FUNCTIONING THORACIC PARAGANGLIOMA - ASSOCIATION WITH VON-HIPPEL-LINDAU-SYNDROME

Functioning thoracic paraganglioma (pheochromocytoma) is unusual and t herefore suggestive of a pathogenesis distinct from that of sporadic a drenal pheochromocytoma. To determine whether the pheochromocytoma-ass ociated syndromes Von Hippel-Lindau disease NHL) and multiple endocrin e neoplasia type 2 (MEN 2) play a role in the development of thoracic functioning paragangliomas, germline DNA from five unselected patients with this rare tumor was analyzed for mutations in the genes that pre dispose to VHL and MEN 2. Genetic investigations and further clinical data revealed that three had VHL, with two different germline mutation s of the vhl gene, but no individual was affected by MEN 2. Two of the three patients with VHL did not show any additional VHL-associated le sions. This result suggests that VHL should be considered in the diffe rential diagnosis of thoracic pheochromocytoma, as such a diagnosis ca rries further important implications for the patient and family. Conve rsely, in patients suspected of a catecholamine-secreting tumor and kn own VHL, thoracic localization should be considered if an adrenal pheo chromocytoma cannot be detected.