62090

Download as pdf or txt
Download as pdf or txt
You are on page 1of 65

Download Full Version ebook - Visit ebookmeta.

com

Gastrointestinal Pathology Correlative Endoscopic


and Histologic Assessment 1st Edition Gregory Y
Lauwers Michael B Wallace Till S Clauditz

https://ebookmeta.com/product/gastrointestinal-pathology-
correlative-endoscopic-and-histologic-assessment-1st-
edition-gregory-y-lauwers-michael-b-wallace-till-s-clauditz/

OR CLICK HERE

DOWLOAD NOW

Discover More Ebook - Explore Now at ebookmeta.com


Instant digital products (PDF, ePub, MOBI) ready for you
Download now and discover formats that fit your needs...

Start reading on any device today!

Gastrointestinal and Liver Pathology: A Volume in the


Series: Foundations in Diagnostic Pathology 3rd Edition
Amitabh Srivastava
https://ebookmeta.com/product/gastrointestinal-and-liver-pathology-a-
volume-in-the-series-foundations-in-diagnostic-pathology-3rd-edition-
amitabh-srivastava/
ebookmeta.com

Hegde s PocketGuide to Assessment in Speech Language


Pathology 4th Edition M.N. Hegde

https://ebookmeta.com/product/hegde-s-pocketguide-to-assessment-in-
speech-language-pathology-4th-edition-m-n-hegde/

ebookmeta.com

Sleisenger and Fordtran's Gastrointestinal and Liver


Disease Review and Assessment 11th Edition Emad Qayed

https://ebookmeta.com/product/sleisenger-and-fordtrans-
gastrointestinal-and-liver-disease-review-and-assessment-11th-edition-
emad-qayed/
ebookmeta.com

Bacterial Diseases of Crop Plants 1st Edition Suresh G


Borkar Rupert Anand Yumlembam

https://ebookmeta.com/product/bacterial-diseases-of-crop-plants-1st-
edition-suresh-g-borkar-rupert-anand-yumlembam/

ebookmeta.com
Lifetime physical fitness wellness a personalized program
15th Edition Werner W. K. Hoeger

https://ebookmeta.com/product/lifetime-physical-fitness-wellness-a-
personalized-program-15th-edition-werner-w-k-hoeger/

ebookmeta.com

Un Convention On Contracts For The International Sale Of


Goods 2nd Edition Stefan Kröll

https://ebookmeta.com/product/un-convention-on-contracts-for-the-
international-sale-of-goods-2nd-edition-stefan-kroll/

ebookmeta.com

Geomorphology in Deserts Ronald U. Cooke

https://ebookmeta.com/product/geomorphology-in-deserts-ronald-u-cooke/

ebookmeta.com

Fruit Cookbook: Discover the Joys of Cooking with Fruits


with Tasty Sweet Recipes 2nd Edition Booksumo Press

https://ebookmeta.com/product/fruit-cookbook-discover-the-joys-of-
cooking-with-fruits-with-tasty-sweet-recipes-2nd-edition-booksumo-
press/
ebookmeta.com

Blood Fire Saga, Hades and Persephone 03.0 - Debauched 1st


Edition Bella Klaus

https://ebookmeta.com/product/blood-fire-saga-hades-and-
persephone-03-0-debauched-1st-edition-bella-klaus/

ebookmeta.com
Insight Guides Sri Lanka 9th Edition Rough Guides

https://ebookmeta.com/product/insight-guides-sri-lanka-9th-edition-
rough-guides/

ebookmeta.com
Gastrointestinal Pathology
Gastrointestinal Pathology

Correlative Endoscopic and


Histologic Assessment

Edited by

Gregory Y. Lauwers, MD, FAGPS


Senior Member and Director, Gastrointestinal Pathology Service
Department of Pathology, Moffitt Cancer Center
Professor, Departments of Pathology and Cell Biology and Oncologic Sciences
University of South Florida
Tampa, FL, USA

Michael B. Wallace, MD, MPH


Consultant – Gastroenterology and Hepatology
Fred C. Andersen Professor of Medicine, Mayo Clinic School of Medicine
Jacksonville, FL, USA

Associate Editor:

Till S. Clauditz, MD
Associate Professor, Head of Gastrointestinal Pathology Service
Department of Pathology with Section Molecular Pathology and Cytology
University Medical Center Hamburg-Eppendorf,
Hamburg, Germany
This edition first published 2021
© 2021 John Wiley & Sons Ltd

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material
from this title is available at http://www.wiley.com/go/permissions.

The right of Gregory Y. Lauwers and Michael B Wallace to be identified as the authors of the editorial material in this work has been asserted in
accordance with law.

Registered Offices
John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK

Editorial Office
9600 Garsington Road, Oxford, OX4 2DQ, UK

For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.

Wiley also publishes its books in a variety of electronic formats and by print-on-demand. Some content that appears in standard print versions
of this book may not be available in other formats.

Limit of Liability/Disclaimer of Warranty


The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and
should not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient.
In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating
to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert
or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and
for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no
representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties,
including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or
extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or
product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors
endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with
the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be
suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this
work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be
liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

Library of Congress Cataloging-in-Publication Data applied for

HB ISBN: 9780470658369

Cover Design: Wiley


Cover Images: © Gregory Y. Lauwers and Michael B. Wallace

Set in 9.5/12.5pt STIXTwoText by SPi Global, Pondicherry, India

10 9 8 7 6 5 4 3 2 1
v

Contents

List of Contributors vii

1 General Principles of Biopsy Diagnosis of GI Disorders 1


Herbert C. Wolfen, Michael B. Wallace, Naohisa Yahaghi and Yutaka Saito

2 Esophagus Inflammatory Conditions 11


Anthony R. Mattia, Gregory Y. Lauwers, Michael B. Wallace and Till S. Clauditz

3 Epithelial Metaplastic, Polypoid, and Neoplastic Conditions of the Esophagus 35


Till S. Clauditz, Gregory Y. Lauwers, Michael B. Wallace and Anthony R. Mattia

4 Inflammatory Disorders of the Stomach 73


Till S. Clauditz , Michael B. Wallace and Gregory Y. Lauwers

5 Polyps of the Stomach 99


K. Kim, Till S. Clauditz, Jun Haeng Lee and Gregory Y. Lauwers

6 Gastric Neoplastic Conditions: Precursor Lesions and Early Gastric Cancer 125
Till S. Clauditz and Gregory Y. Lauwers

­ astric Neoplastic Conditions: Lymphoid Lesions of the Stomach


G 142
Mounir Trimeche and Laurence de Leval

7 Inflammatory and Miscellaneous Conditions of the Small Intestine 161


Ian Brown and Michael B. Wallace

8 Polyps of the Small Intestine 195


Ian Brown and Michael B. Wallace

9 Epithelial and Nonepithelial Neoplasms of the Small Intestine 209


Ian Brown, Michael B. Wallace and Till S. Clauditz

10 Inflammatory Conditions of the Colon 235


Tze Sheng Khor, Till S. Claudtiz, Bence Kővári, Gregory Y. Lauwers, Michael B. Wallace and Priyanthi Kumarasinghe

11 Polyps of the Large Intestine 307


Christophe Rosty, Michael B. Wallace and Till S. Clauditz
vi Contents

12 Epithelial Neoplasms of the Large Bowel 321


Christophe Rosty, Michael B. Wallace and Till S. Clauditz

13 Inflammatory Conditions of the Anus 337


Thomas Arnason and Michael B. Wallace

14 Polyps and Neoplastic Lesions of the Anus 349


Thomas Arnason, Michael B. Wallace and Till S. Clauditz

Index 369
vii

List of Contributors

Thomas Arnason Gregory Y. Lauwers


Queen Elizabeth II Health Sciences Centre and Moffitt Cancer Center
Dalhousie University Tampa
Halifax Florida
Nova Scotia USA
Canada
Jun Haeng Lee
Ian Brown Samsung Medical Center
Envoi Specialist Pathologists Sungkyunkwan University School of Medicine
Brisbane Seoul
Australia South Korea

Till S. Clauditz Laurence de Leval


Department of Pathology Institute of Pathology
University-Medical-Center University of Lausanne
Hamburg Lausanne
Germany Switzerland

Tze Sheng Khor Anthony R. Mattia


PathWest Laboratory Medicine Newton-Wellesley Hospital
Queen Elizabeth II Medical Centre Newton, MA
Nedlands USA
Western Australia
Christophe Rosty
Australia
Envoi Specialist Pathologists
K. Kim Brisbane
Samsung Medical Center Queensland
Sungkyunkwan University School of Medicine Australia
Seoul
Yutaka Saito
South Korea
National Cancer Center
Tokyo Japan
Bence Kővári
Department of Pathology Mounir Trimeche
University of Szeged Institute of Pathology
Szeged University of Lausanne
Hungary Lausanne
Switzerland
Priyanthi Kumarasinghe
Department of Anatomical Pathology Michael B. Wallace
PathWest, QE II Medical Centre Mayo Clinic
Univ. of Western Australia Jacksonville
Perth Florida
Australia USA
viii List of Contributors

Herbert C. Wolfen Naohisa Yahaghi


Mayo Clinic Keio University Cancer Center
Jacksonville Tokyo
Florida Japan
USA
1

General Principles of Biopsy Diagnosis of GI Disorders


Herbert C. Wolfen1, Michael B. Wallace1, Naohisa Yahaghi2 and Yutaka Saito3
1
Mayo Clinic, Jacksonville, Florida, USA
2
Keio University Cancer Center, Tokyo, Japan
3
National Cancer Center, Tokyo Japan

Tissue sampling of the gastrointestinal tract at the time of ­ ndoscopic Equipment for Tissue
E
endoscopy is the cornerstone of many gastrointestinal Sampling
diagnoses. The development of a flexible endoscope and
the subsequent ability to directly acquire tissue under Modern endoscopic equipment can be divided in two gen-
optical guidance has been one of the most important eral categories: the endoscope that allows access to the gas-
advancements in the field of gastroenterology throughout trointestinal tract and accessory devices that are typically
its history. Although tissue sampling can be performed passed through the working channel of the endoscope to
through nonendoscopic devices, the ability to directly cor- directly acquire tissue, including biopsy forceps, snares,
relate precise locations and target biopsies to specific areas fine-needle aspiration devices, and cytology brushes.
of disease is critical to our ability to diagnose and further Recent developments in tissue sampling include devices
understand gastrointestinal pathology. Many of the that are capable of wide-field, often definitive, endoscopic
advancements in our understanding of the basic pathol- resection of early neoplasia and invasive carcinoma.
ogy and molecular biology of gastrointestinal disease can A modern endoscope is a remarkably robust and versa-
be directly attributed to our ability to acquire tissue for tile instrument including a light source, optical lenses with
histological, molecular, and genetic analyses. An excellent a video capture device, image processing, and display
example is our deep understanding of the molecular equipment, and importantly for the purposes of tissue
pathology of colorectal cancer development from normal acquisition, an accessory channel ranging from 1 to 6 mm
colonic epithelium to adenoma to colorectal cancer, a dis- (typically 3–4 mm), which allows passage of devices for
covery made possible because of colonoscopic access to mechanical collection of tissue (Figures 1.1 and 1.2).
precursor lesions such as adenomatous polyps and early There is a general trade-off between the diameter of the
cancers. instrument and the ease and comfort with which it can be
In this chapter, we will review general principles of ­tissue passed through the natural orifices of the body such as the
acquisition at the time of endoscopy including the following mouth and anus. In general the larger the outer diameter,
topics: the larger the accessory channel is to accommodate larger
●● Endoscopic equipment for obtaining tissue including instruments for tissue acquisition. A fundamental limita-
endoscopic accessory channels, biopsy forceps, snare tion of most flexible endoscopes, as opposed to surgical
devices, needle aspiration and cytology brush. instruments, is that all accessories pass through a single
●● General principles of optimal sampling technique. access point of the endoscope. As compared to surgical
●● Methods of tissue preparation in the endoscopy labora- instruments with multiple access points, the endoscopic
tory to optimize diagnostic accuracy. devices do not typically allow triangulation to acquire a
●● The role of endoscopic ultrasound (EUS)-guided fine- large bulk tissue or resect entire organs. For this reason,
needle aspiration cytology. most tissue is sampled through pinch forceps, needle

Gastrointestinal Pathology: Correlative Endoscopic and Histologic Assessment, First Edition. Edited by Gregory Y. Lauwers and Michael B. Wallace.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
2 General Principles of Biopsy Diagnosis of GI Disorders

aspiration, or wire loop snare devices. More recently, elec-


trosurgical needles and other cutting tools have been
developed, which have allowed wide-field resection of tis-
sues of virtually any diameter (Figure 1.3).

­Pinch Biopsy Forceps

The flexible pinch biopsy forceps have been one of the


most versatile of all instruments for tissue acquisition.
These typically involve a flexible steel cable and lever
device with two sharp-edged cups, which can be opened
and closed to acquire tissue (Figure 1.4).
Standard endoscopic sampling typically acquires tissue
from the mucosa and occasionally a submucosal depth of
Figure 1.1 Endoscope with control handle and tip. The tip
contains a light source, imaging window, and accessory channel the intestinal wall; however, large-capacity forceps as
through which various tissue acquisition devices can be passed. well as multiple sampling including “bite on bite” allow
sampling of the deeper layers. Pinch biopsy forceps come
in multiple sizes from very small instruments such as a
pediatric forceps, which can be passed through very
small working channels. Recent development of very
tiny forceps makes it possible to pass them through spe-
cial endoscopes into the bile or pancreas duct and to
pinch biopsy outside of the traditional gastrointestinal
lumen (Figure 1.5).
Studies comparing jumbo forceps to standard forceps
have generally not shown significant advantages of larger
capacity forceps. A limitation of most forceps is the ina-
bility to sample tissue in the submucosa routinely. This is
highlighted in studies looking for Barrett’s esophagus
after the surface epithelium has been ablated. Biopsy for-
ceps can remove tissue with mechanical closure alone or
with electrocautery (“hot biopsy”) although the use of
hot biopsy has diminished significantly due to increased
Figure 1.2 Endoscopic processor, which converts the light
captured from the endoscope tip into a visible image for display. risks of complication and tissue damage in the biopsy
Source: Olympus America, Inc. With permission. specimen.

