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Major Genetic Syndromes

Table 5. Extracolonic Tumor Risks in Familial Adenomatous Polyposis continued...

Stomach tumors

The most common FAP-related gastric polyps are fundic gland polyps (FGPs). FGPs are often diffuse and not amenable to endoscopic removal. The incidence of FGPs has been estimated to be as high as 60% in patients with FAP, compared with 0.8% to 1.9% in the general population.[16,18,50,51,52,53,54] These polyps consist of distorted fundic glands containing microcysts lined with fundic-type epithelial cells or foveolar mucous cells.[55,56]

The hyperplastic surface epithelium is, by definition, nonneoplastic. Accordingly, FGPs have not been considered precancerous; in Western FAP patients the risk of stomach cancer is minimally increased, if at all. However, case reports of stomach cancer appearing to arise from FGPs have led to a reexamination of this issue.[18,57] In one FAP series, focal dysplasia was evident in the surface epithelium of FGPs in 25% of patients versus 1% of sporadic FGPs.[56] In a prospective study of patients with FAP undergoing surveillance with esophagogastroduodenoscopy, FGPs were detected in 88% of the patients. Low-grade dysplasia was detected in 38% of these patients, whereas high-grade dysplasia was detected in 3% of these patients. In the author's view, if a polyp with high-grade dysplasia is identified, polypectomy can be considered with repeat endoscopic surveillance in 3 to 6 months. Consideration for treatment with daily proton-pump inhibitors also may be given.[58]

Complicating the issue of differential diagnosis, FGPs have been increasingly recognized in non-FAP patients consuming proton pump inhibitors (PPIs).[56,59] FGPs in this setting commonly show a "PPI effect" consisting of congestion of secretory granules in parietal cells, leading to irregular bulging of individual cells into the lumen of glands. To the trained eye, the presence of dysplasia and the concomitant absence of a characteristic PPI effect can be considered highly suggestive of the presence of underlying FAP. The number of FGPs tends to be greater in FAP than that seen in patients consuming PPIs, although there is some overlap.

Gastric adenomas also occur in FAP patients. The incidence of gastric adenomas in Western patients has been reported to be between 2% and 12%, whereas in Japan, it has been reported to be between 39% and 50%.[60,61,62,63] These adenomas can progress to carcinoma. FAP patients in Korea and Japan are reported to have a threefold to fourfold increased gastric cancer risk compared with their general population, a finding not observed in Western populations.[64,65,66,67] The recommended management for gastric adenomas is endoscopic polypectomy. The management of adenomas in the stomach is usually individualized based on the size of the adenoma and the degree of dysplasia.

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