Practical Approach to the Pathologic Diagnosis of Gastritis

Practical Approach to the Pathologic Diagnosis 

of Gastritis 

● Context.—Most types of gastritis can be diagnosed on 

hematoxylin-eosin stains. The most common type of chronic 

gastritis is Helicobacter pylori gastritis. Reactive or 

chemical gastropathy, which is often associated with nonsteroidal 

anti-inflammatory drug use or bile reflux, is common 

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- 

Gastritis refers to a group of diseases characterized by 

inflammation of the gastric mucosa. Histologic examination 

of gastric mucosal biopsies is necessary to establish 

a diagnosis of gastritis. In clinical practice, the role 

of the pathologist who evaluates a gastric biopsy for gastritis 

is to find the cause of gastritis because that will provide 

direct targets toward which therapeutic measures can 

be directed. An etiologic classification of gastritis is presented 

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, Hospital 

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). 

Antonia R. Sepulveda, MD, PhD; Madhavi Patil, MD 

sentative gastric biopsy cases from a gastrointestinal pathology 

practice to demonstrate the practical application 

of basic histopathologic methods for the diagnosis of gastritis. 

Conclusions.—Limited ancillary tests are usually required 

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. Helicobacter 

pylori immunohistochemical stains can particularly 

contribute (1) when moderate to severe, chronic gastritis 

or active gastritis is present but no Helicobacter organisms 

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) 

present. If the biopsy shows chronic gastritis, the following 

questions should be posed: 

1. Are there features of chronic gastritis present? Lymphocytic 

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, predominantly 

in antrum, or involving both locations)? 

6. Are there special features (such as granulomas, foveolar 

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, mucormycosis, 

South American blastomycosis, anisakiasis or anisakidosis; 

chronic gastritis associated with parasitic infections; 

and viral infections, such as cytomegalovirus and 

herpesvirus infection. 

1586 Arch Pathol Lab Med—Vol 132, October 2008 Pathologic Diagnosis of Gastritis—Sepulveda & Patil

Figure 1. Helicobacter pylori–associated chronic active gastritis. A, 

Chronic inflammation oriented toward the surface of the mucosa. Neutrophils 

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 (hematoxylin-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 gastritis; 

radiation injury to the stomach; graft-versus-host 

disease; ischemic gastritis; and gastritis secondary to chemotherapy. 

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 because 

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 chemotherapeutic 

drugs and radiation; acids and alkali in suicide 

attempts; uremia; severe stress (trauma, burns, surgery); 

ischemia and shock; systemic infections; mechanical trauma, 

such as intubation associated mucosal lesions; and viral 

infections. 

Case 1 

A 60-year-old man underwent esophagogastroduodenoscopy. 

A biopsy of gastric antrum was submitted to pathology 

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 gastric 

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 available 

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 gastritis 

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 classification 

of gastritis. 

6. Are additional special features present? No. 

7. Are special stains recommended? No. 

Diagnosis. Gastric antral mucosa with H pylori–associated 

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 reported 

as extranodal, marginal zone, B-cell lymphoma in the 

World Health Organization classification. 12 

Helicobacter pylori infection is associated with the histologic 

pattern of active and chronic gastritis, reflecting the 

presence of neutrophils and mononuclear cells (lymphocytes 

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 follicles 

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 gastric 

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 different 

levels of severity. The severity of H pylori gastritis activity 

may be indicated in a pathology report as mild (rare 

neutrophils seen), moderate (obvious neutrophils within 

the glandular and foveolar epithelium), or severe (numerous 

neutrophils with glandular microabscesses and mucosal 

erosion or frank ulceration). 4,14 

Helicobacter pylori–associated chronic gastritis can manifest 

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, 

Arch Pathol Lab Med—Vol 132, October 2008 Pathologic Diagnosis of Gastritis—Sepulveda & Patil 1587

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 inflammation 

(hematoxylin-eosin, original magnification 20). 

or at least multifocal gastritis, is more common in patients 

with gastric carcinoma. The latter generally have significant 

intestinal metaplasia and gastric oxyntic glandular 

atrophy coexisting in the background stomach. It is important 

to make a pathologic diagnosis of atrophic gastritis 

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 developing 

gastric carcinoma, compared with the general population. 

15,17 

When large numbers of H pylori are present in the mucosa, 

the identification of typical organisms is generally 

possible on H&E stains. However, there are cases of chronic, 

active gastritis with features suggestive of H pylori gastritis 

in which the organisms are not detected. Several special 

stains have been extensively used to help identify H 

pylori organisms in the gastric mucosa, including modified-Giemsa, 

Genta, thiazine stains, and immunohistochemistry 

against Helicobacter antigens. The selection of the 

special stain used is largely dependent on preferences related 

to individual practices. Although, overall, no major 

differences in sensitivity and specificity have been reported, 

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 organisms 

are identified on H&E; (2) when extensive intestinal 

metaplasia is present because H pylori density is reduced 

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 presents 

with a history of Crohn disease. The histologic findings 

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 gastric 

antral mucosa shows expansion of the lamina propria 

by chronic inflammatory cells, consisting of admixed plasma 

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 gastritis. 

