPath, FRCPC
Professor of Laboratory Medicine and Pathobiology
University of Toronto
Mount Sinai Hospital
Toronto, Ontario, Canada

Dhanpat Jain, MD

Professor of Pathology
Director, Program in Gastrointestinal and Liver
Pathology
Department of Pathology
Yale University School of Medicine
New Haven, Connecticut, USA

Clinical Editors
Charles N. Bernstein, MD

Professor of Medicine
University of Manitoba
Head, Section of Gastroenterology
Director, University of Manitoba of IBD Clinical and
Research Centre

Bingham Chair in Gastroenterology
Winnipeg, Manitoba, Canada

Sushovan Guha, MD, PhD

Associate Professor and Director of Research
Division of Gastroenterology, Hepatology, and Nutrition
Department of Internal Medicine
The University of Texas Medical School and Health
Science Center at Houston
Houston, Texas, USA

tahir99 - UnitedVRG
vip.persianss.ir
Riddell_FM_Vol-1.indd 3

2/14/2014 6:44:08 PM


Acquisitions Editor: Ryan Shaw
Product Manager: Kate Marshall
Production Project Manager: Marian Bellus
Senior Manufacturing Coordinator: Beth Welsh
Marketing Manager: Dan Dressler
Designer: Stephen Druding
Production Service: SPi Global
© 2014 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business
Two Commerce Square
2001 Market Street
Philadelphia, PA 19103 USA

LWW.com
First Edition © 1992 by Igaku-Shoin Medical Publishers, Inc.
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 official duties as U.S. government employees are not covered by the above-mentioned
copyright.
Printed in China
Library of Congress Cataloging-in-Publication Data
Lewin, Weinstein, and Riddell’s gastrointestinal pathology and its clinical implications / [edited by] Robert Riddell, Dhanpat
Jain. — 2nd ed.
   p. ; cm.
  Gastrointestinal pathology and its clinical implications
  Rev. ed. of: Gastrointestinal pathology and its clinical implications / Klaus J. Lewin, Robert H. Riddell, Wilfred M.
Weinstein. c1992.
  Includes bibliographical references and index.
  ISBN 978-0-7817-2216-2
  1. Gastrointestinal system—Diseases.  I. Riddell, Robert H., 1943-  II. Jain, Dhanpat.  III. Lewin, Klaus J.  IV. Lewin, Klaus
J. Gastrointestinal pathology and its clinical implications.  V. Title: Gastrointestinal pathology and its clinical implications.
  [DNLM:  1. Gastrointestinal Diseases—pathology.  WI 100]
  RC802.9.L48 2011
 616.3'3—dc22
2011011658
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 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 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 the 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 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.

tahir99 - UnitedVRG
vip.persianss.ir

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

Riddell_FM_Vol-1.indd 4

2/14/2014 6:44:08 PM


Dedication
Robert Riddell

To my immortal parents Harry and Joyce.
To my wife Hala, who wrote the gastritis chapter, contributed to
numerous others and whose constant love, support, and encouragement is
greatly appreciated.
To Mark, Juliet, and Mike, and grandchildren Alannah, Natalie, Paisley,
and Eli, all of whom we are so proud of and who give us more pleasure than
they will ever know.

Dhanpat Jain

To my teachers who always showed me the right path.
To my parents Milap Chand and Biraj who always led me to the right path.
To my wife Shilpa without whom nothing would have been possible.
To my daughters Nimisha and Anisha for whom it was all worthwhile.

Charles N. Bernstein

I dedicate any accolades I receive for the hard work put into this book to
Evelyn, Matthew, and Lexie Bernstein. They provide me with the constant
entertainment, support, and love that reminds me constantly of what is really
important in life.

Sushovan Guha

I would like to dedicate this to my wife Sarmistha, to our children Siddarth
and Shivani, to my father Sukumar, and to my mother Dolly for their
collective wisdom, unflinching support, utmost dedication, and unbridled
joy. Also I would like to offer my deepest gratitude to Fred, Klaus, and all the
great teachers that I had at UCLA. Finally I would offer my thanks to all the
patients that motivated me to be a good doctor.

tahir99 - UnitedVRG
vip.persianss.ir
Riddell_FM_Vol-1.indd 5

2/14/2014 6:44:09 PM


tahir99 - UnitedVRG
vip.persianss.ir

Riddell_FM_Vol-1.indd 6

2/14/2014 6:44:09 PM


Contributors

Henry D. Appelman, MD
M.R. Abell Professor of Surgical Pathology
Department of Pathology
University of Michigan
Ann Arbor, Michigan, USA
Charles N. Bernstein, MD
Professor of Medicine
University of Manitoba
Head, Section of Gastroenterology
Director, University of Manitoba of IBD Clinical
and Research Centre
Bingham Chair in Gastroenterology
Winnipeg, Manitoba, Canada
Hala El-Zimaity, MD, MS (Epidemiology)
Professor
Department of Laboratory Medicine
and Pathobiology
University of Toronto
Gastrointestinal Pathology Consultant
University Health Network
Toronto, Ontario, Canada
Karel Geboes, MD, PhD, AGAF
Professor Emeritus

