Gastritis.pdf

1586 Arch Pathol Lab Med—Vol 132, October 2008 Pathologic Diagnosis of Gastritis—Sepulveda & Patil
Practical Approach to the Pathologic Diagnosis
of Gastritis
Antonia R. Sepulveda, MD, PhD; Madhavi Patil, MD
● Context.—Most types of gastritis can be diagnosed on
hematoxylin-eosin stains. The most common type of chron-
ic gastritis is Helicobacter pylori gastritis. Reactive or
chemical gastropathy, which is often associated with non-
steroidal anti-inflammatory drug use or bile reflux, is com-
mon in most practices. The diagnosis of atrophic gastritis
can be challenging if few biopsy samples are available and
if the location of the biopsies in the stomach is not known,
such as when random biopsies are sampled in one jar. If
the biopsy site is not known, immunohistochemical stains,
such as a combination of synaptophysin and gastrin, are
useful in establishing the biopsy location.
Objective.—To demonstrate a practical approach to
achieving a pathologic diagnosis of gastritis by evaluating
a limited number of features in mucosal biopsies.
Data Source.—In this article, we present several repre-
sentative gastric biopsy cases from a gastrointestinal pa-
thology practice to demonstrate the practical application
of basic histopathologic methods for the diagnosis of gas-
tritis.
Conclusions.—Limited ancillary tests are usually re-
quired for a diagnosis of gastritis. In some cases, special
stains, such as acid-fast stains, and immunohistochemical
stains, such as for H pylori and viruses, can be useful. Hel-
icobacter pylori immunohistochemical stains can particu-
larly contribute (1) when moderate to severe, chronic gas-
tritis or active gastritis is present but no Helicobacter or-
ganisms are identified upon hematoxylin-eosin stain; (2)
when extensive intestinal metaplasia is present; and (3) in
follow-up biopsies, after antibiotic treatment for H pylori.
(Arch Pathol Lab Med. 2008;132:1586–1593)
Gastritis refers to a group of diseases characterized by
inflammation of the gastric mucosa. Histologic ex-
amination of gastric mucosal biopsies is necessary to es-
tablish a diagnosis of gastritis. In clinical practice, the role
of the pathologist who evaluates a gastric biopsy for gas-
tritis is to find the cause of gastritis because that will pro-
vide direct targets toward which therapeutic measures can
be directed. An etiologic classification of gastritis is pre-
sented at the end of this section. Comprehensive reviews
of gastritis have been published.1,2,3
The goal of this article
is to present a practical approach to the diagnosis of the
most common types of gastritis encountered in a large
practice of gastrointestinal pathology. The reader will be
presented several cases representative of typical forms of
gastritis; for each case, the reader will be prompted
through a series of questions to examine the histologic
features of the mucosa, leading to a pattern of answers
and to a final diagnosis.
The first question is aimed at determining whether or
not there are features of chronic or acute (active) gastritis
Accepted for publication January 10, 2008.
From the Department of Pathology and Laboratory Medicine, Hos-
pital of the University of Pennsylvania, Philadelphia.
The authors have no relevant financial interest in the products or
companies described in this article.
Presented in part at the 47th Annual Meeting of the Houston Society
of Clinical Pathologists, Houston, Tex, April 21, 2007.
Reprints: Antonia R. Sepulveda, MD, PhD, Department of Pathology
and Laboratory Medicine, University of Pennsylvania, 3400 Spruce St,
Founders Six, Philadelphia, PA 19104 (e-mail: asepu@mail.med.
upenn.edu).
present. If the biopsy shows chronic gastritis, the follow-
ing questions should be posed:
1. Are there features of chronic gastritis present? Lym-
phocytic and plasmacytic inflammatory reaction indicates
chronic gastritis.
2. Are there neutrophils in the mucosa? The presence
of neutrophils indicate active gastritis.
3. Is there Helicobacter?
4. Is there glandular atrophy? Is intestinal metaplasia
present?
5. What is the topography of lesions (predominantly in
the oxyntic mucosa of the body and fundus, predomi-
nantly in antrum, or involving both locations)?
6. Are there special features (such as granulomas, fo-
veolar hyperplasia, viral inclusions)?
