How many pathways to pheochromocytoma?

Pheochromocytomas, like several other tumors, may be either sporadic or the manifestation of a familial cancer syndrome. Recently, major advances have occurred in both the understanding of diverse molecular mechanisms leading to pheochromocytoma and the diagnostic modalities available for detection of the disease. Familial pheochromocytoma may be a manifestation of multiple endocrine neoplasia type 2 (MEN-2), von Hippel-Lindau (VHL), or neurofibromatosis-1 (NF 1) disease. Tumor-suppressor genes responsible for the familial occurrence of extra-adrenal pheochromocytoma, called paraganglioma, have been identified. This wealth of genetic information, coupled with the availability of sensitive and specific biochemical tests as well as imaging studies, allows for genetic screening and early diagnosis of pheochromocytoma. In addition, genetic screening of relatives at risk is now feasible. In this article, we review recent clinical and molecular advances in our understanding of pheochromocytoma.