Incidence and natural history of gastric high-grade dysplasia in patients with familial adenomatous polyposis syndrome

Abstract

Familial adenomatous polyposis (FAP) is characterized by high risks of colonic and extracolonic tumors. Recent studies have suggested a rising risk for gastric cancer (GC). We sought to define the spectrum of premalignant gastric polyps in FAP, focusing on high-grade dysplasia (HGD). The gastric phenotypes of 118 patients diagnosed with FAP or attenuated FAP in our Hereditary Gastrointestinal Cancer Registry were retrospectively reviewed. To analyze the clinical features associated with the diagnosis of HGD, we established an age- and sex-matched control group of FAP patients from our cohort without gastric HGD in a 4:1 ratio. The spectrum and frequency of gastric polyps in individuals with FAP included fundic gland polyps (67.9%), hyperplastic polyps/foveolar hyperplasia (19.6%), tubular adenomas (15.2%), foveolar adenomas (10.7%), and pyloric gland adenomas (6.3%). Ten patients (8.9%) exhibited gastric HGD at a mean age of 55 ± 13 years, and HGD was seen in all polyp types. When compared with control subjects, HGD was associated with a high diversity of gastric polyp histology, prior low-grade dysplasia, severe gastric polyposis, and prior Whipple surgery (P= 2.0E-5, .003, .024, and .04, respectively). Two patients (1.7%) with HGD were diagnosed with GC. However, the remaining 8 patients with HGD have been under surveillance for an average of 5.8 ± 4.5 years without progression to GC. Gastric HGD in FAP may be more common than previously appreciated. The natural history of HGD is variable, and most patients with HGD do not appear to progress to GC.