7. What ancillary studies are indicated, and what are
the results?
TYPES OF CHRONIC GASTRITIS
Infectious Gastritis
Helicobacter pylori infection is the most common cause of
chronic gastritis. Other forms of infectious gastritis include
the following: Helicobacter heilmannii–associated gastritis;
granulomatous gastritis associated with gastric infections
in mycobacteriosis, syphilis, histoplasmosis, mucormyco-
sis, South American blastomycosis, anisakiasis or anisak-
idosis; chronic gastritis associated with parasitic infec-
tions; and viral infections, such as cytomegalovirus and
herpesvirus infection.

Arch Pathol Lab Med—Vol 132, October 2008 Pathologic Diagnosis of Gastritis—Sepulveda & Patil 1587
Figure 1. Helicobacter pylori–associated chronic active gastritis. A,
Chronic inflammation oriented toward the surface of the mucosa. Neu-
trophils cannot be seen at this magnification (original magnification
⫻10) but were identified with high power (hematoxylin-eosin stain). B,
Circled area shows H pylori organisms within the mucus layer close
to the surface of gastric epithelial cells (hematoxylin-eosin, original
magnification ⫻40). C, Gastric mucosa with intestinal metaplasia (he-
matoxylin-eosin, original magnification ⫻20).
Noninfectious Gastritis
Noninfectious gastritis is associated with autoimmune
gastritis; reactive or chemical gastropathy, usually related
to chronic bile reflux or nonsteroidal anti-inflammatory
drug (NSAID) intake; uremic gastropathy; noninfectious
granulomatous gastritis; lymphocytic gastritis, including
gastritis associated with celiac disease; eosinophilic gas-
tritis; radiation injury to the stomach; graft-versus-host
disease; ischemic gastritis; and gastritis secondary to che-
motherapy.
Many cases of gastritis are of undetermined cause and
present as chronic, inactive gastritis with various degrees
of severity.3
TYPES OF ACUTE GASTRITIS
Many of the forms of chronic gastritis may present with
an acute form, with progression to chronic gastritis be-
cause of persisting injury or sequelae. This is the case of
gastritis associated with long-term intake of aspirin and
other NSAIDs and bile reflux into the stomach; excessive
alcohol consumption; heavy smoking; cancer chemother-
apeutic drugs and radiation; acids and alkali in suicide
attempts; uremia; severe stress (trauma, burns, surgery);
ischemia and shock; systemic infections; mechanical trau-
ma, such as intubation associated mucosal lesions; and vi-
ral infections.
Case 1
A 60-year-old man underwent esophagogastroduoden-
oscopy. A biopsy of gastric antrum was submitted to pa-
thology to rule out H pylori. The histologic findings are
shown in Figure 1, A through C.
Findings. Examination of the biopsy material available
gives the following answers:
1. Are there features of chronic gastritis? Yes. The gas-
tric antral mucosa shows expansion of the lamina propria
by chronic inflammatory cells, consisting of plasma cells
and small lymphocytes, predominantly located toward the
luminal aspect of the mucosa, a pattern that is suggestive
of H pylori infection.
2. Are there neutrophils in the mucosa? Yes. Therefore,
this represents active gastritis. This is a mild form of active
gastritis.
3. Is there Helicobacter? Yes. Hematoxylin-eosin (H&E)
examination reveals diagnostic H pylori bacterial forms in
the surface mucus layer in close proximity to the apical
aspect of surface epithelial cells.
4. Is there glandular atrophy? The biopsy sample avail-
able is not adequate for evaluation of atrophic gastritis;
multiple biopsies, including samples of gastric body, are
necessary for adequate evaluation of glandular atrophy. Is
there intestinal metaplasia? Yes.
5. What is the topography of lesions? The chronic gas-
tritis in this case involves, at minimum, the gastric antrum;
it is advisable to obtain biopsy samples of both gastric
antrum and body for a better evaluation of gastritis, as
recommended by the updated Sydney guidelines4
for clas-
sification of gastritis.
6. Are additional special features present? No.
7. Are special stains recommended? No.
Diagnosis. Gastric antral mucosa with H pylori–asso-
ciated chronic gastritis, mildly active, and focal intestinal
metaplasia.
