Gastric dysplastic lesions in Helicobacter pylori‐naïve stomach: Foveolar‐type adenoma and intestinal‐type dysplasia

Abstract

Reports of Helicobacter pylori (Hp)‐naïve gastric neoplasm (HpNGN) cases have been rapidly increasing due to the recent increase in the Hp‐naïve population in Japan. Most HpNGNs exhibit the gastric immunophenotype and a low malignant potential regardless of histological type. Especially, foveolar‐type gastric adenoma (FGA) and intestinal‐type gastric dysplasia (IGD) rarely progress to invasive carcinoma. FGA is a foveolar epithelial neoplasm that occurs in the fundic gland (oxyntic gland) mucosa and is classified as the flat type or raspberry type (FGA‐RA). The flat type is a large, whitish flatly elevated lesion while FGA‐RA is a small reddish polyp. Genomically, the flat type is characterized by APC and KRAS gene mutations and FGA‐RA by a common single nucleotide variant in the KLF4 gene. This KLF4 single‐nucleotide variant reportedly induces gastric foveolar epithelial tumorigenesis and activates both cell proliferation and apoptosis, leading to its slow‐growing nature. IGD consists of an intestinalized epithelial dysplasia that develops in the pyloric gland mucosa, characterized as a superficial depressed lesion surrounded by raised mucosa showing a gastritis‐like appearance. Immunohistochemically, it exhibits an intestinal or gastrointestinal phenotype and, frequently, p53 overexpression. Thus, IGD shows unique characteristics in HpNGNs and a potential multistep tumorigenic process.