Molecular pathology op pheochromocytoma and paraganglioma development

Pheochromocytomas (PCC) are rare tumours of the adrenal medulla. These tumours are derived from the neural crest, similar to paraganglioma (PGL), which are located in the head and neck region and along the sympathetic chain. Histomorphologically these tumours are identical, although the pathogenesis of these two tumour types are mainly different with a minor overlap between the tumours. In the last decades the genes that are associated with the development of PCC and PGL have been identified. Also, the recognition of germline mutations in patients with PCC and PGL has been improved. In patients with PGL germline mutations are identified in more than 50% of the patients and in PCC the percentage of germline mutations is about 25%. Genes involved in the development of PCC are: the RET oncogene and the tunoursupressorgenes VHL, NF1, SDHB, SDHC en SDHD. In the development of PGL the genes mostly involved the SDHB, SDHC en SDHD genes, but also a small percentage is due to mutations in VHL germline mutations. Very recently the SDHA-F2 gene is identified in a subset of hereditary paraganglioma. No clinical of histological markers are available to predict behaviour of PCC and PGL. Some clinical correlation has been found; in patients with PCC and germline RET mutations malignant behaviour is rare. This is in contrast to patients with PCC and SDHB germline mutations that develop metastasis in a large proportion of patients. In this thesis the molecular aberrations in benign and malignant PCC are described and various techniques that can distinguish a subset of PCC and PGL.