H PYLORI–ASSOCIATED CHRONIC GASTRITIS
The Helicobacter species consist of gram-negative rods
that infect the gastric mucosa. Helicobacter pylori bacteria
are 3.5 ␮m long and are generally comma-shaped or have
slightly spiral forms. Helicobacter heilmannii, a rare agent
of chronic gastritis, is a 5- to 9-␮m-long bacterium, with
a characteristic tightly corkscrew-shaped, spiral form.5
Helicobacter pylori infection usually is acquired during
childhood, persisting as chronic gastritis if the organism
is not eradicated. During progression of gastritis over the
years, the gastric mucosa undergoes a sequence of changes
that may lead to glandular atrophy, intestinal metaplasia,
increased risk of gastric dysplasia and carcinoma,6–9
and
mucosa-associated lymphoid tissue lymphoma,10,11
report-
ed as extranodal, marginal zone, B-cell lymphoma in the
World Health Organization classification.12
Helicobacter pylori infection is associated with the histo-
logic pattern of active and chronic gastritis, reflecting the
presence of neutrophils and mononuclear cells (lympho-
cytes and plasma cells) in the mucosa, respectively. The
term active gastritis is preferred to acute gastritis because H
pylori gastritis is a long-standing chronic infection with
ongoing activity. Lymphoid aggregates and lymphoid fol-
licles may be observed expanding the lamina propria, and
rare lymphocytes may enter the epithelium. Helicobacter
pylori organisms are found within the gastric mucus layer
that overlays the apical side of gastric surface cells, and
lower numbers are found in the lower portions of the gas-
tric foveolae. Helicobacter pylori may be found within the
deeper areas of the mucosa in association with glandular
cells in patients on acid blockers, such as the commonly
used proton pump inhibitors.13
Helicobacter pylori–associated gastritis can display differ-
ent levels of severity. The severity of H pylori gastritis ac-
tivity may be indicated in a pathology report as mild (rare
neutrophils seen), moderate (obvious neutrophils within
the glandular and foveolar epithelium), or severe (numer-
ous neutrophils with glandular microabscesses and mu-
cosal erosion or frank ulceration).4,14
Helicobacter pylori–associated chronic gastritis can mani-
fest as a pangastritis involving the area from the pylorus
to the gastric body and cardia, or it may predominantly
involve the antrum. Patients with gastric ulcers generally
have antral-predominant gastritis, whereas pangastritis,

Figure 2. Chronic active gastritis in a patient with Crohn disease. A
glandular abscess is shown; additionally, there are many neutrophils in
the lamina propria admixed with a background of chronic inflamma-
tion (hematoxylin-eosin, original magnification ⫻20).
or at least multifocal gastritis, is more common in patients
with gastric carcinoma. The latter generally have signifi-
cant intestinal metaplasia and gastric oxyntic glandular
atrophy coexisting in the background stomach. It is im-
portant to make a pathologic diagnosis of atrophic gastri-
tis because gastric atrophy is associated with increased
risk of gastric cancer.15,16
Patients with chronic atrophic
gastritis may have up to a 16-fold increased risk of devel-
oping gastric carcinoma, compared with the general pop-
ulation.15,17
When large numbers of H pylori are present in the mu-
cosa, the identification of typical organisms is generally
possible on H&E stains. However, there are cases of chron-
ic, active gastritis with features suggestive of H pylori gas-
tritis in which the organisms are not detected. Several spe-
cial stains have been extensively used to help identify H
pylori organisms in the gastric mucosa, including modi-
fied-Giemsa, Genta, thiazine stains, and immunohisto-
chemistry against Helicobacter antigens. The selection of the
special stain used is largely dependent on preferences re-
lated to individual practices. Although, overall, no major
differences in sensitivity and specificity have been report-
ed, studies have recommended immunohistochemical
stains in a subset of cases.18,19
In our practice, we prefer to
use immunohistochemical stains for detection of H pylori
if organisms are not found on H&E stains in the following
cases: (1) if moderate to severe chronic gastritis or any
grade of active gastritis is present but no Helicobacter or-
ganisms are identified on H&E; (2) when extensive intes-
tinal metaplasia is present because H pylori density is re-
duced in areas of intestinal metaplasia; and (3) during
follow-up biopsies after antibiotic treatment for H pylori.
