Pheochromocytoma (Pheo) is a chromaffin tumor of the adrenal gland. When extra-adrenal, the tumor is called paraganglioma (PGL). At present, the only objective criterion for malignancy is the presence of metastases (i.e. spreading of the tumor in bones, liver, lungs or lymph-nodes where chromaffin tissue is normally absent). Extensive invasion of adjacent tissues can be considered only an indicator of malignant potential as well as high cellularity, necrosis, vascular/capsular invasion and high Ki-67 immunoractivity at histology. Malignancy is more frequently associated with extra-adrenal localizations and with tumor of large size and of irregular shape. Metastases can be found at diagnosis or develop after primary surgery, sometimes also after many years. The biochemical profile of malignant Pheo/PGL is generally represented by high levels of norepinephrine and/or dopamine. Rarely malignant tumors can be non-secreting. Genetic analysis has demonstrated that malignant Pheo/PGLs are frequently associated with mutations of the gene encoding the B subunit of the succinate-dehydrogenase (SDHB). In fact, at variance with carriers of mutations in the other susceptibility genes who present malignancy in about 5%, in patients with a germline SDHB mutation malignancy ranges from 30 to 60%. Unfortunately, at present the therapy of malignant Pheos/PGLs is palliative. Radiometabolic therapy using I-131-MIBG is the first option when metastases result positive at scintigraphy. Chemotherapy has been used alone or in association with radionuclide treatment but always with limited results. Therapy with anti-angiogenetic drugs is a putative option that might be tested in the next future.
25 - 29 Apr 2009
European Society of Endocrinology