Abstract
Head and neck paragangliomas (HNPGLs) are tumors of parasympathetic origin that occur at variable locations and are often secondary to germline mutations in succinate dehydrogenase (SDH) subunit genes. Occasionally, these tumors produce catecholamines. Here, we assessed whether different locations of HNPGLs relate to the presence of SDHx mutations, catecholamine production and other presentations. In this multicenter study, we collected clinical and biochemical data from 244 patients with HNPGLs and 71 patients without HNPGLs. We clarified that jugulotympanic HNPGLs have distinct features. In particular, 88% of jugulotympanic HNPGLs arose in women, among whom only 24% occurred due to SDHx mutations compared to 55% in men. Jugulotympanic HNPGLs were also rarely bilateral, were of a smaller size and were less often metastatic compared to carotid body and vagal HNPGLs. Furthermore, we showed that plasma concentrations of methoxytyramine (MTY) were higher (P < 0.0001) in patients with HNPGL than without HNPGL, whereas plasma normetanephrine did not differ. Only 3.7% of patients showed strong increases in plasma normetanephrine. Plasma MTY was positively related to tumor size but did not relate to the presence of SDHx mutations or tumor location. Our findings confirm that increases in plasma MTY represent the main catecholamine-related biochemical feature of patients with HNPGLs. We expect that more sensitive analytical methods will make biochemical testing of HNPGLs more practical in the future and enable more than the current 30% of patients to be identified with dopamine-producing HNPGLs. The sex-dependent differences in the development of HNPGLs may have relevance to the diagnosis, management and outcomes of these tumors.
Highlights
Head and neck paragangliomas (HNPGLs) arise from parasympathetic ganglia within the skull base or upper neck
Discussion our study did not establish associations of catecholamine-related biochemistry with tumor location or presence of SDHx mutations, we did establish numerous clinical features that differed according to tumor location and SDHx mutation status
We showed for the first time that jugulotympanic HNPGLs without SDHx mutations arise more often in older women and have distinct features compared to other HNPGLs
Summary
Head and neck paragangliomas (HNPGLs) arise from parasympathetic ganglia within the skull base or upper neck. They are highly vascularized, but slowly growing tumors that metastatize in 6 – 13% of cases (Jansen et al, 2000, Lee et al, 2002, Mediouni et al, 2014, Papaspyrou et al, 2012). Syndromic presentations of HNPGLs are associated with mutations in all SDHx genes, the assembly factor SDHAF2 (Guha et al, 2019). Rare cases of HNPGLs in patients with Von Hippel-Lindau syndrome or multiple endocrine neoplasia type 2 have been reported; due to lack of somatic mutation testing their circumstantial association in patients with these syndromes cannot be excluded (Boedeker et al, 2009)
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