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Acute erosive/hemorrhagic gastritis (stress gastritis)
Acute erosive/hemorrhagic gastritis is characterized by an acute gastric injury with an abrupt onset of abdominal pain and bleeding, usually associated with intake of alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), or low hemodynamic state following major trauma, presenting with multiple superficial erosions in the gastric mucosa and histologically characterized by hemorrhage, mucosal defect, and superficial necrosis ( Fig. 3-1 ).
Clinical features
Patients present with abrupt onset of abdominal pain (burning epigastric pain), nausea, vomiting, and gastrointestinal (GI) bleeding with melena, hematemesis, or occult bleeding. Bleeding can be minimal and self-resolving or life threatening. Box 3-1 lists various etiologic agents ( Figs. 3-2 through 3-6 ). 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. Studies have found acute erosive gastropathy as the cause of upper GI bleeding in 6% to 34% of cases; the other important causes of bleeding are peptic ulcer disease, esophageal varices, and Mallory-Weiss tear. Although more often affecting older patients, the reported age range is 29 to 87 years.
- ■
Aspirin, nonsteroidal anti-inflammatory drugs
- ■
Steroids
- ■
Alcohol (see Fig. 3-2 )
- ■
Potassium chloride
- ■
Phenylbutazone
- ■
Iron pills ( Fig. 3-3 )
- ■
Colchicine
- ■
Sodium polystyrene sulfonate (Kayexalate) in sorbitol (see Figs. 3-4 and 3-5 )
- ■
Cocaine, “crack”
- ■
Corrosives, acid and alkali ingestion
- ■
Radiation (see Fig. 3-6 )
- ■
Chemotherapy
- ■
Hypoperfusion type injury
- ■
Major trauma, stress ulcers
- ■
Head injury, Cushing ulcer
- ■
Severe burn, Curling ulcer
- ■
Sepsis, postoperative stage
The pathogenesis of acute hemorrhagic gastritis reflects an imbalance between mucosal irritants such as acid, pepsin, bile salts, NSAIDs, and other chemicals versus mucoprotective factors such as mucin, bicarbonates, prostaglandins, epidermal growth factors, mucosal blood flow, and the remarkable ability of gastric mucosa to re-epithelialize.
- 1.
Direct irritant action of chemical agents such as NSAIDs and alcohol resulting in mucosal erosion, necrosis, and hemorrhage.
- 2.
Additional injury by acid, pepsin, and bile salts that gain entry resulting from the disrupted mucosal barrier.
- 3.
NSAIDs with their cyclo-oxygenase–inhibiting action inhibit prostaglandins, which in turn reduces bicarbonate and mucin secretions that have protective roles on the mucosal surface.
- 4.
In cases of hypoperfusion-related stress ulcers, the pathogenesis is related to reduced gastric mucosal blood flow, vasoconstriction, and reperfusion injury with release of free oxygen radicals.
Definition
- ■
Abrupt onset of abdominal pain and bleeding associated with intake of alcohol, NSAIDs, or low hemodynamic state following major trauma, and presenting with multiple erosions in the gastric mucosa
Morbidity and mortality
- ■
Bleeding can be minimal and self-resolving or life-threatening.
- ■
Patients with comorbid condition such as liver disease have higher morbidity and mortality rates.
Gender, race, and age
- ■
Patients are mostly older: age range, 29 to 87 years.
Clinical features
- ■
Abrupt onset of abdominal pain, vomiting, and GI bleeding
Prognosis and therapy
- ■
Most cases have an uneventful course with full recovery within a short period
- ■
Intravenous fluids and blood transfusion
- ■
Stop the offending agent
- ■
H 2 blockers, proton pump inhibitors, prostaglandin analogues
- ■
Fatal bleeding may require surgical intervention
Pathologic features
Gross and endoscopic findings
Endoscopic examination has superseded radiologic tests in diagnosis and management. Stress-related ulcers are mostly distributed in the fundus and body, whereas NSAID-related erosive gastropathy is present in the antrum. 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.
Microscopic findings
Histologic findings may or may not be impressive owing mostly to the remarkable capacity of stomach mucosa to re-epithelialize. Hence, depending on the interval of the gastritis with the endoscopic biopsy, histologic changes range from subepithelial hemorrhage/superficial lamina propria hemorrhage, mucosal sloughing and necrosis, to neutrophil infiltration. Gastric erosions are limited to the mucosa and do not extend beyond the muscularis mucosae. Gastric ulcers, on the other hand, are deep, with extension beyond the submucosa. The healing phase is associated with regenerative epithelium with increased mitotic activity, dark enlarged nuclei with prominent nucleoli, amphophilic cytoplasm (a feature of active RNA synthesis), and syncytial glandular architecture ( Fig. 3-7 ). These changes can be alarming and should not be mistaken for malignancy. The presence of superimposed ulcer or erosion with active neutrophilic exudates is a feature that should caution against making a diagnosis of malignancy.
Gross findings
- ■
Stress-related ulcers are present in the fundus and body
- ■
NSAID-related erosions are present in the antrum
- ■
Multiple superficial, round, dark erosions, few millimeters in diameter
- ■
The intervening gastric mucosa is edematous and hyperemic
Microscopic findings
- ■
Histologic findings depend on the biopsy interval
- ■
Superficial lamina propria hemorrhage, mucosal sloughing, neutrophil infiltration, and mucosal necrosis.
- ■
Changes limited to the mucosa
- ■
The healing phase is associated with regenerative epithelium with dark enlarged nuclei with prominent nucleoli, and syncytial glandular architecture
- ■
These changes should not be mistaken for malignancy
Differential diagnosis
- ■
Mallory-Weiss tear, peptic ulcers, esophageal variceal bleeding
- ■
Nasogastric tube trauma
- ■
Chronic active Helicobacter pylori gastritis
- ■
Dysplasia, intramucosal carcinoma
- ■
Chemical gastropathy
- ■
Biopsy forceps trauma (artifact)
Differential diagnosis
- •
Mallory-Weiss tear, peptic ulcers, esophageal variceal bleeding: clinical differentials of upper GI bleeding.
- •
Trauma related to nasogastric tube.
- •
Chronic active Helicobacter pylori gastritis: Onset is not acute as the name suggests. Associated with superficial diffuse lymphoplasmacytic inflammation with neutrophilic cryptitis. Modified Giemsa stain highlights the organisms.
- •
Dysplasia, intramucosal carcinoma: True dysplastic change is present on the surface with nuclear stratification, hyperchromasia, and increased mitoses. There may be intestinal metaplasia in the surrounding mucosa. Regenerative epithelial change is present in a setting of erosion/ulcers, and the features are limited to deeper areas with presence of surface maturation. The regenerative epithelial cells have abundant amphophilic cytoplasm, prominent nucleoli, and smooth nuclear membrane.