Emeritus Clinical Chief
Department of Pathology
KU Leuven University
University Hospitals Gasthuisberg
Leuven, Belgium

Dhanpat Jain, MD
Professor of Pathology
Director, Program in Gastrointestinal
and Liver Pathology
Department of Pathology
Yale University School of Medicine
New Haven, Connecticut, USA
Richard Kirsch, MBChB, PhD, FRCPath(SA),
FRCPC
Associate Professor
Department of Laboratory Medicine
and Pathobiology
Mount Sinai Hospital
Toronto, Ontario, Canada
Hiroyoshi Ota, MD, PhD
Professor
Department of Biomedical and Laboratory Sciences
Shinshu University
Staff Pathologist
Department of Laboratory Medicine
Shinshu University Hospital
Matsumoto, Nagano, Japan
Robert Riddell, MD, FRCPath, FRCPC
Professor of Laboratory Medicine and Pathobiology

University of Toronto
Mount Sinai Hospital
Toronto, Ontario, Canada

Joel Kasle Greenson, MD
Professor of Pathology
Department of Pathology
University of Michigan Medical School
Director of Gastrointestinal Pathology
Department of Pathology
University of Michigan Health System
Ann Arbor, Michigan
Sushovan Guha, MD, PhD
Associate Professor and Director of Research
Division of Gastroenterology, Hepatology,
and Nutrition
Department of Internal Medicine
The University of Texas Medical School
and Health Science Center at Houston
Houston, Texas, USA

Masanori Tanaka, MD
Director
Department of Pathology and Laboratory Medicine
Hirosaki City Hospital
Hirosaki, Japan
Michael Vieth, Dr. med habil. Dr. med
Professor of Pathology
Institute of Pathology
University of Magdeburg

Magdeburg, Germany
Director
Institute of Pathology
Klinikum Bayreuth
Bayreuth, Germany

tahir99 - UnitedVRG
vip.persianss.ir
vii

Riddell_FM_Vol-1.indd 7

2/14/2014 6:44:10 PM


tahir99 - UnitedVRG
vip.persianss.ir
Riddell_FM_Vol-1.indd 8

2/14/2014 6:44:10 PM


Preface to the First Edition

The decision to write a textbook of pathology coupled
with clinical implications came primarily because of
the increasing interdependence of the pathologist and
clinician in the investigation and management of gastrointestinal disorders where modern gastrointestinal
pathology plays a dynamic role. In many instances,
it is no longer sufficient for the pathologist to simply

make a morphological diagnosis. Conversely, we hope
that clinicians with gastroenterology interests will
view this book as a requisite companion for a general
textbook of gastroenterology.
Pathologists can achieve their full potential by
understanding the clinical scenarios in which they
are playing a part and by appreciating the effect of
their decisions in clinical management. We hope that
the clinicians who read this book will more readily
maximize the information they obtain from gastrointestinal biopsies through an understanding of the
indications, by appreciating the need for providing
relevant clinical information, which specific questions to ask the pathologist, and also to understand
when biopsies are likely to be of limited value.

We have done our best not to perpetuate some of
the myths of pathologist uncritically. In areas where
issues are controversial, we have tried to state this;
we have also frequently offered our own “solutions” to
these problems in situations that lack data on which
they can satisfactorily be based.
We hope that the greatest criticism that can be leveled against this book is that it assumes that each gastroenterologist, whether medical or surgical, adult or
pediatric, has an interested pathologist with whom to
work and vice versa. We know that this is frequently
not the case. However, by appreciating the necessity
of such a working relationship for the best in patient
care, we hope that pathologists and clinicians will see
the overwhelming benefits of this relationship and
will try to foster it.
Klaus J. Lewin
Robert H. Riddell

Wilfred M. Weinstein

tahir99 - UnitedVRG
vip.persianss.ir
ix

Riddell_FM_Vol-1.indd 9

2/14/2014 6:44:10 PM


Riddell_FM_Vol-1.indd 10

2/14/2014 6:44:10 PM


Preface

The first edition of this book was published over 20
years ago in 1993. The driving force behind that book
came from Klaus Lewin, and was that, to do pathology well, pathologists have to understand the clinical
implications of their diagnoses, which explains the
title of the book. At the same time clinicians need to
understand when to biopsy, where to biopsy, which
questions to ask, as well as which cannot be answered
by pathology, and what to expect from the pathologist.
The book was thus written as a guide for pathologists
and clinicians for circumstances that they have to
deal with on a day-to-day basis, and also as a resource
for any unusual lesion, for difficult diagnoses, and for

