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

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

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Gastric 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. Methods: One 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. Results: GEN-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. Conclusions: We 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.

Original languageEnglish
Pages (from-to)814-828
Number of pages15
JournalJournal of gastroenterology
Volume56
Issue number9
DOIs
Publication statusPublished - Sep 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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