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. Immunohistochemical 

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 evaluation 

of glandular atrophy. There is no intestinal metaplasia. 


involves, at minimum, the gastric antrum. 

6. Are additional special features seen? No. Although 

in a case of Crohn disease gastritis, epithelioid granulomas 

may be present; in this case, no granulomas were 

seen. 

7. Are special stains recommended? Yes. Helicobacter pylori 

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–associated 

gastritis. 

CROHN DISEASE–ASSOCIATED GASTRITIS 

The hallmark histopathologic features of Crohn disease– 

associated gastritis are the presence of patchy, acute inflammation 

with possible gastric pit or glandular abscesses, 

commonly with a background with lymphoid aggregates. 

Recent studies20 reported the presentation of gastritis 

in patients with Crohn disease as a focally enhanced 

gastritis, characterized by small collections of lymphocytes 

and histiocytes surrounding a small group of gastric foveolae 

or glands, often with infiltrates of neutrophils. In 

severe cases, there may be diffuse inflammation in the 

lamina propria, with variable glandular loss, fissures, ulcers, 

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 diagnosis 

includes other forms of granulomatous gastritis. 

There are infectious and noninfectious causes of granulomatous 

gastritis. Noninfectious diseases represent the usual 

cause of gastric granulomas and include Crohn disease, 

sarcoidosis, and isolated granulomatous gastritis. Sarcoidlike 

granulomas may be observed in cocaine users, and 

foreign material is occasionally observed in the granulomas. 

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 atrophy 

(hematoxylin-eosin, original magnification 10). Inset shows 

rare neutrophils into the glandular epithelium (white arrows). B, Immunohistochemical 

stain for H pylori shows a small area with organisms 

attached to the surface epithelium. Insets show individual Helicobacter 

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. Esophagogastroduodenoscopy 

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. Immunohistochemical 

is performed. 

4. Is there atrophy? Yes. There is a reduced number of 

oxyntic glands in the biopsy. There is no intestinal metaplasia. 


involves, at minimum, the gastric body. 

6. Are additional special features seen? No. 

7. Are special stains recommended? Yes. Helicobacter pylori 

immunohistochemical stain, which is positive. 

Diagnosis. Gastric oxyntic mucosa with H pylori–associated 

chronic active gastritis and glandular atrophy, 

moderate. No intestinal metaplasia is identified. Helicobacter 

organisms are identified by immunohistochemistry. 

ATROPHIC GASTRITIS 

Several publications, including those reporting the Sydney 

system and the updated Houston classification of gastritis, 

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 assessment 

of gastric atrophy have been reported. 14 Atrophy 

is more accurately assessed after resolution of severe inflammation 

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 offered, 

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 glandular 

atrophy with intestinal metaplasia). 

Gastric atrophy is usually associated with intestinal 

metaplasia. However, in limited endoscopic biopsies, intestinal 

metaplasia might not be sampled, whereas the 

mucosa shows definitive atrophy. Usually gastric atrophy 

and intestinal metaplasia occur on a background of chronic 

gastritis, hence the term atrophic gastritis. 

Sampling of the mucosa for evaluation of atrophy and 

gastritis is generally adequate by using the 5 biopsies recommended 

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 autoimmune 

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 special 

stains can help the pathologist determine the location 

of the biopsy fragments received. This approach is exemplified 

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 recommendations 

for surveillance have been established in the United 

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 magnification 

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. Immunohistochemical 

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 without 

atrophy. There is no intestinal metaplasia. 

5. Are special stains recommended? Yes. Immunohistochemical 

stains for synaptophysin and gastrin are performed. 

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 antrum 

(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 glandular 

profiles, establishing a diagnosis of atrophy. The linear 

arrays of synaptophysin-positive cells represent enterochromaffin-like 

cell hyperplasia. Enterochromaffinlike 

cell hyperplasia occurs in response to hypergastrinemia 

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 metaplasia 

is identified. No Helicobacter organisms are identified. 

Note: These features are most suggestive of autoimmune 

gastritis. 

AUTOIMMUNE ATROPHIC GASTRITIS 

This form of gastritis (reviewed in Sepulveda et al1 and 

Capella et al24 ) is caused by antiparietal cell and anti-intrinsic 

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 oxyntic 

glands with glandular destruction. Focal mucous 

neck cell hyperplasia (pseudopyloric metaplasia), and hypertrophic 

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 involvement 

of the gastric body and fundus by chronic atrophic 

gastritis associated with multifocal intestinal metaplasia. 

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 disorders. 

