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

(BQ) Part 1 book Gastrointestinal pathology and its clinical implications presents the following contents: Dialogue, biopsies–taking and handling, resected specimens; protocols; vascular disorders and related diseases, immunodeficiency disorders, disorders of endocrine cells, motility disorders, mesenchymal tumors,...

tahir99 - UnitedVRG

vip.persianss.ir

Lewin, Weinstein, and Riddell’s

Gastrointestinal Pathology and Its Clinical Implications

Second edition

VOLUME I

tahir99 - UnitedVRG

vip.persianss.ir

tahir99 - UnitedVRG

vip.persianss.ir

Robert Riddell, MD, FRCPath, FRCPC

Professor of Laboratory Medicine and Pathobiology

University of Toronto

Mount Sinai Hospital

Toronto, Ontario, Canada

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

Lewin, Weinstein, and Riddell’s

Gastrointestinal Pathology and Its Clinical Implications

Second edition

VOLUME I

tahir99 - UnitedVRG vip.persianss.ir

tahir99 - UnitedVRG

vip.persianss.ir

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

pre-pared 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

ap-plication of the information in this book and make no warranty, expressed or implied, with respect to the currency,

com-pleteness, 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

reac-tions, 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.

Visit Lippincott Williams & Wilkins on the Internet: at LWW.com Lippincott Williams & Wilkins customer service

represen-tatives are available from 8:30 am to 6 pm, EST.

10 9 8 7 6 5 4 3 2 1

tahir99 - UnitedVRG

vip.persianss.ir

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

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

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

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

Dhanpat Jain, MD

Professor of PathologyDirector, Program in Gastrointestinal and Liver Pathology

Department of PathologyYale University School of MedicineNew Haven, Connecticut, USA

Richard Kirsch, MBChB, PhD, FRCPath(SA), FRCPC

Associate ProfessorDepartment of Laboratory Medicine and Pathobiology

Mount Sinai HospitalToronto, Ontario, Canada

Hiroyoshi Ota, MD, PhD

ProfessorDepartment of Biomedical and Laboratory SciencesShinshu University

Staff PathologistDepartment of Laboratory MedicineShinshu University Hospital

Matsumoto, Nagano, Japan

Robert Riddell, MD, FRCPath, FRCPC

Professor of Laboratory Medicine and PathobiologyUniversity of Toronto

Mount Sinai HospitalToronto, Ontario, Canada

Masanori Tanaka, MD

DirectorDepartment of Pathology and Laboratory MedicineHirosaki City Hospital

Hirosaki, Japan

Michael Vieth, Dr med habil Dr med

Professor of PathologyInstitute of PathologyUniversity of MagdeburgMagdeburg, GermanyDirector

Institute of PathologyKlinikum BayreuthBayreuth, Germany

tahir99 - UnitedVRG

vip.persianss.ir

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

gas-trointestinal disorders where modern gasgas-trointestinal

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

gastro-intestinal biopsies through an understanding of the

indications, by appreciating the need for providing

relevant clinical information, which specific

ques-tions 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 eled against this book is that it assumes that each gas-troenterologist, 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

lev-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

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

pathol-ogy 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

pro-vide answers for such situations and gave rationale

for what we did and why, sometimes finding that we

did them differently ourselves Teaching new

gastro-enterologists where to sample and why and also to

teach them how to interpret the pathologist’s reports,

which are highly variable themselves, is a

challeng-ing task Pathologists can be just as guilty of providchalleng-ing

defensive and unhelpful descriptions that are not

eas-ily 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

gradu-ally 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 ship 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”

Co-Editor-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 pathol-ogists and clinician Since the last edition, images have changed from B&W and “Kodachromes” to digi-tal, so the challenge was to replace these figures and endoscopic photomicrographs The number of tables and management algorithms has also increased sub-stantially 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 hap-pened 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—endos copists and imagers, gastroenterologists, and surgeons

Robert Riddell Dhanpat Jain

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

con-tributed 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 valu-able 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 pincott Williams & Wilkins, but especially Kate Mar-shall whose unmerciful cajoling helped to get this done as quickly as was possible, and also the expertise

Lip-of Satheesh Velayutham and his team for their help with the page proofs

1 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

KaRel Geboes aNd dhaNpat JaiN

3 Immunodeficiency Disorders 88

Joel Kasle GReeNsoN aNd dhaNpat JaiN

4 Lymphoproliferative Disorders of the

9 Esophagus: Normal Structures,

Developmental Abnormalities, and Miscellaneous Disorders 422

miChael vieth aNd dhaNpat JaiN

10 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

12 Stomach: Normal Structures and Developmental Abnormalities 552

hala el-Zimaity

13 Stomach and Proximal Duodenum:

Inflammatory and Miscellaneous Disorders 570

hala el-Zimaity aNd RobeRt Riddell

14 Gastric Epithelial Polyps and Tumors 705

hiRoyoshi ota aNd RobeRt Riddell

Volume II

15 Appendix 795

RobeRt Riddell

16 Small and Large Bowel Structure:

Developmental and Mechanical Disorders 875

dhaNpat JaiN

17 Small Bowel Mucosal Disease 929

Joel Kasle GReeNsoN aNd dhaNpat JaiN

18 Inflammatory Bowel Diseases 983

KaRel Geboes, RobeRt Riddell aNd dhaNpat JaiN

19 Enteric Infections and Associated Diseases 1209

dhaNpat JaiN

20 Small and Large Bowel Polyps and Tumors 1327

dhaNpat JaiN aNd RobeRt Riddell

21 The Anal Canal 1547

heNRy d appelmaN

Index I-1

Lewin, Weinstein, and Riddell’s

Gastrointestinal Pathology and Its Clinical Implications

Second edition

VOLUME I

Chapter Outline

1

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

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

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

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 Tumors Lymph Node Dissections Depth of Tumor Penetration Venous Invasion by Tumor Sections of Resected Margins Incidental Findings

Most tissue specimens from the gastrointestinal tract

are in the form of mucosal biopsy specimens obtained

at endoscopy The pathologist can provide a

diagno-sis for many polyps and tumors However, for

inflam-matory lesions he or she can provide a description,

but cannot provide a meaningful interpretation of the

biopsy specimen without the relevant clinical

infor-mation, endoscopic findings, and a precise

descrip-tion of the biopsy sites The endoscopist must also be

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 diag-noses and provide those biopsies This is rarely taught

in standard endoscopy training unless there are lar meetings at which such requirements can be dis-cussed 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

regu-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

gastrointesti-nal mucosal biopsy specimens to the point that the

word “pinch” is invariably omitted Most specimens

taken with these instruments yield the full

thick-ness 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

some-times 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

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 position-ing 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

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,

gas-tric 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

allow-ing the forceps to be advanced en face from close up

(“turn-and-suction” biopsy technique) The

esopha-geal mucosa is still the most difficult area in the

gas-trointestinal 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

oblit-eration 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

electrocoagula-tion 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

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 conven-tional 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 tery artifact, although the lack of cautery also results

cau-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

epinephrine/saline to achieve immediate sis 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.

hemosta-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 alterna-tive 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 solu-tion These delayed-delivery polyps often retain sur-prisingly good morphology

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

Flat or depressed polyps are increasingly identified during colonoscopies using either improved imag-ing techniques (chromoendoscopy) or after excel-lent 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 dur-ing 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% glyc-erol/5% fructose, 50% dextrose, sodium hyaluronate, and hydroxypropyl methylcellulose It is preferable

to inject the proximal (far) aspect of the polyp first

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,

elec-trical current is applied to resect the stalk It is

A

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

inten-tionally 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

delib-erately varied).