Helicobacter heilmannii may cause similar pathology, and
the treatment is similar to H pylori.5
Case 2
A 45-year-old man is seen to rule out H pylori. He pre-
sents with a history of Crohn disease. The histologic find-
ings are shown in Figure 2.
Findings. Examination of the biopsy material results
in the following pattern of answers:
1. Are there features of chronic gastritis? Yes. The gas-
tric antral mucosa shows expansion of the lamina propria
by chronic inflammatory cells, consisting of admixed plas-
ma cells and small lymphocytes, throughout the thickness
of the mucosa.
2. Are there neutrophils in the mucosa? Yes, with an
occasional glandular abscess; therefore, there is active gas-
tritis. Of note, the active gastritis has a patchy distribution.
3. Is there Helicobacter? No. Examination with H&E
stain does not reveal such bacterial forms. Immunohisto-
chemical stain is performed.
4. Is there atrophy? The biopsy sample available is not
adequate for evaluation of atrophic gastritis because the
biopsy material is only from the gastric antrum; multiple
gastric body biopsies are necessary for adequate evalua-
tion of glandular atrophy. There is no intestinal metapla-
sia.
tritis involves, at minimum, the gastric antrum.
6. Are additional special features seen? No. Although
in a case of Crohn disease gastritis, epithelioid granulo-
mas may be present; in this case, no granulomas were
seen.
7. Are special stains recommended? Yes. Helicobacter py-
lori immunohistochemical stain, which is helpful in cases
where Crohn disease is suspected because the absence of
H pylori organisms in chronic active gastritis is consistent
with Crohn disease. The H pylori immunohistochemical
stain in this case is negative.
Diagnosis. Gastric antral mucosa with chronic active
gastritis, moderately active, patchy. No H pylori organisms
are identified by H&E or immunohistochemistry. Note:
These features are consistent with Crohn disease–associ-
ated gastritis.
CROHN DISEASE–ASSOCIATED GASTRITIS
The hallmark histopathologic features of Crohn disease–
associated gastritis are the presence of patchy, acute in-
flammation with possible gastric pit or glandular abscess-
es, commonly with a background with lymphoid aggre-
gates. Recent studies20
reported the presentation of gastri-
tis in patients with Crohn disease as a focally enhanced
gastritis, characterized by small collections of lymphocytes
and histiocytes surrounding a small group of gastric fo-
veolae or glands, often with infiltrates of neutrophils. In
severe cases, there may be diffuse inflammation in the
lamina propria, with variable glandular loss, fissures, ul-
cers, transmural inflammation, and fibrosis. Noncaseating
epithelioid granulomas may be present in about one third
of cases of Crohn disease gastritis but are often not seen,
at least in part, because of limited tissue sampling.
When granulomas are identified, the differential diag-
nosis includes other forms of granulomatous gastritis.
There are infectious and noninfectious causes of granulo-
matous gastritis. Noninfectious diseases represent the usu-
al cause of gastric granulomas and include Crohn disease,
sarcoidosis, and isolated granulomatous gastritis. Sarcoid-
like granulomas may be observed in cocaine users, and
foreign material is occasionally observed in the granulo-
mas. Sarcoidosis of the stomach is usually associated with
granulomas in other organs, especially the lungs, hilar
nodes, or salivary glands. A diagnosis of idiopathic, iso-

Figure 3. Helicobacter pylori–associated atrophic gastritis. A, Chronic
active gastritis involving the gastric oxyntic mucosa with glandular at-
rophy (hematoxylin-eosin, original magnification ⫻10). Inset shows
rare neutrophils into the glandular epithelium (white arrows). B, Im-
munohistochemical stain for H pylori shows a small area with organ-
isms attached to the surface epithelium. Insets show individual Heli-
cobacter bacteria (thin arrows) with characteristic elongated, slightly
spiral S shape or clusters of packed bacteria (thick arrowhead) closely
adherent to the surface of epithelial cells. Immunohistochemical stains
are useful in cases such as this one, when H pylori organisms are
closely associated with the surface epithelial cells making it difficult to
ascertain the characteristic bacterial morphology on hematoxylin-eosin
stains (original magnification ⫻40).
lated, granulomatous gastritis is rendered when known
entities associated with granulomas are excluded.
