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autoimmune metaplastic atrophic gastritis

Monday 10 December 2012

AMAG

Definition: Autoimmune metaplastic atrophic gastritis (AMAG) is an early manifestation of pernicious anemia that precedes the hematologic changes by years to decades.

Autoimmune metaplastic atrophic gastritis (AMAG) is associated with metaplastic changes and neoplasms, including pyloric gland adenomas (PGAs).

Diagnosing autoimmune gastritis is important because it carries a risk for pernicious anemia and is associated with an increased risk for gastric cancer.

In AMAG, the parietal cell mass of the body of the stomach is chronically inflamed, resulting in destruction and loss of oxyntic mucosa cells (especially parietal cells) and damage to the overlying foveolar epithelial cells.

This chronic damage results in abnormal re-epithelization manifesting in intestinal and pyloric metaplasia.

The damaged epithelium is at higher risk for neoplastic transformation.

An inpatient hospital registry-based cohort study of patients with pernicious anemia showed an overall 2-fold increase in incidence of gastric adenocarcinomas.

Definition: Autoimmune metaplastic atrophic gastritis (AMAG) is an early manifestation of pernicious anemia that precedes the hematologic changes by years to decades. It is associated with metaplastic changes and neoplasms, including pyloric gland adenomas (PGAs).

Synopsis

- negative gastrin
- linear and nodular enterochromaffin-like cell hyperplasia (chromogranin)
- gastric polyps

  • gastric hyperplastic polyps
  • gastric oxyntic mucosa pseudopolyps
  • intestinal-type gastric adenomas
  • PGAs
  • gastric well-differentiated neuroendocrine neoplasms (gastric carcinoid)
  • gastric gastrointestinal stromal tumor (gastric GIST)
  • gastric lymphomas
  • gastric adenocarcinomas

AMAG occurred with similar frequency across all racial groups. Although PGAs are associated with AMAG, they remain rare in the setting of AMAG.

Microscopy

Early cases of AMAG do not always have complete loss of oxyntic glands, but they do have the histologic findings of:
- (1) body-predominant lymphoplasmacytic infiltrates in the lamina propria,
- (2) oxyntic gland destruction,
- (3) atrophy of oxyntic mucosa with pyloric and/or intestinal metaplasia,
- (4) enterochromaffin-like cell linear hyperplasia (at least 5 adjacent chromogranin labeling cells) or enterochromaffin-like cell nodular hyperplasia.

In completely established autoimmune gastritis, the histologic features used include an atrophic gastritis pattern limited to the body of the stomach with replacement of oxyntic glands with pyloric and/or intestinal metaplasia.

The term “pyloric metaplasia" can be used, although some observers prefer the term “pseudopyloric” as the glands do not secrete gastrin as normal pyloric glands do and lack G cells on immunolabeling.

Gastric hyperplastic polyp

Patients with AMAG are very likely to develop polyps and neoplasms.

The most common type of gastric polyp encountered in our AMAG population, not surprisingly, was the hyperplastic polyp. This confirms the extensively documented association between AMAG and gastric hyperplastic polyps. The hyperplastic polyps that arise in these patients are presumably a result of chronic gastric autoimmune injury.

Type 1 gastric carcinoid

The second most commonly biopsied lesion was formed by a well-differentiated neuroendocrine neoplasm (type 1 carcinoid tumor).

Although such tumors reportedly account for less than 2% of gastric polyps, they are common in the setting of AMAG and in this series they were found in 46 of 461 (approximately 10%) patients.

These neoplasms form as a result of hypochlorohydria from loss of the parietal cell mass leading to stimulation of the patient’s antral G cells which in turn results in gastrin secretion and hypergastrinemia.

Most so-called type 1 gastric carcinoids are indolent lesions. In patients with multiple lesions, however, antrectomy is sometimes advocated to remove the source of excess gastrin, thereby abrogating trophic effects on the neoplasms.

In a study (#20975338#), patients with AMAG were also likely to develop intestinal-type gastric adenomas in association with intestinal metaplasia. Such polyps merit follow-up, as they are associated with the development of additional adenomas and with dysplasia or carcinomas in surrounding flat mucosa.