those issues where good guidelines are lacking. It also
explained the unconventional authorship of the book,
especially having Wilfred (Fred) Weinstein as both an
author and clinical contributor. The book tried to provide answers for such situations and gave rationale
for what we did and why, sometimes finding that we
did them differently ourselves. Teaching new gastroenterologists where to sample and why and also to
teach them how to interpret the pathologist’s reports,
which are highly variable themselves, is a challenging task. Pathologists can be just as guilty of providing
defensive and unhelpful descriptions that are not easily understood and leave the clinician trying to guess
how to interpret the findings of the report, especially
when told that “clinical correlation is required”—in
practice the statement that tends to be a hedge for “I
have no idea why you took these biopsies or what I
should be looking for.”
Most will not be aware that a second edition of
this book was well underway in 2000 when it gradually became clear that Klaus was unable to continue.
He died a few years later in 2005, and we miss him
and his sense of both the important and his sense
of the ridiculous, tremendously. However there was

always encouragement from friends, colleagues, and
strangers alike to bring forth a new edition. With
much encouragement, it began to take shape when
Dr. Dhanpat Jain from Yale accepted the Co-Editorship. Fred Weinstein, the third member of the team,
decided that the book would not really be the same
without Klaus; he did suggest that two of “his boys”
Charles N. ­Bernstein (now in Winnipeg) and ­Sushovan
Guha (at MD ­Anderson at that time) could fill in his
shoes. They agreed to become the “clinical editors” and
it has been an absolute pleasure to work with them.

Our goal for the second edition was to keep the
philosophy similar to the first edition, the challenge
being to incorporate the explosion of knowledge in
molecular pathology, cancer biology, and genomics
that continues to change our field on a daily basis,
and to keep this all relevant for the practicing pathologists and clinician. Since the last edition, images
have changed from B&W and “Kodachromes” to digital, so the challenge was to replace these figures and
endoscopic photomicrographs. The number of tables
and management algorithms has also increased substantially. While adding new material, we were also
conscious not to omit important historical details,
the challenge being to keep the book to a reasonable
size. We have also tried to keep the book relevant on a
global level, and international experts helped to write
some of the chapters; indeed, it could not have happened without them. We hope that we have been able
to fulfill the purpose of the book as a resource not only
for practicing and academic pathologists, but also for
those in training in pathology and gastroenterology,
and our clinical colleagues of all stripes—endos­copists
and imagers, gastroenterologists, and surgeons.
Robert Riddell
Dhanpat Jain

xi

Riddell_FM_Vol-1.indd 11

2/14/2014 6:44:10 PM


Riddell_FM_Vol-1.indd 12

2/14/2014 6:44:10 PM


Acknowledgments

So many people have been involved in ensuring that
this book becomes a reality that it is difficult to know
where to begin. Family and spouses inevitably are first
on the list for their huge support and for bearing with
our relative absence during this time for the cause.
We thank our clinical editors Drs. Charles N.
­Bernstein and Sushovan Guha who went through each
chapter and were wonderfully responsive in carrying
out their roles in a very efficient manner, provided
illustrations where needed, and made our lives much
easier. They have, in turn, expressed their thanks for
the opportunity.
We thank all our authors, who not only contributed their respective chapters but allowed us to
“bend” their chapters out of recognition to avoid the
stylistic issues that can arise with multiple authors.

We are grateful to our colleagues and friends at each
institution for their encouragement, for lending
their material to be used, moral support, and valuable advice. We are deeply indebted to our numerous
trainees and pathology assistants who took excellent
gross photographs, which are an invaluable resource
for teaching and worth their weight in gold. We owe
a lot of gratitude to our support staff at Photographics
division, Yale University, Department of Pathology for

their services.
Lastly, we thank the numerous people with Lippincott Williams & Wilkins, but especially Kate Marshall whose unmerciful cajoling helped to get this
done as quickly as was possible, and also the expertise
of Satheesh Velayutham and his team for their help
with the page proofs.

xiii

Riddell_FM_Vol-1.indd 13

2/14/2014 6:44:11 PM


Riddell_FM_Vol-1.indd 14

2/14/2014 6:44:11 PM


Contents

Contributors vii
Preface to the First Edition  ix
Preface xi
Acknowledgments xiii

12
13

Dialogue, Biopsies–Taking and Handling;
Resected Specimens; Protocols

1
Robert Riddell, Charles N. Bernstein, Sushovan Guha,
and Dhanpat Jain

2

Vascular Disorders and Related Diseases 28

3

Immunodeficiency Disorders

4

Lymphoproliferative Disorders of the
Gastrointestinal Tract

Karel Geboes and Dhanpat Jain

88

14

6

Disorders of Endocrine Cells

705

Hiroyoshi Ota and Robert Riddell

15Appendix

795

Robert Riddell

16

Small and Large Bowel Structure:
Developmental and Mechanical
Disorders875
Dhanpat Jain