- •
Chemical gastropathy: chronic change associated with bile reflux, NSAIDs with mucosal elongation, smooth muscle hyperplasia in the lamina propria, and regenerative change.
- •
Biopsy forceps trauma: commonly seen in mucosal biopsies and should not be mistaken for acute hemorrhagic gastropathy. Histologically characterized by superficial lamina propria congestion without signs of injury or significant inflammation.
Prognosis and therapy
Most patients make an uneventful recovery within a short time period. Depending on the hemodynamic state, management consists of supportive measures such as intravenous fluids and blood transfusion; stopping the offending agent, H 2 blockers, proton pump inhibitors (PPIs), prostaglandin analogues, and so forth. In cases of life-threatening bleeding, surgical intervention may be necessary.
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Chemical (reactive) gastropathy
Chemical gastropathy is a chemical-induced damage characterized by foveolar hyperplasia, regenerative epithelial changes, smooth muscle proliferation in the lamina propria, and vascular congestion of the gastric antral mucosa. Chemical gastropathy is synonymous with type C gastritis, reactive gastritis, reactive gastropathy, and alkaline or bile reflux gastritis.
Clinical features
Chemical gastropathy is a fairly common diagnostic entity in gastric biopsies. Symptoms range from vague upper abdominal pain to nausea, vomiting, gastroduodenal erosions or ulcers, and GI bleeding. Mean age is 66 years (range, 22 to 88 years), and both sexes show equal predilection. Etiologies include chronic aspirin or other NSAID use, bile reflux following gastroenterostomies, vagotomy, and pyloroplasty. In nonsurgical patients, bile reflux may be due to an incompetent pyloric sphincter or gastric dysmotility. Other putative causes include alcohol intake and smoking. The pattern of injury in chemical gastropathy reflects chronic repetitive bouts of injury followed by attempts at regeneration and repair.
Definition
- ■
Chemical-induced damage of the gastric antral mucosa characterized by foveolar hyperplasia, regenerative epithelial changes, smooth muscle proliferation in the lamina propria, and vascular congestion
Morbidity and mortality
- ■
May cause GI bleeding and ulcers
Gender, race, and age
- ■
Mean age group is 66 years (range, 22 to 88 years)
Clinical features
- ■
Vague upper abdominal pain, nausea, vomiting, gastroduodenal ulcers, and GI bleeding
- ■
Etiologies include long-term aspirin use, NSAID use, and bile reflux following gastroenterostomies
Prognosis and therapy
- ■
Treatment involves PPIs and discontinuing offending agents such as NSAIDs
Pathologic features
Gross and endoscopic findings
The endoscopic findings are usually nonspecific, consisting of erythema and erosions in the gastric antrum. Visible gastric bile staining on endoscopic examination can be helpful in diagnosis.
Microscopic findings
The antral mucosa shows foveolar hyperplasia characterized by villiform change of the surface epithelium and elongation and tortuosity of gastric pits with a corkscrew appearance ( Fig. 3-8 ). The surface epithelial cells are immature with cuboidal shape, depleted mucin, and enlarged nuclei, which, when marked, can be mistaken for dysplasia. The lamina propria shows smooth muscle proliferation and vascular congestion. There is usually a paucity of inflammatory cells. Focal erosions may be associated with small pockets of neutrophils and eosinophils. The changes are limited to the antrum. Chronic chemical gastropathy may also be associated with intestinal metaplasia in the gastric antrum, which is thought to be the result of ulcer repair. Oxyntic mucosa occasionally may show reactive changes of the surface, but the findings are usually subtle. Bile reflux gastropathy following Billroth I-II surgery with antrectomy is present in the body or fundus.
Endoscopic findings
- ■
Erythema and erosions in the gastric antrum
- ■
Visible bile reflux on endoscopic examination
Microscopic findings
- ■
Changes are limited to the antrum and prepyloric area
- ■
Marked foveolar hyperplasia characterized by villiform change of the surface foveola, and elongation and tortuosity of the gastric pits resembling a corkscrew
- ■
Reactive surface foveolar epithelium with depleted mucin
- ■
Smooth muscle proliferation and vascular congestion in the lamina propria
- ■
Paucity of inflammatory cells; focal erosions may be associated with small pockets of neutrophils and eosinophils
Immunohistochemistry
- ■
Giemsa stain for Helicobacter pylori is negative
Differential diagnosis
- ■
Hyperplastic polyp
- ■
Gastric antral vascular ectasia
- ■
Mucosa adjacent to ulcers
Ancillary studies
Histochemistry
- •
Giemsa (or immunohistochemical) stain for H. pylori is negative
- •
Periodic acid-Schiff (PAS)/alcian blue at pH 2.5 is helpful (but not necessary for diagnosis) in demonstrating depleted foveolar surface mucin
Differential diagnosis
- •
Hyperplastic polyp: The marked foveolar hyperplasia in chemical gastropathy may resemble hyperplastic polyps. On the other hand, small/early hyperplastic polyps with focal foveolar hyperplasia may resemble chemical gastropathy. The endoscopic appearance of a polyp/nodule is important in making the distinction.
- •
Gastric antral vascular ectasia (GAVE): The typical endoscopic appearance of watermelon stomach and vascular thrombi in the lamina propria differentiate this entity.
- •
Mucosa adjacent to an ulcer with foveolar hyperplasia and edema ( Fig. 3-9 ) can histologically resemble chemical gastropathy. The clinical context of an ulcer is important in distinguishing between these entities.
FIGURE 3-9
Foveolar hyperplasia and edema near an ulcer resembling chemical gastropathy.
- •
Mixed chemical/reactive gastropathy and chronic gastritis: This pattern can coexist in biopsy samples and consists of a mild inflammation in the lamina propria and a disproportionate degree of foveolar hyperplasia and edema. This mixed pattern may suggest an overlap of chemical gastropathy in a background of mild chronic gastritis. Foveolar hyperplasia, by itself, is not specific to chemical gastropathy and can also be seen with chronic H. pylori gastritis. However, the moderate to severe inflammation in H. pylori –associated gastritis is absent in chemical gastropathy.
Prognosis and therapy
This is a benign entity and management involves discontinuing the offending agents such as NSAIDs and medical management with antisecretory drugs such as PPIs.
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Helicobacter pylori gastritis
First described by Australian scientists J. Robin Warren and pathologist Barry J Marshall in 1982, H. pylori gastritis is a chronic infectious form of gastritis caused by spiral, flagellated gram-negative rods and characterized by superficial chronic active gastritis. H. pylori gastritis is synonymous with Campylobacter pylori gastritis, diffuse antral gastritis, chronic superficial gastritis, and type B gastritis.