(a) (b) (c) (d) (e)

Jet B knife IT knife nano CO2 insufflator ST hood short type MucoUp
Zeon medical Olympus medical Olympus Medical Fujifilm medical Johnson and Johnson

Figure 1.3 (a) Tools for performing endoscopic resection including endoscopic submucosal dissection (ESD). Source: Zeon Medical.
(b) Standard and insulated tip electrocautery knives for incision and dissection. Source: © 2017 Korean Society of Gastrointestinal
Endoscopy. (c) CO2 insufflator for luminal distension, which is preferred to air given rapid reabsorption. Source: Olympus. (d) Distal
attachment hood to facilitate maintaining view within the submucosal space. Source: Fujifilm medical. (e) Injection fluid (hyaluronic
acid; Mucoup [Johnson and Johnson]) for submucosal lifting. Source: Gut and Liver.
­Endoscopic Brush Cytolog  3

Figure 1.4 Endoscopic biopsy forceps in the open position. The


needle-like pin in the center holds the tissue in place so one to
two samples can be obtained per pass.
Figure 1.6 Endoscopic snare for polypectomy. The wire loop is
extended in the open position outside the plastic sheath. When
closed, the wire loop is strangulated and resects the polyp
tissue.

Figure 1.7 Endoscopic cytology brush. Note the abrasive brush


Figure 1.5 Micro biopsy forceps <1 mm in diameter, which can extended beyond the protective plastic sheath.
be passed through specialized endoscopes into the bile duct,
pancreas duct, or via 19-gauge needles for extraluminal tissue
sampling. Source: Boston Scientific Corporation with permission. oval, hexagonal, and asymmetric “duck bill.” Snares also
come in various degrees of stiffness, which allow resection
­Endoscopic Snare Devices of lesions of many shapes and sizes. Tissue can be resected
with mechanical closure alone (so-called “cold snare”) or
Endoscopic snare devices have also been widely used for with mechanical plus electrosurgical cutting (“hot snare”).
resection of polypoid as well as flat lesions throughout the Recent studies suggest that cold snare is associated with
gastrointestinal tract. They have been remarkably versatile lower risk of bleeding and bowel wall injury.
and effective over the past four decades. Endoscopic snares
typically involve a metallic wire, which may braided or
monofilament (Figure 1.6). E
­ ndoscopic Brush Cytology
A wire loop is generally constrained within a small caliber
plastic catheter. At the distal end of the catheter, the wire Abrasive brush cytology has been used in many different
loop can be opened to various sizes to grasp and resect pol- fields of tissue sampling. Typical endoscopic brush is con-
yps of different sizes. Typical sizes include loops 5–30 mm strained within a plastic catheter similar to endoscopic
in diameter. There are numerous different shapes including snares (Figure 1.7).
4 General Principles of Biopsy Diagnosis of GI Disorders

After passing through the accessory channel of the endo- E


­ ndoscopic Fine-Needle Aspiration
scope, the abrasive brush is exposed and rubbed against the (FNA) Devices
area of tissue sampling. This is most commonly applied to
obtain specimens for microbiology, particularly fungal The most common application of FNA devices in endos-
specimens. These have also been widely applied in the bil- copy is endoscopic ultrasound-guided tissue sampling
iary tract for sampling of suspicious biliary strictures. More (EUS-FNA). The development of endoscopic ultrasound in
recent advances include a highly abrasive wide-area tissue the 1970s and 1980s significantly expanded the reach of
sampling system that has been recently studied and endoscopic tissue sampling into the pancreas and other
Barrett’s esophagus as an alternative to pinch forceps, as extraluminal organs such as lymph nodes and now virtu-
well as nonendoscopic abrasive sponge sampling, which ally any organ within reach of the proximal or distal GI
has the potential to offer inexpensive population-based tract lumen (Figure 1.9).
screening for esophageal neoplasia (Figure 1.8). Other needle aspiration devices include biliary sampling
needles often used in conjunction with forceps and brush
sampling, or so-called “triple sampling.” EUS-FNA devices
come in various sizes from 19- to 25-gauge. These devices
are typically attached to a handle, which allows the
endoscopist to puncture and make to-and-fro movements
within the target lesion and also apply negative pressure.
With various methods, both cytologic and histologic mate-
rial can be obtained through these needle devices. Recent
efforts to develop Tru-Cut devices have been met with vari-
able success.

2 cm
­ issue Processing in the Endoscopy
T
Laboratory

An excellent recent review on the topic of tissue acquisition


has been published by the American Society for gastrointes-
Figure 1.8 Nonendoscopic abrasive cytology brush. Source: tinal endoscopy. For most routine tissue sampling the biopsy
From Kadri, S.R., Lao-Sirieix, P., O’Donovan, M. et al. (2010). material is placed in formalin and subsequently embedded
Acceptability and accuracy of a non-endoscopic screening test
in paraffin for histological analysis. Other specific prepara-
for Barrett’s oesophagus in primary care: cohort study. BMJ 341:
c4372. doi: https://doi.org/10.1136/bmj.c4372. Open access tions include sampling for microbiological evaluation,
article. molecular or genetic testing, and electromicroscopy. These

(a) (b)

Figure 1.9 (a) and (b) Endoscopic ultrasound endoscope and guided fine-needle aspiration (EUS-FNA) device.
­Specific Organ Sampling Method  5

special samples should be handled according to local insti-


tutional guidelines. In general, samples that are obtained for
culture should be obtained prior to placing forceps into for-
malin as formalin residue can destroy or inactivate live
microbial tissue.

N
­ on-oriented Samples

Most pinch biopsy samples are placed directly in formalin


without orientation. This is also true for small polyps
where the likelihood of invasive cancer is very low. The
sample is placed directly into a small formalin jar. The nee-
dle or forceps should be rinsed if it comes in direct contact
with formalin as subsequent contact with living tissue can
cause chemical injury.
Figure 1.10 Pinned and oriented resection tissue from Barrett’s
esophagus-associated neoplasia. Note the mucosal side facing
up and the lateral margins pinned to prevent curling of the
O
­ riented Samples edges.

Increasingly, endoscopic resection is being used for defini- as Roswell Park Memorial Institute (RPMI) medium that
tive oncologic removal of precancerous and invasive lesions. allow subsequent flow cytometry. As a practical matter,
In these cases it is advantageous to orient the specimen so placement in such a preservative should be considered even
that precise staging as well as margin assessment can be per- when likelihood is low since cells preserved in such solution
formed. A typical situation is in endoscopic resection of can always be examined with routine cytological methods;
early neoplasia in the esophagus such as Barrett’s esopha- however, cells that are placed in formalin or alcohol cannot
gus. In this case a sample is frequently obtained through be evaluated for flow cytometry. The use of rapid on-site
endoscopic mucosal resection. Large pieces of tissue, typi- evaluation (ROSE) cytology has been shown in many stud-
cally 1–2 cm in diameter, can be obtained to a depth of the ies to increase diagnostic yield and reduce the need for
submucosa. In this case the sample should be removed from repeated procedures.
the patient in a way that does not damage or distort the tis-
sue. This is typically performed by suctioning the tissue into
a distal attachment cap/hood and then removing the endo- C
­ ulture Samples
scope. Alternative retrieval devices include a modified snare
with a protective net. These tissues should then be immedi- Samples obtained for culture should be placed in a sterile
ately oriented at the bedside typically by placing them on a specimen container. Sterile saline maybe needed to prevent
paraffin or similar firm block. The tissue should be flattened drying of the specimen. Attention should be paid to mini-
typically with the mucosal side up and the edges carefully mize contamination although it is recognized that the endo-
pinned so that the tissue remains flat (Figure 1.10). scope and the organs throughout which it is passed are not
sterile and is not possible to obtain a purely sterile access into
the gastrointestinal lumen. Contamination with oropharyn-
C
­ ytology Samples geal organisms or colonic organisms is not uncommon.

Cytology samples obtained from either brush or fine-needle


aspiration can be processed in a variety of ways. Most com-
­Specific Organ Sampling Methods
monly these are prepared as thin smear on glass slides,
Esophagus
which can be evaluated either immediately as an air-dried
sample stained with a modified Romanowsky stain, or as an Diagnostic Sampling
alcohol-fixed slide evaluated with Papanicolaou staining. It Indications for diagnostic sampling of the esophagus
is often helpful to place additional excess material in a cyto- include Barrett’s esophagus and other suspected neoplastic
logical preservative or formalin. Special handling is required disorders, inflammatory disorder such as eosinophilic
for samples where lymphoproliferative disease is consid- esophagitis, gastroesophageal reflux disease, and infec-
ered. Typically these include cytological preservatives such tious esophagitis.
6 General Principles of Biopsy Diagnosis of GI Disorders

The most common indication in Western countries for tis-


sue sampling from the esophagus is likely Barrett’s esopha-
gus. There are established guidelines for sampling of the
esophagus. These have traditionally been based on the
notion that early neoplasia is not visible endoscopically and
thus random sampling of the mucosa should be performed
to ensure adequate detection of early neoplasia. The most
widely used standard is the so-called Seattle protocol. The
American Society for Gastrointestinal Endoscopy (ASGE)
guideline for tissue sampling calls for surveillance of non-
dysplastic Barrett’s esophagus in four quadrants every 2 cm
with a large-capacity forceps for the entire Barrett’s mucosa.
Patients with established low-grade dysplasia sampling
should be more intensive with four-quadrant biopsies every
1–2 cm. For patients who choose to undergo surveillance for Figure 1.11 Barrett’s esophagus with flat neoplasia (9 o’clock)
for targeted endoscopic resection.
high-grade dysplasia, sampling every 1 cm should be per-
formed; however, more recent evidence suggests that
patients with established low-grade and high-grade dyspla-
sia should likely undergo therapy to eradicate the Barrett’s
esophagus. Advances in endoscopic imaging, such as high-
definition narrow-band imaging, confocal laser endomi-
croscopy, and chromoendoscopy, have significantly
increased the yield of biopsy and allow much more targeted
sampling although these have not yet replaced the need for
random biopsy. These advances are likely to reduce the need
for random biopsies and focus more on targeted sampling.
For eosinophilic esophagitis the ASGE recommends two
to four biopsies from the proximal esophagus and two to
four biopsies from the distal esophagus. Biopsy should also
be obtained from the gastric antrum and duodenum when
diffuse eosinophilic gastroenteritis is suspected.
For suspected infectious esophagitis, multiple biopsies Figure 1.12 Multiband mucosectomy device. The black rubber
from the margin and base of a visualized ulcer should be bands are mounted on the outside of a plastic cap. The tissue is
suctioned into the cap and a band deployed to create a
obtained and the sample should be sent for standard histol- pseudopolyp, which is then removed by snare.
ogy as well as immunohistochemical and possibly viral cul-
tures and PCR. For candidal esophagitis, multiple biopsies
of the affected area as well as cytology brushings may be
complementary to biopsy.

Therapeutic Sampling
Increasingly, endoscopic resection methods are being
applied to early neoplasia the esophagus, particularly
Barrett’s esophagus and early squamous cell carcinoma.
These are largely confined to tumors suspected to be T1 or
nodular high-grade dysplasia. Endoscopic mucosal resec-
tion (EMR) methods generally involve an EMR device such
as a modified band ligator followed by snare resection of
the pseudopolyp (Figure 1.11–1.13).
Other methods include endoscopic submucosal dissection
(ESD) in which the lateral margins of the suspected area are
Figure 1.13 Area of resection at 6–12 o’clock includes the
incised with electrocautery knife followed by dissection along
entire region of suspected neoplasia at 9 o’clock. The remaining
the submucosal plane to obtain an en bloc specimen. EMR tissue at the 9 o’clock area represents intact deep submucosa
devices can typically obtain samples 1–2 cm in diameter into and muscularis propria.
­Specific Organ Sampling Method  7

the depth of the mid-submucosa. Endoscopic submucosal Gastric Polyps Gastric polyps are very frequently
dissection can obtain samples of any lateral diameter and encountered, particularly in patients who are on chronic
generally to the base of the submucosa. proton pump inhibitor therapy. Current ASGE guidelines
One major advantage of these techniques is the ability to for management of gastric polyps suggest that polyp should
perform wide-field or en bloc resection and orient the sam- be sampled by biopsy. Fundic gland polyps larger than 1 cm
ple. Samples should be retrieved without causing trauma to should be removed by polypectomy. Hyperplastic polyps
the tissue, preferably by removal through the endoscopic larger than 5 mm should be removed by polypectomy, and
cap or through a snare-net as opposed to suctioning via the all adenomatous polyps should be removed by polypectomy.
accessory channel, which can traumatize or fragment the In patients who have numerous polyps, particularly where
tissue. Once retrieved the tissue should be handled as with endoscopic inspection is highly consistent with fundic
other endoscopic resection specimens by orienting the gland polyps, the largest of the polyps should be removed
specimen and pinning it on a fixed material such as a paraf- by polypectomy and representative sampling performed of
fin block. En bloc specimens can be oriented in terms of smaller polyps.
the oral and anal side of the lesion and assessed for lateral
and deep margins. For resections that are performed piece- Ulcer Disease Because of the potential for neoplasia in the
meal such as with multiband mucosectomy, the lateral setting of ulcers, numerous biopsies should be obtained
margins cannot be accurately assessed and so complete from the base as well as the margins of the ulcer to exclude
resection relies on the endoscopic inspection intralumi- malignancy. Cytology may also be helpful. Sampling for
nally. The specimens should still be oriented and assessed concurrent H. pylori infection should be performed as
for the deep margin. suggested above.