Case 3
A 60-year-old man presents with a nodularity of the
gastric body to rule out H pylori. Esophagogastroduoden-
oscopy with biopsy of the nodular areas was performed.
The histologic findings are shown in Figure 3, A and B.
1. Are there features of chronic gastritis? Yes.
2. Are there neutrophils in the mucosa? Yes. There are
neutrophils in the mucosa, representing active gastritis.
stain does not reveal H pylori bacterial forms. Immunohis-
tochemical is performed.
4. Is there atrophy? Yes. There is a reduced number of
oxyntic glands in the biopsy. There is no intestinal meta-
plasia.
tritis involves, at minimum, the gastric body.
6. Are additional special features seen? No.
7. Are special stains recommended? Yes. Helicobacter py-
lori immunohistochemical stain, which is positive.
Diagnosis. Gastric oxyntic mucosa with H pylori–as-
sociated chronic active gastritis and glandular atrophy,
moderate. No intestinal metaplasia is identified. Helicobac-
ter organisms are identified by immunohistochemistry.
ATROPHIC GASTRITIS
Several publications, including those reporting the Syd-
ney system and the updated Houston classification of gas-
tritis, have proposed criteria for the evaluation of atrophic
gastritis. Interobserver variability is significant, especially
in the evaluation of antral atrophy.4,21
Recent advances that
appear to decrease the interobserver variation in the as-
sessment of gastric atrophy have been reported.14
Atrophy
is more accurately assessed after resolution of severe in-
flammation of the mucosa; therefore, if there is H pylori
gastritis, the infection should be eradicated before atrophy
is difinitively evaluated. When marked inflammation is
present, a diagnosis of indefinite for atrophy may be of-
fered, especially if there is no intestinal metaplasia.
The recommended definition of atrophy is the loss of
appropriate glands, and atrophy can be scored according
to the degree of severity as mild, moderate, or severe.22
In
this definition, intestinal metaplasia represents a form of
atrophy described as metaplastic atrophy (or gastric glan-
dular atrophy with intestinal metaplasia).
Gastric atrophy is usually associated with intestinal
metaplasia. However, in limited endoscopic biopsies, in-
testinal metaplasia might not be sampled, whereas the
mucosa shows definitive atrophy. Usually gastric atrophy
and intestinal metaplasia occur on a background of chron-
ic gastritis, hence the term atrophic gastritis.
Sampling of the mucosa for evaluation of atrophy and
gastritis is generally adequate by using the 5 biopsies rec-
ommended by the Sydney system, including 2 biopsies
from the antrum, 2 from the corpus or body, and 1 from
the incisura angularis.4,21
It is essential for the pathologist
to have a means of determining the specific site in the
stomach where a biopsy is sampled from because specific
topography of atrophy characterizes the different types of
atrophic gastritis. In atrophic gastritis associated with H
pylori, glandular atrophy and intestinal metaplasia involve
both the gastric antrum and body, whereas in autoim-
mune atrophic gastritis, the disease is essentially restricted
to the gastric body. Ideally, the precise location is indicated
by the endoscopist, and the biopsies from different sites
are submitted in separate containers. However, using spe-
cial stains can help the pathologist determine the location
of the biopsy fragments received. This approach is ex-
emplified in case 5.
Gastric atrophy and intestinal metaplasia are associated
with increased gastric cancer risk, but unlike the intestinal
metaplasia of Barrett syndrome, no specific recommen-
dations for surveillance have been established in the Unit-
ed States, although published data in other populations
have suggested a benefit.23
In that study,23
patients with

Figure 4. Autoimmune gastritis. A, The gastric biopsy location in
stomach was not provided in this case (hematoxylin-eosin, original
magnification ⫻20). B, Immunohistochemical stain for synaptophysin
demonstrates enterochromaffin-like cell hyperplasia (original magnifi-
cation ⫻20). The inset shows individual enterochromaffin-like cells
staining brown, indicated by the arrow. C, Immunohistochemical stain
for gastrin is negative, indicating the biopsy site to be from the gastric
oxyntic mucosa (original magnification ⫻20).
extensive atrophic gastritis and intestinal metaplasia had
an 11% risk of gastric malignancy.