Clinical features
Signs and symptoms include abdominal pain, nausea, vomiting, dyspepsia, weight loss, iron deficiency anemia, and ulcer-related bleeding. H. pylori gastritis is a universal infection prevalent in 50% of the world’s population. It is more prevalent in developing countries, where up to 75% of population older than 25 years of age is infected, the prevalence reaching 80% to 90%. Most people acquire infection during childhood. Transmission of infection is human to human, with poor sanitary conditions and overcrowding being risk factors. In developed countries, the overall prevalence is 25% to 30%, and the seroprevalence ranges from 5% to 27% in early childhood and exceeding 50% to 60% in adults older than 60 years of age. In the United States, African Americans, Asian Americans, and Hispanics have a higher prevalence than whites (70% versus 35%).
H. pylori is a curved, gram-negative rod with S-shaped or seagull wing appearance. It is motile, using single polar flagellum. It is a microaerophilic bacillus 0.5 μm in width and 2.5 μm in length. This organism has a tropism for gastric mucosa or metaplastic gastric mucosa in organs such as the duodenum. The pathogenesis depends on its ability to colonize gastric epithelium via adhesins such as BabA, SabA, urease; virulence factors such as Cag A, Vac A, and urease, which in turn generates cytokines such as interleukin-8 to attract neutrophils.
The discovery 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. Warren and Marshall became the recipients of the Nobel Prize in Physiology or Medicine in 2005 for this significant discovery. The World Health Organization has classified H. pylori as a group I human carcinogen of gastric cancer. Infected persons have a three- to six-fold greater risk of developing gastric cancer over that of uninfected persons.
Definition
- ■
Chronic infectious form of gastritis caused by curved, flagellated gram-negative rods— Helicobacter pylori— and characterized by superficial chronic active gastritis
Incidence and location
- ■
Universal infection
- ■
In developing countries, up to 75% of the population older than 25 years are infected, with the prevalence reaching 80% to 90%
- ■
In developed countries, the overall prevalence is 25% to 30%; the seroprevalence ranges from 5% to 27% in early childhood and exceeds 50% to 60% in adults older than 60 years of age
- ■
In the United States, African Americans and Hispanics have a higher prevalence than whites (70% vs. 35%)
Morbidity and mortality
- ■
Ulcer-related bleeding
- ■
Association with peptic ulcer disease, gastric lymphoma, and carcinoma
- ■
Definite or group I human carcinogen (World Health Organization)
Clinical features
- ■
Abdominal pain, nausea, vomiting, dyspepsia, weight loss, iron deficiency anemia, and ulcer-related bleeding
Prognosis and therapy
- ■
Triple therapy for 14 days consisting of either bismuth or PPIs combined with two antibiotics such as metronidazole, clarithromycin, tetracycline, or amoxicillin
- ■
Cure rate of greater than 95% is achieved
- ■
Short treatment courses of 1 to 5 days may be effective with an eradication rate of 89% to 95%
Pathologic features
Endoscopic findings
Endoscopic findings are variable and include gastric mucosal erythema, erosions, granularity, and nodularity. The endoscopic appearance may even be normal, placing emphasis on the value of histologic examination. There may be associated gastric and duodenal ulcers. Mucosal nodularity simulating gastric lymphoma or carcinoma can be present. The nodularity is usually caused by florid lymphoid hyperplasia ( Fig. 3-10 ). 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.
Microscopic findings
H. pylori commonly colonizes both antrum and body mucosa. In severe infection, the organisms can be present in biopsy samples of the cardia. The inflammation is prominent in the superficial gastric mucosa and characterized by intense lymphoplasmacytic inflammation admixed with neutrophils ( Fig. 3-11 ). Active or neutrophilic inflammation is prominent in the surface epithelium and gastric pits, with pititis and crypt abscesses ( Fig. 3-12 ). Additional histologic features include foveolar hyperplasia (not just limited to reactive gastropathy), degenerative changes, erosion, hemorrhage, and lymphoid follicles (see Fig. 3-11 B).
The organisms appear as slightly curved seagull wing–shaped rods, most prominent in the gastric mucus, overlying surface epithelium, and gastric pits. The organisms may be visible on hematoxylin and eosin (H&E) examination ( Fig. 3-13 A), but adjunct stains are used and recommended to confirm their presence (see Fig. 3-13 B through D). Active neutrophilic inflammation is usually a marker for the presence of Helicobacter organisms. Table 3-1 highlights other manifestations that may be attributed to H. pylori infection ( Fig. 3-14 ).
| Acute Helicobacter gastritis | This is the acute manifestation when the infection is initially acquired and almost never comes to medical attention and therefore is not biopsied. In fact, the 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 suffered from acute gastritis with nausea, vomiting, and halitosis. |
| 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 and follicular gastritis | Lymphocytic gastritis contains prominent intraepithelial lymphocytosis and follicular gastritis contains florid lymphoid follicles; both entities are seen with H. pylori infection. |
| Granulomatous gastritis | Helicobacter infection may have a more important role to play in gastric granulomas than it is credited for. |
| Hyperplastic polyp | May be a marker of H. pylori infection in the nonpolypoid gastric mucosa. |
| 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 also present in the body and cardia. Unlike in 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. |
Because of the widespread use of PPIs, it is not uncommon to find the Helicobacter organisms in the body/fundus, but not in the antral mucosa: The changing microenviroment and gastric pH may have a role to play. Often, the organisms are impossible to locate by histochemical staining because of the coccoid shape and deep or even intracellular location within glands, making it necessary to perform immunohistochemistry (see Fig. 3-13 D). This phenomenon also emphasizes the need to educate GI specialists to obtain biopsy samples of the antrum and body, and to discontinue PPIs 2 weeks before the endoscopy, or else the infection may be missed.