190

Henry D. Appelman

Motility Disorders

Gastric Epithelial Polyps and Tumors

Volume II

Joel KASLE Greenson and Dhanpat Jain

123

Stomach and Proximal Duodenum:
Inflammatory and Miscellaneous

Disorders570
Hala El-Zimaity and Robert Riddell

Dhanpat Jain

5

552

Hala El-Zimaity

Volume I
1

Stomach: Normal Structures and
Developmental Abnormalities

226

Robert Riddell, Hala El-Zimaity and Dhanpat Jain

7

Mesenchymal Tumors

8

Gastrointestinal Manifestations of
Extraintestinal Disorders and Systemic
Disease378

290

Richard Kirsch

Richard Kirsch

17

Small Bowel Mucosal Disease

18

Inflammatory Bowel Diseases

19

Enteric Infections and Associated
Diseases1209

929

Joel KASLE Greenson and Dhanpat Jain

983

Karel Geboes, Robert Riddell and Dhanpat Jain

Dhanpat Jain

20

Small and Large Bowel Polyps
and Tumors

1327

Dhanpat Jain and Robert Riddell

9

Esophagus: Normal Structures,
Developmental Abnormalities, and
Miscellaneous Disorders

422

Michael Vieth and Dhanpat Jain

10

21

The Anal Canal

1547

Henry D. Appelman

Index I-1

Inflammatory Disorders of the
Esophagus: Reflux and Nonreflux Types 450
Michael Vieth and Robert Riddell

11

Polyps and Tumors of the Esophagus

505

Masanori Tanaka and Robert Riddell

xv

Riddell_FM_Vol-1.indd 15

2/14/2014 6:44:11 PM


Riddell_FM_Vol-1.indd 16

2/14/2014 6:44:11 PM


Lewin, Weinstein, and Riddell’s

Gastrointestinal
Pathology and Its
Clinical Implications

Second Edition
VOLUME I

Riddell_FM_Vol-1.indd 17

2/14/2014 6:44:13 PM


Riddell_FM_Vol-1.indd 18

2/14/2014 6:44:13 PM


Dialogue, Biopsies–
Taking and Handling;
Resected Specimens;
Protocols

1

Chapter Outline
MUCOSAL BIOPSY
USUAL ENDOSCOPIC PINCH BIOPSIES
Hot Biopsy Forceps
Cold Biopsies
Electrocautery snare biopsy
Snare Polypectomy
Snare Polypectomy after Submucosal
Injection (“Lift-and-Cut” Technique)
Shave Biopsy

Endoscopic Mucosal Resection and
Endoscopic Submucosal Dissection
Endoscopic mucosal resection
Endoscopic submucosal dissection
Submucosal lesions
ANCILLARY TECHNIQUES USED
AT ENDOSCOPY
Diagnosis of Infections—Smears,
Brushings, Aspiration, and Culture
Cytology
Direct-vision brush cytology
Balloon mesh cytology
Fine-needle aspirates
Chromoendoscopy
Barrett’s esophagus
Inflammatory bowel disease
Screening and surveillance colonoscopy
for adenomas in otherwise healthy
individuals

Virtual Histology
Biopsy specimen handling and
processing
HANDLING OF THE BIOPSY SPECIMEN
PRIOR TO IMMERSION IN FIXATIVES
Handling Polyps
ROUTINE FIXATION
TISSUE PROCESSING, EMBEDDING,
AND CUTTING
DESCRIPTION OF ENDOSCOPIC

FINDINGS
BIOPSY SPECIMEN LOCATION
NUMBER AND SIZE OF BIOPSY
SPECIMENS
THE HISTORY AND THE QUESTION FOR
THE PATHOLOGIST
APPROACH TO THE MICROSCOPIC
EXAMINATION
A SYSTEMATIC APPROACH TO BIOPSY
SPECIMEN INTERPRETATION
TECHNICAL PROBLEMS IN
INTERPRETATION
Mucosal Hemorrhage and Edema
Pseudoerosions
Other Artifacts
THE PATHOLOGIST’S INTERPRETATION
Mild Nonspecific Chronic
Inflammation

MUCOSAL BIOPSY
Most tissue specimens from the gastrointestinal tract
are in the form of mucosal biopsy specimens obtained
at endoscopy. The pathologist can provide a diagnosis for many polyps and tumors. However, for inflammatory lesions he or she can provide a description,
but cannot provide a meaningful interpretation of the
biopsy specimen without the relevant clinical information, endoscopic findings, and a precise description of the biopsy sites. The endoscopist must also be

SPECIAL FIXATIVES, STAINS,
OR STORAGE CONDITIONS
Immunohistochemical Applications in
Gastrointestinal Disorders

