Unmasking the high-risk phenotype in autoimmune gastritis: A pathologist’s roadmap for the clinician

Abstract

Li et al’s recent work on the risk factors for autoimmune gastritis provides clinical context for the vast majority of gastric neuroendocrine tumors (G-NETs). However, a deeper understanding of the underlying pathology is needed for precise clinical management. Our letter details the predictable stepwise progression of type 1 G-NETs from autoimmune-driven corporal atrophy and hypergastrinemia to a clear microscopic sequence of enterochromaffin-like cell precursor lesions, including linear hyperplasia, micronodular hyperplasia, and dysplasia. We highlight the definitive diagnostic thresholds that separate these precursors from overt neoplasia: The 0.5 mm size rule and the presence of submucosal invasion. We advocate for a “prognostic biopsy protocol” in which pathologists actively report these precursor lesions and use Ki-67 to grade G-NETs, providing a quantitative risk assessment. This pathology-centric approach transforms surveillance, allowing clinicians to act on objective microscopic milestones rather than waiting for macroscopically visible tumors.

Keywords: Pathology; Autoimmune gastritis; Gastric neuroendocrine tumors; Precursor lesions; Dysplasia

Core Tip: Clinical risk models identify patients with autoimmune gastritis who may develop neuroendocrine tumors, but pathology guides what to do next. We advocate for a “prognostic biopsy protocol” where pathologists report the specific stage of microscopic pre-cancerous lesions. Finding high-risk changes, especially dysplasia, serves as a clear trigger to intensify surveillance. This approach allows clinicians to manage risk proactively based on a patient’s real-time biology, rather than waiting for a visible tumor to develop.