Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas

Introduction. Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla and from the extra-adrenal autonomic paraganglia, respectively. Only 1–3% of head and neck PGL (HNPGL) show elevated catecholamines, and at least 30% of Pheo and PGL (PCPG) are associated with genetic syndromes caused by germline mutations in tumor suppressor genes and proto-oncogenes. Clinical Case. A 33-year-old man with a past medical history of resection of an abdominal PGL at the age of eleven underwent a CT scan after a mild traumatic brain injury revealing an incidental brain tumor. The diagnosis of a functioning PGL was made, and further testing was undertaken with a PET-CT with 68Ga-DOTATATE, SPECT-CT 131-MIBG, and genetic testing. Discussion and Conclusion. The usual clinical presentation of functioning PCPG includes paroxistic hypertension, headache, and diaphoresis, sometimes with a suggestive family history in 30–40% of cases. Only 20% of PGL are located in head and neck, of which only 1–3% will show elevated catecholamines. Metastatic disease is present in up to 50% of cases, usually associated with a hereditary germline mutation. However, different phenotypes can be observed depending on such germline mutations. Genetic testing is important in patients with PCPG since 31% will present a germline mutation. In this particular patient, an SDHB gene mutation was revealed, which can drastically influence the follow-up plan and the genetic counsel offered. A multidisciplinary approach is mandatory for every patient presenting with PCPG.

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The phenotype of SDHB germline mutation carriers: a nationwide study

Acta Endocrinologica ◽

10.1530/eje-17-0074 ◽

2017 ◽

Vol 177 (2) ◽

pp. 115-125 ◽

Cited By ~ 21

Author(s):

Nicolasine D Niemeijer ◽

Johannes A Rijken ◽

Karin Eijkelenkamp ◽

Anouk N A van der Horst-Schrivers ◽

Michiel N Kerstens ◽

...

Keyword(s):

Head And Neck ◽

Metastatic Disease ◽

Germline Mutation ◽

Descriptive Study ◽

Germline Mutations ◽

Nationwide Study ◽

B Subunit ◽

Mutation Carriers ◽

Head And Neck Paragangliomas

Objective Succinate dehydrogenase B subunit (SDHB) gene germline mutations predispose to pheochromocytomas, sympathetic paragangliomas, head and neck paragangliomas and non-paraganglionic tumors (e.g. renal cell carcinoma, gastrointestinal stromal tumor and pituitary neoplasia). The aim of this study was to determine phenotypical characteristics of a large Dutch cohort of SDHB germline mutation carriers and assess differences in clinical phenotypes related to specific SDHB mutations. Design Retrospective descriptive study. Methods Retrospective descriptive study in seven academic centers. Results We included 194 SDHB mutation carriers consisting 65 (33.5%) index patients and 129 (66.5%) relatives. Mean age was 44.8 ± 16.0 years. Median duration of follow-up was 2.6 years (range: 0–36). Sixty persons (30.9%) carried the exon 3 deletion and 46 (23.7%) the c.423 + 1G > A mutation. Fifty-four mutation carriers (27.8%) had one or multiple head and neck paragangliomas, 4 (2.1%) had a pheochromocytoma and 26 (13.4%) had one or more sympathetic paragangliomas. Fifteen patients (7.7%) developed metastatic paraganglioma and 17 (8.8%) developed non-paraganglionic tumors. At study close, there were 111 (57.2%) unaffected mutation carriers. Statistical analyses showed no significant differences in the number and location of head and neck paragangliomas, sympathetic paragangliomas or pheochromocytomas, nor in the occurrence of metastatic disease or other tumors between carriers of the two founder SDHB mutations (exon 3 deletion vs c.423 + 1G > A). Conclusions In this nationwide study of disease-affected and unaffected SDHB mutation carriers, we observed a lower rate of metastatic disease and a relatively high number of head and neck paragangliomas compared with previously reported referral-based cohorts.

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Genetic Variants in Patients with Multiple Head and Neck Paragangliomas: Dilemma in Management

Biomedicines ◽

10.3390/biomedicines9060626 ◽

2021 ◽

Vol 9 (6) ◽

pp. 626

Author(s):

Anasuya Guha ◽

Ales Vicha ◽

Tomas Zelinka ◽

Zdenek Musil ◽

Martin Chovanec

Keyword(s):

Head And Neck ◽

Malignant Tumors ◽

Positive Family History ◽

Germline Mutations ◽

Tumor Surveillance ◽

Preventative Measures ◽

Genetic Patterns ◽

Therapeutic Measures ◽

Benign Nature ◽

Head And Neck Paragangliomas

Multiple head and neck paragangliomas (HNPGLs) are neuroendocrine tumors of a mostly benign nature that can be associated with a syndrome, precipitated by the presence of a germline mutation. Familial forms of the disease are usually seen with mutations of SDHx genes, especially the SDHD gene. SDHB mutations are predisposed to malignant tumors. We found 6 patients with multiple tumors amongst 30 patients with HNPGLs during the period of 2016 to 2021. We discuss the phenotypic and genetic patterns in our patients with multiple HNPGLs and explore the management possibilities related to the disease. Fifty percent of our patients had incidental findings of HNPGLs. Twenty-one biochemically silent tumors were found. Four patients had germline mutations, and only one had a positive family history. Three out of five underwent surgery without permanent complications. Preventative measures (genetic counselling and tumor surveillance) represent the gold standard in effectively controlling the disease in index patients and their relatives. In terms of treatment, apart from surgical and radiotherapeutic interventions, new therapeutic measures such as gene targeted therapy have contributed very sparsely. With the lack of standardized protocols, management of patients with multiple HNPGLs still remains very challenging, especially in those with sporadic or malignant forms of the disease.