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

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 sched-ule of a busy endoscopy unit It also needs consid-erable more training than EMR (which itself is quite considerable)

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 sub-mucosal 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

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 iden-tical specimens are obtained when rectal tumor are removed by transanal excision

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

immedi-ately 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

mar-gin of the cushion 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

pres-ence 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

com-pletely 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

squa-mous dysplasia, mucosal or early submucosal

carci-nomas, 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

sub-mucosa 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

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

transanal excision.

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

gastroin-testinal infections, ancillary techniques such as

cul-tures and smears of exudates and of biopsy tissue are

often superior to biopsy

In order to obtain samples from ulcerative or

exu-dative 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 (espe-cially 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

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

thin-ner is used for fine-needle aspiration, usually under ultrasound guidance for submucosal or deeper lesions.

hollow plastic tubing through the biopsy channel of the endoscope (Fig 1-5) The needle is pushed into the wall, suction is applied with a syringe attached to the proximal end of the plastic sheath, and the nee-dle is jiggled back and forth two or three times The needle is then retracted into the sheath and removed from the endoscope, and the contents are blown onto

a slide A second slide is apposed, and a smear is pared just as for a blood smear It is useful to repeat this procedure one or two more times so that four to six slides are available for cytology review Experi-ence with this technique has grown with the advent

pre-of EUS for the evaluation pre-of submucosal lesions, for infiltrative disorders (e.g., lymphoma) associated with

a normal overlying mucosa, and for assessing nodes adjacent to tissues accessible at EUS (i.e., mediasti-num, paragastric, paraduodenal, celiac axis, paracolic, and pararectal)

Chromoendoscopy

Chromoendoscopy (the use of dye stains or an image system that changes the color visualized at endos-copy to enhance visualization of potential neoplastic lesions) either with a magnifying endoscope or with-out has been increasingly explored as an approach

in both Barrett’s esophagus and inflammatory bowel disease (IBD) colitis dysplasia screening (Fig 1-8)

Methylene blue as chromogen is taken up by actively absorbing intestinal-type epithelial cells and dysplas-tic cells but not by squamous or gastric mucosa A lighter intensity of staining would highlight an area

of dysplasia So while methylene blue was introduced

as an agent to distinguish inflammation from normal colonic mucosa in the mid-1980s,11,12 it has been stud-ied as an adjunctive technique for identifying neo-plastic from nonneoplastic mucosa in the esophagus

the endoscope and the suction line (Fig 1-6) If the

duodenum is “dry,” a segment of mucosa can be

rubbed with the cytology brush and smears prepared

for parasite examination It can be useful to obtain

aspirated material or brush smears from the

duode-num whenever small-bowel biopsies are being done

in the evaluation of patients with diarrhea

Cytology

The utility of cytology is almost totally dependent

upon the cytologist’s interest integrating the clinical

and histological information Without this interest,

cytology usually adds very little information or may

even be misleading because of false-positive

diagno-ses or the frequent diagnosis of “suspicious for

malig-nancy.” Cytology has gained increasing importance

with the advent of EUS and passage of needles via EUS

into mass lesions and lymph nodes In fact, in many

EUS centers, a designated cytology assistant is present

in the endoscopy suite to perform the smears and

con-firm that analyzable cells are present By far its most

frequent use is in lesions of the pancreatico-biliary tree

malig-nancy when it is used as an adjunct to biopsy.9

Some-times brush cytology is the only technique available to

establish a diagnosis of malignancy, especially when

there are very tight strictures of the esophagus,

stom-ach, or colon

is used to screen for squamous carcinoma in high-risk

groups.10

be obtained from thickened folds or submucosal

lesions This is done by passing a needle attached to

Figure 1-6. A suction trap is attached to the suction line of the

endoscope to obtain luminal fluids, especially from the duodenum.

Figure 1-7. Balloon surrounded by mesh for esophageal cytology

This is used to screen for esophageal cancer, especially in certain high-prevalence provinces in China The device is passed perorally into the stomach; the balloon is inflated and then removed while inflated Thus, the surface cells are trapped in the mesh.

Confocal endomicroscopy allows visualization of vidual cells and their nuclei, so that the enlarged stratified nuclei of dysplasia may be directly identified

indi-While chromoendoscopy with dye spraying or other novel imaging systems exist, do they actually improve the detection of neoplasia in any of Barrett’s esopha-gus, chronic colitis, or simply for routine screening or surveillance colonoscopy in the search for adenomas

or dysplasia? This is discussed subsequently

Regardless of how they are identified, whenever a neoplastic or presumed neoplastic lesion is removed and when there is a question of having to return sooner rather than later for repeat endoscopic assessment, it

is prudent for the endoscopist to inject India ink (Spot)

at the site of lesion removal This helps for subsequent targeted biopsies either during surveillance or to pro-vide a map for the surgeons who will resect that area

Endoscopists must notify pathologists that biopsies were performed from previously tattooed areas

reported to be highly accurate in identifying dysplasia

in Barrett’s esophagus.14 In one report, methylene blue enhanced the detection of the extent of the Barrett’s but not necessarily of finding dysplastic lesions, most

of which were visible endoscopically.15,27 In another Barrett’s esophagus study, methylene blue staining was only 37% sensitive in picking up dysplastic lesions compared with routine histological assessment of four-quadrant biopsies Although the specificity was good in this latter study (97%), to obviate the need for multiple biopsies, sensitivity would have to be excellent.16 There-fore high rates of predictive value of methylene blue for identifying dysplasia are either operator dependent or may require specialized magnifying endoscopes In one randomized crossover study of methylene blue versus random four-quadrant biopsy in patients with dysplasia

in Barrett’s found methylene blue directed biopsies to

be significantly less sensitive in detecting dysplasia than routine biopsies in Barrett’s esophagus.17 Methylene blue identified dysplasia in 9 of 18 subjects while random biopsy with white light endoscopy found dysplasia in 17

