Clear cell neuroendocrine tumor G1 of the gallbladder without von Hippel-Lindau disease.

Clear cell neuroendocrine tumor (NET) is a rare but distinct histopathological variant of NET most often observed in patients with von Hippel-Lindau disease (VHL). Clear cell NET in non-VHL patients is extremely rare and this report is only the second to describe a case of clear cell NET G1 (carcinoid tumor) of the gallbladder without VHL. A 71-year-old male without past or family history of VHL presented with a polypoid lesion in the fundus of the gallbladder and laparoscopic cholecystectomy was performed. Histopathological study revealed that the polypoid lesion was comprised of nests or trabecular growths of clear cells without atypia. Immunohistochemically, the neoplastic cells were diffusely positive for endocrine markers, but negative for α-inhibin. Clinicopathological review of cases with clear cell NET G1 of the gallbladder revealed that this disease occurs in patients with or without VHL, but that gallbladder stones and cholecystitis were present in non-VHL cases. We hypothesized that the occurrence of clear cell NET of the gallbladder (particularly non-VHL cases) may be associated with chronic cholecystitis induced by gallbladder stones. Moreover, α-inhibin was detected in clear cell NET tumor cells in one VHL case, but not in two non-VHL cases. These findings suggest that α-inhibin expression is a useful determinant of an association between clear cell NET and VHL.