SE M I N A R S I N DI A G N O S T I C P A T H O L O G Y 31 (2014) 114–123

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Pathology and differential diagnosis of chronic,

noninfectious gastritis
Alexandros D. Polydorides, MD, PhDn
Departments of Pathology and Medicine (Gastroenterology), Icahn School of Medicine at Mount Sinai, New York,
New York

article info abstract

Keywords: The histologic finding of chronic inflammation in an endoscopic mucosal biopsy of the
Atrophic gastritis stomach (chronic gastritis) is very common and usually reflects the presence of Helicobacter
Autoimmune gastritis pylori infection. However, infectious organisms are not always present in biopsy material,
Lymphocytic gastritis and some cases of chronic gastritis do not result from H. pylori infection. Thus, the
Inflammatory bowel disease differential diagnosis of this finding is an important one for pathologists to keep in mind.
Crohn disease This review presents the three most common and clinically significant causes of chronic,
Metaplasia noninfectious gastritis, namely, autoimmune atrophic gastritis, lymphocytic gastritis, and
gastric involvement in the setting of inflammatory bowel disease, especially Crohn disease.
For each entity, a brief discussion of its etiology and pathogenesis, a review of the clinical
and endoscopic features, and a description of the microscopic findings are presented in the
context of the differential diagnosis of chronic gastritis with emphasis on helpful
histopathologic hints and long-term sequelae.
& 2014 Elsevier Inc. All rights reserved.

Introduction serial sections and special or immunohistochemical stains,

Chronic gastritis: Definition and significance
Chronic gastritis, defined as the presence of a mixed
chronic inflammatory infiltrate (mostly lymphocytes and
plasma cells) in the lamina propria and occasionally in the
epithelium of the stomach, is a common finding in endo-
scopic mucosal biopsies.1–9 Most cases are due to infection
by Helicobacter pylori (and, less often, by its related species
Helicobacter heilmannii), especially when the chronic inflam-
mation is present as a dense band in the superficial lamina
propria accompanied by neutrophilic infiltration of the
gastric epithelium. Thus, efforts should be made, including
to identify the offending agent. However, it is important to
note that it is not always possible to identify the organism
for various reasons: recent unrelated antibiotic therapy, use
of proton pump inhibitors, inadequate sampling, or sub-
optimal preparation/staining techniques. Furthermore, it is
generally accepted that H. pylori are rarely found in areas of
intestinal metaplasia or near erosions and ulcers, so biopsy
specimens that contain these findings might not yield
organisms.10
If H. pylori organisms are not detected after a reasonably
exhaustive search, alternative causes of chronic gastritis
should be investigated. The goal of this review is to
present three groups of diagnostic entities (autoimmune

n
Correspondence address: Department of Pathology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1194,
New York, NY 10029.
E-mail address: alexandros.polydorides@mountsinai.org

