Clear cell carcinoid tumor of the gallbladder - Another distinctive manifestation of von Hippel-Lindau disease

We describe a morphologically distinctive carcinoid tumor of the gallbladder that occurred in a 38-year-old man with von Hippel-Lindau (VHL) disease. The carcinoid tumor was composed predominantly of lipid-containing clear cells arranged in nests and tubules with pagetoid spread into the biliary epithelium and was interpreted as metastatic renal cell carcinoma. The neoplastic cells showed diffuse immunoreactivity for chromogranin, synaptophysin, cytokeratins (cytokeratin 7 and AE1/AE3) and, unexpectedly, for inhibin, but were negative for monoclonal carcinoembryonic antigen, serotonin and a variety of peptide hormones. This clear cell carcinoid tumor of the gallbladder was histologically similar to the recently described clear cell endocrine pancreatic tumor associated with VHL. Four cases of the latter tumor, which were also inhibin positive showed, in addition, focal and variable reactivity for the pancreatic hormones. Two classical carcinoid tumors of the gallbladder, two renal cell carcinomas associated with VHL and 11 of 13 sporadic endocrine pancreatic tumors (not associated with VHL) did not show immunoreactivity for inhibin. Inhibin appears to be an immunohistochemical marker for gallbladder clear cell carcinoid and clear cell endocrine pancreatic tumors associated with VHL and is a useful tool to distinguish these tumors from metastatic renal cell carcinoma. However, the basis for the inhibin positivity in these endocrine tumors is unknown.