Non-Neoplastic Disorders of the Stomach

Acute Erosive/Hemorrhagic Gastritis (“Stress” Gastritis)

Acute erosive/hemorrhagic gastritis is the result of severe and often acute mucosal injury. It is commonly associated with abrupt onset of abdominal pain and mucosal bleeding. Common causes include alcohol, steroids, nonsteroidal antiinflammatory drugs (NSAIDs), various iatrogenic injuries, and low hemodynamic state after major trauma.

The pathogenesis of acute hemorrhagic gastritis reflects an imbalance between mucosal irritants such as acid, pepsin, bile salts, NSAIDs, and other chemicals and mucoprotective mechanisms such as mucin, bicarbonates, prostaglandins, epidermal growth factors, mucosal blood flow, and the remarkable ability of gastric mucosa to reepithelialize. Various mechanisms can be at play to damage the mucosa (Box 3.1):

Clinical Features

Patients commonly present with abrupt onset of burning epigastric pain, nausea, vomiting, and gastrointestinal (GI) bleeding. The bleeding can be minimal occult bleeding, self-resolving melena, or life-threatening hematemesis. Patients with aspirin- or alcohol-induced injury usually make a quick recovery, whereas hypoperfusion-related gastritis (stress ulcers) is associated with greater morbidity and mortality. Acute erosive gastropathy is a common cause of upper GI bleeding and accounts for 6% to 34% of cases.

Pathologic Features

Gross Findings

The gastric erosions are multiple, 2 to 5 mm in diameter, superficial, round, and dark. The intervening mucosa is edematous and hyperemic with petechial hemorrhage.

Stress-related ulcers are mostly located in the fundus and body, whereas NSAID-related erosions are present in the antrum.

Microscopic Findings

Acute damage presents as mucosal denudation and sloughing, surface hemorrhage, or fibrin exudate with neutrophils, epithelial necrosis, and lack of significant lymphoplasmacytic infiltration in the lamina propria ( Fig. 3.1 ). Mucosal damage ranges from gastric erosions limited to the mucosa to deep ulcers that extend beyond the submucosa. Etiologically specific changes may sometimes be seen ( Figs. 3.2 to 3.4 ). Mucosal healing is associated with regenerative epithelial changes with enlarged hyperchromatic nuclei with prominentf nucleoli, amphophilic cytoplasm, and sometimes syncytial glandular architecture with increased mitotic activity ( Figs. 3.5 and 3.6 ). These changes can be alarming and may be mistaken for dysplasia or adenocarcinoma. The presence of an overlying ulcer or erosion with active fibrin and neutrophilic exudate should caution against making a diagnosis of malignancy.

Reactive (Chemical) Gastropathy

Reactive gastropathy is the result of surface mucosal damage induced by bile, medications, or chemical agents. It is a histologic diagnosis characterized by surface mucin depletion, foveolar hyperplasia, regenerative epithelial changes, smooth muscle proliferation in the lamina propria, and vascular congestion of the gastric mucosa. The lamina propria does not typically show an increase in lymphoplasmacytic infiltrate. Reactive gastropathy is synonymous with type C gastritis, chemical gastropathy , and alkaline or bile reflux gastritis .

Clinical Features

Reactive gastropathy is one of the most common diagnosis rendered in gastric biopsies. It is commonly asymptomatic; however, some patients report vague upper abdominal pain, nausea, and vomiting. The mean age at presentation is 66 years (range, 22–88 years), without any gender predilection. Common causes include chronic aspirin or other NSAID use and various medications (e.g., ferrous sulfate), bile reflux after gastroenterostomies, vagotomy, and pyloroplasty. In nonsurgical patients, bile reflux may be caused by an incompetent pyloric sphincter or gastric dysmotility. Other putative causes include alcohol intake and smoking.

Pathologic Features

Gross and Endoscopic Findings

The endoscopy may be normal or display nonspecific findings, including erythema and localized erosions. Visible gastric bile staining on endoscopic examination can be helpful in the diagnosis.

