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

• DOI: 10.1007/s00535-021-01813-z
• Publication Date: 2021-07-15T21:02:36Z
• Authors: 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 Yahagi; Yumiko 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
• Keywords: Original Article—Alimentary Tract; Male; Middle Aged; 3. Good health; 03 medical and health sciences; Polyps; 0302 clinical medicine; Stomach Neoplasms; Humans; Cell Lineage; Female; Aged; Pain Measurement; Retrospective Studies

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.