Case 4
Esophagogastroduodenoscopy of a 60-year-old man
shows gastritis. The pathologist needs to rule out H pylori
and gastric atrophy. The gastric site of the biopsy is not
specified. Figure 4, A through C, represents the histologic
findings.
1. Are there features of chronic gastritis? Yes.
neutrophils in the mucosa; therefore, there is a component
of active gastritis.
stains do not reveal H pylori bacterial forms. Immunohis-
tochemical stain is performed.
4. Is there atrophy? If the biopsy is from gastric oxyntic
mucosa then there is atrophy, however, if the specimen is
from the antrum, it may represent chronic gastritis with-
out atrophy. There is no intestinal metaplasia.
5. Are special stains recommended? Yes. Immunohis-
tochemical stains for synaptophysin and gastrin are per-
formed. Immunohistochemical stains for synaptophysin
(Figure 4, B), show a linear pattern of synaptophysin-pos-
itive cells, whereas the gastrin stain is negative. Because
gastrin is negative, the biopsy is not from the gastric an-
trum (G cells are characteristically located in the antrum
and pylorus), and therefore, it can be established that the
biopsy is of oxyntic mucosa with reduced oxyntic glan-
dular profiles, establishing a diagnosis of atrophy. The lin-
ear arrays of synaptophysin-positive cells represent en-
terochromaffin-like cell hyperplasia. Enterochromaffin-
like cell hyperplasia occurs in response to hypergastri-
nemia that results from hypochlorhydria associated with
gastric oxyntic cell atrophy.
6. Are additional special features seen? No.
7. Is immunohistochemical stain for H pylori positive?
No.
Diagnosis. Gastric oxyntic mucosa with chronic active
gastritis and glandular atrophy, severe. No intestinal meta-
plasia is identified. No Helicobacter organisms are identi-
fied. Note: These features are most suggestive of autoim-
mune gastritis.
AUTOIMMUNE ATROPHIC GASTRITIS
This form of gastritis (reviewed in Sepulveda et al1
and
Capella et al24
) is caused by antiparietal cell and anti-in-
trinsic factor antibodies and presents as a chronic gastritis
with oxyntic cell injury, and glandular atrophy essentially
restricted to the oxyntic mucosa of the gastric body and
fundus. The histologic changes vary in different phases of
the disease. During the early phase, there is multifocal
infiltration of the lamina propria by mononuclear cells and
eosinophils and focal T-cell lymphocyte infiltration of ox-
yntic glands with glandular destruction. Focal mucous
neck cell hyperplasia (pseudopyloric metaplasia), and hy-
pertrophic changes of parietal cells are also observed.
During the florid phase, there is increased lymphocytic
inflammation, oxyntic gland atrophy, and focal intestinal
metaplasia. The end stage is characterized by diffuse in-
volvement of the gastric body and fundus by chronic atro-
phic gastritis associated with multifocal intestinal meta-
plasia. In contrast to the gastric body, the antrum is
spared. Recently, a distinct form of autoimmune gastritis,
characterized by atrophic pangastritis, was reported in a
small group of patients with systemic autoimmune dis-
orders.25
Autoimmune gastritis is a relatively rare disease but
represents the most frequent cause of pernicious anemia
in temperate climates. The risk of gastric adenocarcinoma
was reported to be at least 2.9 times higher in patients
with pernicious anemia than in the general population,
and there is also an increased risk of gastric carcinoid tu-
mors.
Case 5
A 47-year-old woman presents with a history of celiac
disease. Esophagogastroduodenoscopy was performed,
with biopsy of gastric antrum. The pathologist needs to
rule out H pylori. Figure 5, A and B, illustrates the histo-
logic findings.
1. Are there features of chronic gastritis? Yes. There are
large numbers of intraepithelial lymphocytes.
