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.
Get full access to this article
View all access options for this article.
References
1.
NeumannHPHPawluCPeçzkowskaM, et al. Distinct clinical features characterize paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA2004;292:943–51.
2.
SobolSMDaileyJCFamilial multiple cervical paragangliomas: report of a kindred and review of the literature. Otolaryngol Head Neck Surg1990;102:382–90.
3.
BoedekerCCNeumannHPHRidderGJ, et al. Paragangliomas in patients with mutations of the SDHD gene. Otolaryngol Head Neck Surg2005;132:467–70.
4.
BoedekerCCRidderGJSchipperJ.Paragangliomas of the head and neck: diagnosis and treatment. Fam Cancer2005;4:55–9.
5.
BrouwersFMEisenhoferGTaoJJ, et al. High frequency of SDHB germline mutations in patients with malignant catecholamine producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab2006;Aug 15 (Epub ahead of print).
6.
LeeJHBarichFKarnellLH, et al. National Cancer Data Base report on malignant paragangliomas of the head and neck. Cancer2002;94:730–7.
7.
PerskyMSSettonANiimiY, et al. Combined endovascular and surgical treatment of head and neck paragangliomas: a team approach. Head Neck2002;24:423–31.
8.
SchiaviFBoedekerCCBauschB, et al. Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. JAMA2005;294:2057–63.
9.
NeumannHPBauschBMcWhinneySR, et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med2002;346:1459–66.
10.
BauschBBorozdinWNeumannHPEuropean-American Pheochromocytoma Study Group. Clinical and genetic characteristics of patients with neurofibromatosis type 1 and pheochromocytoma. N Engl J Med2006; 354: 2729–31.
11.
BaysalBEFerrellREWillett-BrozickJE, et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science2000;287:848–51.
12.
NiemannSMllerU.Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat Genet2000;26:268–70.
13.
AstutiDLatifFDallolA, et al. Gene mutations in the succinate dehydrogenase subunit II SDHB cause susceptibility to familial pheo-chromocytoma and to familial paraganglioma. Am J Hum Genet2001;69:49–54.
14.
Gimenez-RoqueploAPFavierJRustinP, et al. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phae-ochromocytomas. Cancer Res2003;63:5615–21.
15.
BennDEGimenez-RoqueploAPReillyJR, et al. Clinical presentation and penetrance of paraganglioma/pheochromocytoma syndromes. J Clin Endocrinol Metab2006;91:827–36.
16.
HensenEFJordanovaESvan MinderhoutIJ, et al. Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families. Oncogene2004;23:4076–83.
17.
NiemannSMllerUEngelhardtD, et al. Autosomal dominant malignant and catecholamine-producing paraganglioma caused by a splice donor site mutation in SDHC. Hum Genet2003;113:92–4.
18.
VanharantaSBuchtaMMcWhinneySR, et al. Early onset renal cell carcinoma as novel extra-paraganglial component of SDHB-associated hereditable paraganglioma. Am J Hum Genet2004;74:153–9.
19.
KwekkeboomDJvan UrkHPauwBK, et al. Octreotide scintigraphy for the detection of paragangliomas. J Nucl Med1993;34:873–8.
20.
HoegerleSGhanemNAltehoeferC, et al. 18F-DOPA positron emission tomography for the detection of glomus tumours. Eur J Nucl Med Mol Imaging2003;30:689–94.
