Genetics of Phaeochromocytomas, Paragangliomas, and Neuroblastoma

Phaeochromocytomas, paragangliomas, and neuroblastomas are the main primary tumours that arise from the autonomic nervous system. The autonomic nervous system is subdivided into the sympathetic and parasympathetic systems. Phaeochromocytomas arise from sympathetic nervous system (chromaffin) cells in the adrenal medulla. Paragangliomas may arise from the sympathetic or parasympathetic system. The former, previously known as extra-adrenal phaeochromocytomas but referred herein as paragangliomas, typically occur along the sympathetic chain and, like phaeochromocytomas, are usually secretory and most commonly present with symptoms of excess catecholamine secretion. Parasympathetic ganglia-derived paragangliomas (herein referred to as head and neck paraganglioma, HNPGL) develop along branches of the vagal and glossopharyngeal nerves (e.g. carotid body tumours, glomus jugulare) and are only rarely secretory. Phaeochromocytoma, paraganglioma, and HNPGL are rare in childhood but neuroblastomas, which are derived from neuroblasts in the developing sympathetic nervous system and are most common in children under the age of 5 years. Familial forms of neuroblastoma are rare but a major feature of phaeochromocytoma and paraganglioma (PPGL) and HNPGL is the high frequency of inherited cases and the major inherited syndromic and non-syndromic disorders that predispose to these tumours are described in Chapter 6.13.