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

J Gastroenterol. 2021 Sep;56(9):814-828. doi: 10.1007/s00535-021-01813-z. Epub 2021 Jul 15.


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.

Keywords: Gastric adenocarcinoma of fundic-gland mucosa type; Gastric adenocarcinoma of fundic-gland type; Gastric epithelial neoplasm of fundic-gland mucosa lineage; Oxyntic gland adenoma.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Cell Lineage*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain Measurement / methods
  • Pain Measurement / statistics & numerical data
  • Polyps / classification*
  • Polyps / pathology
  • Retrospective Studies
  • Stomach Neoplasms / classification*
  • Stomach Neoplasms / pathology

Supplementary concepts

  • Polyposis Of Gastric Fundus Without Polyposis Coli