Microscopic Findings

The mucosa shows marked surface mucin depletion accompanied by foveolar hyperplasia, which is characterized villiform change, elongation, and tortuosity of gastric pits with a corkscrew appearance ( Fig. 3.7 ). The lamina propria shows smooth muscle proliferation and vascular congestion. There is typically a paucity of inflammatory cells in the lamina propria, hence the term gastropathy instead of gastritis . Focal erosions may be associated with small clusters of neutrophils and eosinophils but are restricted to the foci of injured mucosa, and diffuse lamina propria infiltrate is not seen. The changes are commonly limited to the antrum, whereas the oxyntic mucosa occasionally may occasionally show subtle reactive changes limited to the surface with separation of the surface foveolar epithelium from the glandular compartment. Reactive gastropathy may also be, at times, associated with intestinal metaplasia in cases with recurrent injury over a long period. Bile reflux gastropathy after Billroth I to II surgery with antrectomy is present in the body. Findings of histochemical or immunostains for H. pylori are negative.

Reactive (Chemical) Gastropathy—Pathologic Features

Endoscopic Findings

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  Can be normal or show erythema, typically in the gastric antrum

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  Visible bile reflux on endoscopic examination or erosions may also be seen

Microscopic Findings

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  Changes are commonly in the antrum and prepyloric area

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  Marked foveolar hyperplasia characterized by villiform change of the surface foveolae and elongation and corkscrew tortuosity of the gastric pits

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  Surface mucin depletion leads to high nuclear-to-cytoplasmic ratio that may be mistaken for dysplasia

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  Smooth muscle proliferation and vascular congestion in the lamina propria

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  Paucity of inflammatory cells; focal erosions may be associated with neutrophils and eosinophils limited to the injured focus

Ancillary Studies

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  Stains for H. pylori are negative

Differential Diagnosis

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  Hyperplastic polyp

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  Gastric antral vascular ectasia

Helicobacter pylori Gastritis

H. pylori gastritis is a chronic infectious form of gastritis caused by spiral, flagellated gram-negative rods and characterized by a diffuse chronic active gastritis.

Clinical Features

T he prevalence of infection varies worldwide, and most people acquire infection during childhood. Transmission of infection is human to human, with poor sanitary conditions and overcrowding being risk factors. It is more prevalent in developing countries, where up to 75% of the population older than 25 years of age is infected. In developed countries, the overall prevalence is 25% to 30%, and the seroprevalence ranges from 5% to 27% in early childhood to 50% to 60% in adults older than 60 years of age. Currently, despite a decrease of infection worldwide, at least 50% of the world’s population is actively infected. In the United States, African Americans, Asian Americans, and Hispanics have a higher prevalence (70%) than whites (35%).

H. pylori is a 3.5-µm-long, microaerophilic gram-negative rod with S-shaped or seagull wing appearance that appears comma or spiral shaped on routine or special stains. This organism has a tropism for gastric mucosa or gastric metaplasia in the duodenum. The pathogenesis depends on its ability to colonize gastric epithelium via adhesins such as BabA, SabA, urease and virulence factors such as Cag A, Vac A, and urease, which in turn generates cytokines such as interleukin-8 to attract neutrophils.

The majority of infected patients carry and transmit H. pylori without any symptoms or are mildly symptomatic. Other patients may develop moderate to severe symptoms of abdominal pain, nausea, vomiting, dyspepsia, weight loss, and iron-deficiency anemia. The recognition of the Helicobacter organism and its association with peptic ulcer disease, gastric mucosa–associated lymphoid tissue (MALT) lymphoma, and carcinoma has revolutionized modern understanding of disease processes and influenced patient management. The World Health Organization has classified H. pylori as a group I human carcinogen of gastric cancer. Infected persons have a three- to sixfold greater risk of developing gastric cancer over that of uninfected persons. Australian researchers Robin Warren, a pathologist, and Barry Marshall, a gastroenterologist, became the recipients of the Nobel Prize in 2005 for this significant discovery. Noninvasive and invasive tissue-based, serologic, and stool tests for diagnosis of H. pylori infection have been developed and are summarized in Table 3.1 .

