title: Gastric atrophy, metaplasia, and dysplasia: a clinical perspective.
abstract: Gastric carcinoma of the intestinal type originates in dysplastic epithelium, which in turn develops in the milieu of atrophic gastritis and intestinal metaplasia. Cancers also may develop less often from gastric adenomatous polyps, which represent dysplastic epithelium arising in a raised lesion. The main causes of chronic atrophic gastritis and gastric atrophy are autoimmune due to pernicious anemia or chronic Helicobacter pylori infection. In the former condition, there is severe atrophy of the corpus (oxyntic mucosa), with the antrum being speared. In contrast, chronic atrophic gastritis consequent to H. pylori infection is a multifocal pangastritis, involving independent foci in the corpus and antrum of the stomach. For the most part, these clinical conditions are silent; the only manifestation of both these forms of chronic atrophic gastritis is cobalamin (vitamin B(12)) deficiency. In the case of the autoimmune gastritis of pernicious anemia, cobalamin deficiency results form the absence of intrinsic factor. When cobalamin deficiency occurs in patients with H. pylori-related gastritis, for the most part, it is because these patients have hypochlorhydria and are therefore unable to release cobalamin from its bound form in food. Patients may have advanced neuropsychiatric manifestations of cobalamin deficiency and yet not be anemic, have a normal blood smear, and even have serum cobalamin levels in the normal range. The condition may be identified by demonstrating elevated levels of homocysteine and methylmalonic acid. Intestinal metaplasia may be of the enteric (grade I), enterocolic (grade II), or colonic (grade III) type. Grade III intestinal metaplasia has traditionally been thought of as the most sinister variety, although the extent of atrophy and metaplasia may be a better marker for premalignancy than the mere identification of small areas of grade III intestinal metaplasia. Over the years, there has been much disagreement and a high degree of interrater variability, especially between Western and Japanese pathologists, as to the different grades of dysplasia and early gastric cancer. Recent consensus conferences at Vienna and Padova have resulted in better understanding of what constitutes these lesions, and it is hoped that in the near future agreement between pathologists will improve as a consequence. For the present, it is imperative that clinicians obtain second opinions from two or more expert pathologists on biopsy specimens before arriving at a diagnosis of either low- or high-grade dysplasia. The former histologic diagnosis is tantamount to subjecting the patient to endoscopic surveillance and the latter is tantamount to a decision regarding the resection of the lesion, both decisions being psychologically disturbing for patients. At this time, population screening for H. pylori is not recommended in Western countries, but most experts would agree that H. pylori should be eradicated if detected as part of the appropriate investigation of a clinical disorder such as dyspepsia. Certain other specific conditions may also be considered to be precancerous, such as the gastric remnant after a partial gastrectomy and the gastric mucosa in familial adenomatous polyposis syndrome and in familial Peutz-Jeghers syndrome and perhaps Ménétrier disease.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, LMP 1074, P.O. Box 208030, New Haven, CT 06520-8030, U.S.A. cyrus.kapadia@yale.edu
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Kapadia
mesh_terms: D001706:Biopsy; D016099:Endoscopy, Gastrointestinal; D005757:Gastritis, Atrophic / Q000150:complications / Q000473:pathology*; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D008679:Metaplasia / Q000382:microbiology / Q000473:pathology; D011230:Precancerous Conditions / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology / Q000473:pathology*; D014806:Vitamin B 12 Deficiency / Q000150:complications