Approach Considerations
The diagnosis of chronic gastritis can only be established on histologic grounds. Therefore, histologic assessment of endoscopic biopsies is essential. Identification of the underlying cause of chronic gastritis and assessment of specific complications can require several laboratory tests.
Failure to diagnose the underlying cause of chronic gastritis correctly may result in unnecessary morbidity. Failure to identify and treat H pylori infection in the presence of peptic ulcers may result in ulcer recurrence and complications.
Laboratory Studies
Atrophic gastritis may be assessed by measuring the ratio of pepsinogen I (PGI, PGA) to pepsinogen II (PGII, PGC) in the serum. PGI and PGII are synthesized and secreted by gastric chief cells. After being secreted into the gastric lumen, they are converted into proteolytic active pepsins. The level of PGI in the serum decreases as gastric chief cells are lost during gastric atrophy, resulting in a decreased PGI/PGII ratio. Gastric carcinoma occurs, especially the intestinal type, usually in association with severe atrophic gastritis.
Measuring the levels of PGI and PGII and the PGI/PGII ratio in the serum is useful in screening for atrophic gastritis and gastric cancer in regions with a high incidence of these diseases. Pepsinogen determination is especially useful in epidemiologic studies; however, the reported sensitivity and specificity of the assay are relatively low (84.6% and 73.5%, respectively).
A rapid urease test should be done on gastric biopsy tissue. Bacterial culture of gastric biopsy tissue is usually performed in the research setting or to assess antibiotic susceptibility in patients in whom first-line eradication therapy fails.
The following test results suggest the diagnosis of autoimmune gastritis:
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Antiparietal and anti–intrinsic factor (IF) antibodies in the serum
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Achlorhydria, both basal and stimulated, and hypergastrinemia
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Low serum cobalamin (vitamin B-12) levels (< 100 pg/mL)
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Possible abnormal result on Schilling test (this can be corrected by IF)
Endoscopy
Magnifying endoscopy is helpful for analyzing the subepithelial microvascular architecture, as well as the mucosal surface microstructure, without tissue biopsy. [97] Using this technique, investigators from the United Kingdom were able to describe the normal gastric microvasculature pattern and identify characteristic patterns in two cases of autoimmune atrophic gastritis. [98]
Upper gastrointestinal (GI) endoscopy is essential for establishing the diagnosis of gastritis. Although some studies have suggested that H pylori infection can be determined on the basis of unique endoscopic features, particularly the presence of antral nodularity, whether there is a specific relation between H pylori and macroscopic features remains controversial. The endoscopic findings in chronic H pylori infection may include areas of intestinal metaplasia.
Multiple biopsy specimens should be obtained. Tissue sampling from the gastric antrum, incisura, and corpus is essential to establish the topography of gastritis and to identify atrophy and intestinal metaplasia, which usually is patchy. It is recommended that biopsy samples of the gastric body and those from the antrum and incisura be submitted in separate containers for pathologic evaluation.
Endoscopic findings in granulomatous gastritis include mucosal nodularity with cobblestoning, multiple aphthous ulcers, linear or serpiginous ulcerations, thickened antral folds, antral narrowing, hypoperistalsis, and duodenal strictures. Extensive gastric involvement may resemble linitis plastica.
Endoscopic findings in lymphocytic gastritis include enlarged folds and aphthoid erosions, with the appearance of small, heaped-up, volcanolike mounds pocked with a central crater. This endoscopic pattern has also been described as varioliform gastritis.
The endoscopic findings of reflux and chemical gastropathy are those of a gastric mucosa that is red or has red streaks with areas of apparent hemorrhage.
A meta-analysis has shown that for individuals who undergo endoscopy for dyspepsia, the most common finding is erosive esophagitis (though the prevalence was lower when the Rome criteria were used to define dyspepsia), followed by peptic ulcers. [99]
Biopsy
The standard method of determining whether H pylori is the underlying cause of gastritis is histologic identification of the organism. Histologic examination is also used to evaluate the degree and distribution of gastritis. Obtain at least 2 biopsies from the gastric antrum, 2 from the corpus, and 1 from the incisura.
Special stains to identify H pylori (eg, Warthin-Starry, Giemsa, or Genta) or immunohistochemistry may be necessary when the organisms are not observed and chronic gastritis is obvious.