Pathologic Features

Gross Findings

Endoscopic findings are variable and include mucosal erythema, erosions, granularity, and nodularity. Gastric and duodenal ulcers may be present in severe cases. Mucosal nodularity may be prominent in cases associated with marked lymphoid hyperplasia or MALT lymphoma. In rare instances, the mucosa may appear completely normal. For optimal evaluation, at least two mucosal biopsy specimens, one each from the antrum and body, are recommended. Sampling of a single site may reduce the test sensitivity. The Sydney system and the Operative Link for Gastritis Assessment (OLGA) staging system have been proposed for systematic reporting of gastritis but are seldom followed in the West.

Microscopic Findings

H. pylori typically presents as a chronic active gastritis of variable severity. The infection can be antrum predominant or a pangastritis at initial presentation. Posttreatment cases may show persistence of infection in the gastric corpus or cardia with resolution of inflammation and lack of organisms in the distal stomach.

In involved regions, the superficial lamina propria shows a diffuse bandlike mononuclear infiltrate of lymphocytes and plasma cells along with activated lymphoid follicles with germinal centers ( Fig. 3.8 ). The term follicular gastritis has been used in the past for cases with prominent lymphoid aggregates ( Fig. 3.9 ). Various degrees of neutrophilic infiltrate, reported as evidence of activity, may be seen in the surface epithelium and gastric pits and crypt abscesses ( Fig. 3.10 ). A pattern of lymphocytic gastritis can also be seen with H. pylori infection. Severe cases with ulcers may show regenerative foveolar hyperplasia, and intestinal metaplasia is already present in a subset of patients at first diagnosis.

The organisms appear as slightly curved seagull wing–shaped rods, clustered in the gastric mucus, adherent to the gastric surface foveolar epithelium, or deep in the gastric pits. When abundant, the organisms are easily visible on H&E, but special stains (e.g., Giemsa, silver stains) and immunohistochemistry can aid in their detection ( Fig. 3.11 ) when the density is low or posttreatment change has transformed the typical spiral shape of the organisms into a more coccoid appearance. Table 3.2 highlights other manifestations that may be attributed to H. pylori infection. A pattern of chronic inactive gastritis with residual mononuclear cell infiltration in the lamina propria but without any foci of neutrophilic infiltration may be seen in biopsies obtained soon after treatment with antibiotics ( Fig. 3.12 ). The pattern is not etiologically specific, and organisms are usually absent in posttreatment biopsies. The only way to establish the diagnosis is by correlating findings with patient history.

Helicobacter Pylori Gastritis—Pathologic Features

Gross Findings

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  Gastric mucosal erythema, erosions, granularity, and nodularity

Microscopic Findings

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  For optimal evaluation, two mucosal biopsies from both the antrum and body are recommended

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  Chronic active gastritis with marked lymphoplasmacytic inflammation and variable neutrophilic infiltration and prominent lymphoid aggregates

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  The inflammation is predominantly in the superficial mucosa

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  Active (or neutrophilic) inflammation, a marker for the presence of Helicobacter organisms, is prominent in the gastric pits, causing pititis

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  Foveolar hyperplasia, erosion, hemorrhage, reactive epithelial changes, and in severe cases, mucosal erosion and ulceration

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  Mucosal atrophy and intestinal metaplasia may be present

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  Helicobacter pylori appear as slightly curved seagull wing–shaped rods, most prominent in the gastric mucus and the lining surface foveolar epithelium and also in gastric pits

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  The organisms can be visible on hematoxylin and eosin stain, especially when numerous, but ancillary stains can be used in selected situations discussed next

Ancillary Studies

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  Histochemical stains: modified Giemsa, Diff-Quik, Warthin-Starry, Genta stain, and Alcian yellow have all been used in the past

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  Immunohistochemistry for Helicobacter is often used in current practice when:

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    Organisms are not seen on hematoxylin and eosin despite the presence of a chronic gastritis reminiscent of H. pylori infection

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    In posttreatment biopsies when the density of organisms is low and they have transformed into a coccoid appearance

Differential Diagnosis

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  Helicobacter heilmannii gastritis

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  Gastric marginal zone B-cell lymphoma

