Answer: Autoimmune metaplastic atrophic gastritis

Histology: Autoimmune gastritis is an immune-mediated chronic gastritis where the antibodies are directed against gastric parietal cells and intrinsic factor, resulting in loss of oxyntic cells, hypochlorhydria, achlorhydria and vitamin B12 deficiency.

Synonyms: Type A gastritis, diffuse corporal atrophic gastritis, atrophic gastritis, autoimmune chronic gastritis, autoimmune-associated gastritis

Discussion: Autoimmune gastritis is an autosomal-dominant condition, and is responsible for less than 5% of all cases of chronic gastritis. It primarily affects individuals of northern European or Scandinavian descent. Patients are mainly of older, white females in their fifties and sixties (M:F-1:3). Autoimmune gastritis is an immune-mediated injury to the gastric oxyntic mucosa and serum analysis frequently demonstrates anti-parietal cell antibodies and intrinsic factor antibodies. Patients present with abdominal pain, weight loss, pernicious anemia, and rarely subacute combined degeneration of spinal cord related to B12 deficiency. Patients may have other immune related disorders such as insulin-mediated diabetes mellitus, Hashimoto’s thyroiditis, adrenal insufficiency etc.
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Pathologic features Gross/Endoscopic Findings:
Autoimmune gastritis affects gastric body and fundus, and spares the antrum. Endoscopic 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. Patients may present with multiple pseudopolyps which 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 histological findings are limited to the body/fundic mucosa with normal antral findings and consist of
(1) chronic gastritis with prominent lamina propria lymphocytic and plasma cell infiltration directed at fundic glands,
(2) loss of oxyntic glands, i.e, chief and parietal cells,
(3) pseudopyloric metaplasia (glands that resemble mucus glands in the antrum but lack gastrin cells), and
(4) intestinal metaplasia with goblet and paneth cells.

Pancreatic metaplasia may be present. Findings may be variable depending upon the stage of the disease. Biopsies taken during early stages of autoimmune gastritis show chronic gastritis and some loss of oxyntic glands but may lack intestinal metaplasia. In late stages the oxyntic mucosa can resemble small intestine complete with villi lined by absorptive cells, goblet and paneth cells (so called complete intestinal metaplasia)! The low serum B12 in pernicious anemia can cause megaloblastoid change of the foveolar epithelium.

The low acid state created by the loss of parietal cells stimulates Gastrin cell hyperplasia in the antrum, 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 hyplerplasias (linear arrangement of 3 or more neuroendocrine cells) or small neuroendocrine nodules at mucosal base. Patients may also have multiple carcinoid tumors mostly in the body. However hyperplastic polyps are the most common polyps seen.

Ancillary studies
Immunohistochemistry
Gastrin immunostain- useful in distinguishing body mucosa which lacks G cells from the antral mucosa which contains G cells. Gastrin will nicely highlight the G cell hyperplasia in the antrum. Also a useful test to check the biopsy site when it is unspecified in the requisition form especially considering the antralized body mucosa.
Chromogranin A – highlights the linear and nodular ECL cell hyperplasia.
Helicobacter pylori stains-negative

Differential Diagnosis:

Prognosis and Therapy
Autoimmune gastritis carries a 2-9% prevalence of gastric carcinoids and a two to threefold increase in the prevalence of gastric adenocarcinomas. Medical therapies include administering vitamin B12 injections. In cases with multiple carcinoids management includes endoscopic polypectomies, total gastrectomy 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.

Reference(s):
– Abraham SC, Singh VK, Yardley JH, Wu TT. Hyperplastic polyps of the stomach: associations with histologic patterns of gastritis and gastric atrophy. Am J Surg Pathol 2001;25:500-7.
– Krasinskas AM, Abraham SC, Metz DC, Furth EE. Oxyntic mucosa pseudopolyps: a presentation of atrophic autoimmune gastritis. Am J Surg Pathol; 2003;27:236-41.
– Kern SE, Yardley JH, Lazenby AJ et al. Reversal of antrectomy of endocrine cell hyperplasia in the gastric body in pernicious anemia: a morphometric study. Mod Pathol 1990; 3:561-566.
– Kokkola A, Sjoblom SM et al. The risk of gastric carcinoma and carcinoid tumors in patients with pernicious anemia. Endoscopy 1998;33:88-92.
– Moses RE, Frank BB, Leavitt M, Miller R. The syndrome of Type A chronic atrophic gastritis, pernicious anemia, and multiple gastric carcinoids. J Clin Gastroenterol 1986; 8:61-65.
– Appleman HD. Gastritis: terminology, etiology, and clinicopathological correlations. Hum Pathol 1994;25:1006-1019.
– Yardley JH and Hendrix TR. Chapter 66-Gastritis, gastropathy, duodenitis and associated ulcerative lesions. In: Textbook of Gastroenterology, Editor Yamada T. 3th ed: Lippincott Williams & Wilkins; : 1463-1499.
– Solcia E, Fiocca R, Villani L, Luinetti O, Capella C. Hyperplastic, dysplastic, and neoplastic enterochromaffin-like-cell proliferations of the gastric mucosa. Am J Surg Pathol 1995; 19:S1-S7.