of 18 leading these authors to suggest that methylene

and the colon Missing some foci of inflammation

in an otherwise obviously inflamed organ has much

less clinical implication than missing neoplastic foci

in either an inflamed or a noninflamed organ Indigo

carmine as chromogen enhances the mucosal surface

by pooling in the grooves between the mucosal villi

enabling the visualization of the pattern formed by the

mucosal folds and pits Acetic acid achieves the same

goal by means of reversible desaturation of superficial

mucosal proteins The bottom line is that these dyes or

acetic acid can accentuate mucosal pit patterns so that

neoplastic ones become more evident

Because the spraying of solutions can be time

con-suming and messy, the advent of narrow band

imag-ing (NBI) had the potential to be a major advance NBI

involves light of a short wavelength (blue light in the

visible spectrum) penetrating superficially into the

mucosa allowing for improved surface detail As blue

light is highly absorbed by hemoglobin, the vascular

pattern is especially accentuated The major

advan-tages of NBI are that it involves merely the switch

of a button on the head of the endoscope and hence

requires little time and also lacks mess Further it

is uniformly applied, whereas dye spraying can be

nonuniform

Autofluorescence imaging (AFI) uses blue light for

excitation of endogenous tissue fluorophores which

emit fluorescent green light of longer wavelength It

can also highlight neoplastic tissue without the need

for exogenous fluorophores These latter two

modali-ties have the potential advantage of not just

identi-fying neoplasia when present that might be missed

by white light endoscopy, but also by highlighting the

superficial pit patterns of the lesion in question This

could help the endoscopist identify if a lesion is in fact

neoplastic or is merely hyperplastic

Endoscopes are currently available that are

tri-modal These scopes have the usual high-definition

white light endoscopy with buttons that allow

conver-sion to either NBI or AFI.13 These imaging systems

are already widely available, whereas more

sophisti-cated modalities such as confocal microscopy remain

mostly available in research centers

6 cases, of which 10 were dysplastic and 1 was cer) However, chromoendoscopy did not identify sig-

can-nificantly more patients with dysplasia than routine

endoscopy Chromoendoscopy did lead to some false positives and even a few false negatives

Overall the Kiesslich study has been considered a success of chromoendoscopy in ulcerative colitis (UC) which may relate simply to the use of methylene blue, which could be widely adopted by endoscopists with little extra cost However, based on the experi-ence with Barrett’s esophagus, it may have reflected the use of the specialized magnifying endoscopes in combination with the dye The availability of this technique may be dependent on the availability of these specialized endoscopes, and their widespread purchase will likely depend on further validation of this method Elsewhere, the application of indigo car-mine dye immediately after a standard surveillance endoscopy in 100 patients enhanced the yield of find-ing dysplasia in 2 patients to 7 in UC.24

The dye spraying technique may help target sies, so considerably fewer biopsies will be necessary

biop-This technique may also help solve the problem of identifying at endoscopy those lumps that are neo-plastic and not simply inflammatory; this would be

a major advance However, in colons widely studded with inflammatory (pseudo)polyps, the effects of the dye may be obscured.23 False positives are also evident with chromoendoscopy as both highly inflamed areas and neoplastic areas do not take up the methylene blue dye.23 Thus, chromoendoscopy will likely not aid

in the dilemma of distinguishing dysplasia cally in the setting of severe inflammation

histologi-Some studies evaluating dye spraying did not employ

a magnifying endoscope or mucolytics The potential of chromoendoscopy without magnification endoscopy was evaluated in 102 chronic colitis patients undergo-ing surveillance Each patient underwent two passes of the colonoscope; the first pass involved random biopsies with targeted biopsies of raised lesions The second pass was after spraying of methylene blue dye and targeted biopsies of only raised or suspicious lesions The dye spray method yielded 17 patients with dysplasia versus

9 with the targeted nondye technique and only 3 with the random biopsy technique This group advocated consideration of abandoning random biopsies in favor

of targeted biopsying only as directed by dye spraying.25

In practice, chromoendoscopy, as described without a magnifying endoscope, can identify raised lesions that may only be inflammatory and not neoplastic (Fig 1-8) but may also accentuate raised lesions that are neoplas-tic facilitating more focused biopsies (Fig 1-9) Chro-moendoscopy is typically not helpful with widespread inflammatory (pseudo) polyps (Fig 1-10)

NBI identifies vascular changes and is very good

at identifying the extent of inflammation (areas that

blue dye spray with targeted biopsies was inferior to

ran-dom nontargeted biopsies Further, a higher percentage

of biopsies in the random biopsy group were dysplastic

(36%) compared to that of the methylene blue targeted

group (26%, p = 0.05).17 A meta-analysis of nine

stud-ies comparing methylene blue chromoendoscopy with

routine white light endoscopy plus biopsy revealed no

incremental benefit of methylene blue

chromoendos-copy over white light endoschromoendos-copy.18

A series of studies have explored the role of NBI

for detecting dysplasia in Barrett’s esophagus One

of the first observational studies showed a benefit of

using NBI in defining nondysplastic and high-grade

dysplastic Barrett’s epithelium.19 In a prospective

tan-dem study of 65 patients with Barrett’s esophagus, NBI

identified more subjects with higher grades of

dys-plasia than white light endoscopy (18% vs 0), while

standard endoscopy was associated with more

biop-sies (8.5 vs 4.7, p < 0.001).20 While NBI is easy to use,

a study of 8 endoscopists scoring 1,600 NBI images

of Barrett’s esophagus found moderate interobserver

agreement at best, including for high high-grade

dys-plasia This suggests that NBI could not replace

histo-logical evaluation for neoplasia in Barrett’s.21 Perhaps

the most sobering of studies for enhanced imaging

in Barrett’s esophagus was a study comparing white

light endoscopy with the enhancement of any of

indigo carmine chromoendoscopy, acetic acid

chro-moendoscopy, and NBI Twelve endoscopists

exam-ined 22 areas, all assessed with the four techniques

The chromoendoscopy techniques added nothing to

the interobserver agreement achieved on white light

endoscopy So while endoscopists appreciated the

enhancement techniques as revealing more

appeal-ing images, the images did not enhance clinical

out-comes over and above white light endoscopy.22

controlled trial of dysplasia surveillance in IBD was

performed in Germany, where approximately half

the subjects underwent routine dysplasia surveillance

and half underwent dysplasia surveillance with

chro-moendoscopy.23 Chromoendoscopy was performed by

spraying methylene blue 0.1% on the colonic mucosa

in 30-cm segments and observing the mucosa with a

special magnifying endoscope Biopsies were directed

to the paler, less blue, or white areas since

neoplas-tic epithelium is less likely to take up the dye

Dur-ing the course of the chromoendoscopy, the mucosa

was scored for inflammation The investigators found

that chromoendoscopy better delineated the extent of

inflammation by an average of 14 cm More

impor-tantly, chromoendoscopy identified significantly more

neoplastic lesions (35 in 13 cases, of which 32 were

dysplastic and 3 were cancers, vs routine endoscopy

plus biopsy where neoplasia was detected 11 times in

Figure 1-10. Inflammatory (pseudo) polyps can be highlighted using methylene blue but are of no clinical significance.

