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

Author:

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

Abstract

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.

Funder

JSPS KAKENHI

Publisher

Springer Science and Business Media LLC

Subject

Gastroenterology

Reference41 articles.

1. Ueyama H, Yao T, Nakashima Y, et al. Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma. Am J Surg Pathol. 2010;34:609–19.

2. Ueyama H, Matsumoto K, Nagahara A, et al. Gastric adenocarcinoma of the fundic gland type (chief cell predominant type). Endoscopy. 2014;46:153–7.

3. Ueyama H, Yao T, Matsumoto K, et al. Establishment of endoscopic diagnosis for gastric adenocarcinoma of fundic gland type (chief cell predominant type) using magnifying endoscopy with narrow-band imaging. Stomach Intest. 2015;50:1533–47.

4. Ueyama H, Matsumoto K, Nagahara A, et al. Core tips for the endoscopic diagnosis of gastric adenocarcinoma of fundic gland type (chief cell predominant type). Gastrointest Endosc. 2016;58:1169–77.

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