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  Focally enhanced gastritis

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  Autoimmune gastritis

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  Non– H. pylori infectious gastritis

Table 3.2

Histologic Manifestations Indicative of Present or Past Helicobacter pylori Infection

Acute Helicobacter gastritis	Acute manifestation at the time of initial acquisition of the infection. It almost never comes to medical attention and therefore is not biopsied. Best evidence came from Dr. Marshall himself, who drank from a Petri dish containing the organisms from the culture of a patient with H. pylori infection and had acute gastritis with nausea, vomiting, and halitosis.
Chronic active gastritis	Neutrophilic inflammation within the epithelium, most prominent in gastric pits accompanied by diffuse lymphoplasmacytic infiltrate in the lamina propria.
Chronic inactive gastritis	Characterized by clusters of plasma cells in the lamina propria (see Fig. 3.14 ); lacks active inflammation and may reflect past Helicobacter infection.
Lymphocytic gastritis	Lymphocytic gastritis contains prominent intraepithelial lymphocytosis.
Hyperplastic polyp	May be a marker of H. pylori infection in the nonpolypoid gastric mucosa in a subset of cases.
Environmental atrophic metaplastic gastritis (EMAG), multifocal atrophic gastritis, or type B gastritis	H. pylori is an important cause of EMAG, a precursor to gastric dysplasia and carcinoma. Characterized by gradual loss of normal glands and multifocal intestinal metaplasia, predominantly in the gastric antrum but may also present in the body and cardia. Unlike autoimmune gastritis, the gastrin level in EMAG is either low or normal. The antrum is normal in autoimmune gastritis, which is not the case in EMAG.

Differential Diagnosis

Helicobacter heilmannii gastritis (Gastrospirillum hominis) is responsible for approximately 0.3% of the cases of Helicobacter gastritis. It is caused by a tight spiral bacterium that is 5 to 6 μm in length, which is longer than H. pylori ( Fig. 3.13A and 3.13B ). It is also seen in cats and dogs, and the disease in humans may be a zoonotic infection. They can be seen on H&E examination easily because of their large size and are present in the gastric mucus and lumen of gastric pits without coming in close contact with the epithelium. Immunostain for H. pylori also stains H. heilmannii ( Fig. 3.13C ). H. heilmannii infection has been associated with the development of marginal zone B-cell lymphoma but not with gastric cancer.

The florid lymphoid hyperplasia in Helicobacter gastritis can be mistaken for low-grade extranodal marginal zone B-cell lymphoma. However, marginal zone B-cell lymphoma is characterized by aggregates or sheets of monomorphic B cells with destructive lymphoepithelial lesions. The neoplastic lymphoid cells in marginal zone B-cell lymphoma may show aberrant coexpression of CD20 and CD43 and light chain restriction. The intraepithelial lymphocytes in Helicobacter gastritis are mostly CD3-positive T lymphocytes, unlike the CD20-positive neoplastic B-cells in gastric marginal zone B-cell lymphoma. A clonal population of lymphoid cells may be seen in Helicobacter gastritis, and a diagnosis of lymphoma should not be based on molecular studies alone (see details in Chapter 19 ).

Focally enhanced gastritis is typically associated with Crohn’s disease, medication-induced mucosal injury, and the resolving phase of gastric erosions. The biopsy shows a localized increase in lymphoplasmacytic inflammation with neutrophilic infiltration into the epithelium and a cuff of loose histiocytic aggregates around damaged gastric pits.

Autoimmune gastritis typically involves the oxyntic mucosa and shows atrophy with marked reduction in oxyntic glands, pyloric gland and intestinal metaplasia, and enterochromaffin-like (ECL) hyperplasia. The latter feature shows a spectrum of linear to micronodular to adenomatoid hyperplasia culminating in well-differentiated neuroendocrine tumors. The presence of micronodular hyperplasia is helpful in differentiating autoimmune gastritis from H. pylori gastritis. Antibodies to intrinsic factor and parietal cells are diagnostic and lead to hypochlorhydria, vitamin B ₁₂ deficiency, and hypergastrinemia. Hypergastrinemia can also occur in H. pylori gastritis but not to the extent seen in autoimmune gastritis.