Interpretation of Immunohistochemical
Stains
Infections
Tuberculosis and Mycobacterium
avium-intracellulare
SURGICALLY RESECTED SPECIMENS
Examination of the Specimen
FROZEN SECTIONS
PHOTOGRAPHY
OPENING THE SPECIMEN
FIXATION
Insufflation with Fixative
Injection studies for vascular diseases
Examination and dissection of the fixed
specimen
REEXAMINATION OF THE FIXED
SPECIMEN
DISSECTION
Dissections of T
  umors
Lymph Node Dissections
Depth of Tumor Penetration
Venous Invasion by Tumor
Sections of Resected Margins
Incidental Findings

specific concerning the information requested from
the biopsy review. He or she must also be aware of
the criteria the pathologist uses to make specific diagnoses and provide those biopsies. This is rarely taught
in standard endoscopy training unless there are regular meetings at which such requirements can be discussed. This chapter stresses the coordination and

dialogue, which must exist between the clinician who
obtains the biopsy specimens and the pathologist who
interprets them. Table 1-1 summarizes a method that
can be used to obtain high-quality biopsy specimens
and to maximize their clinical value.

1

Riddell_Chap01.indd 1

2/6/2014 7:36:34 PM


2

Lewin, Weinstein, and Riddell’s Gastrointestinal Pathology and Its Clinical Implications

Table 1-1   Recipe to Improve Biopsy Quality and Interpretation Dramatically
I.  ENDOSCOPIST–PATHOLOGIST DIALOGUE
1.  Endoscopist
A. Describe the bowel preparation used.
B. Provide brief but relevant clinical information.
C. Use simple, noninterpretive terms to describe appearance of biopsy specimen (see Table 1-2).
D. Use standardized biopsy site descriptions.
E. Ask specific questions on the pathology requisition.
F. Include endoscopic photos.
G. Give the pathologist important relevant papers from the gastroenterology literature.
2.  Pathologist
A. Explain the terms you use (e.g., acute, chronic, dysplasia, atypia).
B. Do not sign out normal biopsy specimens as “mild nonspecific chronic inflammation.”

C. Provide feedback regarding the quality of specimen.
D. In the report, answer the specific questions asked by the endoscopist.
E. Give the endoscopist important relevant papers from the pathology literature.
II.  HANDLING TISSUE
1.  In the endoscopy unit
A. Make the endoscopy assistant responsible for monitoring uniformity of the terminology used in reports.
B. The endoscopy assistant is responsible for ensuring the labeling on specimen jars is accurate.
C. Endoscopy assistant keeps up-to-date on ancillary techniques (e.g., culture transport conditions).
2.  In the pathology laboratory
A. Designate one or two small-piece technologists.
B. Technologist embeds oriented biopsy specimens on edge but polyps en face.
C. Technologist recognizes when the central core is reached during sectioning.

Surgical or autopsy pathology often deals with
advanced inflammatory or neoplastic processes.
Mucosal biopsies are often used in a more dynamic
dimension, namely, to assess the patient’s response
to therapy or to alter the direction of an investigation.
An example of the latter is the workup of a patient
with diarrhea. The clinician may decide to begin the
investigation with endoscopy and biopsy of the large
bowel. However, if the biopsy specimen is normal, he
or she may then direct their attention to the small
bowel as a possible source of symptoms.

USUAL ENDOSCOPIC PINCH BIOPSIES
Endoscopic pinch biopsy forceps are by far the most
commonly used instruments to obtain gastrointestinal mucosal biopsy specimens to the point that the
word “pinch” is invariably omitted. Most specimens
taken with these instruments yield the full thickness of the mucosa down to the muscularis mucosae.

They may contain a small amount of submucosa or
none at all. In the esophagus, the basal layer of the
squamous epithelium is usually included and sometimes the lamina propria, but rarely the muscularis
mucosae.
The forceps have two cup-shaped jaws and most
contain a central pin (Fig. 1-1). The opened cups are

Riddell_Chap01.indd 2

thrust against the mucosa and closed, and then the
forceps is rapidly withdrawn, avulsing the enclosed
mucosa. Forceps with smaller cups are used in
“skinny” (pediatric) endoscopes with narrow biopsy
channels, yielding inferior biopsy specimens that
are often small and shallow. They may be the only
option for endoscopic biopsy in very young or they
may be used in unsedated upper endoscopies (easier
to swallow). Large biopsy forceps (also referred to
as “jumbo”) require a larger endoscope with a larger
(3.5 mm) endoscopic biopsy channel (Fig. 1-1). It
yields biopsy specimens approximately twice as
long (5–8 mm) as those obtained with conventional
forceps, but they are not much deeper. A variety of
developments include large-capacity biopsy forceps
that can pass through a regular (2.8 mm) biopsy
channel but can yield a biopsy specimen close to
the size obtained from jumbo biopsy forceps. (They
can also be hinged jaws allowing excellent positioning of these forceps on the target [Fig. 1-1B].). It is
often helpful to gently suction the tissue that needs
to be biopsied into the cusps of the biopsy forceps

prior to removal. This technique provides a cleaner
bite and reduces crush artifact. We recommend
the largest forceps possible as they provide better
biopsies, but especially when “tissue is the issue”
at endoscopy.
In certain parts of the gastrointestinal tract, it may
be more difficult to obtain sufficiently deep mucosal