are endoscopically normal may actually have subtle

vascular changes and NBI may identify this) It may

not be as effective at identifying mass lesions as

dye-based chromoendoscopy, although this requires

fur-ther study In one study, 50 patients with UC were

endoscopically inspected with a scope that had the

capacity for usual white light endoscopy, NBI, as well

as autofluorescence—AFI (trimodal endoscopy).26 NBI

can help determine the extent of inflammation and

hence target where increased biopsy sampling should

be undertaken It is not clear that NBI is as good as

dye spraying for colitis-associated neoplasia

Screening and surveillance colonoscopy for

blue staining with and without magnifying endoscopy

has been used to identify flat and raised adenomas in

noninflamed colons in persons who would be

under-going usual screening colonoscopy.27,28,33,34 More recent

studies have focused on the role of NBI in routine colon

cancer (and adenoma) screening In endoscopy units trying to push through a large volume of screening colo-noscopies, it is easy to see how dye spraying and the extra time required to undertake this would be unpopu-lar In one study, 100 patients at high risk for having adenomas underwent trimodal endoscopy (see previ-ous paragraph) AFI did not reduce the adenoma miss rate compared to white light endoscopy Further, both NBI and AFI were somewhat disappointing in terms of diagnostic accuracy.26 In a study of 276 patients who underwent tandem colonoscopy either with a second white light endoscopy or NBI after white light endos-copy, NBI did not enhance the pickup rate, which was approximately 12% for the second endoscopy.29 In a 6-center study of 1,256 patients randomized subjects

to either NBI or white light endoscopy, there was no difference on adenoma detection between these two modalities (?33%) There was a significantly longer withdrawal time in NBI.30 These studies suggest that high-resolution white light endoscopy with careful

of Barrett esophagus D: Confocal laser

endomicroscopy image of the

corre-sponding tissue in vivo The whiter areas

are the lamina propria where fluorescein

is in the highest concentration Orderly, columnar epithelial cells line in the lam- ina propria as seen in the histopatho-

logic image The white arrow indicates a

goblet cell.

to understand because it often influences diagnosis and therapy Those who choose to improve the qual-ity of biopsy specimens for interpretation find that it requires some motivation, very little extra effort, and

an ongoing dialogue between endoscopists, copy nurses, pathologists, and technologists It is surely time to “legislate” that when a specific clini-cal question is being asked, a minimum biopsy set is required for the pathologist to have the best chance

endos-of answering the question While these are discussed

in more detail in the specific chapters, a summary is provided in Table 1-2, which (one could argue) should

be on the wall of every endoscopy suite

HANDLING OF THE BIOPSY SPECIMEN PRIOR TO IMMERSION IN FIXATIVES

Biopsy specimens from different levels or sites of the large bowel should be placed in different fixa-tive bottles (see Table 1-2) One creative approach for reducing the number of blocks is to use standardized marking ink colors for specimens from different parts

of the gut (e.g., brown for rectum, red for cecum) The different colors of the inks are recognizable around each specimen on microscopic examination

Even when multiple specimens are taken from the same site, we avoid placing more than three or four of them in any bottle, although in many labs more than this are placed in >1 block anyway When-ever there is more than this number in the block, sec-tioning through the full face of all specimens becomes increasingly difficult because the specimens vary in size and are not fully represented in the final histolog-ical slide Each bottle is labeled with a separate letter followed by a bracketed number indicating the num-ber of specimens in that bottle The pathology requi-sition is labeled in a similar fashion The pathologist should expect that in 99% of endoscopy units, biopsy forceps are merely swirled in formalin to shake off the specimen without any mounting

Handling Polyps

Polyps removed with the electrocautery snare with a good stalk can just be immersed in formalin Because stalks are usually short and retract quickly, most of the time the pathologist/technologist does their best

to find the cauterized margin and bisect the polyp in

endoscopic examination is so good that it is hard to

improve upon it with the various novel methods for

polyp detection currently available

Could NBI facilitate real-time assessment of which

polyps are likely adenomas (and hence require

resec-tion) versus hyperplastic and hence can be left in situ

reducing endoscopy time and costs of

histopathol-ogy examination? One hundred subjects underwent

screening colonoscopy with high-definition white light

endoscopy followed by NBI NBI had a high degree of

accuracy at determining that polyps were

adenoma-tous versus hyperplastic.31 These findings were

cor-roborated in a single investigator study by Rex.32

Virtual Histology

Despite the possibilities of chromoendoscopy, a dream

of the endoscopist is to obtain virtual histology, which

means “real-time” in vivo histology The endoscopist

can decide what the area of interest is and, if

neces-sary, can remove the lesion in a targeted fashion Many

new optical developments may further advance early

diagnosis of gastrointestinal cancer Raman

spectros-copy, optical coherence tomography, light scattering

spectroscopy, confocal laser fluorescence endoscopy,

and immunofluorescence endoscopy are some of

the newer methods with different advantages and

disadvantages which have been under development

for considerable time.33,34 However, these techniques

potentially allow the pathologists and endoscopists

to work closely together for the proper diagnosis

of the targeted biopsies The best studied to date of

these techniques is confocal laser endomicroscopy

It enables in vivo microscopy of the mucosal layer of

the gastrointestinal tract with subcellular resolution

during ongoing endoscopy Different types of diseases

can be diagnosed with optical surface and subsurface

analysis This can be used for targeting biopsies to

relevant areas, and subsurface imaging can unmask

microscopic diseases or bacterial infection.35,36 In a

randomized study compared to conventional

endos-copy in UC patients, the presence of neoplastic

changes could be predicted by endomicroscopy with

high accuracy (sensitivity, 94.7%; specificity, 98.3%;

accuracy, 97.8%) Endomicroscopy was associated

with a 4.75-fold increase in neoplasias detected (p =

0.005) than with conventional colonoscopy, although

with 50% fewer biopsy specimens (p = 0.008) Hence

endomicroscopy could increase the diagnostic yield

and reduce the need for biopsy examinations.37 This

technique has been explored in a variety of neoplastic

conditions of the gastrointestinal tract.38

the major advances in endoscopy and diagnostic

pathology, it is disheartening to observe that the tahir99 - UnitedVRG

vip.persianss.ir

noma Subsequent endoscopies for dysplasia/carcinoma only

Intestinalization (if required) is best closest to the squamo-Barrett junction

For dysplasia—any endoscopic irregularity/lesion, then four-quadrant biopsies every 2 cm

Gastric biopsies for Helicobactera

Two biopsies of the antrum and two of oxyntic mucosa—organisms migrate proximally under numerous circumstances (see

Chapter 13) It is usually OK to put these in one container, although wisdom/experience suggest the 2 antral in one and the

