Journal Article

Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type

Uchita Kunihisa, Okamoto Kazuhisa, Osako Ayumi, Oono Yasuhiro, Uemura, Naomi, Nagahara Akihito, Maehata Tadateru, Uraushihara Koji, Maruyama Yasuhiko, Hayashi Takuo, Matsumoto Kohei, Saito Tsuyoshi, Yao, Takashi, Kurahara Koichi, Chiba Tsutomu, Matsuo Yasumasa, Yasuhara Yumiko, Murakami Kazunari, Ueyama Hiroya, Oshiro Yumi, Kadota Tomohiro, Akazawa Yoichi, Fujioka Shin, Fukuda Masayoshi, Tomita Natsumi, Kusumoto Chiaki, Yagi Kazuyoshi, Yamane Tetsumi, Matsuo Taiji, Yamada Masayoshi, Watanabe Sumio, Tsuyama Sho, Matsumoto Kenshi, Yada Tomoyuki, Kato Motohiko, Oda Ichiro, Ito Masanori, Kato Mototsugu, Yahagi Naohisa, Ono Shoko, Hashimoto, Takashi

2021

Overview

BackgroundGastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML.MethodsOne hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation.ResultsGEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing.ConclusionsWe have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

• Publisher: Springer Nature B.V
• Subject: Adenocarcinoma / Adenoma / Cancer / Classification / Etiology / Gastric cancer / Glands / Mucosa / Mutation / Next-generation sequencing / Tumors