Clinicopathological characterization of extremely low-grade fundic gland tumors: a study of 11 of a variant of oxyntic gland adenomas.

BACKGROUND: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a well-characterized entity showing differentiation toward oxyntic gland cells. However, extremely low-grade lesions that do not meet the established diagnostic criteria for GA-FG are increasingly encountered in clinical practice. We aimed to characterize these lesions, which we termed a variant of oxyntic gland adenomas (OGAs). METHODS: We retrospectively reviewed 11 lesions in 10 patients with OGAs identified between 2018 and 2025. All lesions were managed via endoscopic surveillance. We evaluated the clinicopathological and endoscopic features of these lesions and performed immunohistochemical staining for MUC6, pepsinogen I, H⁺/K⁺-ATPase (proton pump), and cyclin D1. RESULTS: All lesions were flat, whitish, and located in the upper stomach, notably lacking subepithelial tumor-like elevations. Magnifying endoscopy with narrow-band imaging revealed minimal structural changes on the surface. Histologically, the tumors showed well-circumscribed proliferation in the deep fundic mucosa, consisting of chief cell-like cells with minimal architectural atypia and an extremely low nuclear-to-cytoplasmic ratio. Although all lesions showed diffuse positivity for MUC6 and pepsinogen I, cyclin D1 expression was absent. No lesions showed progression or structural transformation during the follow-up period (range, 6-84 months). CONCLUSIONS: These lesions represent a distinct clinicopathological entity characterized by minimal cytological atypia and lack of surface mucosal changes and cyclin D1 expression. Our findings suggest that these lesions are a variant of OGAs and behave as benign mimics of GA-FG. Recognizing this extremely low-grade variant is crucial to avoid overdiagnosis and unnecessary aggressive interventions.