A variety of other bacterial, viral, fungal, and parasitic infections may rarely involve the stomach and must be excluded when the mucosa is inflamed and Helicobacter organisms are not identified.

Gastric Peptic Ulcer Disease

Peptic ulcer disease is a clinical term used for patients with discrete ulcers in the stomach or duodenum, most often in association with H. pylori gastritis or NSAID use.

Clinical Features

The incidence of gastric peptic ulcer disease has been decreasing since the 1980s. Common locations are stomach and proximal duodenum, with a mean age of 40 years and 20 years, respectively. Symptoms include severe epigastric pain exacerbated by food intake, in contrast to duodenal ulcer pain, which is relieved by food intake. In addition, vomiting, weight loss, hematemesis, melena, and gastric outlet obstruction can be caused by scarring and pyloric stenosis. Peritonitis can develop after perforation. NSAID ulcers are on the rise as the prevalence of H. pylori infection is declining. Certain medications, such as steroids, can also contribute to ulcer development. Other rare causes of peptic ulcers include ZES and multiple endocrine neoplasia type I (MEN-I).

Pathologic Features

Gross Findings

Gastric ulcers are variably sized and usually present in the lesser curvature, round to oval in shape with a smooth base and regular, perpendicular edges ( Fig. 3.14 ), unlike the irregular heaped-up borders of malignant ulcers.

Microscopic Findings

Histologically, mucosal defects are seen extending below the muscularis mucosae with extension into the submucosa and muscularis propria in severe cases. Early ulcers are associated with fibrin, necrosis, inflammation, and granulation tissue reaction. Chronic ulcers are associated with scarring and stenosis ( Fig. 3.15 ).

Autoimmune Gastritis

Autoimmune gastritis is an immune-mediated destruction of the oxyntic glands caused by antiparietal cell antibodies. Patients also have antibodies to intrinsic factor, and loss of oxyntic glands leads to hypochlorhydria, vitamin B ₁₂ deficiency, and endocrine ECL cell hyperplasia. Type A gastritis, diffuse corporal atrophic gastritis , and autoimmune metaplastic atrophic gastritis are all terms used for autoimmune gastritis in the past.

Clinical Features

Autoimmune gastritis affects nearly 2% of the population older than 60 years old and is responsible for approximately 4% of cases of chronic gastritis. It was classically described in individuals of northern European or Scandinavian descent but is now known to be equally represented in African Americans and Latin Americans. White women in the fifth to sixth decade of life are affected three times more commonly than men. Patients may be asymptomatic or present with abdominal pain, weight loss, diarrhea, malabsorption, and neurologic complications, such as peripheral neuropathy and subacute combined degeneration of the spinal cord, related to severe vitamin B ₁₂ deficiency. The antiparietal cell antibodies that target H ⁺ /K ⁺ -ATPase proton pump are present in 60% to 85%, and anti-intrinsic factor antibodies are identified in 30% to 50% of patients ( Table 3.3 ). Reduced gastric acid plays a role in iron deficiency in 20% to 40% of cases because gastric acid is necessary to release iron bound to proteins and to reduce ferric iron to ferrous state for absorption. Pernicious anemia is present in 15% to 25% of patients and is characterized by macrocytosis, megaloblastic anemia, pancytopenia, atrophic glossitis, low serum B ₁₂ concentration, and normal folate level. This is a late manifestation of autoimmune gastritis, taking 20 to 30 years to develop, and is caused by progressive loss of parietal cells, which are necessary for intrinsic factor production. Concomitant autoimmune disorders such as insulin-dependent diabetes mellitus, Hashimoto’s thyroid-itis, adrenal insufficiency, Graves’ disease, vitiligo, or myasthenia gravis can also be seen in patients with autoimmune gastritis.

