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gastric intestinal metaplasia

Thursday 13 December 2007


Definition: Intestinal metaplasia is the transformation (metaplasia) of epithelium, usually of the stomach or the esophagus , to a type that bears some resemblance to the intestine as seen in Barrett’s esophagus.

Chronic infection caused by H. pylori infection in the stomach and GERD in the esophagus are seen as the primary instigators of metaplasia and subsequent adenocarcinoma formation.

Initially, the transformed eptithelium bears resemblance to the small intestine; in the later stages, the epithelium resembles the colon. It is characterized by the appearance of goblet cells and expression of intestinal cell markers such as Cdx2.

Epidemiology - Etiology

Gastric intestinal metaplasia (GIM) is quite common. Thirteen per-cent of consecutive American Caucasians undergoing upper endoscopy and 50% of Hispanics and Blacks had evidence of gastric IM when routine protocol-mapping biopsies of the normal appearing mucosa were performed.

It is believed to represent a response to chronic injury, often caused by HP infections. The risk factors for developing IM resemble those of gastric cancer in high-risk populations. Thus, IM is more frequent in smokers and in Asians than in other nationalities.

Diets deficient in fresh fruits and vegetables combined with a high salt and nitrite content are common to both conditions.

One of the more contentious issues is the significance of IM at the cardia.

Evolution - Complications

IM has been implicated in the development of both gastric and esophageal carcinoma.

However, while gastric IM increases the risk ofgastric cancer, with the increased risk being proportional to the extent of the metaplasia, the risk is much lower than Barrett esophagus (BE) progressing to cancer, at least in the United States.

Thus, it is important to try to distinguish the IM of BE from the gastric type of IM.

As noted earlier, IM often complicates MAG. Over time, widened areas of gastric atrophy, often accompanied by gastric IM, replace the chronic active gastritis associated with HP infections.

IM begins at the antral–corpus junction in a patchy, multifocal fashion, and then spreads both distally and proximally to involve the antrum and fundus.

The areas of IM increase with patient age and often become confluent, replacing large areas of the gastric mucosa.

This process can be highlighted by staining gastric resection specimens for alkaline phosphatase activity since only intestinal-type epithelium expresses the enzyme.

IM more frequently coexists with gastric cancer than with gastric ulcer, but it shows the same distribution when associated with either condition.

Molecular biology

IM may result from mutations caused by nitrosative deamination of DNA by nitric oxide generated by inflammatory cells in stem cells in the replicating compartment of gastric glands in response to HP infection.

IM may also represent a change that raises gastric pH by replacing the oxyntic mucosa with an epithelium that favors the growth of bacteria capable of generating endogenous mutagens.

Down-regulation of Sox2 and ectopic expression of Cdx2, an intestine-specific transcription factor belonging to the caudal-related homeobox gene family, are important inthe development of intestinal metaplasia.

Cdx2 expression may lead to activation of intestine-specific gene transcripts, therebydirecting intestinal epithelial development and differentiation in the metaplastic areas.


In intestinal metaplasia, the cells that normally line the gastric mucosa (surface epithelium, foveolar epithelium, and glands) are replaced by an epithelium resembling that ofthe small or large intestine.

The earliest metaplastic changes consist of the appearance of mucin-negative absorptive enterocytes with a brush border alternating with Alcian blue–positive goblet cells.

In young individuals withless extensive intestinal metaplasia, the metaplastic glands resemble normal small intestinal epithelium.

Initially, only the epithelial type changes, but later the mucosal architecture acquires a small intestinal villiform architecture, often containing Paneth cells at the base ofthe pits.

Paneth cells in areas of intestinal metaplasia do not have the same uniform distribution seen in the intestine.

In some cases, they are limited to the antral corpus border and are lacking in intestinal metaplasia in the distal stomach.

They may lie in the superficial portions of the metaplastic gland; ultrastructurally some Paneth cells contain both Paneth cell granules and mucinous vacuoles.

Goblet cells are easily seen on H&E-stained sections.