Gross (endoscopic) findings
- ■
Gastric mucosal erythema, erosions, granularity, and nodularity
- ■
For optimal evaluation at least two mucosal biopsies, each from the antrum and body are recommended
Microscopic findings
- ■
Chronic active gastritis with marked lymphoplasmacytic inflammation and neutrophils
- ■
The inflammation is predominantly in the superficial aspect (luminal) of mucosal biopsy
- ■
Active or neutrophilic inflammation is prominent in the gastric pits, causing pititis
- ■
Foveolar hyperplasia, features of degeneration, and, in severe cases, erosion, hemorrhage, and mucosal necrosis
- ■
Prominent lymphoid aggregates
- ■
The organisms appear as slightly curved seagull wing–shaped rods, most prominent in the gastric mucin and the lining surface foveolar epithelium and gastric pits
- ■
The organisms can be visible on H&E examination, especially when numerous, but adjunct, stains are used to confirm their presence
- ■
Active inflammation is usually a marker for the presence of Helicobacter organisms; organisms are often absent in cases of atrophy or intestinal metaplasia
Immunohistochemical findings
- ■
Special stains utilized:
- ■
Modified Giemsa stain and Diff-Quik are popular, quick, cheap, and easy to perform
- ■
Silver stains: Warthin-Starry, Genta stain
- ■
Immunohistochemistry for Helicobacter
- ■
Differential diagnosis
- ■
H. heilmannii gastritis
- ■
Gastric marginal zone B-cell lymphoma
- ■
Focal active gastritis: gastric Crohn’s disease
- ■
Autoimmune gastritis
- ■
Non– H. pylori bacteria
Ancillary studies
See Table 3-2 .
| INVASIVE TESTS | ||
|---|---|---|
| Biopsy, special stains | Modified Giemsa, Diff-Quik, silver stains—Warthin-Starry, Genta stain | Diff-Quik and modified Giemsa are preferred over silver stains (cost). Sensitivity 84% to 99% and specificity 90% to 99%. |
| Immunostain for H. pylori | Especially useful in demonstrating variant forms of H. pylori, such as the coccoid forms (see Fig. 3-13 D) that can occur in partially treated cases, patients on antibiotics or proton-pump inhibitors (PPIs), and resistant forms. PPI therapy can drive the organisms into the parietal cells when they become visible by immunostains. | Costly compared with special stains such as Diff-Quik; performed when the findings of special stains are questionable. Immunostain is also positive in H. heilmannii gastritis. |
| Biopsy-based rapid urease tests | Biopsy tissue is placed on urea medium and positive test is indicated by color change caused by an increase in pH as a result of urea breakdown into ammonia catalyzed by urease produced by all strains of Helicobacter organisms. | CLOtest, hpfast, PyloriTek. Sensitivity 89% to 98% and specificity up to 93% to 98%. Sensitivity depends on organism load in the biopsy tissue and number of biopsy samples used. Less sensitive in pediatric population. |
| Culture | Incubation in nonselective mediums such as chocolate or blood agar for 5-7 days. | Sensitivity is 77% to 92%, and specificity is 100%. Not used routinely but may gain importance in the future owing to the emergence of resistant strains. |
| Molecular tests | Polymerase chain reaction (PCR)-based detection of H. pylori using various genetic targets such as 23S ribosome, vac A, ureA, and cag A gene. | |
| NONINVASIVE TESTS | ||
| Serology | Detect IgG antibodies in serum or even whole blood to H. pylori antigens using enzyme-linked immunosorbent assay (ELISA) | Screening test used to detect current or past infection. Performance varies with the different commercial kits with an overall sensitivity and specificity of 88% to 92% and 86% to 95%, respectively. Reduced sensitivity in HIV-infected individuals. Patients with H. heilmannii may have a negative test to anti– H. pylori IgG assays. Serologic results can stay positive for a very long time, making them less useful for follow-up. Follow-up serology to test for eradication should be done only after 6 months. |
| Urea breath test (UBT) | Patient is given radioactively labeled urea to drink. The urease produced by Helicobacter organisms will break down urea and the labeled CO 2 is detected in the exhaled breath. | Sensitivity is 90% to 100% and specificity is 98% to 100%. UBT is used as a follow-up for patients who continue to be symptomatic. |
| Stool antigen test | H. pylori antigens is detected from fecal sample by enzyme immunoassay. | Sensitivity is 89% and specificity 94%. Like UBT, this test can also be used to confirm eradication. |
Differential diagnosis
- •
Helicobacter heilmannii gastritis ( Gastrospirillum hominis ): Rare cause of Helicobacter gastritis responsible for approximately 0.3% cases. Caused by a tight spiral bacterium that is 5 to 6 μm in length, which is longer than H. pylori ( Fig. 3-15 A and B). It is also seen in cats and dogs, raising the possibility of an animal source of infection. Because of their larger size, they can be seen on H&E examination and are present in the gastric mucus and lumen of gastric pits without coming in close contact with the epithelium. They are seen intracellularly as well. Immunostain for H. pylori also stains H. Heilmannii (see Fig. 3-15 C), and treatment is also the same.
FIGURE 3-15
A, Unlike Helicobacter pylori, Helicobacter heilmannii organisms are longer, tightly spiraled, present in the lumen, and less tightly adherent to surface foveolar cells (H&E). B, H. heilmannii in (MGS). C, The antibody for H. pylori also stains H. heilmannii.
- •
Gastric marginal zone B-cell lymphoma or low-grade MALT lymphoma: The florid lymphoid hyperplasia in Helicobacter gastritis can be mistaken for low-grade MALT lymphoma. However, immunostains for CD20 and CD3 demonstrate a reactive pattern consisting of mixed T and B lymphocytes (CD20-positive in the germinal center B-cells and mantle cuff, CD3-positive in peripheral T-lymphocytes). Unlike MALT lymphoma, which is characterized by monomorphic B-cells extending below the muscularis mucosae, Helicobacter gastritis causes superficial inflammation and lacks destructive lymphoepithelial lesions. The neoplastic lymphoid cells in MALT lymphoma coexpress CD20 and CD43 and may show light chain restriction. The intraepithelial lymphocytes in Helicobacter gastritis are mostly CD3-positive T-lymphocytes, unlike the CD20-positive neoplastic B-cells in gastric MALT lymphomas. A word of caution: Features such as lymphoepithelial lesion and dense B-cell aggregates can also be seen in gastritis. Studies have shown a clonal population of lymphoid cells in reactive germinal centers associated with Helicobacter , so one needs to be cautious about interpreting molecular studies.
- •
Conditions that can be associated with focal active gastritis: Crohn’s disease, erosions in chemical gastropathy.
- •
Autoimmune gastritis: The antrum is normal or may show mild chemical gastropathy. The body shows atrophy with reduced to absent oxyntic glands, intestinal metaplasia, and enterochromaffin-like (ECL) cell hyperplasia. Patients have antibodies to intrinsic factor and parietal cells leading to hypochlorhydria, vitamin B 12 deficiency, and hypergastrinemia. Hypergastrinemia also occurs in Helicobacter gastritis, although not to the extent seen in autoimmune gastritis.
- •
Non– H. pylori bacteria: Occasionally, gastric biopsy samples may contain colonies of bacteria that are not H. pylori but that are likely oral contaminants; these are often seen in ulcer beds or atrophic gastritis. These are recognized as follows: (1) coccoid or rod shape and not spirals or curved; (2) size smaller than H. pylori ; (3) bunching together; (4) no close association with foveolar epithelium; (5) negative immunolabeling for H. pylori .