Therapeutic Sampling
Stomach
Endoscopic resection in early gastric cancer is now widely
Diagnostic Sampling performed throughout the world. The endoscopic resection
Major indications for diagnostic sampling of the stomach methods include endoscopic mucosal resection typically with
include assessment for Helicobacter pylori infection, diag- a cap-assisted device as in the esophagus, or injection of a sub-
nosis of gastritis, metaplastic atrophic change, gastric pol- mucosal agent such as saline followed by snare resection of
yps, and suspected neoplasia, particularly in the setting of the lifted tissue. Lesions larger than 1–2 cm should generally
gastric ulceration or early gastric cancer. be removed en bloc by endoscopic submucosal dissection
when early gastric cancer is suspected. Tissue should be han-
H. pylori Sampling Biopsy is one of several recommended dled in the same manner as discussed above in esophagus.
methods for H. pylori sampling that also includes urease
breath testing and stool testing for H. pylori antigen. When
Small Intestine
using endoscopic tissue sampling, there are two general
methods including non-histological testing of the tissue for Major indications for tissue sampling of the small intestine
the presence of urease using the traditional Campylobacter- include celiac disease as well as resection of early neoplasia.
like organism test (CLO-test). In this case, the tissue should
be placed in the standard agar well and visually inspected Diagnostic Sampling
for a pH change following the instructions for use in this Currently established protocols for sampling for celiac dis-
product. Histological sampling can also be performed with ease recommend four to six biopsies from the duodenum
one of two methods. One method is to take three biopsies including the duodenal bulb and distal duodenum.
including one from the angularis corpus antrum junction, All other suspicious areas should be sampled using rou-
one from the greater curvature of the corpus, and one from tine biopsy technique. Sampling of the papilla should be
the greater curvature of the antrum. Alternatively, the performed with caution as biopsy in this area can cause
updated Sydney protocol may be followed, which includes pancreatitis. When a suspected neoplastic lesion is seen in
five biopsies including one from the antrum lesser curve, the region of the papilla, it is preferred to take a biopsy that
antrum greater curve, gastric corpus lesser curve, and does not immediately injure the orifice of the bile duct or
greater curve, and one from the angularis of the stomach. the pancreas duct.

Environmental Metaplastic Atrophic Gastritis (EMAG) Current Therapeutic Sampling


guidelines recommend 7–12 biopsies including 4-quadrant Adenomatous polyps of the duodenum are handled in a
biopsies including an antrum, 2 from the angularis, 4 from similar manner to adenomatous lesions anywhere in the
the corpus, and 2 from the cardia. gastrointestinal tract. Endoscopic mucosa resection can be
8 General Principles of Biopsy Diagnosis of GI Disorders

performed with injection followed by snare. There appears were obtained throughout the colon. Current guidelines rec-
to be higher risks of bleeding and perforation associated ommend biopsy of each colonic segment with four-quadrant
with endoscopic resection of duodenal lesions. This is par- biopsies every 10 cm from the cecum to the rectum for a
ticularly true were using cap-assisted devices where the minimum total of 33 biopsy samples. In cases where the
thin wall of the duodenum is suctioned into the cap lead- entire colon is not affected, four samples should be obtained
ing to inadvertent full-thickness resection. every 10 cm of the affected areas. More recently, it has been
Special attention is required for resection of lesions shown that using dye spray such as indigo carmine or meth-
involving the ampulla of Vater. In these cases, typically the ylene blue can identify areas of dysplasia with high accuracy
lesion is resected followed by placement of a stent in the and thus guide directed sampling without the need for ran-
pancreatic and bile duct orifice to prevent stricturing of dom biopsy. Biopsies should however also be assessed from
these and acute pancreatitis. each colonic segment to assess for inflammation.
Another special situation is polypoid lesions in the distal
small intestine, which can now be accessed with deep ent- Therapeutic Sampling
eroscopy methods. Polyps are generally removed in the Endoscopic resection methods of flat and lateral spreading
same manner as polypoid lesions elsewhere in the gastro- colorectal polyps has expanded rapidly over last 10 years.
intestinal tract by snare polypectomy. Special circum- Most noninvasive neoplastic lesions of the colon can now
stances include numerous polyps such as those developed be removed through advanced endoscopic methods such as
in patients with Peutz–Jeghers syndrome. These can be EMR or ESD avoiding the need for surgery. Lesions less
particularly large and numerous. It may not be possible to than 2 cm can typically be removed en bloc with endo-
resect and retrieve all tissues. Because of the laborious pro- scopic mucosal resection involving injection of a fluid
cess of deep enteroscopy, it is often not feasible to extract cushion under the lesion followed by snare resection.
the endoscope with each large polypoid tissue. Thus diag- Where there is suspected early (mucosal or superficial sub-
nostic sampling can be performed by biopsy of the lesion or mucosal) invasive carcinoma, en bloc resection should be
fragmentation of the lesion with a snare followed by com- performed using either EMR or ESD depending on the size
plete therapeutic excision of the lesion. of the lesion. The tissue processing should be the same as
for other neoplastic lesions with orientation of the speci-
men and pinning of the specimen to assess the lateral and
Colon
deep margins (Figure 1.14).
Major indications for diagnostic sampling of the colon The final histological analysis allows for detailed staging,
include detection of both overt and microscopic colitis and as well as matching the corresponding histological and
surveillance for dysplasia in inflammatory bowel disease. endoscopic findings; note the lavender line overlays indi-
Perhaps the most commonly performed tissue sampling cating sites of advanced neoplasia. The close collaboration
in the field of gastroenterology involves removal of colorec- between pathologists and endoscopists further improves
tal polyps and tissue sampling of more advanced colorectal the accuracy of each procedure (Figure 1.15).
neoplasia.

Diagnostic Sampling S
­ ummary
In patients with chronic diarrhea and suspected microscopic
colitis, random biopsies should be taken throughout the The role of pathology in gastrointestinal endoscopy
colon including at least two biopsies from the right, trans- remains critical. Gastroenterologists should have a thor-
verse, descending, and sigmoid colon. For limited sampling ough knowledge of optimal methods of tissue removal and
the flexible sigmoidoscopy is also a reasonable approach. In initial processing to allow optimal diagnosis and therapeutic
this case at least two biopsies should be obtained from the results. Advances in endoscopic resection have allowed
sigmoid and descending colon as well as transverse colon if complete resection of many early cancers but require closer
this can be reached with the sigmoidoscope. cooperation between the endoscopist and pathologist to
In the setting of inflammatory bowel disease, biopsy sam- ensure the tissue is properly handled and staged. With
pling should be performed to establish the diagnosis and to EUS-FNA, the direct interaction of pathologist with rapid
assess the extent. For the initial diagnosis, the American on-site cytological evaluation has led to higher accuracy,
Society for gastrointestinal endoscopy recommends two biop- and reduced the need for repeat procedures. Finally,
sies from each of five sites including the ileum and rectum. advances in imaging will continue to improve the targeting
Surveillance of inflammatory bowel disease is a special cir- of tissue sampling and reduce the need for low-yield ran-
cumstance and is evolving. Traditionally, random biopsies dom sampling methods.
­Summar  9

Figure 1.14 Endoscopic submucosal dissection (ESD) procedure. A flat neoplastic lesion is seen in panel 1–2 after staining with
cresyl violet. The margins are incised (panel 3) with the endoscope retroflexed (black tube). The submucosal plane is dissected with a
needle knife (panel 4). The final resection site (panel 5) and corresponding resection specimen prepared for pathology processing
(panel 6).

1
2
3
4
5
6

7
8
9
10
11
12
13
14
15

Figure 1.15 Endoscopically resected en bloc well-differentiated adenocarcinoma 28 × 17 mm with superficial submucosal invasion
and no lymphovascular invasion and negative horizontal and vertical margins. This sample meets criteria for endoscopic curative
resection.

Figure 1.16 Large mediastinal lymph node sampled with


EUS-FNA. The needle is seen entering from the upper right
of the screen into the tumor in the center of the image.
10 General Principles of Biopsy Diagnosis of GI Disorders

F
­ urther Reading

Al-Haddad, M. and Eloubeidi, M.A. (2008). Diagnostic and Kadri, S.R., Lao-Sirieix, P., O’Donovan, M. et al. (2010).
therapeutic applications of endoscopic ultrasound-guided Acceptability and accuracy of a non-endoscopic screening
punctures. Dig. Dis. 26 (4): 390–397. test for Barrett’s oesophagus in primary care: cohort study.
Basford, P., George, R., Nixon, E. et al. (2014). Endoscopic BMJ 341: c4372. https://doi.org/10.1136/bmj.c4372.
resection of sporadic duodenal adenomas: comparison of LeBlanc, J.K., Emerson, R.E., Dewitt, J. et al. (2010). A
endoscopic mucosal resection (EMR) with hybrid prospective study comparing rapid assessment of smears
endoscopic submucosal dissection (ESD) techniques and and ThinPrep for endoscopic ultrasound-guided fine-
the risks of late delayed bleeding. Surg. Endosc. 28 (5): needle aspirates. Endoscopy 42 (5): 389–394.
1594–1600. Levy, M.J., Reddy, R.P., Wiersema, M.J. et al. (2005). EUS-
da Cunha Santos, G., Boerner, S.L., and Geddie, W.R. (2011). guided trucut biopsy in establishing autoimmune
Maximizing the yield of lymph node cytology: lessons pancreatitis as the cause of obstructive jaundice.
learned from rapid onsite evaluation of image- and Gastrointest. Endosc. 61 (3): 467–472.
endoscopic-guided biopsies of hilar and mediastinal Mann, N.S., Mann, S.K., and Alam, I. (1999). The safety of
lymph nodes. Cancer Cytopathol. 119 (6): 361–366. hot biopsy forceps in the removal of small colonic polyps.
Eloubeidi, M.A., Tamhane, A., Jhala, N. et al. (2006). Digestion 60 (1): 74–76.
Agreement between rapid onsite and final cytologic Monkemuller, K.E., Fry, L.C., Jones, B.H. et al. (2004).
interpretations of EUS-guided FNA specimens: Histological quality of polyps resected using the cold
implications for the endosonographer and patient versus hot biopsy technique. Endoscopy 36 (5): 432–436.
management. Am. J. Gastroenterol. 101 (12): 2841–2847. Phoa, K.N., van Vilsteren, F.G., Weusten, B.L. et al. (2014).
Falk, G.W., Rice, T.W., Goldblum, J.R., and Richter, J.E. Radiofrequency ablation vs endoscopic surveillance for
(1999). Jumbo biopsy forceps protocol still misses patients with Barrett esophagus and low-grade dysplasia: a
unsuspected cancer in Barrett’s esophagus with high-grade randomized clinical trial. JAMA 311 (12): 1209–1217.
dysplasia. Gastrointest. Endosc. 49 (2): 170–176. Qumseya, B.J., Wang, H., Badie, N. et al. (2013). Advanced
Gupta, N., Mathur, S.C., Dumot, J.A. et al. (2012). Adequacy imaging technologies increase detection of dysplasia and
of esophageal squamous mucosa specimens obtained neoplasia in patients with Barrett’s esophagus: a meta-
during endoscopy: are standard biopsies sufficient for analysis and systematic review. Clin. Gastroenterol.
postablation surveillance in Barrett’s esophagus? Hepatol. 11 (12): 1562–1570. e1561–e1562.
Gastrointest. Endosc. 75 (1): 11–18. Sakamoto, T., Matsuda, T., Nakajima, T., and Saito, Y. (2012).
Hikichi, T., Irisawa, A., Bhutani, M.S. et al. (2009). Efficacy of endoscopic mucosal resection with
Endoscopic ultrasound-guided fine-needle aspiration of circumferential incision for patients with large colorectal
solid pancreatic masses with rapid on-site cytological tumors. Clin. Gastroenterol. Hepatol. 10 (1): 22–26.
evaluation by endosonographers without attendance of Sharaf, R.N., Shergill, A.K., Odze, R.D. et al. (2013).
cytopathologists. J. Gastroenterol. 44 (4): 322–328. Endoscopic mucosal tissue sampling. Gastrointest. Endosc.
Humphris, J.T.J., Kwok, A., and Katelaris, P.H. (2007). Cold 78 (2): 216–224.
snare polypectomy for diminutive polyps: an assessment of Trier, J.S. (1971). Diagnostic value of peroral biopsy of the
the risk of incomplete removal of small adenomas. proximal small intestine. N. Engl. J. Med. 285 (26): 1470–1473.
Gastrointest. Endosc. 69: AB207. Vogelstein, B., Fearon, E.R., Hamilton, S.R. et al. (1988).
Ichise, Y., Horiuchi, A., Nakayama, Y., and Tanaka, N. (2011). Genetic alterations during colorectal-tumor development.
Prospective randomized comparison of cold snare N. Engl. J. Med. 319 (9): 525–532.
polypectomy and conventional polypectomy for small Wang, K.K. and Sampliner, R.E. (2008). Updated guidelines
colorectal polyps. Digestion 84 (1): 78–81. 2008 for the diagnosis, surveillance and therapy of Barrett’s
Ikematsu, H., Yoda, Y., Matsuda, T. et al. (2013). Long-term esophagus. Am. J. Gastroenterol. 103 (3): 788–797.
outcomes after resection for submucosal invasive Watanabe, T., Itabashi, M., Shimada, Y. et al. (2012). Japanese
colorectal cancers. Gastroenterology 144 (3): 551–559. Society for Cancer of the Colon and Rectum (JSCCR)
quiz e514. guidelines 2010 for the treatment of colorectal cancer. Int.
Johanson, J.F., Frakes, J., and Eisen, D. (2011). Computer- J. Clin. Oncol. 17 (1): 1–29.
assisted analysis of abrasive transepithelial brush biopsies Wu, L., Li, P., Wu, J. et al. (2012). The diagnostic accuracy of
increases the effectiveness of esophageal screening: a chromoendoscopy for dysplasia in ulcerative colitis:
multicenter prospective clinical trial by the EndoCDx meta-analysis of six randomized controlled trials. Color.
Collaborative Group. Dig. Dis. Sci. 56 (3): 767–772. Dis. 14 (4): 416–420.
11

Esophagus Inflammatory Conditions


Anthony R. Mattia1, Gregory Y. Lauwers2, Michael B. Wallace3 and Till S. Clauditz4
1
Newton-Wellesley Hospital, Newton, MA, USA
2
Moffitt Cancer Center, Tampa, Florida, USA
3
Mayo Clinic, Jacksonville, Florida, USA
4
Department of Pathology, University-Medical Center, Hamburg, Germany