http://dx.doi.org/10.1053/j.semdp.2014.02.008
0740-2570/& 2014 Elsevier Inc. All rights reserved.
 S E M I N A R S I N D I A G N O S T I C
gastritis, lymphocytic gastritis, and gastric involvement in
the setting of inflammatory bowel disease), which are the
most common and clinically significant differentials of
chronic gastritis when H. pylori organisms are not
present. 10
Current recommendations suggest that five biopsies
should be obtained during endoscopic evaluation for gas-
tric pathology: two each from the antrum and the corpus/
fundus (one each from the greater and lesser curvature,
respectively) and one from the lesser curvature at the
incisura angularis. The pattern of chronic inflammation
(antral-predominant, corpus-predominant, or pangastritis)
as well as the presence, extent, and severity of additional
findings, such as atrophy, metaplasia, and hyperplasia, are
crucial in determining the correct differential diagnosis, as
discussed below. Targeted biopsies from the incisura
angularis are encouraged because atrophy, intestinal
metaplasia, and dysplasia tend to occur in this location
first. 11–13
Gastric atrophy: Definition and patterns
Gastric atrophy is defined as the loss of appropriate (i.e.,
normal for the anatomic location) gastric glandular epi-
thelial cells.6,7,14,15 It is more easily and accurately eval-
uated when lamina propria inflammation is largely
resolved. Thus, H. pylori eradication and passage of some
time for the chronic inflammation to subside are generally
required before attempting to assess the extent of atrophy.
Atrophic gastritis is characterized by replacement, or loss,
of normal glandular elements and expansion of the sur-
rounding lamina propria with fibroblasts and fibrosis and it
is almost always accompanied by metaplasia of intestinal,
pancreatic acinar, or pseudopyloric types, which may be
present singly or in combination. For this reason, atrophic
gastritis has been termed metaplastic atrophic gastritis.
Two distinct pathogenetic types have been identified:
autoimmune (type A) and environmental (type B) atrophic
gastritis.
Metaplastic atrophic gastritis due to environmental
causes (also called multifocal atrophic gastritis or atrophic
pangastritis) usually results from chronic H. pylori infection
(in more than three quarters of cases). It almost always
involves the gastric antrum with variable extension into
the proximal stomach. Presumably, prolonged antral
inflammation leads to reduced gastric acid production
and allows for proximal migration of bacteria to the gastric
body, resulting in pangastritis and multifocal atrophic
gastritis.
Patients with environmental metaplastic atrophic gastri-
tis do not usually develop achlorhydria or pernicious
anemia since the disease does not completely destroy the
oxyntic mucosa and a sufficient volume of parietal cells is
usually preserved. Thus, patients may develop hypochlo-
rhydria, but usually maintain normal to high-normal serum
gastrin levels and do not develop enterochromaffin-like
(ECL) cell hyperplasia. Eradication of H. pylori infection is
not associated with reversal of these histologic findings,
but the effect of eradication on gastric carcinoma risk
requires further study.16–19
P A T H O L O G Y 31 (2014) 114–123 115
Chronic atrophic gastritis: Grading, staging and neoplastic
progression
The presence of gastric intestinal metaplasia has been associ-
ated with neoplastic progression towards dysplasia and
intestinal-type gastric adenocarcinoma.15,20,21 Although intesti-
nal metaplasia is probably not premalignant (it has been
referred to as “paracancerous” rather than “precancerous”),
atrophy and intestinal metaplasia signify a mucosa at risk for
the development of dysplasia that can progress to carci-
noma.20,21 Conferred risk varies with extent, distribution, and
severity of inflammation, atrophy, and metaplasia, but, to date,
no specific recommendations or guidelines have been estab-
lished for the surveillance of patients with these findings.
Unfortunately, there are few data describing the extent of
cancer risk attributable to intestinal metaplasia, and detection
of intestinal metaplasia is limited by sampling errors, which
can be substantial when recommended biopsy protocols are not
followed.6
Several classification systems have been proposed to eval-
uate and quantify the extent of gastric atrophy.1,5 Most
systems assess the degree of inflammation and extent of
atrophy in both the antrum and the body.6,14,22 It is clear that
the pattern of chronic gastritis present and the extent of
atrophy are important while identifying gastric mucosa at
risk for neoplastic progression. Pathologists may be called
upon to provide such information to clinicians in order to
facilitate prognostication and management of such
patients.21
Autoimmune gastritis
Clinical and endoscopic features
Autoimmune gastritis is defined as a corpus-predominant
gastritis characterized by chronic inflammation, atrophy of
oxyntic glands, and metaplasia, accompanied by the pres-
ence of circulating auto-antibodies to parietal cells and/or
intrinsic factor, as well as, pernicious anemia in many cases
(Fig. 1).5,7,10 Autoimmune gastritis is relatively uncommon,
being present in 2–5% of the population. It is more frequent
among elderly women of Northern European descent and
shows a predilection for individuals with blood group A.
Many affected patients also have other immune-mediated
disorders, particularly autoimmune thyroiditis.23–25 Clinical
manifestations are mostly delayed until the loss of a critical
mass of parietal cells leads to hypochlorhydria and hyper-
gastrinemia. Reduced gastric acid levels interfere with
absorption of non-heme iron, leading to iron deficiency and
hypochromic, microcytic anemia in approximately 15% of
patients. Patients with severe disease have insufficient pari-
etal cell mass to produce adequate amounts of intrinsic factor
and that which is produced may be inactivated by auto-
antibodies, so these individuals may suffer from vitamin B12
deficiency and megaloblastic anemia. Destruction of chief
cells typically accompanies inflammation-mediated destruc-
tion of parietal cells and results in reduced levels of pepsin
and pepsinogens. There are few distinct endoscopic changes
early on in the course of autoimmune gastritis, whereas
116 S E M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 114–123