Pathologic Features

Gross Findings

Autoimmune gastritis affects the oxyntic mucosa and spares the antrum in the vast majority of cases. On endoscopic examination, the body or fundic mucosa appears flat and congested with a prominent submucosal vascular pattern caused by mucosal atrophy. Multiple small mucosal elevations or pseudopolyps, representing preserved islands of oxyntic mucosa surrounded by flattened atrophic mucosa, may be seen. Other polypoid lesions in autoimmune gastritis include hyperplastic polyps (most common), pyloric adenomas, well-differentiated neuroendocrine tumors, and dysplastic lesions or adenocarcinoma.

Microscopic Findings

The histologic findings are limited to the oxyntic mucosa lining the gastric corpus. The antrum is normal in the vast majority of cases. The corpus mucosa shows a chronic gastritis with prominent lymphocytic and plasma cell infiltration that is more prominent in the deep aspect of lamina propria. There is a variable loss of oxyntic glands depending on stage of the disease and manifests as atrophy, pyloric gland metaplasia, and intestinal metaplasia with goblet and Paneth cells ( Fig. 3.16A ). Pancreatic acinar metaplasia may also be present.

The gastric atrophy leads to hypergastrinemia, which acts as a trophic signal to the ECL cells in the gastric corpus. This results in a unique hyperplasia to neoplasia continuum culminating in the development of well-differentiated neuroendocrine tumors. Linear, micronodular, adenomatoid hyperplasia and dysplastic nodular lesions have been described, but this subclassification is seldom used in daily practice other than using the presence of neuroendocrine cell hyperplasia to render a diagnosis of autoimmune gastritis. Expansile nodules greater than 0.5 mm or lesions infiltrative into the muscularis mucosa or submucosa are designated as well-differentiated neuroendocrine tumor.

An atrophic corpus in the late stages of the disease can resemble the antrum and the diagnosis can be easily missed when antrum and corpus biopsies are submitted in the same container, a common practice in many parts of the world. Immunostains for gastrin and chromogranin can aid in establishing the diagnosis. Therefore, the presence of a patchy chronic gastritis or intestinal metaplasia restricted to corpus biopsies in the setting of a negative H. pylori immunostain should always lead to work-up for autoimmune gastritis in gastric biopsies.

The antral mucosa may show only limited changes including foveolar hyperplasia or mild chronic inflammation. Furthermore, the low-acid state created by the loss of parietal cells stimulates antral gastrin cell hyperplasia presenting as increased density of gastrin-positive G cells in the gastric pits. Extremely rare cases of an autoimmune pangastritis with antral involvement have also been reported.

Other associated findings in autoimmune gastritis include gastric hyperplastic polyps, pyloric gland adenomas, well-differentiated neuroendocrine tumors of variable size, and gastric dysplasia and adenocarcinoma.

Autoimmune Gastritis—Pathologic Features

Gross Findings

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  Involves the gastric body and fundus and spares the antrum

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  Effacement of rugal folds and prominent submucosal vascular pattern in gastric corpus caused by glandular atrophy

Microscopic Findings

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  Chronic gastritis with prominent lamina propria lymphocytic and plasma cell infiltration, often prominent within the deep lamina propria

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  Loss of specialized glandular epithelium (atrophy) in the gastric corpus

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  Pyloric gland metaplasia, intestinal metaplasia, and linear or micronodular enterochromaffin-like (ECL) hyperplasia is characteristic

Immunohistochemical Features

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  Gastrin and chromogranin A can be used to demonstrate ECL-cell hyperplasia when antrum and corpus biopsies are submitted together in the same container

Differential Diagnosis

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  Helicobacter pylori gastritis

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  Lymphocytic and collagenous gastritis

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  Infectious gastritis, other than H. pylori

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  Pernicious anemia associated with autoimmune polyglandular syndrome

Immunohistochemistry

Gastrin and chromogranin immunohistochemical stains are helpful, especially when the gastroenterologist places multiple biopsies in the same container or if the specimen site is unspecified ( Fig. 3.16B–D ). The neuroendocrine ECL cell hyperplasia stains positive with chromogranin but is negative for gastrin, confirming the corpus-restricted nature of the disease. The gastrin immunostain highlights normal G cells in the gastric antral fragments ( Fig. 3.17 ). H. pylori immunostain is usually negative.