N
­ ormal Histology, Variations I­ nfectious Esophagitis

The esophagus has a pearly white and smooth surface Definition, General Features, Predisposing Factors
under which a network of small vessels is seen (Figure 2.1)
Infection is a common cause of esophagitis, particularly in
except for the distal esophageal sphincter where prominent
immunocompromised patients but can also occur in appar-
longitudinal and palisading vessels (exceeding 100 mm in
ently immunocompetent hosts with certain predisposing
diameter) are observed and used to define the esophago-
conditions. Fungi (Candida species) and viruses are
gastric junction.
responsible for most cases of infectious esophagitis, and
dual infections may be encountered. Bacterial, mycobacte-
Microscopic Features rial, and parasitic esophagitis (e.g. Chagas disease due to
Trypanosoma cruzi) are rarely encountered in esophageal
The esophageal mucosa is composed of a non-keratinizing
biopsy material.
flat stratified squamous epithelium, lamina propria, and
muscularis mucosae (Figure 2.2; Table 2.1). The squamous Fungal Esophagitis
epithelium is 10–20 cell layers thick measuring 300–500 μm Fungal infection due to Candida albicans is the most
in thickness. The prickle cells contain a large quantity of common cause of infectious esophagitis.
cytoplasmic glycogen, which stains positively with periodic Predisposing conditions are broad and include HIV
acid–Schiff (PAS). The basal proliferative zone, the cuboidal infection/AIDS, other immunosuppressed conditions such
or polyhedral basal and parabasal cells account for 15% or as organ transplant, prolonged corticosteroid therapy as
less of the epithelial thickness. A small number of special- well as other conditions such as diabetes, malignancy, anti-
ized cell types, including T lymphocytes, Langerhans cells, biotic therapy, acid-suppressive therapy, and pregnancy.
endocrine cells, and melanocytes are also present in the Infection due to Candida tropicalis and Candida
deep/parabasal epithelium. The lamina propria consists of (Torulopsis) glabrata has also been described, as well as
loose connective tissue with scattered inflammatory cells, infection due to other fungi such as Histoplasma capsula-
vessels, nerves, and small mucous glands. The lamina propria tum and Aspergillus species.
papillae normally extend into the epithelium for 1/3–1/2 of its
thickness. The muscularis mucosae is a thick layer of Viral Esophagitis
smooth muscle bundles oriented longitudinally. In the dis- Herpes simplex (HSV) is the most common etiology of viral
tal 1–2 cm of the esophagus, the basal zone, papillae, and esophagitis, and also occurs primarily in the setting of
intraepithelial cells may be more prominent, and include immunosuppression, such as solid organ and bone marrow
rare eosinophils. Esophageal mucosal biopsies typically transplantation, underlying malignancy, chemotherapy,
include the squamous epithelium and scant lamina propria. and HIV infection (AIDS). These patients may also have
The muscularis mucosae is seldom present, and better iden- disseminated infection at the time of diagnosis. It can also
tified in esophageal mucosal resection specimens. develop in healthy adults including pregnant women and

Gastrointestinal Pathology: Correlative Endoscopic and Histologic Assessment, First Edition. Edited by Gregory Y. Lauwers and Michael B. Wallace.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
12 Esophagus Inflammatory Conditions

children. Both HSV types 1 and 2 can infect the esophagus


with type 1 being most common. Infection by varicella-
zoster virus (VZV) may also rarely occur in immunocom-
promised hosts.
Cytomegalovirus (CMV)-induced esophagitis also typi-
cally occurs in the immunosuppressed population, particu-
larly in the setting of HIV infection/AIDS, organ
transplantation, chemotherapy, corticosteroid therapy, and
other forms of long-term immunosuppression. CMV may
rarely cause esophagitis in immunocompetent patients,
especially in the elderly.

Bacterial Esophagitis
Clinically significant bacterial esophagitis occurs almost
exclusively in immunocompromised patients. Secondary
bacterial colonization of areas of prior esophageal injury
Figure 2.1 Endoscopic appearance of distal esophagus with
normal squamous mucosa. and ulceration is more common. Bacterial invasion of squa-
mous mucosa or the deeper layers is required to establish a
diagnosis of primary bacterial esophagitis. Gram-positive
bacteria are the most common causative organisms (includ-
ing Staphylococcus aureus, Staphylococcus epidermidis,
Streptococcus viridans, and beta-hemolytic streptococci).

Mycobacterial Esophagitis
The rare mycobacterial esophagitis typically occurs in the set-
ting of advanced immunosuppression. Both Mycobacterium
tuberculosis complex and Mycobacterium avium complex can
be encountered.

Parasitic Esophagitis
Chagas disease involving the esophagus is an important
cause of esophageal dysfunction (dysphagia) in endemic
regions, such as Latin America. However, the organism
and its pathologic effects are typically not identified on
biopsy specimens.
Figure 2.2 Normal esophagus squamous mucosa with normal
stratified non-keratinizing epithelium.
Clinical Features and Endoscopic
Characteristics
Table 2.1 Normal esophageal mucosa. Clinical and endoscopic features are specific to each con-
dition. For candidal esophagitis, symptoms vary from
Epithelium: none (especially in patients with mild disease from
Non-keratinizing squamous epithelium chronic inhaled steroids) to severe dysphagia and
Glycogen rich odynophagia in immunosuppressed patients. Candida
10–20 cells thick (300–500 μm) appears as a white, cottage cheese-like exudate, which is
Basal proliferative zone up to 15% partially adherent to the epithelium (Figure 2.3). HSV and
Few scattered parabasal T lymphocytes and other specialized CMV both cause ulcerations. HSV ulcers are typically
cells small, 1–3 mm, whereas CMV ulcers may be both deep
Lamina propria: and wide. Biopsy yield for the virus is highest from the
Papillary length 1/3 to 1/2 of epithelial thickness
edge of HSV ulcers and from the center of CMV ulcers. In
practice, both are usually obtained. Other infections’ eti-
Muscularis mucosae
ologies may have nonspecific findings. The inflammatory
­Infectious Esophagiti  13

Figure 2.3 Endoscopic appearance of white exudate typical of Figure 2.4 Debris of slough off superficial squamous
Candida albicans in a patient on chronic inhaled corticosteroid. epithelium with fungal hyphae and acute inflammation.

reaction of tuberculous esophagitis often imparts a radio-


logically detectable mass-like lesion, whereas mucosal
changes include linear ulcers and induration that prefer-
entially affects the mid-portion of the esophagus. Fistula
formation and perforation may occur. Chagas disease
presentation is similar to that of achalasia with manomet-
ric findings of a poorly relaxing lower esophageal sphinc-
ter and an aperistaltic esophagus body.

Microscopic Features
Candida
The biopsies typically show an active esophagitis with a
mixed inflammatory infiltrate of neutrophils, lymphocytes,
and eosinophils. Neutrophils are often present in small, Figure 2.5 PAS stain of Figure 2.4 illustrating the fungal
superficial clusters associated with parakeratosis or squa- elements of Candida albicans.
mous debris, which may be a diagnostic clue. Prominent
intraepithelial neutrophils may be associated with detached squamous cells. However, in immuno-
abscesses, erosions, or ulcerations. The inflammatory compromised hosts, deeper tissue invasion within
response may be minimal in severely immunocompro- ulcers and erosions may be seen. Candida are often
mised patients. conspicuous in routinely stained sections, although
their appearance is enhanced with periodic acid–
Yeast forms of C. albicans and pseudohyphae (with Schiff (PAS, Figure 2.5) or Grocott methenamine
refractile cell walls) are usually present in superfi- silver (GMS) stains. In Candida (Torulopsis) glabrata
cial desquamated keratin debris (Figure 2.4). The infections, only small budding yeast forms are seen,
yeast are 3–5 μm in diameter basophilic oval forms which may mimic histoplasmosis.
while the, nonseptate sausage-like pseudohyphae Candida can colonize preexisting ulcers or dam-
are 3–5 μm in diameter and are arranged perpendic- aged mucosa of any etiology, and in such cases the
ular to the epithelial surface. Occasional septate possibility of dual infection or pathology should be
hyphae can be present. The presence of psuedohy- considered. Also, when Candida yeast forms are pre-
phal and hyphal forms correlates with active infec- sent only in desquamated keratin debris unassoci-
tion. Most infections are superficial with isolated, ated with inflammation or endoscopic findings, carry
intraepithelial fungal forms, and organisms in over from an oral infection should be suspected.
14 Esophagus Inflammatory Conditions

Figure 2.6 Multinucleated basal keratinocytes typical of HSV Figure 2.7 Erosive esophagitis with prominent granulation and
esophagitis. atypical cellular elements.

Cytologic brushings are also very useful in the diag- esophagitis, CMV rarely infects the squamous epithelium,
nosis of Candida esophagitis, as the organisms are and preferentially involves endothelial cells, stromal cells,
readily identified on Papanicolaou stained smears. and glandular epithelium. Therefore, biopsies of the ulcer
bed should preferentially be performed when CMV esophagi-
Herpes Simplex (HSV) tis is suspected (Figure 2.7). CMV cytopathic effect is charac-
If HSV infection is suspected, in addition to biopsies for terized by nuclear enlargement with classic “owl eye” large
histology, fresh tissue can be sent for viral culture to con- intranuclear inclusions, and granular, eosinophilic cytoplas-
firm the diagnosis and identify strains that may be resistant mic inclusions (Figure 2.8a). Smaller, atypical intranuclear
to acyclovir. HSV infection is associated with ulceration inclusions may be present and are more subtle, simulating
and a mixed inflammatory infiltrate of intraepithelial neu- activated fibroblasts. These infected cells are best identified
trophils, eosinophils, and lymphocytes, as well as aggre- by immunohistochemical staining (Figure 2.8b). CMV may
gates of macrophages that can be a diagnostic clue. HSV coexist with HSV and Candida infection in some cases.
infects squamous cells of intact or denuded epithelium and
is best identified at the edge of an ulcer and in cells within Bacterial Esophagitis
the ulcer slough. Therefore, optimal histologic diagnosis Sheets of bacteria are typically present with associated
requires sampling of the ulcer edge rather than the ulcer necrosis and mucosal erosion, highlighted by a tissue Gram
bed. The typical viral cytopathic effects include multinu- stain. Inflammation may be scant or absent in neutropenic
cleation, ground glass nuclei, and dense intranuclear patients.
eosinophilic inclusions with a thickened nuclear mem-
brane and a clear halo (Cowdry type A inclusion bodies) Mycobacterial Esophagitis
(Figure 2.6). Viral inclusions and multinucleated cells are Histologic features include subepithelial and mural
not always identifiable in biopsies, and ancillary immuno- necrotic and non-necrotic granulomas with fibrosis and
histochemistry (IHC) staining for HSV may be required. chronic inflammation. Acid fast bacilli can be recognized
Concomitant infection of Candida, cytomegalovirus, or on Ziehl–Neelsen stain in approximately 2/3 of cases.
bacteria can exist, particularly in immunocompromised
patients. Varicella Zoster Virus has been associated with
Immunohistochemical Studies and Molecular
esophagobronchial fistula formation.
Features
Cytomegalovirus (CMV) IHC staining for HSV (HSV 1 and 2 cocktail stain) may be
Culture is not used routinely, and does not distinguish the useful for suspected infections if diagnostic inclusions are not
simple presence of CMV from active infection; however, readily identified on H&E sections. Similarly, IHC for CMV is
culture may be useful for identifying drug resistance. useful to highlight infected cells without typical CMV mor-
Ulceration and granulation tissue formation with associ- phology, and may be more sensitive than light microscopy.
ated acute inflammation is common. In contrast to HSV PCR for M. tuberculosis may be useful in selected cases.
­Gastroesophageal Reflux Diseas  15

(a) (b)

Figure 2.8 High-magnification evaluation of Figure 2.7 demonstrated (a) endothelial CMV infection (b) confirmed by
immunohistochemistry.

Differential Diagnosis ­Gastroesophageal Reflux Disease


Clinical
Inflammatory changes of the esophagus can be seen in Definition, General Features, Predisposing
many conditions, most commonly acid reflux disease. Factors
Behcet’s disease may present with focal ulcers, as can pill- The chronic regurgitation of gastroduodenal juice into the
induced (associated with an impacted pill, which may or esophagus causes gastroesophageal reflux disease (GERD).
may not be present during exam) ulcers. The mucosal injury results from the effects of refluxed gas-
tric acid, bile, pepsin, and duodenal contents that overwhelm
Microscopic the normal protective antireflux barriers, such as esophageal
The differential diagnosis of Candida esophagitis includes acid clearance and mucosal resistance. Risk factors and pre-
reflux esophagitis, drug injury, glycogenic acanthosis, disposing conditions include obesity, diet, sedentary life-
ectopic sebaceous glands, and other infections. style, tobacco and alcohol use, hiatus hernia, reduced lower
The differential diagnosis of HSV esophagitis includes esophageal sphincter tone, loss of esophageal peristaltic
other etiologies of mucosal ulceration, including other function, gastric hypersecretory states, and delayed gastric
infections, Crohn’s disease, HIV-associated ulceration, and emptying. Symptomatic GERD is prevalent worldwide, with
drug injury. In some cases, the cytologic atypia induced in considerable geographic variation. Prevalence estimates are
the squamous epithelium by the viral cytopathic effects of approximately 20% in North America and Europe, with only
HSV may be difficult to distinguish from squamous dyspla- East Asia showing estimates <10%.
sia/carcinoma, as well as radiation esophagitis.

Clinical Features and Endoscopic


Prognosis, Evolution, and Clinical Characteristics
Management
There are several endoscopic classifications of gastroe-
Most patients present with dysphagia or odynophagia and sophageal reflux disease (Figure 2.9). The Los Angeles
undergo upper endoscopy with biopsy. Infectious etiolo- Classification divides esophagitis into four grades:
gies are treated with appropriate antimicrobials (e.g. flu-
conazole for candida), typically with high response rates. Grade A: one or more mucosal breaks, each no
In immunosuppressed patients, including those on chronic longer than 5 mm.
inhaled steroids, frequent retreatment, or chronic suppres- Grade B: at least one mucosal break more than
sive treatment, may be necessary after full efforts to restore 5 mm long, but not continuous between the tops of
immune function. 2 mucosal folds.
16 Esophagus Inflammatory Conditions

Table 2.2 Histologic features of GERD.

Basal cell hyperplasia (>15%)


Papillary elongation (>50%)
Dilated intercellular spaces (spongiosis)
Intraepithelial inflammation
Neutrophils
Eosinophils
Mononuclear cells

Figure 2.9 Endoscopic appearance of erosive esophagitis in a


patient with gastroesophageal reflux disease.