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Head and Neck Paragangliomas Radiosurgery: Long-Term, Single-Institution Experience

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0036-1592634 ◽

2016 ◽

Vol 77 (S 02) ◽

Author(s):

Marcello Marchetti ◽

Valentina Pinzi ◽

Francesco Prada ◽

Elena De Martin ◽

Valeria Cuccarini ◽

...

Keyword(s):

Head And Neck ◽

Single Institution ◽

Head And Neck Paragangliomas

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SDHB, SDHC, and SDHD Mutations in Head and Neck Paragangliomas

Skull Base ◽

10.1055/s-2007-983976 ◽

2007 ◽

Vol 17 (S 1) ◽

Author(s):

Franco Trabalzini ◽

Francesca Schiavi ◽

Giuseppe Opocher ◽

Pietro Amistà

Keyword(s):

Head And Neck ◽

Head And Neck Paragangliomas

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Malignant Head and Neck Paragangliomas in Patients with Paraganglioma Syndromes

Skull Base ◽

10.1055/s-2009-1222129 ◽

2009 ◽

Vol 19 (01) ◽

Author(s):

Carsten Boedeker ◽

Zoran Erlic ◽

Roland Laszig ◽

Wolfgang Maier ◽

Jörg Schipper ◽

...

Keyword(s):

Head And Neck ◽

Head And Neck Paragangliomas

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Head and neck paragangliomas: genetic mutation and location of the tumors

Endocrine Abstracts ◽

10.1530/endoabs.56.p152 ◽

2018 ◽

Author(s):

Jose-Maria Recio-Cordova ◽

Cecilia Higueruela ◽

Rocio Caceres ◽

Maria Garcia-Duque ◽

Rogelio Gonzalez-Sarmiento ◽

...

Keyword(s):

Head And Neck ◽

Genetic Mutation ◽

Head And Neck Paragangliomas

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Head and neck paragangliomas: Ten years of experience in a third health center. A cohort study

Annals of Medicine and Surgery ◽

10.1016/j.amsu.2021.102412 ◽

2021 ◽

pp. 102412

Author(s):

Merzouqi Boutaina ◽

El Bouhmadi Khadija ◽

Oukessou Youssef ◽

Rouadi Sami ◽

Abada Redallah Larbi ◽

...

Keyword(s):

Cohort Study ◽

Head And Neck ◽

Health Center ◽

Years Of Experience ◽

Head And Neck Paragangliomas

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Management of Multiple Head and Neck Paragangliomas With Assistance of a 3-D Model

Ear Nose & Throat Journal ◽

10.1177/01455613211009441 ◽

2021 ◽

pp. 014556132110094

Author(s):

Lifeng Li ◽

Hongbo Xu ◽

Xiaohong Chen ◽

Zhenya Yu ◽

Jing Zhou ◽

...

Keyword(s):

Head And Neck ◽

Genomic Analysis ◽

Study Cohort ◽

Bilateral Carotid ◽

Succinate Dehydrogenase Complex ◽

Carotid Body Tumors ◽

D Model ◽

Vessel Rupture ◽

Head And Neck Paragangliomas ◽

Succinate Dehydrogenase Complex Subunit

Introduction: Extirpation of multiple head and neck paragangliomas carries challenge due to close anatomic relationships with critical neurovascular bundles. Objectives: This study aims to assess whether the application of 3-D models can assist with surgical planning and treatment of these paragangliomas, decrease surgically related morbidity and mortality. Methods: Fourteen patients undergoing surgical resection of multiple head and neck paragangliomas were enrolled in this study. A preoperative 3-D model was created based on radiologic data, and relevant critical anatomic relationships were preoperatively assessed and intraoperatively validated. Results: All 14 patients presented with multiple head and neck paragangliomas, including bilateral carotid body tumors (CBT, n = 9), concurrent CBT with glomus jugulare tumors (GJT, n = 4), and multiple vagal paragangliomas (n = 1). Ten patients underwent genomic analysis and all harbored succinate dehydrogenase complex subunit D (SDHD) mutations. Under guidance of the 3-D model, the internal carotid artery (ICA) was circumferentially encased by tumor on 5 of the operated sides, in 4 (80%) of which the tumor was successfully dissected out from the ICA, whereas ICA reconstruction was required on one side (20%). Following removal of CBT, anterior rerouting of the facial nerve was avoided in 3 (75%) of 4 patients during the extirpation of GJT with assistance of a 3-D model. Two patients developed permanent postoperative vocal cord paralysis. There was no vessel rupture or mortality in this study cohort. Conclusion: The 3-D model is beneficial for establishment of a preoperative strategy, as well as planning and guiding the intraoperative procedure for resection of multiple head and neck paragangliomas.

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