Grossly visible non-invasive neoplasm of the gallbladder: method of classification and its relationship to pyloric gland adenoma

Objectives: To devise a classification method for grossly visible non-invasive neoplasms (GVNINs) of the gallbladder and examine their relationship to pyloric gland adenoma (PGA), since clinicopathological features of GVNINs are not well known to date and the relationship between PGA and GVNINs remains unknown. Methods: Eighty-five GVNINs were classified into pedunculated (PE), sessile type 1 (SE1), and sessile type 2 (SE2) groups, and into histologic subtypes. Clinicopathologic data, immunohistochemical data surrogating gene abnormalities, and mutational data of CTNNB1, KRAS, and GNAS were obtained. In five cases of SE1 containing PGA-like lesions, separate analyses for PGA-like and non-PGA-like lesions were performed. The relevance of the mucinous tumor cell ratio was analyzed in PE tumors. Results: The invasion rates were 0%, 33.4%, and 91.2% for PE, SE1, and SE2, respectively. SE2 was more with >= pT2 (78.2%) compared to SE1 (16.7%). All PE and SE1 were of gastric pyloric subtype and gastric type, respectively, whereas pancreatobiliary/intestinal subtypes were predominant in SE2. Approximately 66.7% of SE1 had (3-catenin abnormalities, STK11-loss, and CTNNB1 mutation. SMAD4-loss was exclusively seen in the intestinal subtype. Mucinous cell-predominant PGA was not clinicopathologically different from non-mucinous cell-dominant type except for patients' age and nuclear (3-catenin labeling index. PGA and PGA-like lesions in SE1 shared (3-catenin abnormalities and CTNNB1 mutation, but not STK11-loss. Conclusions: A clinicopathologically relevant classification system for GVNINs was proposed. Histologic subtyping was also important. Non-mucinous cell-predominant PE was suggested to be a similar entity to PGA, while SE1 containing PGA-like lesions were not suggested to be similar.