Prognosis and therapy
Triple therapy for 14 days consisting of either bismuth or a PPI combined with two antibiotics has been the most popular regimen, achieving up to a 95% cure rate. The recommended antibiotics are metronidazole, clarithromycin, and tetracycline or amoxicillin.
However, recent studies have shown that short treatment courses of 1 to 5 days may be equally effective with an eradication rate of 89% to 95% with better compliance, reduced cost, and fewer adverse effects.
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Gastric peptic ulcer disease
- 1.
Benign gastric ulceration caused by acid-pepsin damage.
- 2.
In the United States, peptic ulcer disease develops in 500,000 people each year; 70% of patients are between 25 and 64 years old.
- 3.
Common locations of peptic ulcer disease are stomach and proximal duodenum; duodenum is a more common site.
- 4.
Less common sites of ulceration are lower esophagus, distal duodenum/jejunum, and ectopic gastric mucosa of Meckel’s diverticulum.
- 5.
Causes
- a.
H. pylori infection and NSAIDs are the leading cause of peptic ulcers in 60% to 70% and 24% of cases, respectively, in the United States.
- b.
H. pylori infection: Increased gastrin production, virulence factors such as CagA and mucosal damage by inflammation are all attributed to ulcer development.
- (1)
H. pylori treatment reduces ulcer recurrence in both gastric and duodenal ulcer.
- (1)
- c.
NSAIDs: In patients without H. pylori infection, NSAIDs are the most common cause of peptic ulcer. NSAID ulcers are on the rise as the prevalence of H. pylori infection is declining in the United States.
- d.
Medications, such as steroids.
- e.
Rare causes: Zollinger-Ellison syndrome.
- a.
- 6.
Clinical feature
- a.
Severe epigastric pain exacerbated by food intake.
- b.
Duodenal ulcer pain is relieved by food intake.
- c.
Vomiting, weight loss, hematemesis, melena, and gastric outlet obstruction caused by scarring and pyloric stenosis; peritonitis caused by perforation.
- a.
- 7.
Gross findings
- a.
Gastric ulcers are usually present in the lesser curvature, 2 to 4 cm, and round to oval ulcers with a smooth base and regular, perpendicular edges ( Fig. 3-16 ), unlike the irregular heaped-up borders of malignant ulcers.
FIGURE 3-16
Benign gastric ulcer with a smooth base and regular borders.
- a.
- 8.
Histology
- a.
Mucosal defect extending below the muscularis mucosae with extension into the submucosa and muscularis propria.
- b.
Early ulcers are associated with fibrinoid necrosis, inflammation, and granulation tissue reaction.
- c.
Chronic ulcers are associated with fibrosis and scarring ( Fig. 3-17 ).
FIGURE 3-17
Unlike erosions, gastric ulcers are deep with extension below the muscularis mucosae (A). Chronic ulcers are characterized by fibrosis and stricture (B).
- a.
- 9.
Management
- a.
Eradication of H. pylori infection is key to successful ulcer healing and will reduce the risk of recurrence or rebleeding.
- b.
Acid suppressors, especially PPIs.
- c.
Endoscopic treatment modalities such as epinephrine injection, coagulation, or clipping of bleeding sites.
- d.
Stopping intake of NSAIDs and prostaglandin analogues such as misoprostol.
- e.
Surgical management in cases of perforation.
- f.
Discontinuing smoking, alcohol, and illicit drug use.
- a.
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Autoimmune gastritis (autoimmune metaplastic atrophic gastritis)
Autoimmune gastritis is an immune-mediated chronic gastritis in which the antibodies are directed against gastric parietal cells and intrinsic factor, resulting in loss of oxyntic cells, hypochlorhydria, achlorhydria, and vitamin B 12 deficiency. Autoimmune gastritis is synonymous with type A gastritis, diffuse corporal atrophic gastritis, atrophic gastritis, autoimmune chronic gastritis, and autoimmune-associated gastritis.
Clinical features
First described by Thomas Addison in 1849, autoimmune gastritis affects nearly 2% of the population older than 60 years old and is responsible for less than 5% 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 females in their 50s and 60s are affected more (male-to-female ratio, 1:3). Autoimmune gastritis is an immune-mediated injury to the gastric oxyntic mucosa, and serum analysis frequently demonstrates antiparietal cell antibodies targeted against H + /K + -ATPase in 60% to 85% and intrinsic factor antibodies in 30% to 50% ( Table 3-3 ). Patients present with abdominal pain, weight loss, diarrhea, malabsorption, and neurologic complications, such as peripheral neuropathy and subacute combined degeneration of spinal cord related to severe vitamin B 12 deficiency. Iron deficiency anemia can be seen in 20% to 40% of patients, whereas pernicious anemia is seen in 15% to 25% of patients. Reduced gastric acid plays a role in iron deficiency because gastric acid is necessary to release iron from bound protein, as well as reduce ferric iron to ferrous state necessary for absorption. Pernicious anemia is characterized by macrocytosis, megaloblasts, pancytopenia, atrophic glossitis, low serum B 12 concentration, and normal folate level. Pernicious anemia 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, as well as autoantibody targeted at intrinsic factor preventing the formation of B 12 -intrinsic factor complex. Patients may have other autoimmune disorders such as insulin-dependent diabetes mellitus, Hashimoto’s thyroiditis, adrenal insufficiency, Graves’ disease, vitiligo, or myasthenia gravis.
| Antiparietal cell antibodies | Positive (target H + /K + ATPase): 60% to 85% |
| Intrinsic factor antibodies | Positive: 30% to 50% |
| Serum gastrin | Elevated |
| Gastric pH | Alkaline or neutral |
| Vitamin B 12 level | Reduced |
| Serum pepsinogen I | Reduced (loss of chief cells) |
| Schilling test | Positive and corrected by vitamin B 12 injection |
| Helicobacter pylori serology | Usually negative |
| HLA haplotypes | HLA −B8, DR-3 |
Helicobacter infection can also be associated with autoantibody formation, with studies implicating antibodies against H. pylori directed at H + /K + -ATPase of the parietal cells, as are the antiparietal cell antibodies in autoimmune gastritis.
