Head and Neck Paragangliomas (HNP) are hypervascular tumours characterised by a slow growth pattern and a strong hereditary context that originate from the neural crest derived paraganglia, which... Show moreHead and Neck Paragangliomas (HNP) are hypervascular tumours characterised by a slow growth pattern and a strong hereditary context that originate from the neural crest derived paraganglia, which are associated with the autonomous nervous system and are situated at several locations in the head and neck region. Inactivating mutations in subunits of complex II (SDH) of the mitochondrial respiratory chain are responsible for hereditary tumours and have lead to a novel concept of mitochondrial tumoursupressor-genes and further insight in the intricate association of cellular oxygen sensing mechanisms and (pseudo)-hypoxia as environmental risk factors. However, further characterisation of the tumour biology is warranted for better understanding of the natural behaviour of HNP and possible identification clinicopathological parameters that could aid the clinician in his treatment decisions. In this thesis several studies on the molcular pathology of HNP are discussed including genotype-fenotype relations, the role of bFGF in tumourgenisis, the interplay between proliferation, cell cycle activity and apoptosis, and the nature of sustentacular cells in these apparent biphasic tumours. Additionally, in a clincal study the prevalence of synchronic or metachronic pheochromocytomas in patients with SDHD-linked HNP was determined. Show less