Fig. 1 – Histopathologic features of autoimmune atrophic gastritis. (A) A biopsy from the gastric body shows mild chronic
inflammation and extensive intestinal and pancreatic metaplasia. Note the complete absence of parietal cells, which may
make it difficult to recognize the site of the biopsy. (B) An immunohistochemical staining performed on the same sample is
negative for gastric, confirming the site of the biopsy in the gastric body. (C) However, a chromogranin immunohistochemical
stain highlights linear and micronodular ECL cell hyperplasia, which is practically diagnostic of AIG in the context of mucosal
atrophy. (D) An antral biopsy from the same patient is essentially normal. (E) Early autoimmune gastritis displays a dense
lymphoplasmacytic infiltrate in the deep lamina propria with destruction of oxyntic glands and compensatory hypertrophy of
remaining parietal cells in the upper right corner. (F) A patient with long-standing autoimmune gastritis has a well-
differentiated, type 1 endocrine tumor. ((A) and (D)–(F): H&E-stained sections; (B) and (C): immunohistochemical stain for
gastrin and chromogranin, respectively; and original magnification: 100
in (F) and 200
in (A)–(E)).

advanced disease produces mucosal atrophy in the gastric found and represent hyperplastic polyps, residual islands of
corpus, which appears thinner than normal with flattening or intact oxyntic mucosa on a background of atrophy,
loss of rugal folds. Multiple polyps or nodules can often be enterochromaffin-like (ECL) cell hyperplasia, or polypoid
 S E M I N A R S I N D I A G N O S T I C
dysplasia, as described below. Most of these are sessile
lesions that are smaller than 1–2 cm.8,26
Etiology and pathogenesis
Patients with autoimmune gastritis typically have circulating
auto-antibodies against the Hþ/Kþ ATPase of parietal cells
and slightly more than half have auto-antibodies against
intrinsic factor.8 Serum levels of pepsinogen I are usually low,
whereas compensatory hypergastrinemia results from hypo-
chlorhydria. Data from several recent studies suggest that
disease results from infection with H. pylori. Bacterial infec-
tion initiates a process of molecular mimicry and leads to the
production of auto-antibodies against antigens in the gastric
epithelium.27–29 Indeed, up to a quarter of patients with
H. pylori-associated gastritis have auto-antibodies against
the Hþ/Kþ ATPase.28,29 It is thus possible that H. pylori
initiates development of autoimmune gastritis in genetically
susceptible individuals.1
Microscopic pathology
Early changes of autoimmune gastritis include dense chronic
inflammation in the lamina propria and lymphoid follicles.3
The infiltrate consists of predominantly CD4-positive T lym-
phocytes, B cells, and plasma cells and is mostly located in
the deep mucosa around oxyntic glands, in contrast to the
characteristically superficial band of lymphoplasmacytosis
seen in H. pylori-associated gastritis (Fig. 1E).8,23,24,30 Active
inflammation with neutrophils is usually not prominent,
although eosinophils are typically present. With time, pro-
gressive destruction of oxyntic glands leads to atrophy,
metaplasia, and hyperplastic polyps (Fig. 1A). Intestinal
metaplasia may be incomplete (goblet cells interspersed
among gastric foveolar-type epithelial cells) or complete
(goblet cells surrounded by absorptive intestinal cells and
Paneth cells). The gastric antral mucosa is relatively unin-
volved by inflammation, but may show features of chemical
gastropathy or concomitant H. pylori infection. Antral G-cell
hyperplasia resulting from hypochlorhydria may be evident
in routinely stained sections or enhanced with immunohis-
tochemical stains for gastrin or endocrine markers (Fig. 1D).
Neoplastic progression
Endocrine cell lesions
Antral G cells proliferate in response to reduced acid produc-
tion by oxyntic mucosa and secrete gastrin. Gastrin is
a trophic hormone that stimulates proliferation of
enterochromaffin-like (ECL) cells in the gastric body
(Fig. 1C). ECL cell hyperplasia is seen early on in up to 80%
of patients with autoimmune gastritis and may appear as a
simple linear pattern of 5 or more endocrine cells along the
bases of deep glands or form small clusters within glands
(micronodules).8,30–32 A small percentage of patients (approx-
imately 5%) develop multiple, small (r1 cm) ECL cell nodules
that are classified as well-differentiated gastric (neuro) endo-
crine tumors (Type 1). Virtually all nodular ECL cell prolifer-
ations are low-grade and have an excellent prognosis,
P A T H O L O G Y 31 (2014) 114–123 117
particularly when hypergastrinemia is clinically controlled
(Fig. 1F).8
Epithelial cell lesions
Overall, 20–40% of patients with advanced disease have
multiple, endoscopically apparent polyps of the proximal
stomach. Most of these are hyperplastic polyps that have
no malignant potential, but up to 10% show dysplasia.26
Pyloric gland adenomas are less commonly associated with
autoimmune gastritis and may show variable degrees of
dysplasia or even carcinoma, which may be detected in 12–
30% of cases.33–35 Patients with autoimmune gastritis are also
at risk of gastric adenocarcinoma unrelated to pyloric
adenoma. Approximately 1–3% of patients with advanced
disease develop adenocarcinoma, which represents a three-
fold increased risk over the general population. Presumably,
carcinogenesis results from a multistep process through an
atrophy–metaplasia–dysplasia sequence.32
Diagnosis
Late-stage autoimmune gastritis is easily recognized in
biopsy samples, provided the pathologist is aware that the
sample was obtained from the body or fundus. Biopsies show
near-complete loss of parietal cells with replacement by
lobules of neutral mucin-containing glands (Fig. 1A). Immu-
nohistochemical stains can be helpful in confirming the site
of the biopsy: atrophic oxyntic mucosa displays chromogra-
nin-positive, gastrin-negative endocrine cells, whereas antral
biopsies contain G cells that coexpress gastrin and chromog-
ranin (Fig. 1B). Recognition of early autoimmune gastritis is
much more challenging. The features that suggest a diag-
nosis of autoimmune gastritis include the presence of
corpus-predominant chronic active gastritis with eosinophils
based in the deep mucosa, loss of oxyntic glands with
compensatory pseudohypertrophy of the remaining parietal
cells, any type of metaplasia of the epithelium, and ECL cell
hyperplasia (Fig. 1E).36 If present, ECL cell hyperplasia is a
useful distinguishing feature of autoimmune gastritis, since it
is generally lacking in metaplastic atrophic gastritis due to
environmental causes (Fig. 1C). Of note, some patients with
systemic autoimmune disease develop an atrophic autoim-
mune pangastritis in which intense inflammation and atro-
phy are present, which affects both the gastric body and the
antrum. These cases do not show detectable H. pylori organ-
isms and lack endocrine cell hyperplasia.37
Lymphocytic gastritis
Clinical and endoscopic features
Lymphocytic gastritis is a histologic pattern of injury charac-
terized by gastric lymphocytosis affecting the foveolar epi-
thelium of the stomach, as defined by more than 25
intraepithelial lymphocytes (IELs) per 100 epithelial cells
(Fig. 2).2,3,5,8–10,38 A diagnosis of lymphocytic gastritis may be
rendered regardless of the pattern of lamina propria inflam-
mation present, although cases associated with superficial
chronic active gastritis are usually related to H. pylori
118 S E M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 114–123

