Pathological Diversity of Gastric Cancer from the Viewpoint of Background Condition

<b><i>Background:</i></b> The prevalence of <i>Helicobacter pylori</i> infection and chronic atrophic gastritis is decreasing in Japan, which has led to a decline in the incidence of gastric cancer. However, there are various subtypes of gastric cancer that arise from the background mucosa without <i>H. pylori</i> infection, and their histological characteristics are distinct from those of gastric cancer with chronic atrophic gastritis. <b><i>Summary:</i></b> In this review, after a brief overview of conventional gastric carcinoma with <i>H. pylori</i> infection, including its molecular classification, histological characteristics of gastric cancer after eradicating <i>H. pylori</i> are described. The clinicopathological characteristics of gastric cancer independent of <i>H. pylori</i> infection are then explained. Autoimmune gastritis (type A gastritis) increases the risk of gastric adenocarcinoma and neuroendocrine tumors. Gastric carcinoma without <i>H. pylori</i> infection has various histological subtypes, including fundic gland-type adenocarcinoma (oxyntic gland adenoma), foveolar-type adenocarcinoma/adenoma, signet ring cell carcinoma, and adenocarcinoma of the esophagogastric junction. In addition, some familial gastric cancer syndromes, including hereditary diffuse gastric cancer, familial adenomatous polyposis, and gastric adenocarcinoma and proximal polyposis of the stomach, are also discussed. <b><i>Key Messages:</i></b> Although the incidence of gastric cancer will decrease in the near future, the diversity of gastric cancer pathology will be enhanced because <i>H. pylori</i>-negative gastric cancer will have a significant impact on the clinical practice guidelines for gastric cancer. Gastroenterologists and pathologists should be aware of the morphological diversity of <i>H. pylori</i>-negative gastric cancer, and attention should be paid to the status of the background gastric mucosa while examining gastric cancer.