Clinicopathological and Genetic Features in Superficial Nonampullary Duodenal Epithelial Tumors.

Abstract

Background and Aim: Superficial nonampullary duodenal epithelial tumors (SNADETs) that are pathologically classified as gastric-type might manifest a more aggressive behavior than the intestinal type. However, the details of their histologic and genetic features remain unclear because of their rarity. This study was aimed at identifying clinicopathological findings and early genomic events in gastric-type SNADETs treated with endoscopic resection. Methods: We retrospectively analyzed 204 patients with SNADETs between January 2011 and September 2020. Immunohistochemical analysis for β-catenin and targeted exome sequence analysis of 50 cancer-related genes using next-generation sequencing were performed for the representative cases. Results: Among the 204 SNADETs cases, only nine (4.4%) were gastric type; the remaining 195 cases were intestinal type. Among the gastric-type tumors, seven were adenomas and two were adenocarcinomas, whereas only three of the 195 intestinal-type tumors were adenocarcinomas. Nuclear expression of β-catenin was observed in three of the nine (33%) gastric-type tumors and in eight of the 10 (80%) intestinal-type tumors. The most prevalent abnormality among the 50 genes tested in gastric-type tumors was GNAS mutation (89%), whereas that in intestinal-type tumors was APC mutation (67%). All gastric-type adenocarcinomas had GNAS mutations as well as adenomas, while APC mutations were absent in intestinal-type adenocarcinomas and present in most adenomas. Conclusions: GNAS mutations are more common in gastric-type SNADETs than in the intestinal type. As GNAS mutations are continuously present from adenoma to adenocarcinoma, resection at the adenoma stage is desirable.