Fig. 2 – Histopathologic features of lymphocytic gastritis. (A) Biopsies of the antral mucosa display increased intraepithelial
lymphocytes and expansion of the lamina propria by a lymphoplasmacytic infiltrate. (B) Higher magnification reveals
profound lymphocytosis in the surface foveolar, neck, and pit epithelium. (C) A biopsy of the gastric body reveals mild
inflammation in the superficial mucosa with intraepithelial lymphocytosis. (D) This antral biopsy shows a paucity of lamina
propria inflammation with intense intraepithelial lymphocytosis. (E) An immunohistochemical stain for CD3 highlights
intraepithelial lymphocytes in a case of lymphocytic gastritis; these are mostly CD8-positive cytotoxic T cells. (F) This biopsy
shows a lymphocytic gastritis pattern of injury, but numerous H. pylori organisms are adherent to the epithelium. H. pylori
infection and celiac disease are the most common underlying causes of lymphocytic gastritis pattern of injury and together
account for more than 75% of all cases. ((A)–(D) and (F): H&E-stained sections; (E): immunohistochemical stain for CD3; and
original magnification: 100
in (D), 200
in (A), (C) and (E), and 400
in (B) and (F)).

infection. Lymphocytic gastritis is relatively uncommon, It is more common in middle-aged adults, with no particular
being present in 1–4% of gastric biopsies from patients sex predilection. Presenting symptoms range from mild
undergoing upper endoscopy for indications of dyspepsia.39–43 nausea, weight loss, and anorexia in a third to half of patients
 S E M I N A R S I N D I A G N O S T I C
to more severe dyspepsia and vomiting.40,44,45 Up to a fifth of
patients have protein loss with hypoalbuminemia and
peripheral edema.46,47 Approximately 80% of patients with
lymphocytic gastritis have varioliform or verrucous gastritis
with erosions, aphthous ulcers, and mucosal nodularity, but
the stomach may be endoscopically normal.40,41,44 A Méné-
trier disease-like variant of lymphocytic gastritis with
enlarged hypertrophic folds has also been described.48,49
Lymphocytic gastritis is a chronic disease with only rare
reports of spontaneous resolution. Patients are treated symp-
tomatically with proton pump inhibitors as well as H. pylori
eradication, if present.
Etiology and pathogenesis
A number of different conditions have been associated with
gastric lymphocytosis, including H. pylori infection, celiac
disease, Crohn disease, syphilis, HIV infection, Ménétrier
disease, medications (e.g., ticlopidine and NSAIDs), common
variable immunodeficiency, and other autoimmune disorders
such as autoimmune enteropathy and autoimmune gastri-
tis.2,9,38,50 Of these, H. pylori is most common, being identified
in up to 36–41% of patients with lymphocytic gastritis.
Conversely, 4–13% of patients with histologically documented
H. pylori infection have a lymphocytic gastritis pattern of
injury.39,43,50,51 These observations do not necessarily imply
that H. pylori is a causative agent of lymphocytic gastritis, but
its eradication does improve gastric lymphocytosis, suggest-
ing that at least a component of inflammation is due to
infection by the organism.52–55 The association between
lymphocytic gastritis and gluten-sensitive enteropathy is
better established. Approximately 46–52% of patients with
lymphocytic gastritis prove to have celiac disease, especially
if lymphocytosis is predominantly located in the antrum.50,56
Most studies indicate that 10–33% of patients with celiac
disease have antral-predominant lymphocytosis that may
subside upon gluten removal from the diet.43,50,57–60 Gastric
lymphocytosis may also be seen in association with other
disorders, including collagenous gastritis, invasive adenocar-
cinoma, and lymphoma.61,62,63,64 However, up to 20% of
patients with lymphocytic gastritis do not have an identifi-
able cause and are diagnosed with idiopathic lymphocytic
gastritis.38,50
Microscopic pathology