2/6/2014 7:36:34 PM


Chapter 1  Dialogue, Biopsies–Taking and Handling; Resected Specimens; Protocols

3

Chapter 1



A

B

Figure 1-1. A: Endoscopic pinch biopsy forceps. These are passed through a side channel in the endoscope. The forceps on the right
is small and fits into a 1.8-mm pediatric-sized scope but commonly yields suboptimal biopsy specimens. The middle forceps is often
the standard size fitting into a 2.8-mm endoscopy channel. The forceps on the left has an 8-mm open span and is the best; it requires
a larger biopsy channel and hence a slightly larger-diameter endoscope. Most of these forceps have a central spike to help impale the
mucosa. B: Biopsy forceps that produce larger biopsies. The swing jaw mechanism enables easier cup positioning for biopsy sites
approached tangentially such as in the esophagus. That on the right produces jumbo biopsy-sized pieces of tissue but fits down a
scope’s standard 2.8-mm biopsy channel.

biopsy specimens. These are areas, which normally
lack folds or valves, especially the esophagus, gastric antrum, and duodenal bulb. In these areas, the
endoscopist should partially collapse the lumen by
suctioning out insufflated air just prior to biopsy.
­
In the esophagus, the tip of the endoscope may be
deflected 90 degrees against the wall, thus allowing the forceps to be advanced en face from close up
(“turn-and-suction” biopsy technique). The esophageal mucosa is still the most difficult area in the gastrointestinal tract from which to obtain sufficiently
deep, high-quality biopsy specimens.

Hot Biopsy Forceps
Some endoscopists use the hot biopsy technique,
whereby coagulation current is passed through the
jaws of an insulated pinch biopsy forceps. This is most
commonly used for removal and simultaneous obliteration of diminutive colonic polyps, that is, those
<6 mm in diameter. The forceps is used to grasp and
tent the mucosal lesion upward and then to heat the
localized area for several seconds with electrocoagulation current before pulling off the specimen contained
in the cups of the forceps. This seemingly innocuous
technique is not without potential complications, and
some investigators have suggested more limited use.1
An issue with only using forceps without coagulation
to remove polyps is the potential for local recurrence.
When the hot biopsy forceps is used to fulgurate
adenomas, the assumption is made that any residual

Riddell_Chap01.indd 3

adenoma has been destroyed. With the hot biopsy

technique, the pathologist may expect to see some
coagulation necrosis artifact with streaming of nuclei
at the edges of the sections. Some endoscopists use
conventional biopsy forceps to remove diminutive
polyps and then use the argon plasma coagulation
technique to ablate the remaining area instead of
using hot biopsy forceps. However, one or more large
forceps biopsy specimens can be taken with a conventional forceps to remove these diminutive polyps or to
use a mini snare to guillotine these lesions (without
cautery). The hot biopsy forceps is most useful when
it is used simply to obliterate multiple tiny polyps
after a few of them have been taken for histological
interpretation.

Cold Biopsies
Diminutive polyps (5 mm or less in diameter) can
be removed using hot biopsies as in the previous
section or without the use of cautery—cold biopsies.
Morphology is better preserved as there is no cautery artifact, although the lack of cautery also results
in a slightly higher recurrence rate (29% vs. 21%
in one study).2 Larger polyps can also be removed
with cold snare, in which the snare is placed over
the polyp, which is mechanically strangulated and
removed. The risk of perforation is reduced, but
the risk of bleeding increased, so that cold biopsy is
relatively contraindicated in patients with bleeding
­abnormalities.