However, an Alcian blue/PAS stain is commonly used to identify the goblet cells since it stains all acidic mucins blue-purple and neutral mucins magenta and is easy to performand interpret.

Some metaplastic cells exclusively secrete sialomucins and contain a “complete” set of normal small intestinal digestive enzymes (sucrase, trehalase,and alkaline phosphatase).

This type of metaplasia is characterized by weak expression of (intestinal) MUC2 and absence of gastric (MUC1, MUC5AC, and MUC6) mucins and cytokeratin (CK) immunoreactivity.

These cells have a complete switch in their differentiation program from a gastric to an intestinal phenotype, and they have been termed small intestinal, complete ,or type I IM.

Later, as the disease becomes more extensive, the enterocytes disappear and are replaced by columnar cells containing abundant mucous droplets in their cytoplasm.

These metaplastic cells lack a well-developed brush borderand secrete both sialomucins and sulfomucins.

They lack the complete set of digestive enzymes. This type of metaplasia has been termed enterocolonic, colonic, type II, or incomplete metaplasia.

Incomplete metaplasia strongly expresses MUC1, MUC5AC, MUC6, MUC2, Das-1 (a largeintestinal antigen), and CK7.

Incomplete IM shows amixed gastric and intestinal phenotype reflecting aberrant differentiation programs that do not reproduce any phenotype occurring in normal adult gastrointestinal epithe-lia (213).

Several types of metaplastic epithelium maydevelop within the same stomach.

Intestinal metaplasia occurs concurrently with atrophic gastritis or independently.

Incomplete IM frequently associates with areas of dysplasia and carcinoma.

The endocrine cell population in the different types of metaplasia changes with the phenotype ofthe non endocrinecells.

In patients with antral gastritis, the proportion of gastrin and somatostatin neuroendocrine cells decreases as the glands pass from a mixed gastric–intestinal phenotype to a pure intestinal phenotype.

There is a corresponding increase in intestinal-type endocrine cells that produce glicentin, gastric inhibitory polypeptide, and glucagon-like peptide 1.

Gastrin-positive cells emerge in the areas of pyloric metaplasia.

A distinct cellular subset consisting of groups of undifferentiated columnar cells lies on the interfoveolar crests of the gastric mucosa.

These cells differ from both normal foveolar cells and metaplastic cells, and they show a close association with atrophic gastritis, particularly in the presence of sulfomucin-secreting IM.

This lesion, termed gastric tip lesion, may provide a link between this type of metaplasia and the intestinal variant of gastric adenocarcinoma that develops in intestinalized areas.

Histologically the large, columnar, pseudostratified cells have central nucleiand lack the prominent cup-shaped mucus collection typical of foveolar cells.

The cells cluster in groups ofup to 25 cells and they show an abrupt transition with the adjacent normal foveolar epithelium.

There is no consensus on the role ofthe various IM sub-types and subsequent risk ofdeveloping carcinoma, and the question then arises as to what to do with a patient witha diagnosis ofgastric IM.

The answer to this depends onwhether the patient has a family history ofgastric cancer, has migrated from a high-risk geographic location, lives in a high-risk location, or is a member of an ethnic population with a high risk of developing carcinoma, and whether there is evidence of dysplasia on the biopsy.

It can be assumed that any person with an increased cancer risk as defined by the factors noted in the previous sentence or those with extensive metaplasia is at high risk for gastric cancer and should be subject to periodic screening.

The extent of the IM is probably more important than the metaplastic subtype.

The prudent thing to do if IM is detected in a biopsy is to describe the type of metaplasia that is present, to make some estimate as to whether the process is focal or diffuse in nature, and to note whether or not dysplasia is also present.


The guidelines of the Sydney System can be used to grade the intestinal metaplasia.

See also

- gastric anomalies

  • gastric lesions


  • Intestinal metaplasia in stomach (ABPAS)
  • Intestinal metaplasia in stomach (ABPAS)
  • Intestinal metaplasia in stomach (ABPAS)
  • Intestinal metaplasia in stomach (ABPAS)
  • Intestinal metaplasia in stomach (ABPAS)
  • Normal ABPAS in stomach