Malignant head and neck paragangliomas in SDHB mutation carriers

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). Through November 2005, we screened 195 HNP patients for mutations of the genes SDHB, SDHC, and SDHD. 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. SDHB mutations are associated with a high rate of malignant HNPs. In SDHB patients, a three−body region imaging and scintigraphy or DOPA-PET must be performed to exclude metastases.