Malignancy in pheochromocytomas

Review article


Kaisa Salmenkivi, Department of Pathology, Haartman Institute, P.O.Box 21, FIN-00014 University of Helsinki, Finland. e-mail:


A catecholamine-secreting tumor arising from the chromaffin cells of the sympathoadrenal system was first termed pheochromocytoma by Poll in 1905. The term refers to the dysky (pheo) color (chromo) of the cut surface of the tumor when exposed to dichromate. Pheochromocytomas most commonly arise from the adrenal medulla. Extraadrenally located pheochromocytomas are called paragangliomas, and arise from the paraganglion system. An adrenal pheochromocytoma is usually a rounded, gray-white, firm tumor 3 to 5 cm in diameter. When larger, they can adhere to adjacent structures, although still not metastasizing. Most pheochromocytomas are benign. However, approximately 10% of these tumors metastasize. It is almost impossible to differentiate a benign from a malignant tumor only by histological criteria. Classically only metastasized tumors are considered malignant for certain. Many attempts have been made to find markers that would predict the future behavior of an unmetastasized pheochromocytoma. In this overview of malignancy in pheochromocytomas, different steps of the tumorigenesis and several markers associated with them are discussed.