Comparison of dysplastic fundic gland polyps in patients with and without familial adenomatous polyposis

Aims: Dysplastic fundic gland polyps (d-FGPs) typically arise in patients with familial adenomatous polyposis (FAP) but may occur in non-syndromic patients. They rarely become malignant, but their significance is unclear, especially in non-syndromic patients. We aimed to compare d-FGPs in patients with and without FAP, using clinicopathologic findings and beta-catenin immunohistochemistry (IHC). Methods and results: We identified 124 fundic gland polyps with low-grade dysplasia (LGD) or high-grade dysplasia (HGD) or indefinite for dysplasia (IFD) from 66 patients (27 with FAP; 39 non-syndromic). We recorded patient sex, age at first d-FGP, time until subsequent d-FGP (if any), history of non-gastric cancer (no patients had gastric cancer), proton-pump inhibitor use, and the presence of Helicobacter pylori. beta-Catenin IHC was performed on cases with available blocks. The mean age at d-FGP diagnosis was 31 years for FAP patients and 61 years for non-syndromic patients (P < 0.0001). Sixteen FAP patients (59%) developed at least one subsequent d-FGP, as compared with 10 (27%) non-syndromic patients (P = 0.0099). The median time between d-FGP detection was 11.5 months in FAP patients and 7 months in non-syndromic patients (P = 0.82). Six FAP patients (22%) and 17 non-syndromic patients (44%) had non-gastric malignancies (P = 0.11). beta-Catenin IHC showed nuclear positivity in 14 of 112 (13%) d-FGPs: 12 of 94 with LGD, two of three with HGD, and none of 15 with IFD polyps. Conclusions: Familial adenomatous polyposis patients develop d-FGPs earlier and more often develop additional ones than non-syndromic patients. d-FGPs in FAP and non-syndromic patients have similar low rates of beta-catenin nuclear IHC positivity. FAP and non-syndromic patients developed non-gastric cancers at similar rates, suggesting that d-FGPs may portend a general increased risk of carcinogenesis in non-syndromic patients.