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

We describe a morphologically distinctive carcinoid tumor of the gallbladde r that occurred in a 38-year-old man with von Hippel-Lindau (VHL) disease. The carcinoid tumor was composed predominantly of lipid-containing clear ce lls arranged in nests and tubules with pagetoid spread into the biliary epi thelium and was interpreted as metastatic renal cell carcinoma. The neoplas tic cells showed diffuse immunoreactivity for chromogranin, synaptophysin, cytokeratins (cytokeratin 7 and AE1/AE3) and, unexpectedly, for inhibin, bu t were negative for monoclonal carcinoembryonic antigen, serotonin and a va riety of peptide hormones. This clear cell carcinoid tumor of the gallbladd er was histologically similar to the recently described clear cell endocrin e pancreatic tumor associated with VHL. Four cases of the latter tumor, whi ch were also inhibin positive showed, in addition, focal and variable react ivity for the pancreatic hormones. Two classical carcinoid tumors of the ga llbladder, two renal cell carcinomas associated with VHL and 11 of 13 spora dic endocrine pancreatic tumors (not associated with VHL) did not show immu noreactivity for inhibin. Inhibin appears to be an immunohistochemical mark er for gallbladder clear cell carcinoid and clear cell endocrine pancreatic tumors associated with VHL and is a useful tool to distinguish these tumor s from metastatic renal cell carcinoma. However, the basis for the inhibin positivity in these endocrine tumors is unknown.