Advances in the Diagnosis and Treatment of Pheochromocytomas and Paragangliomas in the Era of Personalized Genetic Diagnostic

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells. Almost 40% of all PPGLs cases are caused by germline mutations and 30–60% have somatic mutations. The incidence of hereditary syndromes in apparently sporadic cases is as high as 35%. Currently, more than 20 susceptibility genes have been identified, including at least 12 distinct genetic syndromes, with particular clinical features and prognosis. In this chapter, we summarize recent advances in the management of PPGLs from clinical diagnosis to targeted molecular treatment, based on the genetic profile. Classically, patients with PPGLs were diagnosed by sign and symptoms, e.g., hypertension (with or without paroxysms) and headache. Nowadays, about half of PPGLs are diagnosed as incidentalomas or during the surveillance screening in patients with known mutations for PPGL susceptibility genes, familial syndromes, or with a previous PPGL; a high percent of these patients have normal blood pressure. Plasma or urinary fractionated metanephrines remain the major biochemical tests for confirmation. Functional imaging, with a radiopharmaceutical chosen according to the tumor genotype and biology, improves tumor detection (notably for metastases and multifocal tumors) and links to targeted radionuclide therapy. Detecting the germline and somatic mutations associated with PPGLs is a promising approach to understand the clinical behavior and prognosis and to optimize the management of these tumors.