New developments in the detection of the clinical behavior of pheochromocytomas and paragangliomas

Pheochromocytomas (PCC) are catecholamine-producing tumors that are, by definition, located in the adrenal medulla. Extra-adrenal catecholamine- producing tumors are called paragangliomas (PGL), which should be distinguished from head and neck paragangliomas, which are of parasympathetic origin. As is true for many (neuro)endocrine tumors, but unlike most other epithelial tumors, histopathological analysis does not allow a distinction to be made between PCC and PGL that will follow a benign course and those that have metastasized or will do so, a condition associated with poor prognosis. Therefore, many studies have been undertaken in the past decade, with the aim of providing a marker or a set of markers that allows clinical behavior in PCC and PGL to be predicted. Despite promising results in some areas, such as histopathological scoring systems, the use of the MIB-1 labeling index, and the analysis of telomerase activity, no single test or combination of tests has thus far yielded sufficiently high sensitivity and specificity to result in widespread acceptance in every day clinical practice. The relative rarity of PCC and PGL combined with a frequency of malignancy from as low as 2% up to 25% has hampered the power of past research and can only be overcome by multicenter collaborative efforts. In this article, recent attempts at marker detection, such as those mentioned above, as well as emerging knowledge on the molecular abnormalities in benign and malignant PCC and PGL will be presented.