A diagnosis of lymphocytic gastritis requires the presence of
more than 25 intraepithelial lymphocytes per 100 foveolar
epithelial cells (Fig. 2A and B). These are predominantly CD3-/
CD8-positive cytotoxic T cells, but immunohistochemical
stains are not required for the diagnosis (Fig. 2E). The pattern
of intraepithelial lymphocytosis is usually extensive, contin-
uous, and diffuse and more commonly affects the corpus
than the antrum (Fig. 2C). A mixed, lymphoplasmacytic
pattern of chronic inflammation may be present in the
lamina propria and can affect both the antrum and the body
(Fig. 2A and D). Lymphoepithelial lesions are generally not a
feature of lymphocytic gastritis. In contrast, H. pylori-associ-
ated gastritis tends to have a dense lymphoplasmacytic
infiltrate in the superficial lamina propria, lymphoid follicles
P A T H O L O G Y 31 (2014) 114–123 119
often with germinal centers, much fewer IELs, and generally
prominent neutrophils (Fig. 2F). Lymphocytosis due to
H. pylori-related chronic gastritis tends to be focal rather than
diffused.5
Gastric manifestations in inflammatory bowel
disease (IBD)
Clinical and endoscopic features
Involvement of the upper gastrointestinal tract is relatively
common among patients with idiopathic inflammatory bowel
disease (Fig 3). Although most patients with gastric involve-
ment by inflammatory bowel disease have Crohn disease, a
substantial number of ulcerative colitis patients have mild
chronic inflammation in gastric biopsies as well. Early reports
suggested that only 0.5–7% of patients with Crohn disease
had clinically evident gastric involvement, but more recent
data suggest that endoscopic and histopathologic abnormal-
ities are present in 30–83% of patients, with higher numbers
in the pediatric population.2,3,8,9,65–70 Symptoms include epi-
gastric pain, vomiting, and delayed gastric emptying. Endo-
scopic abnormalities are present in one-third of patients with
Crohn disease. They are more common in the distal stomach
and range from friability and loss of vascular pattern to
nodular or thickened rugae with aphthous or linear ulcers.2
A multitude of recent studies suggest that 5–8% of patients
with ulcerative colitis have endoscopic evidence of inflam-
mation in the upper gastrointestinal tract and more than half
have histologic inflammation of the stomach and/or duode-
num. Gastric involvement by ulcerative colitis is usually mild
and asymptomatic, although severe disease is infrequently
encountered, particularly among patients with a history of
colonic resection and pouchitis.70–73
Microscopic pathology
Histologic findings vary from a mild, focally increased inflam-
mation to a dense lymphoplasmacytic infiltration of the lamina
propria with lymphoid follicles and neutrophilic activity (Fig. 3A
and B) that is practically indistinguishable from changes related
to H. pylori-associated gastritis.2,3,7–9,65–68,70,74 The prevalence of
granulomas in gastric biopsies from patients with Crohn disease
is approximately 10%, but it has been reported to be as high as
20% and is higher among pediatric patients.2,65,67,75 Detection of
granulomata in patients with chronic gastritis should raise the
possibility of Crohn disease as well as prompt evaluation of
other possibilities including systemic granulomatous diseases,
infectious agents, and medications. A diagnosis of isolated
(idiopathic) granulomatous gastritis may be rendered when no
other cause for granulomata is apparent (Fig. 3E and F).3,7,10
Focally enhanced gastritis (FEG)
Focally enhanced gastritis is defined as an isolated inflam-
matory lesion involving a few adjacent foveolae, pits, or
glands. The infiltrate consists of CD3-positive T lymphocytes,
plasma cells, and macrophages with occasional neutrophils
(Fig. 3C and D).3,4,7–9 The surrounding mucosa is either devoid
120 S E M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 114–123

