Answer: D - von Hippel-Lindau (VHL)

On gross examination, the pancreas appeared to have a large solid and cystic mass, as well as some scattered smaller cysts.  Sections show two distinct lesions within the pancreas, which are closely associated in areas.   The cystic areas are lined by simple cuboidal epithelium, with round regular nuclei, modest amount of clear cytoplasm and a surrounding fibrotic stroma (features consistent with a serous cystadenoma). The solid portion of the mass is composed of nests of cohesive clear cells with foamy-appearing cytoplasm and small round nuclei. Fibrous bands can be seen separating the tumor nests. Immunostains show that these tumor cells are positive for pancytokeratin and synaptophysin, supporting a diagnosis of well-differentiated neuroendocrine tumor, clear cell type.  

The combination of pancreatic serous cystadenomas and neuroendocrine tumors (NETs), especially those with clear-cell morphology, can be seen in von Hippel-Lindau (VHL) syndrome. VHL syndrome is caused by a mutation in the VHL gene on chromosome 3, which encodes a tumor suppressor protein involved in the regulation of hypoxia-inducible factors (HIFs) and angiogenesis. As a result, VHL deficiency can give rise to a constellation of distinct tumors. In addition to the two mentioned above, other VHL-associated tumors include clear cell-renal cell carcinoma, hemangioblastoma, pheochromocytoma, and endolymphatic sac tumor.