Pathological reevaluation of gastric neoplasms with differentiation into the fundic gland

In the original classification, oxyntic gland neoplasms (OGNs) are classified as carcinoma based on the submucosal (SM) involvement and differentiation into MUC5AC- and MUC6-positive cells. Some cases without structural or nuclear atypia or desmoplastic reaction (DR) in the SM layer, which is essential for typical carcinoma, are also categorized as carcinoma of OGNs. To address potential overdiagnoses, we conducted a histopathological review of OGNs to propose a clinically relevant reevaluation.

Forty-one OGNs diagnosed pathologically in our institution between 2010 and 2022 were included. We defined carcinoma based on the structural or nuclear atypia of the tumor cells and evaluated DR in cases of SM involvement. Furthermore, our novel classification was compared to the original one.

Among 41 OGNs, 10 were classified as carcinoma and 31 as adenoma. Carcinoma had a significantly larger endoscopic and pathological tumor size (p = 0.03, p < 0.01) and more MUC5AC/MUC6 co-expression than adenoma (p < 0.01). All cases of SM involvement with DR were recognized in nine carcinoma (90%), and all 20 cases without DR were adenoma (65%). According to the original classification, 47% (14/30) of OGNs were categorized as noncurative endoscopic resection according to the Japanese guidelines, which recommended additional gastrectomy; however, no cases of lymph node metastasis and recurrence were observed.

Our definition of carcinoma could categorize all cases of SM involvement with DR and lymphatic invasion as carcinoma. This novel classification for OGNs may be possible to overcome the issue of overdiagnosis caused by the original classification.