Gastric Epithelial Neoplasms in Helicobacter pylori-Uninfected Patients

In recent years, several studies have described the clinicopathological characteristics of Helicobacter pylori (H. pylori)-uninfected gastric cancer. This entity is now recognized as one of the major topics in gastric cancer research and clinical practice.

Currently, H. pylori-uninfected gastric epithelial neoplasms (HpUGENs; excluding adenocarcinomas of the esophagogastric junction and gastric neuroendocrine tumors) are classified into seven subtypes in our research results: raspberry-type gastric epithelial neoplasm (GEN; foveolar-type adenoma), whitish flat elevated-type GEN (GEN with gastric phenotype), gastric adenocarcinoma of fundic gland type (GA-FG), gastric adenocarcinoma of the fundic gland mucosa type (GA-FGM), other GEN with a gastric phenotype (complex type of GEN with gastric phenotype), GEN with an intestinal or gastrointestinal mixed phenotype arising in the pyloric gland region, and signet ring cell carcinoma.

This study outlines our analysis of current cases, detailing the endoscopic and clinicopathological characteristics of HpUGENs, and provides practical insights for their endoscopic and pathological diagnosis. Since many of these neoplasms histologically show low-grade atypia, they are sometimes diagnosed as gastric adenoma or gastric dysplasia rather than adenocarcinoma in the World Health Organization classification, highlighting the need for standardized histopathological diagnostic criteria of GENs with low-grade atypia. Moreover, as no clinical practice guidelines have yet been established for HpUGENs, future research should aim to elucidate the relationship between early and advanced lesions, perform comprehensive analyses of H. pylori-uninfected advanced gastric cancer, and conduct molecular biological studies to achieve a better understanding of the entire disease spectrum and to establish evidence-based clinical guidelines.