At late stages of infection with extensive atrophic gastritis, the numbers of H pylori organisms are markedly decreased because intestinal metaplasia creates an unfavorable environment for H pylori. In these cases, other tests (eg, the urea breath test) and serologic indicators of infection may provide evidence for H pylori infection.
Histologic Findings
H pylori–associated gastritis can display different levels of severity. H pylori organisms are found within the gastric mucous layer and frequently accumulate in groups at the apical side of gastric surface cells, occasionally in the lower portions of the gastric foveolae, and rarely within the deeper areas of the mucosa in association with glandular cells (see the images below).
Helicobacter pylori–caused chronic active gastritis. Genta stain (×20). Multiple organisms (brown) are visibly adherent to gastric surface epithelial cells.
Chronic gastritis associated with Helicobacter pylori infection. Numerous plasma cells are present in the lamina propria.
Patients with typical infections initially develop chronic active gastritis in which H pylori is observed in both the antrum and the corpus (usually in greater numbers in the antrum). Polymorphonuclear leukocytes (PMNs) infiltrate the lamina propria, glands, surface epithelium, and foveolar epithelium, occasionally spilling into the lumen and forming small microabscesses. Lymphoid aggregates and occasional well-developed lymphoid follicles are observed expanding the lamina propria of the mucosa, and occasional lymphocytes permeate the epithelium.
In a disease of longer duration, significant loss of gastric glands is observed, a condition known as gastric atrophy. Gastric atrophy may result from the loss of gastric epithelial cells that were not replaced by appropriate cell proliferation, or it may result from replacement of the epithelium with intestinal-type epithelium (intestinal metaplasia).
In advanced stages of atrophy associated with chronic H pylori infection, both the corpus and the antrum display an extensive replacement by intestinal metaplasia that is associated with the development of hypochlorhydria. With expansion of intestinal metaplasia, the number of H pylori organisms that are detected in the stomach decreases because H pylori is excluded from areas of metaplastic epithelium.
The histologic changes of autoimmune atrophic gastritis vary in different phases of the disease. During an early phase, multifocal diffuse infiltration of the lamina propria by mononuclear cells and eosinophils and focal T-cell infiltration of oxyntic glands with glandular destruction are seen. Focal mucous neck cell hyperplasia (pseudopyloric metaplasia) and hypertrophic changes of parietal cells are also observed.
During the florid phase of the disease, increased lymphocytic inflammation, oxyntic gland atrophy, and focal intestinal metaplasia occur. The end stage is characterized by diffuse involvement of the gastric corpus and fundus by chronic atrophic gastritis associated with little intestinal metaplasia. The antrum is spared.
Granulomatous gastritis predominantly affects the gastric antrum. In early stages, the only findings may be isolated granulomas in the mucosa and submucosa. In later stages of the disease, inflammation extends to the muscularis propria, and fibrosis may be prominent. Granulomas associated with tuberculosis are typically caseating. Poorly formed granulomas can also be observed in syphilitic involvement of the stomach in the tertiary stage of the disease.
Noninfectious causes of gastric granulomas typically result in noncaseating granulomas; such causes include the following:
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Crohn disease
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Sarcoidosis
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Isolated granulomas
Crohn disease affecting the stomach consists of patchy inflammation with pit or gland abscesses. Lymphoid aggregates are common. Severe cases may show fissures, ulcers, transmural inflammation, and serosal and submucosal fibrosis. Noncaseating epithelioid granulomas may be observed. Diffuse inflammatory infiltration in the lamina propria and glandular atrophy occur. Gastric involvement is almost invariably synchronous with Crohn disease in the ileum or colon.
Sarcoidosis and isolated granulomas are characterized by bland granulomas with mild associated inflammation. Although sarcoidosis affecting the stomach typically coexists with sarcoidosis involving other organs, isolated granulomatous gastritis only affects the stomach and is a diagnosis of exclusion.
Cytomegalovirus (CMV) infection of the stomach is observed in patients with underlying immunosuppression. Histologically, typical intranuclear eosinophilic inclusions and, occasionally, smaller intracytoplasmic inclusions are found (see the image below). Patchy, mild, inflammatory infiltrate is observed in the lamina propria. Viral inclusions are present in the gastric epithelial cells and in endothelial or mesenchymal cells in the lamina propria. Severe mucosal necrosis may result in severe ulceration.
Chronic gastritis. Typical cytomegalovirus inclusions in the lamina propria capillary endothelial cells. Image courtesy of Sydney Finkelstein, MD, PhD, University of Pittsburgh.