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 tumors. 

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 histologic 

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 numerous 

CD3-positive T lymphocytes staining dark brown (original magnification 

20). The lymphocytes predominantly infiltrate the surface 

and foveolar epithelium. The thick arrow points to light-brown background 

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. Immunohistochemical 

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 intraepithelial 

lymphocytosis. Immunohistochemical stain for CD3 is 

positive, highlighting a population of T lymphocytes in 

the mucosa and, typically, many intraepithelial lymphocytes. 


stain for H pylori, which is negative. 

Diagnosis. Chronic gastritis with increased intraepithelial 

T lymphocytes. No Helicobacter organisms are identified. 

Note: These features are consistent with lymphocytic 

gastritis–associated with celiac disease. 

LYMPHOCYTIC GASTRITIS 

Lymphocytic gastritis is a type of chronic gastritis characterized 

by marked infiltration of the gastric surface and 

foveolar epithelium by T lymphocytes and by chronic inflammation 

in the lamina propria. A diagnosis can be rendered 

when 30 or more lymphocytes per 100 consecutive 

epithelial cells are observed, and the counts are recommended 

in biopsies from the gastric corpus. The endoscopic 

pattern is, in some cases, described as varioliform 

gastritis. The cause of lymphocytic gastritis is usually unknown, 

but some cases are seen in patients with glutensensitive 

enteropathy/celiac disease and in Ménétrier disease. 

Smaller numbers of intraepithelial lymphocytes can also 

be seen in H pylori gastritis, but the diagnosis of lymphocytic 

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 esophagogastroduodenoscopy. 

Gastric antrum shows gastritis; the pathologist 

is asked to rule out H pylori. The histologic findings 

are shown in Figure 6. 



1. Are there features of chronic gastritis? There is minimal 

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 reduced 

cytoplasmic mucin. The lamina propria shows congestion 

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 consistent 

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 oxyntic 

mucosa. The usual underlying causes include chronic 

bile reflux and long-term NSAID intake. The histopathologic 

features include mucosal edema, congestion, fibromuscular 

hyperplasia in the lamina propria, and foveolar 

hyperplasia with a corkscrew appearance in the most severe 

forms. The foveolar epithelium characteristically 

shows reactive nuclear features and reduction of mucin. 

The epithelial changes occur with little background chronic 

inflammation. However, if there is erosion of the mucosa, 

superficial neutrophils may be present. Erosive gas- 


Figure 6. Reactive gastropathy (hematoxylin-eosin, original magnification 

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 

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, alterations 

induced by bile reflux also affect the intact stomach. 

A recent study 26 reported altered mucin expression in reactive 

gastropathy, including aberrant expression of 

MUC5Ac in pyloric glands. Evaluation of mucin-expression 

patterns can be useful to support a diagnosis of reactive 

gastropathy; however, additional studies are warranted 

to validate this potential application of mucin immunohistochemistry. 

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 sample 

of gastric mucosa reveals mucosal erosion with granulation 

tissue and associated chronic and acute inflammation. 


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 suspicion 

of cytomegalovirus inclusions in the granulation tissue. 


stain for cytomegalovirus reveals rare but characteristic 

viral inclusions (not shown). 

Diagnosis. Gastric antral mucosa with erosion and cytomegalovirus 

inclusions, consistent with cytomegalovirusassociated 

gastritis. 

CYTOMEGALOVIRUS GASTRITIS 

Cytomegalovirus infection of the stomach is observed 

in patients with underlying immunosuppression. Histologically, 

intranuclear eosinophilic inclusions and smaller 

intracytoplasmic inclusions in enlarged cells are characteristic. 

A patchy, mild inflammatory infiltrate is observed 

in the lamina propria. Viral inclusions are present in endothelial 

or mesenchymal cells in the lamina propria and 

may be seen in gastric epithelial cells. Severe activity may 

result in mucosal ulceration. 

← 

cytomegalovirus inclusion. This single inclusion is identified by the arrow 

on the background granulation tissue (hematoxylin-eosin, original 

magnifications 20 and 40 [inset]). 


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 location 

of the biopsy is not indicated. If the biopsy site is 

not known, immunohistochemical stains for synaptophysin 

and gastrin can help determine the biopsy location, 

permitting a specific diagnosis of atrophic gastritis type. 

Helicobacter pylori immunohistochemical stains can be particularly 

useful when moderate to severe chronic gastritis 

or any active gastritis is present but no Helicobacter organisms 

are identified on H&E stains, when extensive intestinal 

metaplasia is present, and to evaluate follow-up biopsies 

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 histopathologic 

examination alone. This may be accounted for 

by limited tissue sampling, nonspecific focal, mild, chronic 

inactive gastritis associated with various systemic disorders, 

or as yet uncharacterized forms of gastritis. 

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Practical Approach to the Pathologic Diagnosis of Gastritis

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