Mixed neuroendocrine-non-neuroendocrine
neoplasms (MiNENs) of the gallbladder are generally composed of
adenocarcinoma and
neuroendocrine carcinoma (NEC). Rare cases associated with intracholecystic papillary
neoplasm (ICPN) have been reported. Although recent molecular data suggest that the different components of digestive MiNENs originate from a common precursor stem cell, this aspect has been poorly investigated in gallbladder MiNENs. We describe the clinicopathologic and molecular features of a MiNEN composed of ICPN,
adenocarcinoma, and NEC. A 66-year-old woman presented with severe
abdominal pain. She underwent radical
cholecystectomy and an intracholecystic mass was found. Histologically, it was composed of ICPN associated with
adenocarcinoma and large cell neuroendocrine
carcinoma (LCNEC). The three components were positive for DNA repair
proteins and p53. EMA was positive in the ICPN and
adenocarcinoma components, while it was negative in the LCNEC. Heterogeneous expression of Muc5AC,
cytokeratin 20, and CDX2 was only observed in the ICPN component.
Cytokeratin 7 was diffusely positive in both
adenocarcinoma and LCNEC components, while it was heterogeneously expressed in the ICPN. The copy number variation analysis showed overlapping results between the
adenocarcinoma and LCNEC components with some minor differences with the ICPN component. The three
tumor components showed the same mutation profile including TP53 mutation c.700T > C (p. Tyr234His), without mutations in other 51 genes known to be frequently altered in
cancer pathogenesis and growth. This finding may support the hypothesis of a monoclonal origin of the different
tumor components. We have also performed a review of the literature on gallbladder MiNENs.