Management of Locally Advanced and Metastatic Pheochromocytoma and Paraganglioma

Abstract

Malignant pheochromocytoma and malignant paraganglioma are diagnosed when metastases are present. These rare tumors have a variable clinical presentation and there are no clear pathological factors predictive of metastasis. However, a primary tumor size larger than 5 cm, succinate dehydrogenase B (SDHB) mutations, or extra-adrenal location are clinical predictors of metastatic disease. Patients with these factors at the initial presentation should have close lifelong follow-up with metanephrines and imaging. Metastatic pheochromocytoma and paraganglioma are associated with a genetic germline mutation in up to 50 % of cases. The most common genetic alteration is a mutation of the SDHB gene. Today, advanced genetic test such as next-generation sequencing with a panel to detect all mutations associated with this neuroendocrine tumor is possible. It is suggested that any patient with a pheochromocytoma and/or paraganglioma should be given the opportunity for genetic testing. Malignant pheochromocytoma and paraganglioma patients should have genetic counseling in order to clarify patient’s expectations and decide when to perform a genetic evaluation. Patients with metastatic disease may be classified according to type of metastasis and the burden of the disease. Patients with synchronous disease and high tumor burden have worse prognosis. Once metastatic disease is present there are several management options including observation and systemic therapies with chemotherapy, molecular targeted therapies, or radiopharmaceutical agents such us 131I metaiodobenzylguanidine (MIBG) therapy.