Spectrum of gastric neoplasms in Helicobacter pylori‐naïve patients

Chronic Helicobacter pylori ( Hp ) infection is the largest etiological factor for gastric cancer, but in recent years the reports of Hp ‐naïve gastric neoplasms (HpNGNs) have increased as the Hp ‐infected population in Japan has been declining. The histopathologic spectrum of HpNGNs differs significantly from that of conventional Hp ‐infected gastric neoplasms. Molecularly, the former harbor considerably fewer genetic and epigenetic abnormalities, reflecting the absence of chronic inflammatory conditions in the gastric mucosa. The majority of HpNGNs fall within several specific histological entities; each arise from particular background mucosa. Most originate from the fundic gland mucosa and have a gastric immunophenotype, as seen in foveolar‐type gastric adenoma (FGA), oxyntic gland adenoma (OGA)/gastric adenocarcinoma of fundic gland type (GA‐FG), signet‐ring cell carcinoma (SRCC), and sporadic fundic gland polyp with dysplasia (FGPD). In contrast, tumors arising from the pyloric or cardiac gland mucosa have a diverse immunophenotype, as seen in intestinal‐type gastric dysplasia (IGD) and gastric cardiac carcinoma. FGA, FGPD, SRCC, and IGD are mostly found as small intramucosal lesions. OGA/GA‐FG frequently progresses to invasive carcinoma, but only a few have lymph node metastases. Thus, these tumors are regarded as precancerous lesions by Western pathologists, while in Japan they tend to be diagnosed as carcinomas, even in cases of low‐grade dysplasia. Gastric cardiac carcinomas, on the other hand, are often found as advanced carcinomas and harbor a high malignant biological potential. A new diagnostic framework for gastric neoplasms is required in the present era of Hp ‐naïve individuals in Japan.