autoimmune gastritis

Definition: Corpus-restricted chronic atrophic gastritis associated with serum anti-parietal cell and anti-intrinsic factor (IF) antibodies.

The minority (approximately 20%) of cases of chronic gastritis fall into type A or autoimmune gastritis. Autoimmune gastritis results from immune-mediated destruction of parietal cells and is therefore restricted to the body and fundus. It shows a characteristic hypochlorhydria and an associated neuroendocrine cell hyperplasia.

Patients with autoimmune gastritis often have pernicious anemia and intrinsic factor autoantibodies and autoantibodies directed against other organs.

Chronic atrophic gastritis restricted to body-fundic mucosa associated with presence of circulating antibodies against H⁺/K⁺ATPase and intrinsic factor

Clinical synopsis

 Epithelial dysplasia is observed in up to 40% of cases.
 Carcinoid tumors arise occur in 5–8% of patients with severe hypergastrinemia
 Anemia
 Hypochlorhydria, hypergastrinemia, and loss of pepsin and pepsinogens develop over time
 Most patients develop either iron deficiency anemia or pernicious anemia
 Endoscopic Findings

• Atrophic body/fundic mucosa with loss of mucosal folds
• Intestinal metaplasia
• Polyps

Laboratory Tests

 Circulating antibodies against H⁺/K⁺ATPase
 Circulating antibodies against IF
 High serum gastrin concentration
 Low serum pepsinogen
 Vitamin B12 deficiency

Epidemiology

Reported prevalence rate of 1-2% among older patients and in high-incidence countries (Nordic Europe)

The classic form of the disease tends to affect individuals of Scandinavian or northern European descent. It is rare among other ethnic groups. The predilection for autoimmune gastritis to affect blue-eyed individuals with blood group A suggests a genetic predisposition to the disease.

Etiology

Patients receiving methyldopa treatment may develop Parietal Cell Antibodies (PCAs) and chronic autoimmune gastritis.The changes disappear upon cessation ofthedrug.

Recently, HP infections have been recognized as a cause of autoimmune gastritis. The majority of patients with HP infections have autoantibodies directed against the canalicular membranes of parietal cells or the luminal membrane of foveolar epithelium.

The canalicular antibody targets the H ,K-ATPase proton pump.

Patients with autoimmune gastritis have PCAs, autoanti-bodies to intrinsic factor, and the gastrin receptor.

The PCAs target the catalytic subunit ofthe H,K-ATPase proton pump. The antibodies against intrinsic factor are of two types.

The most common inhibits the attachment of vitamin B12 to intrinsic factor and the other binds the intrinsicfactor–vitamin B12 complex, interfering with its small intestinal absorption.

Therefore, many patients with autoimmune gastritis develop pernicious anemia secondary to a vitamin B12 deficiency.

Macroscopy

 Mucosa in corpus is thinner than normal with reduced rugal folds
 Polyps

Microscopy

 Diffuse or multifocal dense lymphoplasmacytic infiltration of entire thickness of lamina propria.
 Lymphoid nodules.
 Oxyntic glands vanishing and replacement by mucin-producing flands.
 rarefaction of parietal cells (oxyntic cells)
 foveolar hyperplasia.
 pseudopyloric metaplastic epithelium
 Metaplastic changes

• complete intestinal metaplasia
• pyloric metaplasia
• pancreatic metaplasia

 Hypochlorhydria and achlorhydria cause physiologic hypergastrinemia leading to enterochromaffin-like cell (ECL cell) proliferations.
 hyperplasia of enterochromaffin-like cells

• linear or nodular hyperplasia of enterochromaffin-like cells (ECL cells)

 Autoantibodies against parietal cells (H⁺/K⁺ATPase)
 Autoantibodies against IF

Destruction of the oxyntic mucosa occurs over a period of years, ultimately leading to mucosal atrophy with hypo- or achlorhydria and decreased serum PG1 levels. PG1 levels below 20 mg/dL characterize the disease.

Patients with severe disease often have mucosal flattening that stops abruptly at the antrum.

Mucosal mononuclear cell infiltrates containing lymphocytes (both T and B lymphocytes), plasma cells, and eosinophils center around the oxyntic glands, eventually leading to their destruction.

Neutrophils are not a prominent component of the inflammation.

The degree of parietal and chief cell loss and atrophy varies with disease stage.

In the preatrophic phase of the lesion biopsies reveal cellular lamina propria infiltrates rich in plasma cells. T cells infiltrate the oxyntic glands resulting in lymphoepithelial lesions.

Thechanges progress from a superficial gastritis to atrophic gastritis and eventually gastric atrophy.

The patchy loss of parietal cells and chief cells is accompanied by an increased space between the glands that is readily appreciated when the atrophy is moderate or severe.

