Deciphering the clinical spectrum of gastric disease in patients with juvenile polyposis syndrome

Abstract

Background and Aims

Juvenile polyposis syndrome (JPS) is a rare hereditary autosomal dominant cancer-predisposition syndrome caused by germline pathogenic variants (PVs) located in SMAD4 or BMPR1A genes. Accurate clinical and endoscopic data regarding the evolution of gastric lesions remain sparse.

Methods

Clinical, endoscopic, genetic, and pathologic data from patients with SMAD4 or BMPR1A PVs included between 2007 and 2020 in the French network on rare digestive polyposis (RENAPOL [French National Polyposis Register]) database were prospectively collected to address uncertainties regarding gastric involvement.

Results

Thirty-six patients were included: 25 (69.5%) had SMAD4 PVs, and 11 had BMPR1A PVs. For SMAD4 PV carriers, median age at inclusion was 43.0 years (range, 10-78 years). At baseline EGD, 22 (88%) of 25 patients exhibited at least 1 gastric juvenile polyp, and 5 (20%) of 25 had macroscopic signs of inflammatory gastritis. Early gastric disease was mostly located under the cardia, then progressed to the gastric antrum and body. During a mean follow-up period of 55.0 months, 12 of 25 patients had gastric disease progression (ie, new juvenile polyps [91.6%], diffuse gastric involvement [41.6%], inflammatory flat progression [25%]). Among 62 biopsies, low-grade dysplasia was observed in 5 (7.5%) samples from 2 patients. Nine carriers (36%) underwent gastrectomy (mean age, 47.2 years) due to diffuse gastric involvement or worsening clinical symptoms. Gastric adenocarcinoma (T1) was found in 1 gastrectomy specimen. Among the 11 patients with BMPR1A PVs, 2 had gastric hamartomatomas at baseline EGD, none with dysplasia or symptoms.

Conclusions

Gastric involvement in JPS seems to be progressive over a lifetime, initiates in the cardia area, and mostly involves SMAD4 PV carriers.