2 body in a second

Any areas of redness, erosions, or ulcers

Gastric polyps

Remove/sample polyp and take biopsies from background mucosa as for Helicobacter (overt gastric fundic gland polyps may

be excluded from this, unless the question of Helicobacter is also an issue), but it frequently saves an additional endoscopy

if the “soil” is included automatically

Duodenum for celiac disease

Four biopsies of second part and two or more of the bulb (5%–10% of adults/children have changes limited to the bulb and

need to be taken into account (see Chapter XX)

terminal ileal biopsies for Crohn’s disease

Edge of any erosions/ulcers, plus two close by for focal disease

Biopsies of cecum/ascending colon (backwash ileitis must have similar disease in continuity and so demonstrate its presence

or absence)

Colitis—Query nature of underlying colitis (including microscopic colitis) Demonstrate distribution and focality of disease

throughout the colon—Minimum are biopsies from terminal ileum (microscopic disease), right colon, transverse colon,

descending colon, sigmoid colon, and rectum Put EACH site in separate containers or distribution changes are lost Also

inflammation is greatest in right colon and to a lesser extent the rectum (see Chapters 16 and 18)

Surveillance in IBD

Any suspicious lesions (targeted biopsies)

If polypectomy is carried out take biopsies around its base to demonstrate the adequacy (or not) of polypectomy and whether

any dysplasia exists in the flat mucosa adjacent to the polyp which would be an indication for colectomy as opposed to

ongoing surveillance

Four biopsies every 10 cm from cecum to rectum The distance may be decreased in the rectosigmoid as this is the prime site

for dysplasia and carcinoma Ideally each site into separate containers (see Chapter 18)

a Whenever the stomach or proximal duodenum is biopsied, the issue of whether any changes found are Helicobacter-related arises,

so anticipate it and take biopsies accordingly.

this plane In some units, a dye is used to identify this

(bright colors work best), and this greatly facilitates

cutting the polyp in the correct plane so that, should

invasive carcinoma be present, its proximity to the

cauterized margin can be assessed

ROUTINE FIXATION

Formalin is now used almost exclusively Nonformalin

fixatives such as Bouin’s solution or Hollande’s

modi-fication of Bouin’s solution for gastrointestinal biopsy

specimens cause leaching out the granules of

eosino-phils and other cells such as Paneth and mast cells and

cause major problems with immunohistochemistry, and are not recommended Fixation for 6 hours usually suffices, although this is basically alcohol fixation and overnight fixation is preferred, especially for polyps

TISSUE PROCESSING, EMBEDDING, AND CUTTING

All too often, biopsy specimen interpretation is severely compromised or impossible because of tech-nical flaws that are readily preventable These include misorientation during embedding, sections that are too thick, and shattering by dull microtome knives or

tahir99 - UnitedVRG

vip.persianss.ir

Figure 1-11. Examples of poor processing and

cutting techniques A: This slide was submitted for

a second opinion concerning dysplasia in UC Any possibility of assessing architectural change was precluded by the fact that the biopsy specimen

was sectioned completely tangentially B: Detail of

Figure 1-11A The section is also overstained and too thick, so that there is a lack of nuclear detail

(arrows) in the area that was suspicious for

dys-plasia C: Biopsy section of duodenal mucosa from

a patient with chronic diarrhea Severe chatter and

poor orientation are obvious at this low power D:

The chatter and wrinkles are even more obvious at this power Villi with these sorts of artifacts make

it virtually impossible to diagnose abnormalities such as untreated celiac sprue, while abnormalities such as intraepithelial lymphocytosis that might provide a clue to the cause of the chronic diarrhea similarly cannot be assessed.

by overcooling of blocks prior to cutting (Fig 1-11) In

any pathology laboratory, it is invaluable to have one

or two technologists assigned primarily to biopsies

All technologists should be aware that biopsies need

to be embedded on edge and not en face, to be able

to cut into its core Polyps are embedded en face by

sectioning them in the plane of the stalk (Fig 1-12)

During the embedding process, the technologist

can check to ensure that the number of biopsy

speci-mens designated for a given cassette is correct When

several specimens are embedded in the same tissue block, they should be closely aligned in a straight row to make viewing of the stained sections easier (Fig 1-13) They must be embedded quickly so that they are placed at approximately the same level in the paraffin block

The paraffin block should be trimmed with straight parallel edges Trimming should be done fairly close

to the tissue so that only a small rim of paraffin rounds the specimens This allows multiple sections

sur-tahir99 - UnitedVRG

vip.persianss.ir

from each ribbon, and sometimes more than one row

on a slide

Sections should be 3 to 5 mm thick High- quality

sections cannot be obtained without very sharp knives

Technologists who section gastrointestinal mucosal

biopsy specimens must learn to recognize what the

central oriented core looks like in each region of the

gut Although rarely carried out, this involves

check-ing each group of wet, untrained sections under a

the ghost-like patterns of normal mucosal histology

in each part of the gastrointestinal tract can be

rec-ognized (Fig 1-14) The major landmarks are the

der-mal papillae in the esophagus, the gastric pits, sder-mall

intestinal villi and their crypts, and rectal crypts

The technologist must recognize that cross-sectioned

“doughnuts” are seen at the edges of biopsy specimens

(necessitating further cutting into the block) or in

specimens that have been improperly oriented, either

Figure 1-13 Two tissue specimens in a single block top: A representative ribbon of serial sections Bottom: Embedding the

biopsy specimens close to each other helps to ensure they will both be represented with the best orientation.

B

Figure 1-12 Handling endoscopically removed polyps A: A

stalk as long as the one shown here is very uncommon for the

reason outlined in Figure 1-2B B: Macroscopic picture of polyps showing the stalk at its base suture C: Polyp sectioned through

its stalk so that the resected margin is visible in the section.

C

tahir99 - UnitedVRG

vip.persianss.ir

A

Figure 1-14 A: Appearance of a rectal biopsy section in the unstained “wet” state The technologist must look for the landmark

(oriented crypts) that indicates that the section is in the oriented core of the specimen B: The stained section.