As the oxyntic glands are lost, the lymphoepithelial lesions disappear and the lamina propria inflammation tends to be mild in nature.

Eventually,the fundic mucosa becomes replaced by pyloricand/or intestinal glands, foveolae may become hyperplastic, and pancreatic metaplasia may develop.

If the patient has coexisting untreated pernicious anemia, the epithelial cells may appear megaloblastic.

Retention cysts may be present in the mucosa and superficial submucosa.

In severe disease, the entire gastric wall becomes atrophic, including even the musculature.

Patients with coexisting HP infections exhibit histologic features of both diseases.

Gastric adenocarcinoma affects 1% to 3% of patients with autoimmune gastritis via intervening steps of intestinal metaplasia and dysplasia.

Autoimmune gastritis also leads to G-cell hyperplasia, multi-focal gastric ECL hyperplasia, ECL micronests, and multifocal carcinoid tumors.

Early Phase

 Diffuse or multifocal dense lymphoplasmacytic infiltration of entire thickness of lamina propria

• Predominantly CD4(+) T cells often mixed with eosinophils and mast cells
• Patchy destruction of individual oxyntic glands by lymphocytes may be seen

 patchy pseudopyloric metaplasia.
 Intestinal metaplasia occurs rarely and only focally.
 Pseudohypertrophy of individual residual parietal cells may form small polypoid nodules.

Florid Phase

 Marked atrophy of oxyntic glands with diffuse lymphoplasmacytic infiltration

 Normal or reduced thickness of mucosa with relative increase in foveolar region

 Metaplastic changes ranging from complete intestinal metaplasia to pancreatic metaplasia

• Metaplastic origin of glands is confirmed immunohistochemically by absence of G cells

 Antral mucosa is devoid of significant inflammation but displays G-cell hyperplasia

 Proliferation of enterochromaffin-like (ECL) endocrine cells, secondary to hypergastrinemia

End Stage

 Marked reduction in oxyntic glands

 Various degrees of pyloric metaplasia, pseudopyloric metaplasia, pancreatic acinar metaplasia, and intestinal metaplasia

 Foveolar hyperplasia with elongation, microcystic change, and hyperplastic polyp formation

 Inflammation is usually minimal or absent, although scattered lymphoid aggregates and follicles may persist

ECL Cell Hyperplasia

 Proliferation, secondary to hypergastrinemia, parallels degree of mucosal atrophy

• Takes form of linear chains, small nodules, ribbons, and tubules deep in body/fundic mucosa

 Composed of small clear cells with round nuclei and finely dispersed chromatin

 Intramucosal carcinoids

• Expansile or infiltrative endocrine growth > 0.5 mm

 Invasive carcinoids

• Any tumor invading submucosa

Differential diagnosis

 multifocal atrophic gastritis

• Most severe in antrum
• Gastrin and chromogranin stains may help if biopsy specimens of uncertain origin

Autoimmune Diseases Associated with Autoimmune Gastritis

 Graves disease
 idiopathic hypoadrenalism
 Hashimoto thyroiditis
 idiopathic hypoparathyroidism
 thyrotoxicosis
 insulin-dependent diabetes
 dermatitis herpetiformis
 juvenile autoimmune thyroid disease
 celiac disease

Prognosis

 Polyps are found in 20-40% of cases

• Mostly sessile, @<@ 2 cm in diameter, and often multiple
• Most are hyperplastic
• 10% contain dysplastic foci

 Epithelial dysplasia is observed in up to 40% of cases.
 Some patients will develop gastric cancers.
 Carcinoid tumors arise in 5–8% of patients with severe hypergastrinemia.

See also

 juvenile forms of pernicious anemia

Open references

 Autoimmune gastritis: Pathologist’s viewpoint.
Coati I, Fassan M, Farinati F, Graham DY, Genta RM, Rugge M.
World J Gastroenterol. 2015 Nov 14;21(42):12179-89. doi : 10.3748/wjg.v21.i42.12179
PMID: 26576102 (Free)

References

 Jhala NC et al: Pancreatic acinar cell metaplasia in autoimmune gastritis. Arch Pathol Lab Med. 127(7):854-7, 2003.

 Torbenson M et al: Autoimmune gastritis: distinct histological and immunohistochemical findings before complete loss of oxyntic glands. Mod Pathol. 15(2):102-9, 2002.

 Annibale B et al: Atrophic body gastritis patients with enterochromaffin-like cell dysplasia are at increased risk for the development of type I gastric carcinoid. Eur J Gastroenterol Hepatol. 13(12):1449-56, 2001.

 Rappel S et al: [Carcinoid tumors of the stomach in atrophic autoimmune gastritis: classification, differential diagnosis and prognosis.] Verh Dtsch Ges Pathol. 80:199-207, 1996.