Fig. 3 – Gastric manifestations of inflammatory bowel disease. (A) An antral biopsy from a patient with Crohn enteritis shows
a dense, lymphoplasmacytic infiltrate located mostly in the superficial lamina propria that is indistinguishable from of H.
pylori-related gastritis. (B) Higher magnification reveals focal neutrophilic activity in the foveolar epithelium and lamina
propria. Infection with H. pylori was excluded with an immunohistochemical stain. (C) This antral biopsy was obtained from a
9-year-old child with a family history of ulcerative colitis who presented with abdominal pain and proved to have chronic
active colitis on biopsy. There is a single focus of inflammation on a background of fairly normal mucosa. (D) Higher
magnification shows focally enhanced gastritis affecting a couple of gastric pits. The pits are infiltrated by lymphocytes and
plasma cells with occasional neutrophils. (E) This antral biopsy was obtained from a 60-year-old man with gastroesophageal
reflux disease. The mucosa contains minimal inflammation, but there is a single epithelioid granuloma between several
glands. (F) Higher magnification reveals that this well-formed granuloma is not necrotic. The differential diagnosis includes
Crohn disease, as well as other infectious and noninfectious causes. Unfortunately, the etiology of granulomatous
inflammation is infrequently determined when granulomata are discovered as incidental findings in gastric biopsies such as
this one. (H&E-stained sections and original magnification: 100
in (A) and (C), 200
in (E), and 400
in (B), (D) and (F)).
 S E M I N A R S I N D I A G N O S T I C
of inflammation or is only minimally inflamed. Focally
enhanced gastritis is detected in 29–76% of patients with
Crohn disease and is more common among pediatric
patients. However, it is not specific for Crohn disease and
may be observed in 12–30% of patients with ulcerative colitis,
as well as in patients without inflammatory bowel disease,
albeit the frequency is much lower (2–19%) in the latter
population.68,69,73–81 The positive predictive value of focally
enhanced gastritis for Crohn disease is highly variable
depending on the population, but it may be a useful marker
among pediatric patients.76,78
Conclusions
There is generally poor correlation between endoscopic and
histologic findings in the stomach.82–89 Endoscopically nor-
mal stomachs may show severe histologic inflammation,
whereas gastric erythema often corresponds to a normal
biopsy. The most common cause of histologically evident
chronic gastritis is H. pylori infection and this agent should be
excluded in all gastric biopsies that show chronic gastritis.
However, a limited number of other etiologies may also cause
chronic gastritis and these should be excluded by patholo-
gists. The three most important such differential diagnoses
are autoimmune atrophic gastritis, lymphocytic gastritis, and
gastric manifestations of idiopathic inflammatory bowel dis-
ease. Recognition of these entities by the pathologist provides
valuable information to the clinician, as they may require
specific interventions and may even herald the presence of
other disorders, including increased cancer risk and celiac
disease.
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