Malignant Head and Neck Paragangliomas in SDHB Mutation Carriers

OBJECTIVE: Three of four paraganglioma syndromes (PGLs) have been characterized on a molecular genetic basis. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D ( SDHD) gene, PGL 3 is caused by SDHC gene mutations, and PGL 4 is caused by SDHB gene mutations. The objective of this study was to investigate whether PGLs are associated with malignant head and neck paragangliomas (HNPs). STUDY DESIGN AND SETTING: Through November 2005, we screened 195 HNP patients for mutations of the genes SDHB, SDHC, and SDHD. RESULTS: We detected 5 SDHC, 13 SDHB, and 45 SDHD gene mutations. In seven SDHB mutation carriers, there were distant metastases. No signs of metastases were found in SDHC and SDHD patients. One patient with a sporadic HNP presented with locally metastatic disease. CONCLUSIONS: SDHB mutations are associated with a high rate of malignant HNPs. SIGNIFICANCE: In SDHB patients, a three-body region imaging and scintigraphy or DOPA-PET must be performed to exclude metastases.

Download Full-text

Calculating the optimal surveillance for head and neck paraganglioma in SDHB-mutation carriers

Familial Cancer ◽

10.1007/s10689-016-9923-3 ◽

2016 ◽

Vol 16 (1) ◽

pp. 123-130 ◽

Cited By ~ 21

Author(s):

Karin Eijkelenkamp ◽

Thamara E. Osinga ◽

Mirjam M. de Jong ◽

Wim J. Sluiter ◽

Robin P. F. Dullaart ◽

...

Keyword(s):

Head And Neck ◽

Sdhb Mutation ◽

Mutation Carriers ◽

Head And Neck Paraganglioma

Download Full-text

SDHD GENE MUTATIONS: LOOKING BEYOND HEAD AND NECK TUMORS

AACE Clinical Case Reports ◽

10.4158/ep172003.cr ◽

2018 ◽

Vol 4 (3) ◽

pp. e186-e190

Author(s):

Sushma Kadiyala ◽

Yasmin Khan ◽

Valeria de Miguel ◽

Megan N. Frone ◽

Fiemu Nwariaku ◽

...

Keyword(s):

Head And Neck ◽

Gene Mutations ◽

Head And Neck Tumors ◽

Neck Tumors ◽

Sdhd Gene

Download Full-text

Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients

Endocrine Related Cancer ◽

10.1530/erc-11-0369 ◽

2012 ◽

Vol 19 (2) ◽

pp. 149-155 ◽

Cited By ~ 49

Author(s):

Valentina Piccini ◽

Elena Rapizzi ◽

Alessandra Bacca ◽

Giuseppe Di Trapani ◽

Raffaele Pulli ◽

...

Keyword(s):

Head And Neck ◽

Clinical Laboratory ◽

Germ Line ◽

Strong Predictor ◽

Missense Mutations ◽

Mutation Carriers ◽

Germ Line Mutations ◽

Group A ◽

Group B ◽

Head And Neck Paragangliomas

Head and neck paragangliomas (HNPGLs) are neural crest-derived tumors. In comparison with paragangliomas located in the abdomen and the chest, which are generally catecholamine secreting (sPGLs) and sympathetic in origin, HNPGLs are, in fact, parasympathetic in origin and are generally nonsecreting. Overall, 79 consecutive patients with HNPGL were examined for mutations in SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, MAX, and TMEM127 genes by PCR/sequencing. According to a detailed family history (FH) and clinical, laboratory (including metanephrines), and instrumental examinations, patients were divided into three groups: a) patients with a positive FH for HNPGL (index cases only), b) patients with a negative FH and multiple HNPGLs (synchronous or metachronous) or HNPGL associated with an sPGL, and c) patients with negative FH and single HNPGL. The ten patients in group a) proved to be SDHD mutation carriers. The 16 patients in group b) proved to be SDHD mutation carriers. Among the 53 patients in group c), ten presented with germ-line mutations (three SDHB, three SDHD, two VHL, and two SDHAF2). An sPGL was found at diagnosis or followed up in five patients (6.3%), all were SDHD mutation carriers. No SDHC, SDHA, MAX, and TMEM127 mutations were found. In SDHD mutation carriers, none of the patients affected by HNPGL associated with sPGL presented missense mutations. In conclusion, a positive FH or the presence of multiple HNPGLs is a strong predictor for germ-line mutations, which are also present in 18.8% of patients carefully classified as sporadic. The most frequently mutated gene so far is SDHD but others, including SDHB, SDHAF2, and VHL, may also be affected.

Download Full-text

The Changing Paradigm of Head and Neck Paragangliomas: What Every Otolaryngologist Needs to Know

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489420931540 ◽

2020 ◽

Vol 129 (11) ◽

pp. 1135-1143

Author(s):

Nathan D. Cass ◽

Melissa A. Schopper ◽

Jonathan A. Lubin ◽

Lauren Fishbein ◽

Samuel P. Gubbels

Keyword(s):

Head And Neck ◽

Susceptibility Gene ◽

Tumor Development ◽

Gene Mutations ◽

Whole Body ◽

Whole Body Imaging ◽

Biochemical Testing ◽

Multifocal Disease ◽

Hereditary Pheochromocytoma ◽

Head And Neck Paragangliomas

Background: Recommendations regarding head and neck paragangliomas (HNPGL) have undergone a fundamental reorientation in the last decade as a result of increased understanding of the genetic and pathophysiologic basis of these disorders. Objective: We aim to provide an overview of HNPGL and recent discoveries regarding their molecular genetics, along with updated recommendations on workup, treatment, and surveillance, and their implications for otolaryngologists treating patients with these disorders. Results: SDHx susceptibility gene mutations, encoding subunits of the enzyme succinate dehydrogenase (SDH), give rise to the Hereditary Pheochromocytoma/Paraganglioma Syndromes. SDHA, SDHB, SDHC, SDHD, and SDHAF2 mutations each result in unique phenotypes with distinct penetrance and risk for variable tumor development as well as metastasis. Genetic and biochemical testing is recommended for every patient with HNPGL. Multifocal disease should be managed in multi-disciplinary fashion. Patients with SDHx mutations require frequent biochemical screening and whole-body imaging, as well as lifelong follow-up with an expert in hereditary pheochromocytoma and paraganglioma syndromes. Conclusion: Otolaryngologists are likely to encounter patients with HNPGL. Keeping abreast of the latest recommendations, especially regarding genetic testing, workup for additional tumors, multi-disciplinary approach to care, and need for lifelong surveillance, will help otolaryngologists appropriately care for these patients.

Download Full-text

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.

Download Full-text