An emerging entity of gastric adenocarcinoma: clinicopathological features and differential diagnosis of gastric adenocarcinoma of fundic-gland type in 25 retrospective cases.

Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare gastric cancer with an extremely low rate of vascular and lymph node metastases. It can be cured with endoscopic submucosal dissection (ESD). However, inadequate understanding of GA-FG may lead to overtreatment, negatively impacting patient quality of life. We analyzed the clinical, endoscopic, and pathological characteristics of 25 cases of GA-FG. Immunohistochemical markers (CEA, MUC2, MUC5AC, MUC6, H + /K + ATPase, Pepsinogen-I, CgA, P53, and Ki67) were used to differentiate GA-FG from conventional gastric adenocarcinoma (CGA), neuroendocrine tumor (NET), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM), and other related conditions. The expression of β-catenin and Yes-associated protein (YAP) was also analyzed. All 25 GA-FG cases were located in the proximal stomach, with maximum diameter ranging from 4 to 20 mm. Histologically, the tumors displayed branching, mutual pulling or fusion of glandular duct structures, occasional sieve-like patterns, and mild cellular atypia. Some cases exhibited foveolar hyperplasia, with indistinct boundaries between proliferating and normal epithelium. The absence of an abrupt transition at low magnification was a critical feature to distinguish GA-FG from GA-FGM. Immunophenotypically, GA-FG resembled gastric-type adenocarcinoma with a low Ki67 index. The wild-type expression of P53 and varying Ki67 intensity patterns were helpful for diagnosing non-neoplastic hyperplasia. Abnormal β-catenin nuclear expression was found in 1 case, while 6 out of 12 showed positive YAP expression. GA-FG is a well-differentiated adenocarcinoma mimicking gastric fundic glands growth patterns. Accurate diagnosis of GA-FG is essential to accurate treatment and avoid oversurgery.