2/6/2014 7:36:39 PM

4

Lewin, Weinstein, and Riddell’s Gastrointestinal Pathology and Its Clinical Implications

ELECTROCAUTERY SNARE BIOPSY
Snare Polypectomy
The electrocautery snare wire is used for endoscopic polypectomy. Its main application is for
pedunculated colonic polyps. The electrocautery
snare can also be used to remove the much less
commonly encountered pedunculated polyps
­
of the upper g­astrointestinal tract. The wire is
looped over the polyp to encircle the stalk (Fig.
1-2A) and is progressively tightened until it firmly
grasps the stalk of the polyp. At that point, electrical current is applied to resect the stalk. It is

A

important to recognize that the full length of the
polyp stalk is underrepresented in the specimen
because the endoscopist intentionally keeps the
snare away from the bowel wall in order to prevent
intramural or transmural burns (Fig. 1-2B). Thus,
a small amount of cauterized polyp stalk often
remains after snare polypectomy removal. To avoid
postpolypectomy bleeding specially after resec­
tion of large polyps (>2 cm) or in the right colon,
endoscopists often inject submucosally 1:10,000
epinephrine/saline to achieve immediate hemostasis followed by placement of endoscopic hemoclips

when necessary. Other methods of hemostasis can
also be successful including bipolar cautery and
band ligation. This technique can also be used for
large sessile polyps.
The technique recommended to identify the
stalk zone of endoscopically removed polyps is
referred to later in this chapter. Small polyps can
be sucked into the biopsy/suction channel and
retrieved by having a special trap placed where the
wall suction attaches to the endoscope. An alternative for larger polyps is to grasp them with a device
passed through the biopsy channel of the endoscope
and to remove the endoscope. This device can be
either a tri-pronged device or a mesh basket (Roth
Retrieval Net). Sometimes these resected polyps are
lost. A variety of creative stool-straining techniques
have been used to retrieve them, often after the
patient takes (reluctantly) additional lavage solution. These delayed-delivery polyps often retain surprisingly good morphology.

Snare Polypectomy after Submucosal
Injection (“Lift-and-Cut” Technique)

B

Figure 1-2.  Electrocautery snare used for polypectomy. A: The
device is attached to an electrocautery unit. The handle is used
to extend and retract the snare. B: Snare tightened around the
stalk of a polyp in transverse colon. Some stalks can be intentionally left behind (arrow) to avoid cauterizing too close to the
wall (possibly making a mockery of proximity to the cauterized
margin as an indication of nodal metastases if this can be deliberately varied).

Riddell_Chap01.indd 4

Flat or depressed polyps are increasingly identified
during colonoscopies using either improved imaging techniques (chromoendoscopy) or after excellent bowel preparation. These polyps can be resected
using snare polypectomy technique described above
or after submucosal injection. The fluid lifts the polyp
and increases the distance between the base of the
polyp and the muscularis propria and serosa. This
submucosal “cushion” of fluid (bleb formation) has
been shown to prevent deeper thermal injury during polypectomy. The most commonly used fluid
is saline (normal or hypertonic), with or without
1:10,000 epinephrine. With time, this fluid will be
reabsorbed; thus, other fluids have been used in an
attempt to prolong the effect, including 10% glycerol/5% fructose, 50% dextrose, sodium hyaluronate,
and hydroxypropyl methylcellulose. It is preferable
to inject the proximal (far) aspect of the polyp first.

2/6/2014 7:36:42 PM


Chapter 1  Dialogue, Biopsies–Taking and Handling; Resected Specimens; Protocols

If the distal aspect (closest to the endoscope, and
the most tempting) is injected first, the polyp can be
tilted away from the colonoscope, making subsequent
resection more difficult. If a bleb does not immediately form, the needle can be slowly withdrawn and
lifted slightly while injecting until bleb formation is
observed. It is often helpful to inject at the lateral margin of the c­ ushion ­produced by the previous injection
(which has already separated the mucosal layer from
the muscularis propria). However, if a bleb does not

form, the needle may have penetrated the colon wall
and so the fluid is being injected into the peritoneum.
Alternatively, the failure to lift may indicate the presence of invasive cancer that is tethering the polyp to
the underlying muscularis propria. This is called the
“nonlifting sign.”3

Shave Biopsy
A shave biopsy technique is occasionally used to
remove large, sessile, adenomatous polyps from the
colon. This is reserved mainly for high-risk surgical
patients. The technique involves serial loopings and
excisions of parts of the sessile lesion until it is completely removed. The main concern is always whether
there is residual submucosal or deeper involvement
by the adenomatous process.

Endoscopic Mucosal Resection and
Endoscopic Submucosal Dissection
These are techniques developed in Japan that are
used for removing large lesions endoscopically. These
can be large adenomas or areas of glandular or squamous dysplasia, mucosal or early submucosal carcinomas, or primary submucosal tumors. The area to be
resected may be tattooed if not obvious (e.g., an area of
dysplasia). These techniques are extraordinarily safe,
with virtually no mortality and minimal morbidity,
which often contrasts with its surgical counterparts to
the point that it is the preferred mode of therapy for
many lesions that would otherwise require surgical
resection.4–6
Endoscopic mucosal resection.  Endoscopic mucosal resection (EMR) is a technique in which the submucosa is raised by injection with fluid (see above),
and, using one of a variety of techniques the entire
lesion is removed in one or more pieces that include

part of the submucosa. Currently, the most popular
technique uses a specially designed cap that is placed
over the lesion to facilitate resection. A disadvantage
is that lesions are commonly removed piecemeal, so
that while the submucosal margin can be identified

