Aim:Helicobacter pylori-naïve gastric cancers(GCs) have not been well documented. We aimed to characterize early H. pylori-naïve GCs. Subjects and Methods: Of 666 patients with GC resected by endoscopic submucosal dissection, H. pylori-naïve patients were extracted according to the definition: no H. pylori eradication history, negative for serum H. pylori-antibody and current H. pylori-infection tests, and no gastric atrophy by pepsinogen (PG) test, endoscopy, and histology. Results: It was found that 16 GCs were H. pylori-naïve, and classified into undifferentiated and differentiated type adenocarcinoma. All 9 undifferentiated type GCs were pale, depressed, mucosal pure signet ring cell adenocarcinoma except one of them and 7 differentiated type GCs were classified into 3 fundic gland type GCs and 4 foveolar type GCs. All fundic gland type GCs positive for PG-1 were cardia small submucosal tumor (SMT)-like protrusions with dilated vessels on the surface. All 4 foveolar type GCs were composed of dysplastic clear cells resembling foveolar epithelium, negative for PG-1 but positive for mucin 6 (MUC6) and MUC5AC. Endoscopically, all were laterally spreading elevations with papillary or villous surface. Conclusions:H. pylori-naïve GCs were infrequent at 2.5%, and classified into 3 types: a small pale depression of signet ring cell adenocarcinoma, a small SMT-like protrusion of fundic gland type GC, and a large laterally spreading elevation of foveolar type GC.

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