Grade C: at least one mucosal break that is con-


tinuous between the tops of 2 or more mucosal
folds, but which is not circumferential.
Grade D: a circumferential mucosal break, ero-
sions and ulceration, often resulting in scarring and
stenosis if the reflux is recurrent.

Mucosal bridges and esophagogastric fistulae may be


encountered.
The endoscopic findings in reflux esophagitis have been
classified into three main stages: active, healing, and scar-
ring. Relapse and healing occur repeatedly in patients with
gastroesophageal reflux disease (GERD), and a mixture of
the stages is often seen in biopsy specimens.
Figure 2.10 Characteristic appearance of low-power view of
reflux esophagitis with basal cell hyperplasia, elongation of
Microscopic Features papillae, lymphocytic and eosinophilic infiltrate.

The typical features of GERD are basal cell layer hyperpla-


sia, papillary elongation, dilated intercellular spaces eosinophils is typical of GERD, although large numbers
(intercellular edema/spongiosis), and intraepithelial of intraepithelial eosinophils mimicking eosinophilic
inflammation, including neutrophils, eosinophils, and esophagitis may be identified. Notably, eosinophils are not
mononuclear cells (Table 2.2; Figures 2.10, 2.11). However, found in all GERD biopsies and can be seen in asympto-
none of these features is specific for this diagnosis. matic patients. Neutrophils may be present, and are more
The proliferative epithelial changes are more common numerous in areas of erosion and ulceration. Lymphocytes,
than inflammatory infiltration. Basal cell hyperplasia is often with irregular nuclear contours (squiggle cells), are
diagnosed when the thickness of the basal layer exceeds usually scattered through the epithelium. Finally, severe
15% in a well-oriented section. Papillary elongation, inflammation with ulceration may be associated with
defined as extending >50% of the epithelial thickness, inflammatory pseudotumor formation, with marked
should also be only assessed in well-oriented sections. atypia of the reactive stromal cells.
Finally, in minimal GERD, dilated intercellular spaces in In practice, the report should provide a descriptive sum-
the basal and parabasal areas may be the only finding. mary of the histologic features and injury patterns present,
Esophageal squamous mucosa normally contains few or as well as their severity. A note can be added to state that
no inflammatory cells and the inflammatory infiltrate in the findings are compatible with reflux injury pattern in
GERD is highly variable. The presence of occasional the appropriate clinical setting.
­Eosinophilic Esophagiti  17

Ulceration with regenerative squamous epithelial atypia


may be difficult to distinguish from in situ-squamous cell
carcinoma and dysplasia. The regenerating epithelial cells
have round nuclei with minimally thickened nuclear mem-
branes; fine chromatin; and large, irregular nucleoli, and
generally have abundant cytoplasm. Further, maturation
toward the epithelial surface can usually be found. In diffi-
cult cases, additional biopsies should be requested after med-
ical treatment of the esophagitis. However, in some cases,
inflammatory pseudotumors with marked atypia of the reac-
tive stromal cells will need to be differentiated from poorly
differentiated carcinoma or sarcoma. Cytokeratin immuno-
histochemistry (IHC) may be helpful when trying to distin-
guish between reparative reactions and malignancy.
Less commonly, activated lymphocytes in areas of ulcer-
Figure 2.11 High-power magnification of reflux esophagitis ation may appear atypical and raise the suspicion for lym-
with basal cell hyperplasia, spongiosis, and eosinophilic
infiltrate.
phoma. In some cases, immunohistochemistry and/or flow
cytometry may be necessary to assess for clonality.
Differential Diagnosis
Prognosis, Evolution, and Clinical
Clinical Management
Clinically, erosive esophagitis from GERD is typically in
the lower third of the esophagus and contiguous with the GERD management is based on the severity and potential for
gastroesophageal junction as opposed to other inflamma- complications and largely consists of lifestyle modification,
tory or infectious etiologies that may occur more proxi- anti-acid medications or surgery. Most nonerosive or mini-
mally. The presence of a normal distal esophagus with mally erosive (Los Angeles Grade A) responds to a combina-
more proximal inflammation virtually excludes GERD- tion of lifestyle modifications and low-dose (single daily
associated inflammation. Typical symptoms are heartburn proton pump inhibitor [PPI] such as omeprazole) anti-acid
and regurgitation. Ph- metry (monitoring the acid reflux therapy. Lifestyle modifications include weight loss, avoiding
events by a wired or wireless sensor in the distal esopha- large meals with two to three hours of bedtime (where grav-
gus) can be used in challenging cases but is rarely neces- ity no long prevents “upward” reflux), and minimizing spe-
sary with obvious symptoms and when esophagitis is seen. cific refluxogenic foods (alcohol, mint, fatty food, chocolate,
caffeine). PPI therapy is highly effective, even for severe ero-
Microscopic sive GERD but may require twice-daily therapy. More than
As none of the histologic features are specific for GERD, 95% of patients will heal erosive disease on PPI therapy.
other etiologies such as infection, eosinophilic esophagitis, Surgical therapy is aimed at restoring the lower esopha-
iatrogenic injuries, Crohn’s disease, and inflammatory skin geal sphinter pressure zone and angle of His, and reducing
disorders involving the esophagus may enter into the dif- hiatal hernias. Surgery is also highly effective with more
ferential diagnosis. than 80% of individuals having sustained elimination or
The presence of large numbers of neutrophils in the reduction in GERD symptoms and use of PPI. The major
superficial epithelium should suggest the possibility of side effect of surgery is retention of gas in the stomach
fungal infection or superinfection, and special stains (“gas-bloat syndrome”) due to the inability to naturally
(PAS-diastase, GMS) should be performed to exclude belch swallowed air.
Candida organisms. Large numbers of intraepithelial
eosinophils raising the possibility of eosinophilic
esophagitis and correlation with clinical findings and PPI
E
­ osinophilic Esophagitis
treatment status are required (see Section “Eosinophilic
Definition, General Features, Predisposing
Esophagitis”). Numerous intraepithelial lymphocytes, if
Factors
predominant, may suggest an alternative diagnosis such
as lymphocytic esophagitis or lichen planus-associated Eosinophilic esophagitis (EOE) is a chronic, immune-
esophagitis (see Sections “Lymphocytic Esophagitis” and mediated or antigen-mediated inflammatory condition
“Dermatological Diseases Involving the Esophagus”). characterized by symptomatic esophageal dysfunction and
18 Esophagus Inflammatory Conditions

eosinophil predominant mucosal inflammation. EOE rep- Clinical Features and Endoscopic
resents a type 2 (Th2) helper T cell and cytokine-mediated Characteristics
disorder involving genetic predisposition, environmental
Eosinophilic esophagitis (EOE) is increasing in prevalence
exposures, and allergic background. Food-based antigens
and often seasonal with spikes during typically airborne
appear to be the dominant mediators of EOE, although aer-
allergy season. It presents with dysphagia to solids, classi-
oallergens may also act as triggers in susceptible patients.
cally with pills sticking. Other atopic symptoms are com-
Since it was first established as a distinct clinicopatho-
mon. At endoscopy, the esophagus has white punctate
logic entity in 1993, EOE has become an increasingly rec-
spots (eosinophilic microabscess), rings, longitudinal fur-
ognized cause of dysphagia and esophageal dysfunction,
rows (Figure 2.12), and desquamates easily with insuffla-
particularly among patients refractory to medical treat-
tion or dilation. In late stages, the esophagus may be very
ment of gastroesophageal reflux disease.
narrowed and poorly distensible.
EOE is reported worldwide, with highest prevalence in
the United States and Western Europe. It occurs more fre-
quently in children and young adults, although it is increas- Microscopic Features
ingly recognized in older adults, and is more common in Esophageal biopsies are required to diagnose EOE.
males (male-to-female ratio of 3–4 : 1). A history of other Eosinophils are generally absent from the esophageal squa-
allergic conditions may be present, such as asthma and mous epithelium in normal individuals. The histologic
atopic dermatitis, as well as peripheral eosinophilia, which hallmark is the presence of an increased number of eosino-
are more common in children. phils within the squamous epithelium (Figure 2.13).
Current diagnostic criteria for EOE include a combina- Although there is no exact threshold number that estab-
tion of clinical and pathologic features (Table 2.3). lishes a diagnosis, 15 eos/HPF (peak count) in at least one
biopsy is considered a “minimum” threshold.
Table 2.3 Definition of eosinophilic esophagitis and diagnostic Eosinophilia may be patchy, and it is recommended
criteria.
that two to four biopsies from at least two locations in
Symptoms related to esophageal dysfunction the esophagus should be taken to maximize diagnostic
Eosinophil-predominant inflammation on esophageal biopsy, yield. The distribution of eosinophilia is important, as
characteristically consisting of a peak value of 15 eosinophils they may be identified in both proximal and distal biop-
per high-power field (EOS/HPF) sies or be more prominent in proximal biopsies.
Mucosal eosinophilia is isolated to the esophagus and persists Practically, only intact eosinophils with visible nuclei
after a PPI trial should be counted and eosinophilic granules should not
Secondary causes of esophageal eosinophilia excluded be included, although degranulated eosinophils may be
(Table 2.5) a useful clue.
A response to treatment (dietary elimination; topical Other histologic findings may be present although none
corticosteroids) supports the diagnosis of EOE, but is not of these should be considered pathognomonic. These fea-
required.
tures include moderate-marked reactive basal hyperplasia,

(a) (b)

Figure 2.12 Endoscopic appearance of eosinophilic esophagitis (a) with so-called feline esophagus appearance and (b) with
extensive white microabcesses. Subtle circular rings and longitudinal furrows also present.
­Eosinophilic Esophagiti  19

distinguishing eosinophilic esophagitis from gastroesopha-


geal reflux disease and other conditions remains unproven.
Immunohistochemical stains targeting eosinophil per-
oxidase, major basic protein, and eosinophil-derived neu-
rotoxin, have been reported to enhance detection of
eosinophils compared to evaluation of H&E sections, but
these stains are not widely used in routine clinical practice.
A recent study suggested that the presence of intra-squa-
mous IgG4 deposits by immunohistochemistry may be a
useful adjunctive marker for EOE.
Molecular analyses of esophageal tissues, such as gene
expression analysis of chemokines such as eotaxin-3
(CCL26), and transcriptome analysis show promise to
improve diagnosis and clinical monitoring, and to guide
patient-specific therapy.

Differential Diagnosis
Clinical
Dysphagia and rings in the esophagus can occur from any
inflammatory condition. Even eosinophils may be present
in GERD alone. EOE typically requires a confirmatory
biopsy from the upper and lower esophagus showing
Figure 2.13 Characteristic histology of eosinophilic esophagitis
with basal cell hyperplasia, marked eosinophilic infiltrate with
eosinophilic infiltrates. Desquamative conditions that
eosinophilic microabscesses. should be excluded include bullous pemphigoid and
lichen planus. These typically require deep biopsies and
special immunofluorescence staining; thus, communica-
tion between endoscopist and pathologist is critical.
eosinophilic microabscesses (superficial aggregates of
4 eosinophils), superficial layering of eosinophils, and Microscopic
subepithelial fibrosis. The presence of subepithelial fibro- The histologic appearance of EOE is not specific, and
sis is also associated with eosinophils in the lamina propria mucosal infiltration by eosinophils is a component of
and correlates with fibro-stenotic complications of EOE, a variety of other esophageal inflammatory conditions
but may not be identifiable depending on biopsy depth. (Table 2.4).
Other inflammatory cells, such as lymphocytes and mast GERD and PPI-responsive esophageal eosinophilia
cells, can also be increased. When reporting the cases, a exhibit considerable histologic overlap with EOE. In an
note is useful to summarize additional relevant histologic untreated patient, fewer numbers of eosinophils with dis-
features and to provide an overall assessment of the case tal predominance may be suggestive of GERD. Correlation
based on all available biopsies (including prior biopsies, if with response to PPI therapy is paramount.
applicable). For example, active esophagitis with intraepi- In eosinophilic gastroenteritis, obtaining biopsy speci-
thelial eosinophils (peak count of # per HPF) followed by a mens from the stomach and duodenum and other clinical
note. When large numbers of eosinophils are present (e.g. symptoms such as nausea, vomiting, and diarrhea may be
>40 per HPF), an exact count may be difficult and it is helpful in establishing a diagnosis.
appropriate to report the peak count as such (e.g. “peak The presence of granulomas is helpful in diagnosing
count of >40 per HPF”). esophageal involvement by Crohn’s disease, but they are
uncommon. Eosinophils may also be admixed with neutro-
phils and lymphocytes, and involvement of other parts of
Immunohistochemical Studies and Molecular
the GI tract is typically present.
Features
Infections are recognized by the identification of viral
Currently, the examination of esophageal mucosal biopsies inclusions (such as HSV), and fungal or parasitic organ-
by hematoxylin and eosin (H&E) stained sections, with isms. Mixed inflammation with neutrophils may also be
clinical correlation, remains the most reliable diagnostic present. Rare cases of HSV esophagitis occurring in a back-
test for EOE. The diagnostic value of ancillary studies in ground of EOE have been described.
20 Esophagus Inflammatory Conditions

Table 2.4 Endoscopic and histologic features of the major causes of infectious esophagitis.