Granulomatous Gastritis

Granulomatous gastritis is an uncommon form of gastritis, comprising 0.27% to 0.35% of all gastritides. It encompasses a wide spectrum of diseases that lead to the development of mucosal or submucosal granulomas as the defining histologic feature. The types of granulomas vary widely from discrete nodular circumscribed collection of epithelioid histiocytes, reminiscent of sarcoidosis, to those admixed with lymphocytes, eosinophils, and even neutrophils, with or without giant cells, to others with prominent central necrosis and a lymphoid cuff similar to necrotizing granulomas seen in Mycobacterium tuberculosis infection. Notably, determining the underlying cause usually requires correlation with the clinical, radiologic, endoscopic, and microbiological findings and sometimes the response to treatment ( Table 3.5 ). When a granuloma is seen on H&E examination, additional studies such as the use of polarized light to rule out presence of foreign body and special stains such as acid-fast bacilli, Gomori methenamine silver, and periodic acid–Schiff (PAS) are obligatory parts of the diagnostic assessment. A controversial diagnosis of idiopathic granulomatous gastritis has been reported in the literature to define patients with large and compact granulomas limited to the stomach and after exclusion of known entities such as Crohn’s disease and sarcoidosis. Some authors have linked these granulomas to an inflammatory response to H. pylori infection after reporting the disappearance of the granulomas following successful eradication of the bacteria. Other authors have found an association with vasculitis.

Gastric Crohn’s Disease

Approximately 30% to 50% of patients with Crohn’s disease have upper GI manifestations. Patients with both small and large bowel involvement are more likely to have upper GI involvement. Patients are usually younger and often belong to the pediatric age group. Patients may present with symptoms of abdominal pain, nausea, and vomiting, often combined with lower GI symptoms such as chronic diarrhea and weight loss. In the West, Crohn’s disease accounts for 17% to 55% of all cases with granulomatous gastritis.

Endoscopically, the mucosal appearance is quite variable and ranges from completely normal mucosa to findings that include erythema, erosions or ulcers, nodules, thickened folds (so-called bamboo stomach), and even gastric outlet stenosis. Findings are usually predominant in the antrum.

The finding of granulomas is helpful in establishing the diagnosis of Crohn’s disease in the appropriate clinical setting. However, granulomas are present in only 7% to 34% of cases. Crohn’s granulomas usually consist of small clusters of epithelioid histiocytes. Notably, granulomas can also be detected in apparently normal mucosa, thus emphasizing the importance of sampling.

More commonly, the gastric involvement in patients with Crohn’s disease may show a spectrum of inflammatory changes that range from focally enhanced gastritis to a patchy or diffuse chronic active gastritis of variable severity ( Fig. 3.18 ). Focally enhanced gastritis is a patchy inflammatory process composed of inflamed gastric pits surrounded by a cuff of loose lymphohistiocytic aggregates ( Fig. 3.19 ). Focally enhanced gastritis, particularly in adults, can also be associated with drug-induced mucosal injury, graft-versus-host disease, or incompletely treated H. pylori gastritis.

Gastric Sarcoidosis

Sarcoidosis is a systemic granulomatous disorder that commonly affects the lungs and hilar lymph nodes. It usually affects young adults and is more common in African Americans. Gastric antral involvement can be seen in 10% of patients with systemic disease.

The gastric mucosa may be macroscopically nodular ( Fig. 3.20 ) with ulcers, thickening, and a segmental linitis plastica–like appearance. Gastric outlet obstruction and bleeding have been reported.

Compact noncaseating granulomas ( Figs. 3.21 ) are seen in gastric sarcoidosis, which is a diagnosis of exclusion and confirmed by correlation with clinical and imaging findings. Patients often respond to steroid therapy.

Lymphocytic Gastritis

Lymphocytic gastritis is an uncommon form of chronic gastritis characterized by marked intraepithelial lymphocytosis in the gastric surface and pit epithelium; the glandular compartment is often spared. Lymphocytic gastritis is synonymous with varioliform gastritis , which refers to the endoscopic appearance and with chronic erosive verrucous gastritis.