Figure 1-15 Duodenal biopsy specimen illustrating orientation artifacts A: Normal duodenal bulb specimen B: The edge of the

same specimen away from the central core gives the false impression of villous blunting because of tangential artifact Here the clue

to tangential sectioning is the presence of numerous multilayered, cross-sectioned crypts in the bottom half of the section A similar

appearance is produced when the specimen is improperly oriented during embedding There is also no reason for a flat mucosa as

the inflammatory cell component is normal, there is no intraepithelial lymphocytosis and no surface damage.

in the endoscopy unit or in the pathology laboratory

(Fig 1-15)

Up to 30 (two ribbons, each containing 15 sections)

serial sections can be obtained from the best-oriented

core of each mucosal biopsy specimen (Fig 1-13)

If serial sections are not prepared, a plan for the

mini-mum number of random (serial-step) sections through

the central core of each specimen must be established

One approach is to cut groups of sections from at least

three different levels of the central core of the biopsy

specimen While we routinely perform only

hematoxy-lin and eosin stains, if the biopsy concerns require

spe-cial stains (e.g., Helicobacter), a strip of sections from the

central core is set aside in advance Unless carried out routinely, this requires the technologist to survey all the pathology requisitions before beginning to section

If multiple serial sections are not routinely pared, the pathologist must be prepared to provide levels/deepers as required This also presupposes that the clinician has alerted the pathologist to specific ques-tions, such as concern about the presence of granulomas

pre-or parasites, both of which may be sparsely distributed

In the final analysis, it is clearly better to have several well-cut, well-oriented sections from the thickest part of the biopsy specimen than strips of multiple mis-oriented sections laden with scratch marks and folds

tahir99 - UnitedVRG

vip.persianss.ir

Erosions —depressed or nondepressed

—white based; black based

To replace “ectasia” or “angiodysplasia”

Describe the actual lesion (e.g., “3-mm smooth,

nonraised cherry-red spot”)

Note: For each lesion, a description of the size, extent, or both should be

given.

Source: Weinstein WM, Hill TA Gastrointestinal mucosal biopsy In:

Berk J, ed Bockus Textbook of Gastroenterology Philadelphia, PA: W.B

Saunders; 1985:626–644.

DESCRIPTION OF ENDOSCOPIC

FINDINGS

The endoscopist and pathologist must establish an

understanding for the description of mucosal

appear-ances For the endoscopist, this is essential so that all

persons concerned can develop a mental picture of

what was seen For the pathologist, this is important

in order to integrate the gross pathology (endoscopic

appearance) with the microscopic findings Table

1-3 lists terms that have a simple descriptive

con-notation, rather than some of the commonly used

editorial jargon, which is subject to a variety of

inter-pretations or misinterinter-pretations Simply describing

the appearance of a mucosal biopsy specimen as

gastritis or duodenitis can embrace a perception of

factors ranging from color changes to distinct

ero-sions Concerning the latter, the pathologist must

be aware of the fact that the endoscopic distinction

between ulcers and large erosions may be purely

arbitrary Endoscopists can still interpret their

descriptive findings provisionally at the end of the

endoscopy report and in the clinical history section

of a pathology requisition

The photos may be present in electronic records, but it takes far more time to look up, the pictures may not be available, and there may be sufficient delay that it may not be available when the pathologist is signing out the case Most pathologists will not bother to pull up the endoscopic report, so if it accompanies the pathology requisition that is a great advantage for the pathologist

As discussed subsequently, it is also useful for gists to see how biopsy specimens are taken and how polyps are snared in order to understand the source of some of the histological artifacts they encounter

patholo-BIOPSY SPECIMEN LOCATION

The histological appearance of the mucosa in a given organ may vary according to the location of the biopsy specimen within that organ This is especially true in the upper gastrointestinal tract The best way to ensure that different endoscopists in a given endoscopy unit provide uniform information is to make the endos-copy assistant aware of the prerequisites for location description Precise, uniform descriptions of lesion and biopsy specimen locations also permit other clini-cians to interpret the findings The dilemma for many pathologists is that they are simply given the organ source, with no specific description of sites within that organ Table 1-4 outlines the minimum requirements for describing lesion and biopsy sites

NUMBER AND SIZE OF BIOPSY SPECIMENS

For many disorders, the number of biopsy specimens provided influences the ease or precision of interpre-tation (see Table 1-2) The endoscopy assistant should

be trained to recognize what constitutes an acceptably sized biopsy specimen and to provide ongoing feed-back during the procedure For example, it is useful if

a biopsy specimen is reported as tiny or shallow when

it is only 2 or 3 mm in diameter or when it is ent when placed on the finger The latter indicates marked shallowness, except for squamous esophageal biopsy specimens, which are commonly transparent

transpar-tahir99 - UnitedVRG

vip.persianss.ir

for flexible sigmoidoscopy may create epithelial and inflammatory changes.39 The large-volume purging solu-tions used prior to colonoscopy do not appear to create any morphologic havoc Oral sodium phosphate prep-arations may also create “skid marks” in the colon In relation to corticosteroids, especially in enema form, the histology for a disorder such as UC might be different in the treated compared to the untreated state

Sometimes clinicians are disappointed because they fail to obtain histological confirmation of their endoscopic interpretations The pathologist must com-municate the limitations of the ability to make a histo-logical diagnosis in certain disorders One example is in the case of red streaks or even frank tiny erosions in the stomach, where the histology may be very nonspecific

or even normal (see Chapter 13) It is not uncommon for endoscopists to use the term gastritis and colitis when in fact there might simply be some redness that others might view as within normal limits This is espe-cially a problem in the stomach, and gastritis is one of the most overused endoscopic diagnoses The patholo-gist should not feel bullied into overinterpreting nor-mal gastric biopsies because of an endoscopic diagnosis

of gastritis A second example concerns appearances believed to represent small vascular ectasia The clini-cian may not realize that the histological verification of such vascular lesions may be possible in only 50%40 or less of these cases The factors responsible for this low yield include tissue shrinkage and vessel collapse in the fixative, failure to represent the lesion in the sections that were stained, or the location of the vascular abnor-mality in the submucosa (see Chapter 2) When polyps have been biopsied, it may be necessary either to cut through the entire block or re-embed it When the latter was actually carried out in large-bowel polyps showing normal mucosa, 10% were found to have lesions.41

APPROACH TO THE MICROSCOPIC EXAMINATION

It is possible to adopt very different approaches to the initial microscopic examination Both approaches will be described, and the reader can decide which is preferred

One view holds that the histology is examined first, without prior review of the clinical information

A systematic initial examination “without expectation bias” is believed to be more accurate After this initial review, the clinical information is incorporated into

a final interpretation If a firm diagnosis is made, the issue is whether the clinician got it right One gets very good at identifying the precise sites, but some-times the diagnosis cannot be made without knowl-edge of the precise site (intestinal metaplasia in the stomach vs gastric metaplasia in the proximal duode-num vs Barrett’s esophagus)

When the endoscopy assistant reports that only a tiny

fragment has been obtained, the endoscopist should

rebiopsy the same site Even the most skilled

endos-copists using large biopsy forceps have to go back to

a given site periodically to get a better-quality

speci-men Increasingly large forceps can be passed through

standard 2.8-mm channels (see Fig 1-1B)

THE HISTORY AND THE QUESTION FOR

THE PATHOLOGIST

In biopsy specimens taken for malignancy, the question

is self-evident However, in benign diseases, especially

suspected infections and inflammatory bowel diseases,

enough clinical details should be provided so that the

pathologist can give an informed diagnosis or

differen-tial diagnosis In addition, the specific question should

be clearly outlined for the pathologist to help guide the

direction and intensity of the pathologist’s review

For all biopsy specimens taken from the colon, it is

helpful if the type of purgative preparation used is stated

and also whether the patient is taking anti-inflammatory

drugs is recorded on the pathology requisition The

rea-son for the former is that certain irritant laxatives used

table 1-4 recommended Approach

to Describe the Locations

of Endoscopic Lesions and Biopsy Sites

Esophagus—Give all as number of centimeters from the

incisor region

Location of the region of the squamocolumnar junction

(Z-line) Location of the lesion or biopsy site

Stomach

Fundus

Body—For each, proximal, mid, or distal

Antrum—For each, give curvature or wall

Duodenum

Bulb

Descending portion—proximal, mid, or distal

Third and fourth portions—need x-ray confirmation for

Rectum—number of centimeters from anal verge

Note: These are minimum prerequisites; in many circumstances,

addi-tional descriptions are required to depict the location accurately.

