Beyond metaplasia: unraveling the complex pathogenesis of autoimmune atrophic gastritis and its implications for gastric cancer risk.

This article focuses on the relationship between autoimmune gastritis (AIG) and gastric neoplasms, particularly gastric adenocarcinoma and neuroendocrine tumors (NETs). AIG is characterized by immune-mediated destruction of gastric parietal cells, leading to oxyntic atrophy, achlorhydria, and hypergastrinemia. While AIG has been historically linked to an increased risk of gastric adenocarcinoma, recent evidence suggests that this risk is lower than previously thought, especially in Helicobacter pylori (H. pylori)-negative patients, with much of the cancer risk attributed to concurrent or past H. pylori infection. In contrast, AIG is strongly associated with a higher incidence of type I gastric NETs, driven by hypergastrinemia-induced enterochromaffin-like (ECL) cell hyperplasia. The article highlights distinct immune and molecular mechanisms in AIG, including a T cell-dominated microenvironment, reduced macrophage infiltration, and specific metaplastic patterns (pseudopyloric and complete intestinal metaplasia), which may limit carcinogenic progression compared to H. pylori-associated gastritis. Diagnostic challenges persist due to overlapping features with H. pylori gastritis, but emerging immune profiling and molecular assays offer promise for improved accuracy. Given these findings, tailored surveillance focusing on NETs and adenomatous polyps is recommended for AIG patients, particularly those with hypergastrinemia and extensive atrophy, while further research is needed to clarify AIG's carcinogenic potential and refine management strategies.