Organism Endoscopic features Morphological features Ancillary studies

Candida Focal or confluent Parakeratosis with neutrophils PAS-diastase,


white plaques Colonization of ulcers GMS stains
Budding yeast, pseudohyphae, occasional septate hyphae
Superficial invasion typical
Herpes Superficial ulcers, Edge of ulcer—inclusions in squamous cells and/or squamous IHC
simplex multiple debris of ulcer slough
Multinucleation, ground glass nuclei, dense eosinophilic nuclear
inclusions (Cowdry type A)
CMV Single deep ulcer, Base of ulcer—inclusions in endothelial and stromal cells IHC
linear ulcers Intranuclear (“owl’s eye”) and granular cytoplasmic inclusions
Atypical inclusions common

Table 2.5 Conditions associated with esophageal eosinophilia Elimination Diet; SFED) or suppression with topical corti-
in the differential diagnosis of EOE. costeroids, which can be from a swallowed metered dose
inhaler, or from peroral viscous budesonide. For late-stage,
GERD
fibrotic disease, repeated, carefully monitored esophageal
PPI-responsive esophageal eosinophilia
dilation is effective.
Eosinophilic gastrointestinal diseases
Crohn’s disease
Infection (Candida, HSV, parasites)
Hypereosinophilic syndrome L
­ ymphocytic Esophagitis
Achalasia
Definition, General Features, Predisposing
Drug hypersensitivity injury
Factors
Vasculitis
Pemphigus This uncommon and poorly characterized condition is his-
Connective tissue diseases tologically defined as the presence of dense lymphocytic
infiltrates involving the esophageal mucosa without con-
Graft versus host disease (GVHD)
comitant evidence of significant active inflammation. It is
described in approximately 1/1000 esophageal biopsies,
In drug-induced esophageal eosinophilia, there is a tem- predominantly affecting older females (median age
poral relationship and resolution when the offending agent 63 years). This controversial entity lacks clearly defined
is withdrawn. clinical associations in adults, and likely represents a non-
specific reaction pattern to a wide variety of mucosal
Ancillary Studies (if Applicable) insults (Table 2.6), including GERD, medications, infec-
IHC for virus (HSV) and/or special stains for fungi (GMS, tion, motility disorders, and other immune-mediated dis-
PAS-diastase) are indicated if infection is suspected. orders. In the pediatric population, lymphocytic esophagitis
has been described in association with Crohn’s disease and
celiac disease.
Prognosis, Evolution, and Clinical
Management
Clinical and Endoscopic Characteristics
EOE is initially treated with proton pump inhibitors. There
is emerging evidence that PPIs affect specific inhibition of About 75% of patients present with esophageal symptoms,
the chemokine, eotaxin, which blunts eosinophil infiltra- most commonly dysphagia or odynophagia, which may
tion. It may be difficult to distinguish GERD-associated raise the suspicion of eosinophilic esophagitis. Similarly,
eosinophilia from EOE in this subgroup. For those that do the endoscopic impression may suggest eosinophilic
not respond to PPI, options include identification and esophagitis, with the presence of rings, furrows, plaques,
avoidance of food antigens (typically through a Six Food and strictures.
­Drug-Induced Esophagiti  21

Table 2.6 Conditions associated with esophageal Differential Diagnosis


lymphocytosis (lymphocytic esophagitis).
The clinical and endoscopic differential diagnosis includes
GERD EOE, although by definition eosinophils are rare or absent.
Medications If neutrophils are present, special stains for candida may be
Infection warranted. Intraepithelial lymphocytes may be prominent
Motility disorders in lichen planus esophagitis/lichenoid esophagitis, although
Immune-mediated disorders (e.g. CVID) the additional presence of a band-like lymphocytic infiltrate
in the lamina propria and necrotic keratinocytes is a distin-
Lichen planus/lichenoid esophagitis
guishing feature. Characteristic direct immunofluorescence
Crohn’s disease (pediatric)
findings of lichen planus DIF may or may not be demon-
Celiac disease (pediatric) strated. Lymphocytosis may also be associated with esopha-
geal involvement by Crohn’s disease in children, although
other histologic and clinical features of Crohn’s disease are
typically present, particularly elsewhere in the gut.

Prognosis
Follow-up clinical and biopsy data are limited, although in
some patients sequential biopsies have demonstrated per-
sistent lymphocytosis, suggesting a chronic process.

D
­ rug-Induced Esophagitis

Definition, General Features, Predisposing


Factors
Medication-related injury to the esophageal mucosa (“pill
esophagitis”) is an increasingly recognized complication of
Figure 2.14 Characteristic histology of lymphocytic
orally administered drugs. Mucosal injury is typically caused
esophagitis.
by prolonged direct contact and local caustic effects of the
offending agent, although mechanisms of toxicity may be
complex and multifactorial. Numerous drugs have been
Microscopic Features
implicated (Table 2.7). Most cause a nonspecific injury pat-
Recently proposed histologic criteria include the presence tern, and the diagnosis is suggested by the clinical history.
of dense lymphocytic infiltrates involving esophageal squa- Elderly patients and women are most commonly affected.
mous mucosa with marked spongiosis in the absence of sig- The elderly often have multiple underlying risk factors,
nificant numbers of neutrophils or eosinophils (Figure 2.14). and the female predominance is attributed to the more
The findings are most pronounced in the peripapillary epi- common use of certain medications in this group, such as
thelium. There is no required or established “minimum” iron supplements and bisphosphonates. Risk factors
count or density of intraepithelial lymphocytes, and the pat- include pills taken with little or no water or while recum-
tern and distribution of the lymphocytic epithelial injury is bent, underlying disorders of esophageal motility (e.g. dia-
most important. betes, strictures, achalasia) and disorders of local anatomy
causing external compression (enlarged left atrium, aortic
aneurism). However, many patients do not exhibit abnor-
Immunohistochemical Studies and Molecular
mal esophageal function or other risk factors.
Features
Ancillary testing, including the subtyping of the intraepi-
Clinical and Endoscopic Characteristics
thelial CD3, CD4, and CD8 T cells is generally noncontrib-
utory and not required for the diagnosis. A subset of cases Typically, there is a temporal relationship between the
with CD4 predominant T cells and dysmotility has been onset of symptoms and ingestion of a potentially injurious
reported. drug. Common symptoms include sudden-onset chest
22 Esophagus Inflammatory Conditions

Table 2.7 Medications implicated in causing esophagitis


and histologic features.

Medication Histologic features

NSAIDs Nonspecific, ± crystalline debris


Antibiotics (e.g. Doxycycline—vascular injury
tetracyclines/
doxycycline,
clindamycin)
Potassium chloride Nonspecific
Iron Bluish-brown crystalline debris, Fe
stain +
Bisphosphonates Nonspecific, ± crystalline debris and
(e.g. alendronate) multinucleated squamous cells
Quinidine Nonspecific
Resins (e.g. Kayexalate: Figure 2.15 Endoscopic appearance of inflammatory stricture
kayexalate, bile Basophilic crystals with “fish scales,” of the esophagus with sloughing mucosa.
acid sequestrants) AFB (black), PAD, Diff-quick
bile acid sequestrants:
with doxycycline injury often exhibit a distinct capillary/
Orange-black crystals, lack “fish
scales,” AFB (yellow) vascular injury with degenerative changes and possible
fibrin thrombi. In iron pill-associated mucosal injury, blu-
Mycophenolate Increased apoptosis (GVHD-like)
ish-brown crystalline iron debris is found adjacent to the
Taxanes Mitotic arrest, ring mitoses
surface epithelium, admixed with the inflammatory exu-
date, or within granulation tissue (Figure 2.16). The iron
can be highlighted by a Prussian Blue stain, which may
pain, odynophagia and/or dysphagia that occur within a also demonstrate crystalline debris in the lamina propria or
few hours or days after taking the medication. Severe reflux underlying vessels. Although iron is well recognized as a
injury is often an initial diagnostic concern. The chest caustic agent in the esophagus and elsewhere in the GI
pain may be pleuritic in nature, mimicking a pulmonary tract, some cases may represent secondary deposition in
embolism, or may suggest an acute cardiac syndrome. preexisting lesions. Alendronate has been associated with
Hematemesis and perforation are rare complications. multinucleated squamous cells, in addition to the presence
Endoscopically, most lesions occur in the middle third of of polarizable crystalline material.
the esophagus, at the level of the aortic arch, although any Kayexalate (sodium polystyrene sulfonate) in sorbitol
level may be involved. Findings include erythema, ero- can be recognized by the presence of characteristic lightly
sions, ulcers (including “kissing” ulcers), and strictures. basophilic, refractile, nonpolarizable crystals that display a
Discrete erosions in this region, away from the Z-line, are mosaic pattern that resembles fish scales. The crystals can
an important clue suggesting a drug-related etiology be highlighted by acid fast (black), PAS/Alcian blue and
(Figure 2.15). Occasionally, a diffuse mucosal sloughing Diff-Quik stains. Bile acid sequestrants (e.g. colestipol,
pattern has been described. colesevelam, cholestyramine) may be recognized by their
orange-black crystals, which lack a striated, fish-scale
Microscopic Features (Table 2.7) appearance and may appear pale yellow on acid fast stain.
Mycophenolate, used in solid organ transplantation, is
Biopsies most commonly show nonspecific esophagitis associated with increased apoptosis of esophageal squa-
characterized by erosions, ulcers, active inflammation with mous epithelial cells, resembling GVHD. Taxane-based
neutrophils and occasionally eosinophils, surface epithe- chemotherapy leads to striking mitotic arrest with ring
lial damage, and granulation tissue. Adjacent mucosa is mitoses, along with epithelial necrosis or ulceration.
relatively normal. A careful search of the exudate and ulcer
bed for refractile or polarizable foreign material is war-
Differential Diagnosis
ranted, which may be an important diagnostic clue.
However, in most cases the clinical history is necessary to The major histologic differential diagnostic considera-
make the diagnosis. tion is infection, particularly fungal (Candida) or viral
Some medications are associated with additional charac- (HSV, CMV), which may need to be excluded with appro-
teristic histologic features. Erosions and ulcers associated priate histochemical and immunohistochemical stains or
­Sloughing Esophagiti  23

(a) (b)

Figure 2.16 (a) Iron tablet erosive esophagitis with fibrinopurulent debris. (b) The Prussian Blue iron stain is diagnostic.

recognized by characteristic viral cytopathic effect. In rare appearance to the mucosa. Sloughing esophagitis has also
cases, exuberant granulation tissue and excessive exudates been included under the terms esophagitis dissecans super-
mimic the gross appearance of a neoplasm. If eosinophils ficialis and acute necrotizing esophagitis, which includes
are prominent, reflux or eosinophilic esophagitis may broader inclusion criteria and more diverse causes of
enter into the differential diagnosis. GVHD should be esophageal injury. It occurs in middle-aged to older adults
excluded if prominent apoptosis is present, such as with (median age 56 years), frequently with debilitating comor-
mycophenolate injury. Finally, lichen planus involvement bidities and who are commonly on multiple medications,
of the proximal esophagus with stricture formation can especially central nervous system depressants and drugs
also mimic drug injury. In all of these considerations, the known to cause esophageal mucosal injury. It most likely
clinical context is critical to the evaluation of the histo- represents a form of direct contact injury, rather than an
pathologic findings. ischemic injury, and may represent a unique pattern of
drug-induced esophagitis. Acute necrotizing esophagitis
Prognosis, Evolution and Clinical Management (“black esophagus”) is a rare condition that arises in debili-
tated patients with severe comorbidities such as hypoper-
Most cases are self-limited and resolve without complica- fusion, sepsis, diabetic ketoacidosis, and malignancy, and
tions. Discontinuing the suspected caustic agent and sup- results from the combining effect of ischemia and corrosive
portive management, such as PPI therapy, hydration, injury of gastric contents. A rare case occurring in a child
sucralfate, or topical anesthetics, typically results in an who was associated with a history of vomiting has also
uneventful recovery. Local epinephrine may be needed for been reported.
active bleeding. Dilatation may be required if strictures
develop, and surgical management is rarely needed for
severe complications such as perforation. Most patients Clinical and Endoscopic Characteristics
can resume their medications with recommendations for Dysphagia, odynophagia, chest pain, heartburn, vomiting
proper administration, which will assist in avoiding recur- or cough are reported in 45% of patients, include. The mid-
rent injury. distal esophagus is most commonly involved. Endoscopy
reveals white plaques or membranes, and there may be
sloughing of the epithelium as well as other nonspecific
S
­ loughing Esophagitis
findings such as erythema, erosions, rings, or webs. In
black esophagus, the sloughing necrotic membrane may
Definition, General Features, Predisposing
appear blackened (Figure 2.17). The clinical presentation is
Factors
distinctive with bleeding and a characteristic diffuse cir-
Sloughing esophagitis is characterized by extensive super- cumferential black mucosal discoloration of the distal
ficial squamous mucosal necrosis or desquamation, associ- esophagus with an abrupt transition at the gastroesopha-
ated with endoscopic plaques imparting a sloughing geal junction.
Another Random Document on
Scribd Without Any Related Topics
of houses, or a sharp bend in the road, a barricade may be made in
one part and a passage round one end left for traffic.
Inundations. They may be formed by damming streams at
convenient points, specially in the valleys, or by damming up the
arches of bridges. In the latter case, care must be taken not to
endanger the stability of the bridge. The ditches of field works form
a good obstacle when flooded. Destroyed trenches in front of a
breastworks may be filled with water, and with barbed wire thrown
into it, will prove an effective obstacle.
Fougasses. These are used in connection with obstacles and are
really land mines loaded with stones, bricks, etc. An excavation is
made in conical shape with an axis inclined to about 40 degrees
toward the enemy horizon. A box of powder is then placed in a
recess at the bottom and on the box is placed a wooden platform or
shield 3 to 4 inches thick, over which stones are piled.
A fuse is placed in a groove cut at the back of the excavation. A
line of least resistance must be so arranged that by placing the
excavated earth on the back edge of the fougasse, the powder will
act in the direction of the axis and not vertically. A fougasse charged
with 80 pounds of powder may be constructed in this manner to
throw five tons of brick and stone over a surface about 160 yards
long by 120 yards wide.
All of the foregoing are labors of working parties, as well as
construction of dugouts, carrying of supplies, ammunition, etc.,
drainage and building of the trenches and the many other jobs
behind the lines. Always, no matter how small the job, careful
forethought must be given to the planning and arrangement
necessary to carry it out.
ORGANIZATION OF BOMBING
SQUADS
Every infantry soldier must and does receive instruction in
grenade throwing. Some men do not possess the temperament and
qualifications necessary to make efficient bombers, and for this
reason in every platoon there should be a bombing squad of one
N. C. O. and 8 men, with a higher degree of training and efficiency
as bomb throwers than the remainder, although all hope must not be
given up for the remainder.
These men are available either to work with the platoon or to
provide a reserve of bombers for any special job, such as raids,
cutting-out parties, and clearing trenches just occupied. Only the
very best men in each platoon should be chosen, taking into
consideration physique, courage and steadiness, although it is not
always the big man physically that makes the best bomber. The
responsibility for the training of these men rests with the battalion
and company commanders.
TRAINING
The first step is to overcome a man’s natural fear of the grenade
itself. This is only done by explaining how it is to be used, the
method of lighting and the length of time taken for the fuse to burn.
A good idea is to have some of the fuses of the length used lighted
and the men told to count while the fuse burns out. Dummy
grenades with fuses attached can then be introduced and the men
taught to light them, observing carefully how long it takes for the
fuse to burn down to the grenade.
The second step is to develop accuracy in throwing. Normally,
the bomb should be bowled overhand, although it is certainly not
wrong to throw, but it has been found in tests that a man throwing
bombs has tired a great deal quicker than a man bowling them
overhand.
Stick grenades may be thrown over short distances like a dart,
although this is unhandy and can only be done by a carefully trained
man. Great care must be taken while in the trenches in throwing
percussion bombs, as very often a man swinging his arm back to
throw such a bomb has exploded it in the trench, with disaster to
himself and those near him.
Men should be taught to throw standing, kneeling and prone. It
should be impressed upon them from the beginning that if a
grenade with a time fuse is dropped in the act of throwing there is
ample time to pick it up and throw it out of the trench before it
explodes, but this must be done immediately.
A B

