Introduction: Malignant paragangliomas have been well described in carriers of mutations of the succinate dehydrogenase B (SDHB) gene, but have rarely been associated with mutations in the succinate dehydrogenase D (SDHD) gene.

Aim: To report the different clinical expression patterns of malignant paragangliomas in 5 patients with SDHD (D92Y) mutations observed in approximately 200 SDHD (D92Y) mutation carriers followed in our institution.

Results: Metastasis and/or local tumor invasion was documented 0 (n=2), 1, 18, and 30 years, resp, after the initial diagnosis of paraganglioma. Malignancy was proven by paraganglioma bone metastases (n=2), intrathoracic paraganglioma with lymph node metastases, locally invasive head-and-neck paraganglioma with destruction of the petrosal bone and locally invasive paraganglioma of the bladder with lymph node metastases, resp. Four of the 5 patients developed catecholamine excess during follow up due to intra-adrenal paraganglioma (pheochromocytoma) (n=1), extra adrenal paraganglioma (n=2) and presumed subclinical disease (n=1).

Conclusion: SDHD mutations (D92Y) are associated with malignant paragangliomas and catecholamine excess with remarkable inter-individual variations despite the same mutation. We estimate that the prevalence of malignancy in carriers of D92Y mutations is at least 2.5%.