Clear cell endocrine pancreatic tumor mimicking renal cell carcinoma - A distinctive neoplasm of von Hippel-Lindau disease

The dominantly inherited von Hippel-Lindau disease is characterized by clea r cell neoplasms in various organs including the kidney and pancreas. Deter mination of primary versus metastatic lesion in this setting can be a diagn ostic dilemma. The authors present five cases of clear cell endocrine pancr eatic tumor (EPT) closely mimicking renal cell carcinomas in five patients with a family history or histologic evidence of von Hippel-Lindau disease. In fact. two of these tumors were confused with metastatic renal cell carci noma by fine-needle aspiration. All five tumors had a component of clear ce lls arranged in nests, cords, and tubules with central hemorrhage separated by thin-wall vessels resembling renal cell carcinoma. However, these tumor s also exhibited cords and festoons and a gyriform pattern suggestive of an endocrine neoplasm, and expressed chromogranin and synaptophysin. Vascular invasion was identified in four tumors, one of which metastasized. The con current primary renal cell carcinomas and the multicentric microcystic aden omas found in three patients did not show reactivity for the neuroendocrine markers. Focal clear cell change was noted in only one of 29 endocrine pan creatic tumors arising in patients without von Hippel-Lindau disease. Eleve n metastatic renal cell carcinomas in the pancreas did not show immunoreact ivity with the endocrine markers. Clear cell EPTs closely mimicking renal c ell carcinoma are distinctive neoplasms of von Hippel-Lindau disease. In co ntrast to clear cell EPT. metastatic renal cell carcinoma does not express neuroendocrine markers and lacks neurosecretory granules by electron micros copy. Von Hippel-Lindau disease should be strongly suspected in patients wi th renal cell carcinoma, clear cell EPT. and multifocal microcystic serous adenomas.