Gallbladder adenocarcinoma with florid neuroendocrine cell nests and extensive Paneth cell metaplasia

We report a unique case of gallbladder adenocarcinoma associated with flori d neuroendocrine cell nests and extensive Paneth cell metaplasia that has n ot been described previously. The patient was a 79-yr-old woman with a pedu nculated, polypoid mass in the gallbladder. Microscopically, the mass was c omposed of tumor cells showing tubular and papillary growth patterns, consi stent with well-differentiated adenocarcinoma. One-third or more of the tum or cells showed Paneth cell appearance. Goblet cell-type tumor cells were a lso intermingled. In addition, neuroendocrine cell nests, that were connect ed to the neoplastic glands, were scattered throughout the stroma. Immunohi stochemically, the labeling index of MIB-1 in adenocarcinoma cells includin g Paneth cell-type carcinoma cells was approx 40%. Neuron-specific enolase, chromogranin A, and synaptophysin were positive in the neuroendocrine cell s forming solid nests and intermingled within neoplastic glands. They were immunopositive for serotonin but negative for insulin, glucagon, somatostat in, and pancreatic polypeptide (PP). Although MIB-1-positive neuroendocrine cell nests were very few with weak staining, we th ink that the neuroendoc rine cell nests were neoplastic in nature. The formation of the multifocal neuroendocrine nests may be a consequence of the trophic effects of unknown substance(s), which can promote serotonin-producing neuroendocrine cells t o proliferate. We postulate that Paneth cell-type carcinoma cells may be in timately related to such substance(s) in our case.