Definition
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Immune-mediated form of chronic gastritis resulting in loss of oxyntic cells, hypochlorhydria, achlorhydria, and vitamin B 12 deficiency
Incidence and location
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Affects nearly 2% of people older than 60 years
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No racial predilection (in the past, there was a belief that Northern Europeans were preferentially affected)
Gender, race, and age
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Patients are usually older white women in their 50s and 60s
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Male-to-female ratio of 1:3
Clinical features
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Abdominal pain and discomfort, weight loss, pernicious anemia, and rarely subacute combined degeneration of spinal cord
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Patients may have other immune-related disorders such as insulin-mediated diabetes mellitus, Hashimoto’s thyroiditis, or adrenal insufficiency
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Serum analysis frequently positive for antiparietal cell antibodies and intrinsic factor antibodies
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Elevated serum gastrin
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Reduced B 12 ; positive Schilling test corrected by administering intrinsic factor
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Helicobacter serology is usually negative
Prognosis and therapy
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2% to 9% prevalence of gastric carcinoids and a twofold to threefold increase in gastric carcinomas
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Medical management includes vitamin B 12 injections
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Surgical management for multiple carcinoids includes endoscopic polypectomies, total gastrectomy, or antrectomy
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Screening is not advocated at present given the high cost-benefit ratio
Pathologic features
Gross and endoscopic findings
Autoimmune gastritis affects the gastric body and fundus and spares the antrum. On endoscopic examination, the body mucosa appears shiny and red, resulting from effacement of rugal folds, with a prominent submucosal vascular pattern, which becomes visible as a result of mucosal atrophy. Patients may present with multiple pseudopolyps that represent preserved islands of oxyntic mucosa surrounded by flattened body mucosa. Other associations include hyperplastic polyps (most common polyps), multiple carcinoids, and even adenocarcinoma.
Microscopic findings
The histologic findings are limited to the body/fundic mucosa with normal antral findings and consist of (1) chronic gastritis with prominent lymphocytic and plasma cell infiltration of the lamina propria directed at oxyntic glands (the chronic inflammation often being more prominent in the deeper mucosa), (2) loss of oxyntic glands (i.e., chief and parietal cells), (3) pseudopyloric metaplasia (glands that resemble mucous glands in the antrum but lack gastrin cells), and (4) intestinal metaplasia with goblet and Paneth cells ( Fig. 3-18 AB). Pancreatic acinar metaplasia and mild active inflammation may be present. Findings may vary depending on the stage of the disease. Biopsy specimens taken during early stages show chronic gastritis and some loss of oxyntic glands, but intestinal metaplasia may be lacking. It is not unusual to see parietal cell pseudohypertrophy in this early active stage. In late stages, the oxyntic mucosa can resemble small intestine complete with villi lined by absorptive, goblet, and Paneth cells (so-called complete intestinal metaplasia). The low serum B 12 in pernicious anemia can cause megaloblastoid change of the foveolar epithelium.
The antral mucosa is not atrophic and usually has chemical gastropathy or a mild chronic gastritis ( Fig. 3-19 A). The low acid state created by the loss of parietal cells stimulates gastrin cell hyperplasia in the antrum (see Fig. 3-19 B), which in turn causes nodular and linear hyperplasia of the enterochromaffin-like (ECL) cells in the body responsible for histamine secretion. These appear as linear hyperplasias (linear arrangement of five or more neuroendocrine cells) or small neuroendocrine nodules at mucosal base (see Fig. 3-18 C). Patients may also have multiple carcinoid tumors, mostly in the body. However, hyperplastic polyps are the most common polyps seen.
Gross findings
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Affects gastric body and fundus and spares the antrum
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Endoscopic and gross features consist of thinning of body mucosa with effacement of rugal folds and prominent submucosal vascular pattern, which become visible as a result of mucosal atrophy
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Associated findings include hyperplastic polyps (most common polyps), multiple carcinoids, and even adenocarcinoma
Microscopic findings
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Histologic findings are limited to the body and fundic mucosa with normal antral findings
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Chronic gastritis with prominent lamina propria lymphocytic and plasma cell infiltration directed at oxyntic glands
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Loss of oxyntic glands (i.e., chief and parietal cells)
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Pseudopyloric metaplasia, intestinal metaplasia, and pancreatic metaplasia
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Findings may be variable depending on the stage of the disease
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Linear and nodular ECL hyperplasia in the body mucosa
Immunohistochemical features
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Gastrin and chromogranin A
Differential diagnosis
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Environmental atrophic metaplastic gastritis (diffuse antral or multifocal atrophic gastritis caused by Helicobacter pylori infection)
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Pernicious anemia related to autoimmune polyglandular syndrome type I
Ancillary studies
Immunohistochemistry
Gastrin immunostain is useful in distinguishing body mucosa (lacks G cells; see Fig. 3-18 D) from the antral mucosa, which contains G cells. In autoimmune gastritis, when the body mucosa becomes “antralized” resulting from destruction of oxyntic glands and pseudopyloric metaplasia, gastrin immunostain can be useful to check the biopsy location, especially when unspecified in the requisition form. Gastrin highlights the G-cell hyperplasia in the antrum (see Fig. 3-19 B). Rare gastrin-positive cells may be seen in foci with intestinal metaplasia.
Chromogranin A highlights the linear and nodular ECL cell hyperplasia (see Fig. 3-18 C), as well as gastric carcinoids.
H. pylori stains are negative.
Differential diagnosis
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Environmental metaplastic atrophic gastritis ( Table 3-4 ).
TABLE 3-4
Features of Autoimmune versus Environmental Atrophic Gastritis
Autoimmune Metaplastic Atrophic Gastritis (AMAG)
Environmental Metaplastic Atrophic Gastritis (EMAG)
Synonyms
Type A gastritis
Diffuse corporal gastritis
Type B gastritis
Diffuse antral gastritis
Multifocal atrophic gastritis
Population affected
Northern European and Scandinavian descent
Worldwide
Sex
Female predominance
No sex predilection
Etiology
Immune mediated
H. pylori infection
H. pylori colonization
<20%
90% to 100%
Location
Body and fundus
Antrum predominantly with extension to body, multifocal
Antiparietal cell antibody
Positive
Negative
Anti-intrinsic factor antibody
Positive
Negative
Vitamin B 12 level
Low
Normal
Serum gastrin
Very high
Normal or low
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Pernicious anemia related to autoimmune polyglandular syndrome type I: Rare disorder presenting in childhood and characterized by a generalized loss of GI endocrine cells including gastrin cells, caused by antibodies directed against endocrine cells. Patients have a low serum gastrin and do not have antiparietal cell antibody. The gastric body can resemble autoimmune gastritis, and the loss of parietal cells is a result of the low serum gastrin (a trophic factor for parietal cells).
Prognosis and therapy
Autoimmune gastritis carries a 2% to 9% prevalence of gastric carcinoids and a twofold to threefold increase in the prevalence of gastric adenocarcinomas. Gastric carcinoid tumors associated with autoimmune gastritis are usually indolent.
Medical therapies include administering vitamin B 12 injections. In patients with multiple carcinoids, management includes endoscopic polypectomies with close surveillance or antrectomy. Antrectomy has been shown to cause resolution of the hypergastrinemic state, leading to reduction in the size of carcinoids. Screening is not advocated at present given the high cost-benefit ratio.
