Gallbladder MiNEN arising in association with an intracholecystic papillary neoplasm exhibiting divergent p53 expression.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the biliary tract are exceptionally rare and predominantly involve the gallbladder (GB). Their reported association with precursor epithelial lesions raises important questions regarding histogenesis. We report the case of a 74-year-old woman who underwent cholecystectomy for calculus-associated carcinoma. Histological examination revealed a heterogeneous neoplasm composed of three intimately admixed components: an intracholecystic papillary neoplasm (ICPN), a large cell neuroendocrine carcinoma (LCNEC), and a pancreatobiliary-type adenocarcinoma. Both the ICPN and adenocarcinoma components exhibited aberrant p53 immunostaining, whereas the LCNEC showed a wild-type pattern. All components were mismatch repair proficient and demonstrated membranous β-catenin expression. In line with previous reports, this case further suggests that ICPN may represent a common precursor lesion with the potential for divergent differentiation to GB MiNEN. The discordant p53 profiles observed across tumor components may be further explained by clonal evolution and intratumoral heterogeneity.