Not surprisingly, patients with AMAG do not develop fundic gland polyps, which are otherwise the most common type of gastric polyp as fundic gland polyps typically arise in intact oxyntic mucosa, which is absent in patients with AMAG. (#20975338#)

However, patients with AMAG do form oxyntic gland pseudopolyps; there were 20 oxyntic gland pseudopolyps in our patients with AMAG.

These pseudopolyps are islands of residual intact oxyntic mucosa in a flattened sea of attenuated atrophic mucosa. (#20975338#)

As oxyntic mucosa pseudopolyps seem histologically as relatively unremarkable oxyntic mucosa, diagnosing them requires attention to the atrophic appearance of the surrounding flat body mucosa and correlation with the endoscopic impression of a polyp. (#20975338#)

PGAs are a rare neoplasm of the gastric epithelium which has been frequently associated with AMAG.

PGA was briefly mentioned in the 1990 World Health Organization classification of esophageal and gastric tumors but interest in the entity remained dormant until 2003 when Vieth and his colleagues reported a large series of such lesions.

PGAs may also arise in a host of other sites; for example, in our earlier series they were more common in the small intestine than in the stomach.

PGAs may be cytologically bland without conventional adenomatous dysplasia.

As they are recently recognized and associated with AMAG, we expected to uncover examples that had been previously interpreted as hyperplastic polyps in our archives.

However, review of archived cases from patients with well-characterized autoimmune gastritis (using immunolabeling for gastrin and chromogranin) only revealed a single case of PGA that was not recognized at the original time of diagnosis.

There were a total of 3 cases of PGAs identified in this 20-year study of autoimmune gastritis in a high-volume hospital’s “in-house” material.

This paucity of cases is unexpected and somewhat disappointing as prior studies of PGAs indicated a strong association with a background of AMAG.

As this study is limited to cases with a well-established diagnosis of AMAG, it is possible that this study did not include PGAs from patients with no diagnosis of the background gastric mucosa.

Indeed, if a PGA arising out of AMAG had been previously classified as an intestinal-type gastric adenoma, and no material was available to characterize the background of AMAG, then it would not have been included in this study.

In cases diagnosed with a background of AMAG, PGA is a rare entity.

Epidemiology

AMAG occurred with similar frequency across all racial groups. Although PGAs are associated with AMAG, they remain rare in the setting of AMAG.

Autoimmune metaplastic atrophic gastritis (AMAG) and its end manifestation, pernicious anemia, have been historically regarded as conditions of elderly female patients of northern European descent.

However, studies in the past 2 decades have clearly indicated that pernicious anemia is neither racially nor ethnically specific for Europeans.

In a population study of people above 60 years of age, pernicious anemia was slightly more prevalent in African-American women (4.3%) compared with White women (4.0%).

Indeed, the median age of diagnosis of pernicious anemia in African-American and non-white Hispanics is younger than that in White patients.

Pernicous anemia

Autoimmune gastritis is the precursor and etiologic cause of the majority of cases of pernicious anemia and may precede pernicious anemia by years to decades.

Given the recent epidemiologic studies of pernicious anemia, the differential diagnosis of AMAG should be considered in a wider range of age and ethnicity.

Pyloric gland adenomas (PGAs)

Pyloric gland adenomas (PGAs) are one type of neoplasm that can arise in the setting of AMAG, presumably through a metaplasia-neoplasia sequence akin to that associated with intestinal metaplasia.

In the 2 largest studies of gastric PGAs, greater than one-third of PGAs arose in background gastric mucosa with AMAG.

The molecular pathogenesis of PGAs has not been extensively investigated, but the high association with AMAG suggests that they may arise through a common mechanism in the damaged epithelium of autoimmune gastritis.

See also

- body-predominant autoimmune gastritis
- autoimmune gastritis
- gastritis
- pyloric gland adenoma

References

- Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting. Park JY, Cornish TC, Lam-Himlin D, Shi C, Montgomery E. Am J Surg Pathol. 2010 Nov;34(11):1591-8. PMID: #20975338#

- Hyperplastic, dysplastic, and neoplastic enterochromaffin-like-cell proliferations of the gastric mucosa. Classification and histogenesis. Solcia E, Fiocca R, Villani L, Luinetti O, Capella C. Am J Surg Pathol. 1995;19 Suppl 1:S1-7. PMID: #7762735#

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