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Granulomatous gastritis
Granulomatous gastritis is an uncommon form of gastritis, comprising 0.27% to 0.35% of all gastritis and characterized by granulomatous infiltrate in the stomach. It encompasses a wide spectrum of diseases that have mucosal or submucosal granulomas in the stomach as the defining histologic feature. Granulomas consist of a nodular, circumscribed collection of epithelioid histiocytes admixed with lymphocytes, eosinophils, giant cells, and even neutrophils, with or without central necrosis and a lymphoid cuff. The final diagnosis depends on the clinical, radiologic, endoscopic, microbiological, and histologic findings and treatment response ( Table 3-5 ). When a granuloma is seen on H&E examination, additional studies such as the use of polarized light to rule out foreign body, special stains such as AFB, GMS, and PAS become a vital part of the assessment.
| Gastric Crohn’s disease—52% Sarcoidosis-1—21% Foreign body granuloma-food, suture material, barium, mucin—10% Isolated granulomatous gastritis—25% Tumor-associated granulomas—7% Infections (tuberculosis, histoplasmosis, schistosomiasis Whipple’s disease, leprosy, syphilis) Vasculitis associated granulomas (Churg Strauss disease) Helicobacter pylori gastritis |
Gastric crohn’s disease
In the Western world gastric Crohn’s disease accounts for 17% to 55% of cases of granulomatous gastritis. Approximately 30% of patients with Crohn’s disease have upper GI findings; patients with both small and large bowel involvement are at increased risk. Patients are younger, often in the pediatric age group. Symptoms consist of abdominal pain, nausea, and vomiting. Patients may present with coexisting lower GI symptoms such as chronic diarrhea and weight loss.
Radiologic findings
Radiologic findings include ulcers, strictures, and gastric outlet obstruction.
Pathologic features
Gross and endoscopic findings
Findings range from normal mucosa to erythema, aphthoid-type erosions, superficial or deep ulcers, nodules, thickened folds, and stenosis. Findings are usually predominant in the antrum.
Microscopic findings
Gastric biopsies in patients with Crohn’s can range from normal to H. pylori– negative mild chronic gastritis, or patchy chronic active gastritis ( Fig. 3-20 ). The finding of granulomas is very helpful in establishing the diagnosis of Crohn’s disease, although granulomas are present in only 7% to 34% cases. Foveolar isthmi are common sites for Crohn’s granulomas, and they consist of small loose clusters of epithelioid histiocytes. Granulomas are usually seen in younger patients and often correspond to the nodules or aphthoid erosions seen on endoscopy. Granulomas can also be present in normal gastric mucosa, thus emphasizing the importance of sampling normal mucosa for biopsy. Other histologic findings include pit abscesses and focal active gastritis or focally enhanced gastritis, which is composed of a focal lymphohistiocytic cluster with admixed acute inflammation. Focally enhanced gastritis is not limited to Crohn’s, however, and can be seen in ulcerative colitis and graft versus host disease.
On gastric resections, the diagnosis of Crohn’s disease is easier, and histologic features such as linear fissures, undermining ulcers, transmural inflammation with lymphoid follicles, granulomas, and neural hyperplasia are all helpful.
Taking multiple biopsy samples, using jumbo forceps, and examining multiple serial sections increase the chances of finding granulomas in Crohn’s disease.
Ruling out H. pylori infection by special stains is important. Ten percent to 15% of Crohn’s patients may have H. pylori gastritis.
Gastric sarcoidosis
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Sarcoidosis is a multisystemic granulomatous disease, characterized by hypercalcemia and commonly affecting lungs and hilar lymph nodes.
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Affects young adults.
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Common in African Americans.
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Gastric antrum can be involved in 10% of patients with systemic disease.
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Grossly the gastric mucosa may be nodular ( Fig. 3-21 ) with ulcers, thickening, and a segmental linitis plastica–like appearance.
FIGURE 3-21
Gastric sarcoidosis with a nodular mucosal appearance on endoscopy.
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Patients may present with gastric outlet obstruction or bleeding.
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Sarcoid granulomas are compact noncaseating granulomas with a surrounding lymphocytic cuff ( Figs. 3-22 and 3-23 ).
FIGURE 3-22
Antral mucosa showing noncaseating granulomas in the lamina propria in a patient with sarcoidosis.
FIGURE 3-23
Compact noncaseating with lymphoid cuff granulomas in a patient with gastric sarcoidosis.
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It is a diagnosis of exclusion, and diagnosis is usually reached on clinical correlation and chest computed tomography findings.
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Patients respond to steroids.
Isolated granulomatous gastritis
Idiopathic granulomatous gastritis was a term coined by Fahimi in 1963, after excluding known entities such as Crohn’s disease and sarcoidosis. The granulomas are large and compact and are limited to the stomach. There have been a number of papers challenging this concept, and many authors link the granulomas to an inflammatory response to H. pylori infection. Miyamoto and colleagues reported disappearance of the granulomas following successful eradication of two such cases after treatment of Helicobacter infection. Another paper found an association with vasculitis. The conclusion seems to be that, in most cases, if we seek an etiology, we may be successful.
Lymphocytic gastritis
Lymphocytic gastritis is an uncommon form of chronic gastritis, which was described by Haot and colleagues in 1988. It is characterized by marked intraepithelial lymphocytosis in the gastric surface and pit epithelium. Lymphocytic gastritis is synonymous with varioliform gastritis (refers to the endoscopic appearance) and chronic erosive verrucous gastritis.
Clinical features
Lymphocytic gastritis has a prevalence of 1% to 4% in upper GI endoscopies. Symptoms include dyspepsia, iron deficiency anemia, and diarrhea. It is seen in adults and children (age range, 1 to 89 years). A slight female predominance is present. According to Wu and colleagues, approximately 38% of lymphocytic gastritis patients have celiac disease and 29% have H. pylori gastritis. Other less common associations consist of varioliform gastritis, Crohn’s disease, human immunodeficiency virus (HIV) infection, lymphocytic gastroenterocolitis, esophageal carcinoma, and gastric lymphoma. Lymphocytic gastritis is found in 33% of celiac patients who undergo gastric biopsies, and 4% of patients with H. pylori gastritis have lymphocytic gastritis. Celiac patients with lymphocytic gastritis may also have lymphocytic colitis (38%). Lymphocytic gastritis has also been described in patients with lymphocytic enterocolitis. This reiterates the importance of taking gastric, duodenal, and colonic biopsy samples for a complete evaluation of the histologic findings. Lymphocytic gastritis can present with Ménétrier’s-like protein-losing gastropathy. Lymphocytic gastritis resolves with treatment for H. pylori .
Radiologic features
Nodules with central erosion give rise to classic volcano-like lesions on radiography. A double-contrast upper GI series shows discrete radiolucent halos with central barium flecks.
