Diana Loreta Păun

By Diana Loreta Păun and Alexandra Mirică

Pheochromocytomas and paragangliomas are rare tumors, characterized by catecholamine synthesis, release, and metabolism, with the same embryological origin. Pheochromocytomas develop from chromaffin cells of the adrenal medulla, whereas paragangliomas arise extra-adrenal from sympathetic and parasympathetic nervous chains. During the past 10 years, there have been significant advances in the understanding of these tumors as it is now known that 30–40% of pheochromocytomas and paragangliomas have an underlying genetic cause. Pheochromocytomas and paragangliomas have classically been associated with three syndromes: von Hippel-Lindau (VHL), multiple endocrine neoplasia type 2 (MEN 2), and neurofibromatosis type 1 (NF1). To date, more than 21 gene mutations have been identified that are involved in the development of these tumors. Identification of such gene mutations associated with pheochromocytomas and paragangliomas will ensure early diagnosis, prompt treatment, and better prognosis for patient and family members. The recent developments in molecular pathogenesis of pheochromocytomas and paragangliomas will provide future treatment options toward personalized therapy for patients. This chapter summarizes the most important aspects of genetics and clinical characteristics, together with a focus on the new susceptibility genes.

Part of the book: Clinical Management of Adrenal Tumors

By Diana Loreta Paun and Alexandra Mirica

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, with genetic background in about 40% of cases, involving more than 30 susceptibility genes. The susceptibility genes can be divided into three main molecular clusters: pseudohypoxic, kinase signaling, and Wnt signaling. Biochemical characterization of these particular tumors should be integrated into the diagnostic algorithm because it can help apply personalized medicine principles and targeted therapy. These tumors can present with very different genotype-phenotype correlations, and their characterization can help the clinical practitioner make optimal clinical management decisions and prioritize genetic testing. This chapter summarizes the most important aspects of genetics and clinical characteristics, together with new genotype-phenotype correlation data.

Part of the book: Pheochromocytoma, Paraganglioma and Neuroblastoma