A is a diagram of a bombing field where men are trained in


practice with dummy bombs. 1 is the target marked on the ground
and having the same general plan as a firing target, with Bull, Inner,
Magpie, and Outer, the score counting 5, 4, 3, & 2 respectively, or
according to the instructor’s taste. 2 is the first line, 20 yards from
the center of the inner ring. The men must be trained to a high
degree of accuracy at this range. 3 is the second line, 25 yards from
the center of target. There are lines every five yards back until the
40 yard line is reached, which latter is the extreme range for
bombing practice.
At each range the men should practice standing, kneeling, and
prone. At 35 and 40 yards bombing from the kneeling and prone
positions is very difficult and the time spent on practice here should
not interfere with the obtaining of great accuracy at the shorter
ranges.
At all ranges the men should be allowed to throw any number of
dummy bombs, but should not be permitted to fatigue their arms.
B is a diagram showing the arrangement for trench practice with
dummy bombs. Small trenches are built on the surface of the ground
by screens of wire mesh covered with burlap or other similar
material. 1 is the thrower’s trench and is built so high that he cannot
see over the top. From this he throws, using a periscope for
observation. 2 represents part of a traverse and fire-bay, the front
part of which is about 20 yards from the throwing trench. 3 is a
section of straight trench about 25 yards half right from the
thrower’s front. 4 is a section of curved trench about 20 yards half
left from the thrower’s front.
The general custom in the practice trenches is to give the man
any desirable number of dummy bombs, say 18; 6 for each trench.
Four out of six are required to be put in No. 2, and 3 out of 6 in Nos.
3 & 4. Men must not be kept at bombing practice too long at a time
as it spoils both their interest and their aim.
In taking a line of trenches, it is well to remember that the
attack will take place on a relatively small front by a large number of
men, and therefore when the trenches are finally reached, there is
liable to be great overcrowding in them. This can only be prevented
by extending them along the trenches as quickly as possible, and is
of the utmost importance as heavy casualties will result from
allowing this overcrowding. To make this extending possible, it is the
duty of the bombing parties to work along to both flanks of the
trenches and take advantage of the temporary confusion of the
enemy by obtaining as much of his trenches as possible, thus
allowing for the extension of men. In a narrow trench the only
portion of an attacking party coming into contact with the enemy is
the head, or what is known as the Bayonet Man. The bombing party
is composed of the following:
1. Bayonet man,
2. First thrower,
3. First carrier,
4. First spade man,
5. N. C. O. first squad,
6. Second bayonet man,
7. Second thrower,
8. Second carrier,
9. Spade man, in charge of second party.
These parties will work up a trench until they come to a
junction, when the first party in charge of the N. C. O. will continue
straight on and the second party branch to the right or left, as the
case may be, and as they come on other parties keep working up
behind them, and the infantry gradually following taking possession
of the line and starting consolidation work at once.
Communication throughout these lengths of grenade parties is
very difficult with men extended in single file, and the attendant
confusion which accompanies such a stand.
A system is required which will enable supplies of bombs to be
passed up and casualties replaced automatically. This system cannot
be laid down on any cut and dried lines, but must be figured out
before the attack, with due consideration being given to the line of
trenches to be attacked and the difficulties which will be
encountered in getting supplies to that line, and it is only on the
spot that such a system can be worked out.
During an attack three grenades per man are issued to each unit
detailed to open the attack, and these grenades are turned over to
the bombers or used by the men themselves if necessary. When out
of grenades themselves, the men take over the casualty’s, and it is
the duty of a casualty when he is so able to, to leave his grenades
and ammunition to the care of some other man before “going
down.” Small depots should be established at frequent intervals
along the trenches from which the attack starts, with careful
consideration given to their safety from shell fire, if at all possible.
Other depots must be established in the support and assembly
trenches, and these will generally be supplied through a central
station probably controlled by a brigade or division.
Before starting the attack, every man and party should have had
explained them in detail exactly what is required of them, and
generally the following system is adopted:

First bombing party of group—


Two bayonet men to protect grenade throwers,
First bomber,
First carrier,
Second bomber,
Second carrier,
Group leader (N. C. O.),
Two bayonet men to protect the group leader and the rear
of party.

* * * * *
Second bombing party—
Formation as above. The head of the party must be in
touch with the rear of the first party. Officer
commanding in rear of second party.

* * * * *
Third and fourth bombing party—
Formation as above. Second in command in touch with
rear of fourth party.
Machine gun detachment, if available or considered
necessary.

The machine gunners are generally used at the rear of a party,


so that they can bring their guns into action from behind and sweep
the top of the ground around the trenches being attacked, in order
to prevent an overland attack on the bombing party. In all these
formations the number of men detailed must allow for casualties.
Rapidity of movement is essential, as crawling and stalking will give
the waiting enemy an advantage. The leading bayonet men
generally move along the trench, from corner to corner, in a
succession of rushes, followed by first bomber, and the thrower hurls
as directed by the bayonet man. The duty of the bayonet man is to
protect the thrower and carrier at all costs. Second bomber and
carrier follow the leader, keeping one corner behind to replace
casualties. Each party must be regarded as reserves to the party in
front, and some method must be found every time a new attack is
carried out for giving the aerial service notice of trenches occupied.
If the head of a party is checked, that which has been gained must
be held by throwing up a barricade. In all attacks bombing parties
are supported by a party of sandbag men, under an experienced
N. C. O., so that while bombers keep the enemy at bay a strong
barracade may be put up as quickly as possible.
This is generally done by placing what is known as a demolition
tube about 1½ feet from the bottom of the trench and in each side
of the trench. This will bring down enough of the sides of the trench
to make a good enough barricade for the moment, but great care
must be taken that while watching and protecting the barricade the
enemy do not come overland and drop in behind the barricade, with
disastrous results to the garrison.
Although the main defense of a line of trenches is infantry
supported by artillery and machine gun fire, parties of bombers
should be distributed throughout the front system of trenches. The
best position is in the support trenches close to the main
communication trenches, where they can make an immediate
counter-attack should the enemy succeed in gaining a footing. A
bombing trench back about 20 yards in the rear from which bombs
may be thrown into the front trench, is a distinct advantage.
The bombs stored in the trench should be kept ready-fused and
with detonators inserted. They must be distributed in a number of
dry, enclosed, as nearly as bomb-proof depots as possible,
established at frequent intervals along the trenches. A good type of
grenade depot is one built in a “T” shaped trench, slightly off the
main trench.
EXPLOSIVES
Relative strengths of explosives: Gunpowder 5; cordite 8;
dynamite 9; guncotton 10; gelignite 10; gelatine dynamite 11;
blasting gelatine 12. Guncotton is available in two forms, wet and
dry. The dry, while being utilized in making bombs, is mostly used to
explode the wet guncotton. For this purpose it is made up in one-
ounce primers, which are perforated in the center for a detonator.
These primers are packed in metal cylinders, each containing ten
threaded on a tape. Each case contains six cylinders. In this state,
although not as powerful, dry guncotton is much more dangerous to
handle than wet, being susceptible to both shock and friction.
Wet guncotton is that which has absorbed 30% of its weight in
water, and is made up in 15-ounce slabs 6 x 3 x 1⅜ inches, and
packed in tin foil and air-tight boxes containing 16 slabs each.
Whether wet or dry, guncotton, like other explosives, can be
exploded by one detonator, so long as the charges or slabs are in
direct contact with each other.
Dynamites include the following compounds: (1) dynamite; (2)
gelignite; (3) gelatine dynamite; (4) blasting gelatine. All of these
are now being used. Their advantages over guncotton are that,
being soft and plastic, they can be used in bombs where it would be
impossible to use guncotton slabs or primers on account of size and
shape. Dynamite and its compounds freeze very easily (42° F.),
becoming hard and brittle. In this state they are exceptionally
dangerous, and they should be thawed before use, but this process
should not be attempted by any one other than a competent person.
Wooden implements should always be used for cutting and piercing
holes for detonators in any of these explosives, and care should be
taken to protect them from damp, as when wet they become highly
dangerous. Dynamite explosives are usually supplied in parchment
cartridges weighing two ounces, and are packed in boxes of 5 or 50
pounds.
Lyddite and picric acid are both high explosives, used mostly in
shells. They are easily melted and in this way the shell is filled. They
are very safe and difficult to detonate.
Ammonal. A new explosive which is absolutely safe to handle,
not being sensitive to shock or even bullets. It does not freeze and
can only be exploded by means of a detonator. It easily absorbs
moisture and should be kept dry.
Cordite. Is made in strands and is the explosive used in small
arms ammunition.
BOMBS
There are three kinds of bombs: (1) percussion; (2) ignition;,
and (3) mechanical. It is not possible to describe every bomb in use
under these three headings, but the most typical are selected for
description, although it does not follow that they are all in use at the
present time, but will give a fairly good idea of what is required.
Percussion Bombs.

1. Hand Grenade No. 1.


2. Hand Grenade No. 2, formerly known as Mexican Hand
Grenade.
3. Rifle grenade No. 3, formerly known as Hale’s Rifle
Grenade.
Hand Grenade No. 1.

Hand Grenade No. 1 consists of a brass case screwed on to a


block of wood, to which is fixed a small cane handle about half way
up the case. Outside it is a cast iron ring serrated into 16 parts. The
upper end is covered by a moveable cap with a striker pin in the
center. On the cap are the words “Remove,” “Travel,” and “Fire” in
duplicate. These are marked in red and can be made to correspond
with red pointers painted on case. To prepare a bomb, turn cap so
that pointer is at “Remove,” take off cap, insert detonator in hole
and turn it to the left until the spring on the flange is released and
goes into position under the pin; replace cap and turn to “Travel,”
which is a safety position. When the bomb is to be thrown, turn cap
to “Fire” and then remove safety pin. This bomb explodes on impact,
and to insure its falling on the head, streamers are attached. Care
should be taken that streamers do not get entangled. The bomb
must be thrown well into the air.
Hand Grenade No. 2 is similar to the above, except that a special
detonator is screwed in from the head, and that the striker pin, in
this case, is at the bottom. The detonator having been inserted in
the bomb is ready for throwing as soon as the safety pin has been
drawn.
Rifle Grenade No. 3, more commonly known as Hale’s Rifle
Grenade, consists of a serrated steel case filled with T.N.T. and a
composite explosive. At the bottom of the case is a brass ring fitted
with wind vanes, which keeps in place two small steel retaining
plugs, securing the striker. In order to prepare this grenade for
firing, the steel rod attached must be put down the bore of the rifle.
The safety pin is then withdrawn, the collar pulled down and the
wind vane given a slight turn. The rifle is then loaded with a special
cartridge containing 43 strands of cordite. When charging the rifle
the bolt must be well pushed home. When the rifle is fired, the
explosion of the cartridge speeds the grenade on its way and the air
passing through wind vanes causes the ring mentioned above to
unscrew, and the two retaining plugs to fall out. The striker is now
free, and when the grenade reaches its destination and comes in
contact with the ground the shock compresses the creep spring and
the needle of the striker is forced into the detonator, exploding the
grenade.
Special screw-in detonators are supplied with this grenade, as
well as in Grenade No. 2, and care should be taken not to mix the
two detonators, as the Rifle Grenade Detonator is slightly longer, and
if fixed in the wrong grenade will cause premature explosion and
much sadness. These grenades have an accurate range of from 250
to 350 yards.
Ignition Bombs. The following bombs come under this heading:

Hand Grenade No. 6.—Grenade light friction pattern.


Hand Grenade No. 7—Grenade heavy friction pattern.
Hand Grenade No. 8—Formerly known as double-cylinder
light pattern.
Hand Grenade No. 9.—Formerly known as double-cylinder
heavy pattern.
Battye Hand Grenade.
Pitcher Hand Grenade.
Oval Hand Grenade.
Ball Hand Grenade.

Hand Grenades Nos. 6 and 7 consist of metal cases filled with


T.N.T and a composite explosive and are exactly alike, except that
No. 7 contains shrapnel bullets or scrap iron, while No. 6 contains
only explosive. At the top of each case is a place to fix the friction
igniter, which is supplied separately. When these bombs are to be
used, detonator fuse and igniter are put in and firmly fixed. Before
throwing the becket on, head of igniter should be pulled smartly off.
Hand Grenades Nos. 8 and 9 are similar to the above, except
1
that the fuse is lighted by a Nobel Patent Lighter . The Battye
Grenade consists of a grooved cast iron cylinder filled with explosive.
The top is closed by a wooden plug pierced centrally for insertion of
detonator and fire.

1
The Nobel lighter consists of two cardboard
tubes, one fitting over the other. Inside the top
end of the outer tube there is a layer of friction
composition; fixed to the top end of the inner
tube is a forked brass friction head, which is held
in position by a safety pin fastened through both
tubes. Inside the other end of the inner tube is a
small copper band, into which the fuse is fitted.
At the joint of the two tubes there is a narrow
tape band with a loose end. To light the fuse,
pull off tape and safety pin, then press down
outer tube and turn slightly. This lighter has a
five-second fuse attached.

The Pitcher Hand Grenade is very similar to the Battye, only


different in that it is slightly heavier and having a different patent
lighter. This lighter is somewhat complicated and special instructions
should be given before the grenade is used.
Hand Grenade No. 7.
Ball Hand Grenade.