Riddell_Chap01.indd 5

5

in the retrieved fragments, it can be very difficult to
piece the fragments back to be certain that the entire
lesion has been removed. In North America and
Europe, endoscopic resections of dysplastic lesions in
Barrett’s esophagus are the most common use of this
technique.7

Chapter 1



Endoscopic submucosal dissection.  Endoscopic submucosal dissection (ESD) is a technique in which the
lesion is removed using an endoscopic knife, again
at the level of the submucosa. The advantage of this
technique is that the entire lesion can be removed
in one piece, pinned out, and sent to pathology, so
that even circumferential esophageal lesions can
be removed using this technique. The disadvantage
is that it takes far longer, which can be one or more
hours, so it is difficult to accommodate into the schedule of a busy endoscopy unit. It also needs considerable more training than EMR (which itself is quite

­considerable).
Submucosal lesions.  Some discourage the biopsy of
large submucosal lesions of the esophagus. The reason
is that if the lesion is a smooth muscle tumor, fascial
planes will be disturbed, making it difficult to shell
out at surgery. In other sites, it is often desirable to
biopsy endoscopically benign-appearing submucosal
lesions. One reason is to prove that the lesion is submucosal by documenting the presence of a normal
overlying mucosa. A second reason is to determine
the type of lesion (e.g., in the stomach, to differentiate
between stromal tumor, pancreatic rest, cacinoid, and
a submucosal metastasis). Some biopsy specimens
taken with the jumbo pinch biopsy forceps reach the
upper submucosa and thus reveal the nature of the
tumor if it involves that zone. Another technique
that some endoscopists use is to take multiple biopsy
specimens from the same site directed progressively
deeper.8 The optimal practice, where available, is to
have the lesion assessed by endoscopic ultrasound
(EUS). Then, using a special cap placed over the tip
of the endoscope and a snare technique, termed endoscopic mucosal resection (EMR), these lesions can be
shelled out and removed in total endoscopically, if
<1.8 cm, and piecemeal, if larger. In ESD, mucosal
lesions are removed by the dissection of submucosa
under the lesion using endoscopic knives, such as the
insulated-tip diathermy knife and hook knife. Large
specimens can be removed in toto (Fig. 1-3), and
pinned out for pathology (Fig. 1-4). These techniques
have been used throughout the gastrointestinal tract,
but ESD is mostly practiced by Japanese endoscopists

and is less used in the West. In practice, virtually identical specimens are obtained when rectal tumor are
removed by transanal ­excision.

2/6/2014 7:36:42 PM


6

Lewin, Weinstein, and Riddell’s Gastrointestinal Pathology and Its Clinical Implications

Figure 1-3.  Endoscopic submucosal
dissection. A: Large bowel lesion to be
resected. B: The lesion is highlighted
using chromoscopy. C: The limitation of
the dissection is outlined by tattooing.
D: The lesion has almost been removed.
E: Removal is complete leaving a
smooth base (F) pathology specimen.
(Courtesy: Dr. C. Streutker.)

ANCILLARY TECHNIQUES USED AT
ENDOSCOPY
Diagnosis of Infections—Smears,
Brushings, Aspiration, and Culture
The diagnostic specificity of endoscopic biopsy may
be enhanced markedly by other techniques used at
the same endoscopy session. In the case of gastrointestinal infections, ancillary techniques such as cultures and smears of exudates and of biopsy tissue are
often superior to biopsy.
In order to obtain samples from ulcerative or exudative lesions from the gastrointestinal tract, brushes

(Fig. 1-5) may be passed through the same channel of
the endoscope that is used to pass biopsy instruments.
The material on the brush can be smeared on slides
for direct examination for fungi or parasites (especially amebae) and for preparation of cytology smears
when herpes infection or malignancy is a concern.
Similarly, brushes with their adherent material can be
swirled in transport media for appropriate cultures. In
this regard, the most common purposes are to exclude
herpes simplex infection of the esophagus and rectum
and Chlamydia infection of the distal rectum.
When upper endoscopy is done in patients who
have a suspected parasitic infestation (e.g., Giardia
or Cryptosporidium), aspirated duodenal fluid can
be obtained by attaching a suction trap between

Figure 1-5.  Accessories used to complement endoscopic

Figure 1-4.  Pinned out specimen from rectum obtained by
transanal excision.

Riddell_Chap01.indd 6

biopsy. Top: Cytology brush. This is passed through the biopsy
channel enclosed in a plastic sheath and is then advanced, using
a handle at the head end. Bottom: A 21-gauge needle or thinner is used for fine-needle aspiration, usually under ultrasound
guidance for submucosal or deeper lesions.

2/6/2014 7:36:46 PM