2. Are there neutrophils in the mucosa? No.

Figure 5. Lymphocytic gastritis. A, Gastric mucosal surface epithelium
is studded with intraepithelial small lymphocytes (hematoxylin-eosin,
original magnification ⫻20). B, Immunohistochemistry highlights nu-
merous CD3-positive T lymphocytes staining dark brown (original mag-
nification ⫻20). The lymphocytes predominantly infiltrate the surface
and foveolar epithelium. The thick arrow points to light-brown back-
ground stain found in some glandular cells. The inset shows a higher
magnification of the surface epithelium containing many intraepithelial
lymphocytes (original magnification ⫻40). One individual lymphocyte
is indicated by the arrow. T lymphocytes stain dark brown, whereas
the nucleus of the epithelial cell nuclei stain with the blue counterstain.
stain does not reveal H pylori bacterial forms. Immunohis-
tochemical is performed.
4. Is there atrophy? No. There is no glandular atrophy
and no intestinal metaplasia.
6. Are additional special features seen? Yes. The specific
features in this biopsy include a characteristic intraepithe-
lial lymphocytosis. Immunohistochemical stain for CD3 is
positive, highlighting a population of T lymphocytes in
the mucosa and, typically, many intraepithelial lympho-
cytes.
tochemical stain for H pylori, which is negative.
Diagnosis. Chronic gastritis with increased intraepi-
thelial T lymphocytes. No Helicobacter organisms are iden-
tified. Note: These features are consistent with lympho-
cytic gastritis–associated with celiac disease.
LYMPHOCYTIC GASTRITIS
Lymphocytic gastritis is a type of chronic gastritis char-
acterized by marked infiltration of the gastric surface and
foveolar epithelium by T lymphocytes and by chronic in-
flammation in the lamina propria. A diagnosis can be ren-
dered when 30 or more lymphocytes per 100 consecutive
epithelial cells are observed, and the counts are recom-
mended in biopsies from the gastric corpus. The endo-
scopic pattern is, in some cases, described as varioliform
gastritis. The cause of lymphocytic gastritis is usually un-
known, but some cases are seen in patients with gluten-
sensitive enteropathy/celiac disease and in Ménétrier disease.
Smaller numbers of intraepithelial lymphocytes can also
be seen in H pylori gastritis, but the diagnosis of lympho-
cytic gastritis should be reserved for cases with marked
intraepithelial lymphocytosis in the absence of active H
pylori gastritis. Lymphocytic gastritis can be observed in
children but is usually detected in late adulthood, with
average age of diagnosis of 50 years.
Case 6
A 75-year-old woman presents after esophagogastro-
duodenoscopy. Gastric antrum shows gastritis; the pa-
thologist is asked to rule out H pylori. The histologic find-
ings are shown in Figure 6.
1. Are there features of chronic gastritis? There is min-
imal chronic gastritis.
2. Are there neutrophils in the mucosa? No.
3. Is there Helicobacter? No. Examination of H&E stains
does not reveal H pylori bacterial forms.
4. Is there atrophy? No. There is no atrophy or intestinal
metaplasia.
6. Are additional special features seen? Yes. There are
diagnostic special features, including foveolar hyperplasia
with a corkscrew appearance of the foveolae. The foveolar
epithelium shows reactive cytologic features, including re-
duced cytoplasmic mucin. The lamina propria shows con-
gestion and smooth muscle hyperplasia, with prominent
muscularization of the most superficial mucosa.
7. Are special stains recommended? No ancillary tests
are performed.
Diagnosis. Gastric antral mucosa with features con-
sistent with reactive gastropathy. No H pylori organisms
are identified.
CHRONIC, REACTIVE (CHEMICAL) GASTROPATHY
Chronic reactive gastropathy (also know as chemical
gastropathy) is very common in current clinical practice.
The mucosal changes are usually more prominent in the
prepyloric region, but they may extend to involve the ox-
yntic mucosa. The usual underlying causes include chron-
ic bile reflux and long-term NSAID intake. The histopath-
ologic features include mucosal edema, congestion, fibro-
muscular hyperplasia in the lamina propria, and foveolar
hyperplasia with a corkscrew appearance in the most se-
vere forms. The foveolar epithelium characteristically
shows reactive nuclear features and reduction of mucin.
The epithelial changes occur with little background chron-
ic inflammation. However, if there is erosion of the mu-
cosa, superficial neutrophils may be present. Erosive gas-

Figure 6. Reactive gastropathy (hematoxylin-eosin, original magnifi-
cation ⫻20).