Herpes simplex causes basophilic intranuclear inclusions in epithelial cells. M avium-intracellulare infections are characterized by diffuse infiltration of the lamina propria by histiocytes, which rarely form granulomas (see the image below).
Chronic gastritis. Mycobacterium avium-intracellulare in the gastric lamina propria macrophages. Image courtesy of Sydney Finkelstein, MD, PhD, University of Pittsburgh.
In cases of gastritis associated with graft versus host disease (GVHD), the stomach is rarely affected. Typical epithelial cell apoptosis and pit or gland dilatation occur. Pit and gland abscesses and nonspecific inflammation of the lamina propria may be observed. In severe disease, glandular atrophy, focal intestinal metaplasia, and severe mucosal denudation may occur.
In eosinophilic gastritis, the mucosa shows intense patchy infiltration by numerous eosinophils, with occasional pit abscesses. The infiltrate typically contains 10-50 eosinophils per high-power field, as well as plasma cells. Mucosal edema, congestion, and necrosis of the surface epithelium with small erosions may be present. Mucosal infiltration by a bandlike eosinophil infiltrate in the lower portion of the lamina propria above the muscularis mucosa characterizes eosinophilic gastroenteritis associated with connective tissue disorders.
In lymphocytic gastritis, the lamina propria and pit epithelium are infiltrated by large numbers of small mature T lymphocytes. Abundant T lymphocytes typically permeate the surface epithelium. A diagnosis can be rendered when 30 or more lymphocytes are observed per 100 consecutive epithelial cells, and performing the counts in biopsies from the gastric corpus is recommended.
In chemical gastropathy, the changes are more prominent in the prepyloric region but may extend to involve the oxyntic mucosa. Histologic changes associated with chronic bile reflux and long-term nonsteroidal anti-inflammatory drug (NSAID) intake include mucosal edema, congestion, fibromuscular hyperplasia in the lamina propria, and pit or foveolar hyperplasia that may create a corkscrew pattern. Cellular proliferation is associated with reactive nuclear features and epithelial reduction of mucin. Epithelial changes occur with a paucity of inflammatory cells.
In radiation gastritis, radiation causes degenerative changes in the epithelial cells and a nonspecific chronic inflammatory infiltrate in the lamina propria. These changes are reversible in a period of a few months. Higher amounts of radiation cause permanent mucosal damage, with atrophy of the fundic glands, mucosal erosions, and capillary hemorrhage. Associated submucosal endarteritis results in mucosal ischemia and secondary ulcer development.
In ischemic gastritis, chronic ischemia may produce superficial erosions and, rarely, deep ulcers. Inflammatory changes are observed in the context of ulcer repair. Ischemic ulcers are more frequently antral and are often surrounded by multiple erosions.
Idiopathic granulomatous gastritis demonstrates histopathology similar to sarcoid involvement of the stomach. Antral narrowing caused by transmural, noncaseating, granulomatous inflammation occurs. Inflammation and fibrosis are usually limited to the mucosa. Idiopathic granulomatous gastritis may represent isolated or limited forms of gastric sarcoid or Crohn disease.
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Helicobacter pylori–caused chronic active gastritis. Genta stain (×20). Multiple organisms (brown) are visibly adherent to gastric surface epithelial cells.
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Chronic gastritis associated with Helicobacter pylori infection. Numerous plasma cells are present in the lamina propria.
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Granulomatous chronic gastritis. Noncaseating granulomas in the lamina propria. Image courtesy of Sydney Finkelstein, MD, PhD, University of Pittsburgh.
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Chronic gastritis. Mycobacterium avium-intracellulare in the gastric lamina propria macrophages. Image courtesy of Sydney Finkelstein, MD, PhD, University of Pittsburgh.
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Chronic gastritis. Typical cytomegalovirus inclusions in the lamina propria capillary endothelial cells. Image courtesy of Sydney Finkelstein, MD, PhD, University of Pittsburgh.
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Chronic gastritis. Chemical gastropathy. Image courtesy of Sydney Finkelstein, MD, PhD, University of Pittsburgh.
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Lymphocytic chronic gastritis. Gastric epithelium is studded with numerous lymphocytes (left). Intraepithelial lymphocytes are T-cell lymphocytes shown by immunoreactivity to CD3 (brown stain, right).