Pathologic features
Gross and endoscopic findings
Endoscopic appearance may be normal or consist of mucosal nodules, erosions, and enlarged gastric folds. These latter gross appearances may mimic carcinoma or lymphoma. The nodules may contain central depression or erosion and are described as varioliform or aphthoid erosions.
Microscopic findings
Histologic findings include marked intraepithelial lymphocytosis of gastric surface and pit epithelium comprising more than 25 lymphocytes per 100 epithelial cells. Normal gastric controls have 3.5 lymphocytes per 100 cells, and diseased controls such as patients with Helicobacter gastritis have 5 lymphocytes per 100 cells. The deeper glandular epithelium is spared. The lamina propria is also expanded by lymphocytes and plasma cells ( Fig. 3-24 ). The intraepithelial lymphocytes are recognized by their condensed, dark nuclei surrounded by a clear halo ( Fig. 3-25 ). The foveolar pits are slightly tortuous and elongated. Areas with erosions may contain active inflammation with neutrophils.
Lymphocytic gastritis can involve the gastric antrum, as well as the body. It is antrum predominant in celiac patients, whereas in H. pylori and varioliform gastritis, the body is commonly involved.
Ancillary studies
Immunohistochemistry
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The intraepithelial lymphocytes are CD3- and CD8-positive cytotoxic/suppressor T-lymphocytes.
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In gastric maltomas the neoplastic lymphocytes in lymphoepithelial lesions are CD20-positive B-cells.
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Stains for Helicobacter organisms.
Differential diagnosis
Gastric malt lymphoma
This is a low-grade monoclonal B-cell lymphoma with CD20- and CD43-positive malignant B-lymphocytes infiltrating epithelial cells. There is significant epithelial and lamina propria destruction by the neoplastic lymphoid infiltrate with formation of characteristic lymphoepithelial lesions. The intraepithelial lymphocytes in lymphocytic gastritis are CD3-positive mature T-lymphocytes.
Chronic active h. pylori gastritis
The histologic appearance is that of a superficial chronic active gastritis with neutrophils and plasma cells. The surface epithelium lacks the characteristic lymphocytosis that is seen in lymphocytic gastritis. Intraepithelial lymphocytes usually number 4 to 5 lymphocytes per 100 epithelial cells.
Gastric endocrine cell hyperplasia
These can sometimes mimic lymphocytes. Stains for gastrin or chromogranin help differentiate the diagnoses.
Prognosis and therapy
Lymphocytic gastritis is an inflammatory condition. Treatment is directed at associated conditions such as celiac disease (gluten-free diet) or eradication of Helicobacter gastritis (antibiotics). Patients with lymphocytic gastroenterocolitis may be refractory to a gluten-free diet and need steroids. Patients with ulcers/erosions are also treated with PPIs.
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Infectious gastritis
The most common and important cause of infectious gastritis is H. pylori infection. The following sections discuss various other etiologies of gastric infections. As is true with most infections, these infections are more common in immunocompromised patients.
Viruses
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Cytomegalovirus (CMV): The inclusions in CMV gastritis are often present in gastric glandular epithelium along with the mesenchymal cells such as endothelial cells and fibroblasts. There are cytoplasmic and nuclear inclusions characterized by enlarged cells with eosinophilic nuclear inclusions, perinuclear halo, and cytoplasmic reddish granules ( Figs. 3-26 and 3-27 ). Infection of vascular endothelial cells causes a picture similar to ischemic gastritis can be present on biopsies ( Fig. 3-28 ). Immunostains ( Fig. 3-29 ), molecular studies such as polymerase chain reaction, and viral cultures are helpful adjunctive studies. CMV infection can present in children with protein-losing enteropathy with enlarged gastric folds simulating Ménétrier’s disease (MD). Endoscopic appearance consists of gastric ulcers, polypoid lesions and may mimic an infiltrative process. Diagnostic yield is increased by taking multiple biopsies from the base as well as edge of an ulcer.
FIGURE 3-26
Cytomegalovirus gastritis. Gastric foveolar epithelial cells with cytomegalovirus inclusions. Note both nuclear and cytoplasmic inclusions.
FIGURE 3-27
Endothelial cells and stromal cells. Cytomegalovirus cytopathic effect is shown (nuclear and reddish granular cytoplasmic staining).
FIGURE 3-28
Gastric mucosal biopsy. Lamina propria condensation and glandular dropout consistent with ischemic change in a case of CMV gastritis.
FIGURE 3-29
Positive immunohistochemistry for CMV. Demonstrated by dark brown nuclear staining. (Also note staining in endothelial cells.)
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Herpes: Can rarely cause erosions and gastritis in immunosuppressed patients. Nuclear inclusions with ground-glass appearance and the three Ms: multinucleation, margination, and moulding. Often associated with necrosis.
Bacteria
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Mycobacteria tuberculosis: Still an important cause of infection in developing countries, the granulomas show central caseation with Langerhans giant cells and lymphocytes. Stains for acid-fast bacilli (often the organisms are very scarce, thus the need to use oil immersion) and tuberculosis cultures are important. Patients can present with weight loss, anorexia, night sweats, and indolent fever with symptoms of gastric outlet obstruction or bleeding from an ulcer.
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Mycobacterium avium intracellulare (MAI): Common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS); the stomach is only rarely involved. The gastric mucosa is expanded by foamy histiocytes stuffed with acid-fast bacilli ( Fig. 3-30 ). Unlike tuberculosis, granulomas are not a feature of MAI infection.
FIGURE 3-30
Mycobacterium avium intracellulare infection, showing macrophages stuffed with acid-fast bacilli (Fite stain).
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Syphilis: Presents with ulcers, thickened folds, and strictures (hourglass stomach). Intense plasma cell infiltration, mononuclear vasculitis, presence of spirochetes, Treponema pallidum . Silver stains such as Warthin-Starry are helpful.
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Whipple’s disease
Fungal
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Histoplasma
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Aspergillus, Mucor : Immunocompromised state; invasive forms are almost always fatal.
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Candida: Fungal colonization can be seen in approximately 20% of benign gastric ulcers. The fungal yeasts and pseudohyphae are usually admixed in the ulcer exudate and do not affect ulcer healing. Most ulcers heal with acid-suppressive medications and do not require antimycotics. Nonhealing ulcers may benefit from fluconazole.
Parasites
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Anisakiasis: Caused by ingesting raw fish and seen in countries such as Japan and the Netherlands.
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Strongyloides stercoralis ( Fig. 3-31 ): Nematode infection; biopsy often shows all stages of the worm (adults, larva, eggs) embedded in crypts. Disseminated strongyloidiasis can be fatal.