Source: Weinstein WM, Hill TA Gastrointestinal mucosal biopsy In:

Berk J, ed Bockus Textbook of Gastroenterology Philadelphia, PA: W.B

Saunders; 1985:626–644.

tahir99 - UnitedVRG

vip.persianss.ir

biopsies stated to be “consistent with” whatever is on

the requisition form The issue is whether complete

detachment really can be obtained from the

informa-tion on the requisiinforma-tion form before looking at the slide

A SYSTEMATIC APPROACH TO BIOPSY

SPECIMEN INTERPRETATION

Interpretation of biopsy specimens from different

areas of the gastrointestinal tract is dealt with in the

individual chapters The theme, however, is the same

for each area: try to maintain a uniform and

system-atic approach Much of the examination is done at low

power to get an impression of the overall architecture

and lymphoid aggregates and to determine whether

there are striking inflammatory or neoplastic changes

Abnormal-appearing areas are focused on selectively

One purpose of serial sections is to follow suspicious

lesions such as granulomas and early crypt abscesses

With experience, such lesions can also be scanned for

at low power; higher magnification is used only to

confirm their presence

Table 1-5 outlines a systematic approach to

muco-sal biopsy examination, beginning with the

examina-tion of luminal contents (i.e., cell fragments, exudate,

and organisms adherent to or near the surface

epithe-lium) Within exudate, there may be superficial

frag-ments of a carcinoma or evidence of infection The

organisms found in luminal contents or attached to

the surface epithelium are listed in Table 1-6 Some

other infections are recognized in an intracellular

location in surface epithelium (e.g., Isospora belli) or

as transformed cells in deeper zones of granulation

tissue (e.g., cytomegalovirus)

TECHNICAL PROBLEMS IN

INTERPRETATION

Mucosal Hemorrhage and Edema

Biopsy specimens for benign disorders are usually

taken after a complete examination of the region in

question In a sense, the mucosa is “massaged,”

some-Lymphoid aggregates (focal, diffuse)

High power

Lumen: organisms Surface epithelium Organisms Type—any dysplasia Cells within epithelium?—neutrophils, intraepithelial Lymphocytes

Subepithelial collagen Crypt/pit epithelium Height

Mitoses, any dysplasia Paneth/endocrine cells Lamina propria

Predominant cells Abnormal cells (histiocytes, pigment cells, carcinoma) Eosinophils

Fibrosis Submucosa if present Inflammation Ganglion cells Vessels (amyloid, ectasia)

table 1-6 Some Infections that May

Be Found in Exudate or

as Attachments to the Surface Epithelium

SItE OF BIOPSY OrGANISMS

Esophagus Stomach Small intestine Large bowel

Candida, herpes simplex Helicobacter pylori, Candida Giardia, Cryptosporidium Amoeba, Cryptosporidium, spirochetes

times vigorously, by repeated passage back and forth

in order to examine all areas Biopsy specimens are then usually taken at the end of the procedure Thus, theoretically, a certain amount of mucosal edema and congestion can be induced by the endoscopy procedure itself Also, most pinch biopsy forceps do not have sharp cup edges; the mucosa is pinched off and avulsed rather than cut Trauma can be induced by this procedure Additional congestion and hemorrhage may be induced by a maneuver called

slowly retracted to produce a mucosal “tent” in order

to obtain some reassurance that the tissue sample

tahir99 - UnitedVRG

vip.persianss.ir

is not too deep The ideal way to take the biopsy

specimen is to retract the forceps back quickly after

it is closed on a given area of mucosa

Given these technical considerations, we tend

to ignore focal congestion, hemorrhage, and edema

in mucosal biopsy interpretation because we cannot

exclude the possibility that they were induced by

trauma For example, in the stomach, up to one-

quarter of the horizontal span of a biopsy specimen

may contain lamina propria hemorrhage and edema

that are presumed to be due to some or all of the

above factors.42 When there is extensive hemorrhage

or edema in a biopsy specimen, especially if it is

pres-ent in a focal lesion seen at endoscopy and not in

adja-cent grossly uninvolved mucosa, we mention it in the

biopsy report

Pseudoerosions

In a similar vein, there is a problem in relation to

appar-ent microscopic erosions Portions of the surface

epi-thelium of mucosal biopsy specimens are commonly

detached (Fig 1-16) Erosions should not be diagnosed

histologically unless there are other accompanying

features—specifically, thin restituting epithelium

that may cease abruptly, evidence of necrosis, fibrin

over the erosion, neutrophils, or granulation tissue

beneath the area of denuded epithelium (Fig 1-17)

Traumatic artifact with surface epithelial denudation

and crush is especially common at the edges of biopsy

specimens This is because of compression of the

tis-sue at the point of closure of the biopsy forceps This

compression may cause inflammatory cells to appear

A

B

Figure 1-17. Gastric biopsy specimen with NSAID erosion and denudation of surface epithelium However there are marked reactive changes with mucin depletion suggesting that this is not artifact The lack of lamina propria inflammation is a feature

of many NSAID/ASA erosions as seen in (B) A: There is

super-ficial loss of epithelium with a loose pseudomembrane

superfi-cially B: True erosion of gastric mucosa Surface epithelium is

absent, and there is only a superficial fibrin exudate only, out inflammatory cells or granulation tissue.

with-Figure 1-18. Artifact Compression artifact at the edge of

a rectal biopsy specimen (arrow) This is almost the rule in all

pinch biopsy specimens obtained at endoscopy The crush can simulate lymphoid aggregates and fibrosis.