The Oval Hand Grenade is an egg-shaped cast iron receptacle


filled with ammonal. One egg has a steel plug and the other a
flanged brass plug bored centrally, to which a hollow copper tube is
fixed to take the detonator. This grenade is set off by a Brock fuse
2
and lighter .
2
The Brock lighter consists of a match-head
and fuse combined. The head consists of a small
cardboard cup filled with friction composition and
covered with waterproof paper. With this type of
lighter an armlet covered with match
composition is worn by the bomber on the left
forearm. To ignite fuse, first pull off waterproof
paper and then strike head against armlet. Time
of fuse 5 seconds.

The Ball Hand Grenade consists of a cast iron sphere, 3 inches in


diameter, filled with ammonal and closed by a screwed steel plug
which has attached to it a covered tube to take detonator in the
center of grenade. It is also lighted by a Brock lighter.
Jam-pot Bombs. In the early stages of the war it was found
necessary to make bombs on the spot. The material used was
generally a jam tin filled with shrapnel bullets, scrap iron, powdered
glass and grass, etc. This was exploded by 2 one-ounce primers, two
ounces gelignite, blastene or ammonal, and detonated by a No. 6 or
7 detonator, to which was attached a five-second fuse. The time
could be regulated by length of fuse.
Mechanical Bombs. Hand Grenade No. 5, known as Mills’ Hand
Grenade. Mills’ Hand Grenade No. 5 weighs about one and one-half
pounds and is in constant and steady use at the front, being the
best known of all grenades. It consists of an oval cast iron case,
containing explosives and serrated to provide numerous missiles on
detonation. In the center is a spring striking pin, kept back by a
lever or handle, which, in its turn, is held in position by a safety pin.
Hand Grenade No. 5 (Mills).

Detonators and percussion caps connected by a short length of


fuse are supplied with these bombs. When the bomb is to be used
the bottom is unscrewed and the combined detonator and
percussion cap is inserted in the space provided for it, the
percussion cap being placed in the boring under the striking pin.
When this is done the bottom is screwed on again as tightly as
possible, using the special spanner provided for this in each box.
Before throwing, the safety pin is removed and the bomb held with
the lever in the palm of the hand. When the bomb is actually thrown
the lever or handle is released; this releases the spring, which forces
striker down on to the percussion cap, ignites fuse, sets off
detonator and explodes bomb.
GAS WARFARE
The use of poisonous and asphyxiating gases, which was first
adopted by the Germans in the Ypres salient in April of 1915, is now
becoming an accepted fact in the present war. It is to a certain
extent in one shape or another, before one every day of his life in or
near the trenches. Every one should therefore be well acquainted
with the various ways in which gases are used in an attack, as well
as precautionary methods to be taken in counteracting its effects
while on the defense.
In an attack there are only two methods which can be used—
emanation and shells and grenades. The emanation method can only
be employed under very favorable circumstances and in a few cases
where rather a long chance was taken, it reacted very badly on the
enemy. The first thing to make a gas attack successful must be a
favorable breeze of about five miles an hour, as if the wind blows
any faster it does not give the gas a chance to settle down into the
trenches. The object of this gas is to create a poisonous and irritant
atmosphere, and this is accomplished either by a gas forced through
tubes in the direction of the enemy, or a liquefied gas stored in
cylinders under very high pressure. To be successful, as before
mentioned, the wind must be a steady breeze of not much over 5
miles per hour, no rain, and the element of surprise must figure very
largely. The gas used must be heavier than air and not allow of
being held back by any protective measures taken by the enemy. If
the wind is too strong, it is obvious that any gas employed will be
carried too quickly over the enemy’s trenches, so that it cannot
settle to any degree which will allow of its obtaining the desired
effect. If the wind is too light, it will be carried up into the air by
local eddies, or may even be blown back.
For these reasons it is impossible to fix a definite hour for gas
attacks, as everything depends on the wind.
Arsenic and phosphorus compounds are used in the tube
method, and their presence can be detected at once by the smell of
garlic. Should such gases get into your own trenches, chloride of
lime scattered freely about will disperse them.
The gases used in liquid form from cylinders are a mixture of
chlorine and other matter annoying to the ordinary infantry officer
and soldier. If successful in surprising the enemy, their trenches
should be cleared at once, but if the element of surprise is not there
and time is given for defensive measures to be taken, the effect is
lost. In an assault following a gas attack, men should always wear
smoke helmets for at least 30 minutes after the gas dissemination
has ceased, and the assaulting party must have the strictest orders
not to remove their helmets until the officer in charge has given the
command.
In the shell and grenade method of dissemination, shells and
bombs are used containing liquid gas, or a substance which gives off
irritant fumes.
It is easy to tell a gas shell when it lights as it comes down, the
same as a “dud” shell; that is, one which does not explode, the
outer casing of the shell simply collapsing. The liquid soaks into the
ground, and men should be warned against standing over this
ground and inhaling any of the fumes, which are very slight and
rather hard to notice but very powerful and with very quick action.
When a man thinks he has inhaled any of this gas he should at once
be made to lie down, not undergo any exercise whatever, and as
soon as possible have him carried out on a stretcher to the dressing
station.
Tear shells, which are used in great profusion during an attack,
are for the moment blinding in their effect, causing smarting of the
eyes and a great amount of watering. This effect is only for a
minute, and the men must be impressed with the fact that if they
continue moving forward instead of sitting down and rubbing their
eyes, it will pass off almost at once. These shells are also greatly
used against the artillery during heavy bombardments. Adequate
protection is furnished in the shape of goggles to fit over the eyes,
as the gas has no other effect whatever.
As in other branches of military art, the best means of learning
defense is to have a thorough knowledge of attack. Thus, direction
of wind must always be noted, and if favorable for an enemy attack,
special observers must be placed to give warning and surprise
guarded against in every way. Sentries are specially placed in the
trench, and often in listening posts, to get early warnings of an
impending attack. If a sentry at a listening post discovers that a gas
attack is being made, he at once warns the sentry at the end of his
cord or wire, giving a pre-arranged signal. This sentry passes the
alarm on a Strombon horn, which is something similar to a Klaxton,
and will automatically give a warning which can be heard for 3 or 4
miles, and which lasts about a minute.
When a horn is not in use, generally shell cases are hung in the
trenches. These are beat on by the sentry who is warned and taken
up all along the line. It is then the duty of that sentry not for the
instant to put on his gas helmet, but to proceed along the front line
waking all the occupants of dugouts, etc., who may be sleeping in
the area guarded by him. Every man without exception stands to in
his trench with his helmet on and will not reënter dugouts until first
given permission by officer or N. C. O.
These attacks are generally carried out, when possible, just
before dawn or during the middle of the night, and the only warning
given before the actual gas reaches a trench, is a slight hissing
sound which is made and can be easily heard as the gas escapes
from the cylinder. Great care must be taken when the wind is
favorable for an attack that this sound be listened for.
Any man wounded during a gas attack must not be placed in a
dugout or on the bottom of a trench, and even if considerable shell
fire be going on it is far better that he be laid out in the open on the
top of the ground, where he will have a far better chance than lying
in the bottom of the trench or in a dugout. After gas has passed
through a trench system, and before the officer thinks that it is safe
to remove the helmets, the trenches must be sprayed with a
machine known as Vermeral Sprayer. A man with this sprayer on his
back and wearing his helmet, slowly traverses the trench working
the spray. This small tank on his back is charged with nothing more
or less than “hypo” (sodium hyposulphite), about 6 pounds of which
is dissolved in a bucket of water and a handful of ordinary washing
soda added.
Garden syringes and buckets may be used if sprayers are not
available, but their effect is not so quick.
When the officer thinks that the trench has been sprayed
sufficiently and all gas has gone, he may then allow the men to take
off their helmets, but not to reënter their dugouts until they have
been thoroughly cleaned.
This is sometimes done by fanning the gas out, sometimes by
building a fire and smoking it out, and by the use of the sprayer.
Great care must be taken that no one enters until every last vestige
of gas is gone, and it is generally well that the medical officer should
inspect infected dugouts before allowing the men to return.
GAS MASKS OR RESPIRATORS
The Box Respirator at present in use on the Western Front is the
latest improvement, and proof against any gas that so far has been
used, but should such a thing happen that a man be caught without
his box respirator, any of the following improvised methods are
good:
1. Wet and ring out any woolen article, such as a stocking,
muffler or cap comforter, so as to form a thick pad large enough to
cover the nose and mouth, and press firmly over both.
2. Place in a scarf, stocking or handkerchief, a pad of about three
handfuls of damp earth, and tie firmly over the nose and mouth.
3. A wet cap comforter will be found useful as additional
protection, especially against certain gases other than chlorine.
4. A cap comforter wetted with water and soda solution or tea,
folded into eight folds and firmly held over the nose.
5. A sock folded fourfold similarly wetted and held or tied. If the
sock or comforter has been soaked in soda solution it will act
efficiently when dry, though, if possible, it should be moist. The
spare tapes from puttees may be used for tying on the sock or cap
comforter.
6. Any loose fabric, such as a sock, sandbag, woolen scarf or
comforter, soaked in urine, then wrung out sufficiently to allow of
free breathing and tied tightly over the nose and mouth.
In the absence of any other cloths, the flannel waistbands issued
for winter use could be used for this purpose.
Every officer defending a trench against an enemy gas attack
should endeavor to collect information whenever possible to be sent
to headquarters regarding the capture of apparatus used by the
enemy either for disseminating or protection from gas. If a gas shell
attack is made, unexploded shells or portions of them should be
sent; the time of day, duration of attack, color, taste or smell of gas
used, effect on the eyes, breathing, and all other symptoms should
be noted. New gases may be used at any time, and speedy
information greatly helps the adopting of protective measures.
The area of the gas attack is very large and will sometimes cover
as far back as 12 to 15 miles behind the lines, although at that point
it is not generally dangerous, but for three to four miles the gas has
a killing power, and precaution should be taken anywhere within that
length of the firing line the same as though in the firing line.
Another nuisance resulting from a gas attack is the wholesale
slaughter of rats and other animals that infest the trenches, and
while a very unpleasant job, steps should at once be taken to gather
these beasts up and bury them in some place, obviously for sanitary
reasons.
DUTIES OF A PLATOON
COMMANDER AT THE FRONT
General Notes: The selection and training of section commanders
is of the highest importance, and a commander must assure himself
that the man selected has the confidence of the men as well as his
own.
A platoon commander should know his men and all about them,
and keep a record in a book arranged in sections always kept up-to-
date. This is easy to say, but harder to do, when the platoon
changes day by day.
He should know his drill and be capable of moving the platoon
into any position easily and by the shortest possible route.
He should know how to organize a task allotted to him, such as
delivering over a working party, placing a line of sentries, arranging
posts and reliefs, and occupying a line of trenches.
He should be able to assume responsibility for all trench stores,
bombs, periscopes, etc., handed over to him.
He should know the geography of his battalion trenches, the
position of company and battalion headquarters, and keep trained
guides at hand who can find their way to all important points by day
or night.
GOING INTO THE TRENCHES
Platoons generally enter by not more than two sections at a
time, thus minimizing the danger from shell fire and delay at
entrance to communication trenches.
Before leaving billets, platoon commanders should explain fully
to sergeants and sections commanders the extent of trench to be
taken over and the steps to be taken in case they are caught by
shelling or rapid fire going up to the trenches. Arrangements should
also be made that if casualties occur among the soldiers, relief will
proceed as arranged.
IN THE FIRING LINE
On relieving the fire trenches, the men should make no noise,
and rifles must be carried so that they do not show over the
parapet. This is necessary even if enemy’s trenches are at a
distance, as there is always the possibility of a listening or
observation post being quite near.
Each man should pair off with one of the party occupying the
trench and find out from him any points which may be useful.
A commander should consult the officer or N. C. O. in charge of
the outgoing party and obtain the fullest information possible in
connection with the position.
Particular points on which information should be obtained from
the outgoing officer are generally: (a) behavior of enemy during
period preceding relief and any point in their line requiring special
information, such as enemy may have cut wire as though preparing
to attack; (b) machine gun implacement may be suspected at some
particular point; (c) anything ascertained by patrols about ground
between firing lines, thus avoiding unnecessary reconnoissance; (d)
any standing arrangement for patrols at night, including point at
which wire can best be passed, ground to be patrolled, or place
where they can lie under cover; (e) any parts of trench from which it
is not safe to fire. Such positions are apt to occur in winding
trenches, and are not always recognizable in the dark; (f) special
features of trench, recent improvements, work not completed,
dangerous points (on which enemy machine guns are trained at
night), useful loopholes for observation; (g) places from which wood
and water can be safely obtained; (h) amount of ammunition,
number of picks, shovels and empty sandbags in that section of the
line.
Information on these points cannot always be given by word of
mouth. Written notes and plans should, therefore, be handed over to
a platoon commander taking over for the first time.
In the meantime the incoming party should fix bayonets and all
go temporarily on sentry at posts taken over. Occasional shots
should be fired, so that the enemy’s suspicions may not be roused.
The outgoing party then starts back, and when clear, the relieving
party should be numbered off and sentries posted and dugouts
allotted. When practicable sentries should be taken from the dugout
closest to his post.
By day the number of sentries varies, but should not be less
than one in six. The platoon sergeant is responsible for changing
sentries, who are generally not on duty more than one hour at a
time, unless under exceptional circumstances. When the maximum
amount of labor must be obtained from the battalion holding the
line, sentry duty is of any length that fits in with working
arrangements.
Every man must see that he has a good clear position for all
directions. Section commanders must satisfy themselves that men
have done this and reported such. When these arrangements are
completed, word must be quietly passed down for men not on sentry
to stand clear, and they are all not in that position again until the
“Stand to” hours, generally the hour nearest dusk and the hour
before dawn.
After dark, unless the moon is bright, rifles should be kept in a
firing position on the parapet, and all men not on duty should keep
rifles with bayonets fixed while in the trench.
Observation. Continuous survey of the enemy’s lines through
disguised steel loopholes should be made when the trenches are
being held for any lengthy period, and such loopholes must always
be sideways. Sites may be chosen by day, and made and disguised

You might also like