Head and Neck Paragangliomas in Von Hippel-Lindau Disease and Multiple Endocrine Neoplasia Type 2

Boedeker, Carsten C.; Erlic, Zoran; Richard, Stéphane; Kontny, Udo; Gimenez-Roqueplo, Anne-Paule; Cascón, Alberto; Robledo, Mercedes; Campos, José M. de; Nederveen, Francien H. van; Krijger, Ronald R. de; Burnichon, Nelly; Gaal, José; Walter, Martin A.; Reschke, Kirsten; Wiech, Thorsten; Weber, W.; Rückauer, K; Plouin, Pierre François; Darrouzet, V.; Giraud, Sophie; Eng, Charis; Neumann, Hartmut P. H.

doi:10.1210/jc.2009-0354

Cited by 111 publications

(87 citation statements)

References 24 publications

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“…However head and neck paragangliomas have been observed in 0.5% of VHL patients, mostly as carotid body tumours. 37 Epididymal cystadenomas occur in up to 60% of males with VHL disease and are often bilateral. 38 They are usually asymptomatic and do not require treatment.…”

Section: Pancreasmentioning

confidence: 99%

von Hippel–Lindau disease: A clinical and scientific review

Neumann²,

2011

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Section: Pancreasmentioning

confidence: 99%

von Hippel–Lindau disease: A clinical and scientific review

Neumann²,

2011

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“…97 While pheochromocytomas and sympathetic paragangliomas are seen more frequently in individuals with inherited cancer predisposition syndromes, including multiple endocrine neoplasia Type 2, neurofibromatosis Type 1, and von Hippel-Lindau disease, parasympathetic SHNPGs are observed in less than 0.8% of individuals with these syndromes. 16,75 However, up to 30% of SHN-PGs have a distinct familial component, 14,31,67,87 which has been critical to identifying key susceptibility genes through linkage analysis studies. Most notably, mutations in genes coding for the succinate dehydrogenase enzyme complex, which participates in the citric acid cycle and mitochondrial electron transport chain, have been found to be the most significant drivers of paraganglioma tumorigenesis.…”

mentioning

confidence: 99%

Molecular genetics of paragangliomas of the skull base and head and neck region: implications for medical and surgical management

Hussain¹,

Husain²,

Baredes

et al. 2014

JNS

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Paragangliomas are rare neuroendocrine tumors derived from neural crest cells of the autonomic nervous system. Tumors occurring in the thorax, abdomen, and pelvis are usually derived from sympathetic paraganglia, which are associated with catecholaminemia, headaches, and resistant hypertension. Pheochromocytomas, arising from chromaffin cells of the adrenal medulla, are histologically similar to sympathetic paragangliomas and can have identical clinical presentations. In contrast to these tumors, skull base and head and neck region paragangliomas (SHN-PGs) are usually derived from parasympathetic paraganglia and rarely secrete catecholamines. These tumors can present in a variety of locations, most commonly arising from glomus Type I (chief) cells of the carotid body. Less commonly they arise in regions of the temporal bone including the middle ear (glomus tympanicum) and jugular fossa (glomus jugulare) (Fig. 1A), as well as along the length of the vagus nerve (glomus vagale) and in the nose and paranasal sinuses (sinonasal paraganglioma). 60,69,75,77,93,99 These tumors Paragangliomas are rare, slow-growing tumors that frequently arise in the head and neck, with the carotid bodies and temporal bone of the skull base being the most common sites. These neoplasms are histologically similar to pheochromocytomas that form in the adrenal medulla and are divided into sympathetic and parasympathetic subtypes based on functionality. Skull base and head and neck region paragangliomas (SHN-PGs) are almost always derived from parasympathetic tissue and rarely secrete catecholamines. However, they can cause significant morbidity by mass effect on various cranial nerves and major blood vessels. While surgery for SHN-PG can be curative, postoperative deficits and recurrences make these lesions challenging to manage. Multiple familial syndromes predisposing individuals to development of paragangliomas have been identified, all involving mutations in the succinate dehydrogenase complex of mitochondria. Mutations in this enzyme lead to a state of "pseudohypoxia" that upregulates various angiogenic, survival, and proliferation factors. Moreover, familial paraganglioma syndromes are among the rare inherited diseases in which genomic imprinting occurs. Recent advances in gene arrays and transcriptome/exome sequencing have identified an alternate mutation in sporadic SHN-PG, which regulates proto-oncogenic pathways independent of pseudohypoxia-induced factors. Collectively these findings demonstrate that paragangliomas of the skull base and head and neck region have a distinct genetic signature from sympathetic-based paragangliomas occurring below the neck, such as pheochromocytomas. Paragangliomas serve as a unique model of primarily surgically treated neoplasms whose future will be altered by the elucidation of their genomic complexities. In this review, the authors present an analysis of the molecular genetics of SHN-PG and provide future directions in patient care and the development of novel therapies. 321Abbreviations used in ...

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“…Apart from which, extra-adrenal tumours were also found in rare EGLN1 mutation (47). Although, rare extra adrenal tumours can also be found in VHL, TMEM 127, NF1, and RET mutations as well (11,12,14,21,26,42,53).…”

Section: Location Of the Tumourmentioning

confidence: 97%

“…They are more frequently benign, intraadrenal and bilateral. However, rarely mediastinal, abdominal and pelvic sympathetic paragangliomas as well as head and neck parasympathetic paragangliomas have also been reported (26).…”

Section: Neurofibromatosis Type 1 (Nf1)mentioning

confidence: 99%

“…In addition, bilateral phaeochromocytomas are mostly found with these same mutations (11,12,14,21,26,42,45,53). On the other hand, SDH mutations cause intra-adrenal tumours less commonly; 25% of SDHB-related tumours are phaeochromocytomas while the frequency of intraadrenal tumours in SDHD, SDHA and SDHC are even lower (4,7,36,37,41,53).…”

Section: Location Of the Tumourmentioning

confidence: 99%

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The clinical genetics of phaeochromocytoma and paraganglioma

Gunawardane

Grossman

2017

Arch. Endocrinol. Metab.

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Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with germline mutations seen in approximately 30% of patients. They can be a part of genetic syndromes such as MEN 2 or Neurofibromatosis type 1, or can be found as apparently sporadic tumours. Germline mutations are almost always found in syndromic patients. Nonetheless, apparently sporadic phaeochromocytoma too show high germline mutation rates. Early detection of a genetic mutation can lead to early diagnosis of further tumours via surveillance, early treatment and better prognosis. Apart from this, the genetic profile has important relevance for tumour location and biochemical profile, and can be a useful predictor of future tumour behaviour. It also enables family screening and surveillance. Moreover, recent studies have demonstrated significant driver somatic mutations in up to 75% of all tumours. Arch Endocrinol Metab. 2017;61(5):490-500

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Head and Neck Paragangliomas in Von Hippel-Lindau Disease and Multiple Endocrine Neoplasia Type 2

Abstract: Our observations provide evidence that molecular genetic testing for VHL or RET germline mutations in patients with HNP should be done only if personal and/or family history shows evidence for one of these syndromes.

Cited by 111 publications

References 24 publications

von Hippel–Lindau disease: A clinical and scientific review

von Hippel–Lindau disease: A clinical and scientific review

Molecular genetics of paragangliomas of the skull base and head and neck region: implications for medical and surgical management

The clinical genetics of phaeochromocytoma and paraganglioma

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