Figure 1-16. Artifact Pseudoerosions versus early erosions

top: Large-bowel biopsy in which the surface mucosa has been

artifactually stripped The clue is the abrupt cessation of

epithe-lium (blue arrows) without acute inflammation, fibrin,

hemor-rhage, restitution, or reactive changes in the underlying crypts

Bottom: Early erosion Surface epithelium is markedly

attenu-ated, with hemorrhage, reactive changes in the adjacent crypts

and usually (not always) neutrophils (inset).

dense and may concentrate connective tissue, lating fibrosis (Fig 1-18) Some conditions (e.g., col-lagenous colitis) are frequently stripped of epithelium but lack fibrin or neutrophils or any reaction

simu-tahir99 - UnitedVRG

vip.persianss.ir

clearly that this was the case and should only indicate which features or diagnoses, if any, can be excluded

on the basis of the available suboptimal material

Well-intentioned pathologists are sometimes overly helpful in relation to their friends, the endosco-pists One example is when an endoscopist submits a biopsy specimen of a “polyp” that proves histologically

to be normal mucosa The pathologist should resist the urge to assuage the endoscopist and not sign out such a case as a “mucosal tag,” a “redundant fold,” or, even worse, a “polypoid fold.” In such a situation, the truth cannot be ascertained The possibilities include endoscope suction artifact, a submucosal lesion, a true mucosal polyp that the endoscopist did not tar-get accurately and that did not appear in the sections examined, or a “wrinkle” equivalent

The pathologist’s final interpretation should address the specific questions raised by the clinician either positively or negatively A provisional differ-ential diagnosis can be added, based on the history, endoscopic findings, and microscopic findings Terms

such as nondiagnostic should be avoided In the

inves-tigation of benign disease of the gastrointestinal tract, the issue is often not whether a given lesion is non-diagnostic, since many are, but whether there is any mucosal abnormality at all When a biopsy specimen,

is normal, we encourage the use of the word normal

in the final diagnosis

Mild Nonspecific Chronic Inflammation

One of the greatest challenges for even the most experienced morphologist is to differentiate between

a normal appearance and one that is very mildly abnormal “Mild chronic inflammation” is an exces-sively used final diagnosis for many biopsy specimens that are actually normal The term “nonspecific” as

a descriptor of inflammation is a waste of words, as all inflammation is nonspecific Granulomas have numerous causes, and even Warthin– Finkeldy giant cells are not specific for measles One of the most com-mon complaints that endoscopists have in relation to

Figure 1-19. Artifact Intraepithelial tears (arrows).

Figure 1-20. Artifact Air-filled spaces in duodenal mucosa.

Other Artifacts

In the surface epithelium, there may be dramatic

intraepithelial spaces (Fig 1-19), which could

theoretically be labeled as intracellular edema but

probably represent a technical artifact’s Another

artifact is air-lined spaces43 in the mucosa and

submu-cosa (Fig 1-20) This appearance is common enough

that it is usually recognized, but it can be

mistak-enly attributed to fat or to dilated lymphatics

Dur-ing endoscopy, air is routinely insufflated to permit

visualization; presumably it penetrates the mucosa

Biopsy specimens that are shallow may create

an illusion of villous blunting in the small intestine

(Fig 1-21) or of sparse crypts in the large intestine

THE PATHOLOGIST’S INTERPRETATION

All too often, the pathologist is given biopsy specimens

that are overly traumatized or too small for

interpre-tation The final pathology report should indicate

Figure 1-21. Artifact Shallow small-bowel biopsy men creates an illusion of villous blunting (Courtesy of Cyrus

speci-E Rubin.)

tahir99 - UnitedVRG

vip.persianss.ir

Immunohistochemical Applications

in Gastrointestinal Disorders

Immunohistochemical methods are used in the everyday practice of diagnostic pathology The appli-cation of this technology has been facilitated by the development of highly sensitive immunohistochemi-cal methods and the production of antibodies to new markers that can be identified in paraffin-embedded tissue The main value of immunohistochemistry in the gastrointestinal tract is in the diagnosis of tumors and hyperplasias and, to a lesser extent, infections and motility disorders

Immunohistochemistry or in situ hybridization is often of great help in determining the cell of origin

of poorly differentiated tumors such as gastric nomas, lymphomas, carcinoids, and gastrointestinal mesenchymal tumors including stromal tumors The primary objective of this section is to outline certain principles that have special relevance to gastrointesti-nal tract pathology

carci-Interpretation of Immunohistochemical Stains

Immunohistochemistry can be carried out with antibodies requiring dilution and optimal titration, prediluted, and in kit form Kits contain all the nec-essary reagents to be applied to the tissues and are generally as reliable as methods using individually purchased reagents However, whichever is used, one must still be constantly aware of potential arti-facts, that is, false positives and false negatives

With an ever-increasing number of antibodies available for diagnosis, it is useful to check with

an expert in the field concerning sensitivity and specificity before using a newly touted reagent, and ensuring that appropriate controls and dilu-tions are used

interpretation of their specimens is that the

patholo-gists in their institution never call anything normal

and sign out virtually all cases as “mild nonspecific

chronic inflammation.” At one end of the spectrum,

the clinicians, in turn, may ignore this diagnosis,

per-haps doing the patient a disservice At the other, in

the presence of a normal colonoscopy, this may be

interpreted as evidence of microscopic colitis, and

the whole therapeutic armamentarium for this swung

into place One general rule is that mild inflammation

is rarely an isolated finding in a biopsy specimen, and

virtually never is the cause of symptoms unless part of

more general disease (e.g., Crohn’s disease) Bona fide

microscopic inflammation in the colon can contribute

to diarrhea but in the absence of other findings is not

cause of abdominal pain or gastrointestinal bleeding

There are also usually other accompaniments, such as

epithelial changes For certain disorders, namely,

gas-tritis and duodenitis, “mild chronic inflammation” has

undefined clinical implications On the other hand, in

the small bowel and colon, this finding may point the

clinician to the source of the symptoms or may dictate

the need for an additional search for the cause of this

change (e.g., parasitic infestation or Crohn’s disease)

Overdiagnosis of normal biopsy specimens is

avoided when the pathologist gains experience with

the normal histological spectrum and the technical

artifacts In badly oriented and traumatized material,

it is virtually impossible to make a diagnosis of mild

abnormalities with certainty A study of biopsies in the

cecum and rectum in healthy individuals has shown

that there is increased inflammation in health in the

right colon.44 Hence pathologists need to be careful in

assessing what they consider to be increased

inflam-mation when the biopsies are from the right colon

The pathologist must communicate with the

clini-cians he or she works with concerning the meaning of

certain terms that are used in biopsy reports

Other-wise, the findings may be misinterpreted in their

clin-ical context For example, the terms acute and chronic

to the nature of the inflammatory cell infiltrate The

clinician should not interpret these terms as

necessar-ily having a temporal connotation

Effective communication is also important in

conditions such as Barrett’s esophagus and UC when

surveillance biopsy specimens are taken The

clini-cian must understand that the term dysplasia refers to

a neoplastic change in the epithelium and that

high-grade dysplasia in the gastrointestinal tract may be

equated with carcinoma in situ Another term, which

requires clarification to avoid misunderstanding and

needless worry, is atypia We prefer to use it in the

context of nonneoplastic change, and that in

pathol-ogy reports it be prefaced with a reassuring term such

as reactive or inflammatory. tahir99 - UnitedVRG

vip.persianss.ir