Figure 7. Erosive gastritis and cytomegalovirus-associated gastritis. A,
Gastric mucosa with erosion in a patient with history of nonsteroidal
anti-inflammatory drug use (hematoxylin-eosin, original magnification
⫻20). B, Gastric mucosal erosion with granulation tissue. Inset shows
←
cytomegalovirus inclusion. This single inclusion is identified by the ar-
row on the background granulation tissue (hematoxylin-eosin, original
magnifications ⫻20 and ⫻40 [inset]).
tritis (Figure 7, A) can present clinically as acute gastritis,
often associated with NSAID intake.
The features associated with bile reflux are typically
found in patients with partial gastrectomy, in whom, the
lesions develop near the surgical stoma. However, alter-
ations induced by bile reflux also affect the intact stomach.
A recent study26
reported altered mucin expression in re-
active gastropathy, including aberrant expression of
MUC5Ac in pyloric glands. Evaluation of mucin-expres-
sion patterns can be useful to support a diagnosis of re-
active gastropathy; however, additional studies are war-
ranted to validate this potential application of mucin im-
munohistochemistry.
Case 7
A 45-year-old woman presents with a history of bone
marrow transplant. Esophagogastroduodenoscopy shows
gastric erosion. The histologic findings are represented in
Figure 7, B.
1. Are there features of chronic gastritis? Yes. The sam-
ple of gastric mucosa reveals mucosal erosion with gran-
ulation tissue and associated chronic and acute inflam-
mation.
superficial neutrophils in the mucosa, but they are limited
to the area of mucosal erosion.
stain does not reveal such bacterial forms.
4. Is there atrophy? No. There is no atrophy or intestinal
metaplasia.
5. What is the topography of lesions? Away from the
areas of erosion, there is no evidence of gastritis; therefore,
the location of the biopsy is not contributory in this case.
6. Are additional special features seen? Yes. There are
special features including enlarged cells, arousing suspi-
cion of cytomegalovirus inclusions in the granulation tis-
sue.
tochemical stain for cytomegalovirus reveals rare but char-
acteristic viral inclusions (not shown).
Diagnosis. Gastric antral mucosa with erosion and cy-
tomegalovirus inclusions, consistent with cytomegalovirus-
associated gastritis.
CYTOMEGALOVIRUS GASTRITIS
Cytomegalovirus infection of the stomach is observed
in patients with underlying immunosuppression. Histo-
logically, intranuclear eosinophilic inclusions and smaller
intracytoplasmic inclusions in enlarged cells are charac-
teristic. A patchy, mild inflammatory infiltrate is observed
in the lamina propria. Viral inclusions are present in en-
dothelial or mesenchymal cells in the lamina propria and
may be seen in gastric epithelial cells. Severe activity may
result in mucosal ulceration.

COMMENT
Most types of gastritis can be diagnosed with H&E
stains. To reach a determination of etiology and a specific
diagnostic entity, a limited list of questions can be used
to evaluate the histopathology of gastric biopsies, which
can lead to a pattern of answers that corresponds to a
specific diagnosis of the most common types of gastritis.
Although not ideal, the diagnosis of gastritis can be
reached from limited biopsy material, even when the lo-
cation of the biopsy is not indicated. If the biopsy site is
not known, immunohistochemical stains for synaptophy-
sin and gastrin can help determine the biopsy location,
permitting a specific diagnosis of atrophic gastritis type.
Helicobacter pylori immunohistochemical stains can be par-
ticularly useful when moderate to severe chronic gastritis
or any active gastritis is present but no Helicobacter organ-
isms are identified on H&E stains, when extensive intes-
tinal metaplasia is present, and to evaluate follow-up bi-
opsies after antibiotic treatment for H pylori.
At the end of the day, there are a number of cases with
a diagnosis of chronic inactive gastritis, generally mild, for
which a specific etiology cannot be determined by histo-
pathologic examination alone. This may be accounted for
by limited tissue sampling, nonspecific focal, mild, chronic
inactive gastritis associated with various systemic disor-
ders, or as yet uncharacterized forms of gastritis.
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