Combined large cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder

Large cell neuroendocrine carcinoma (LCNEC) is a high-grade malignant neuroendocrine tumor that was first defined in the lungs. There are six previous reports on LCNEC in the gallbladder, comprising three cases combined with another tumor and three pure LCNECs. We describe a tumor combined with LCNEC and adenocarcinoma elements arising in the gallbladder and give a review of the literature. A 68-year-old woman was diagnosed as having gallbladder wall thickening and a hepatic mass. The surgically resected tumor had a dumbbell shape with gallbladder and liver elements. Histological examination revealed LCNEC in the liver and a deep infiltrative portion of the gallbladder, as well as a well-differentiated tubular adenocarcinoma in the mucosa of the gallbladder. The pseudoglandular structures of LCNEC were marked in the transitional area. Immunoreactivities for carcinoembryonic antigen and CA19-9 as well as for chromogranin A and synaptophysin were detected in the LCNEC element. High p53-protein expression and high proliferative activity estimated by Ki-67 positivity were observed in both elements. The results suggest a close relationship between LCNEC and adenocarcinoma, and support the theory that these elements originate from common cancer stem cells.