Gastric oxyntic gland adenomas: A multi-institutional retrospective study of 27 patients with immunohistochemical and molecular characterization of 8 samples.

Oxyntic gland neoplasms (OGNs) are rare chief cell-predominant gastric tumors ranging from benign oxyntic gland adenoma (OGA) to malignant gastric adenocarcinoma of fundic gland type (GA-FG). Twenty-eight OGAs identified between 1995 and 2024 from twenty-seven patients across five participating institutions were included. The study evaluated their clinicopathologic features, assessed the diagnostic utility of cyclin D1 immunohistochemistry (IHC) and underlying molecular alterations. The majority were in the cardia and fundus of stomach (53.6%), presenting as a single nodular/polypoid lesion (92.9%) on endoscopy. Two tumors (7.1%) arose from gastric heterotopia in the duodenum. Most tumors were confined to the mucosa (85.7%), consisting predominantly of chief cells and displaying characteristic deep mucosal "endless glands" pattern. Four tumors (14.3%) showed prolapse-type submucosal displacement. High-grade dysplasia was identified in one of these four cases (25%). None exhibited features of true invasion to classify as GA-FG. Mean tumor size was 5.64 mm. Clinical follow-up was available for fourteen patients, with a mean follow-up of 24.5 months (range, 3-78 months), and revealed no evidence of recurrence. Cyclin D1 IHC and molecular profiling was performed on eight samples. Diffuse and strong cyclin D1 expression was identified in 6 of 8 samples (75%). Targeted NGS identified recurrent missense mutations in GNAS (3/8 cases, 37.5%; c.601C>T, p.R201C, in two cases and c.602G>T, p.R201H, in one case). Recognition of the characteristic morphology of this exceedingly rare and likely underdiagnosed tumor, is critical for establishing the correct diagnosis.