SDHx-related pheochromocytoma/paraganglioma – genetic, clinical, and treatment outcomes in a series of 30 patients from a single center

Purpose Germline mutations in the four genes that encode the succinate dehydrogenase complex ( SDHx ) are a risk factor for developing pheochromocytomas and/or paragangliomas. The precise genotype–phenotype correlations are still uncertain and the most common SDHx genetic defects in the Portuguese population are poorly described. The objectives of our study were to characterize the genetic alterations, clinical features, and treatment outcomes of a cohort of SDHx- related pheochromocytomas and/or paragangliomas patients. Methods Single center, retrospective analysis based on the presence of a SDHx mutation in cases diagnosed from 1986 until October 2016. Results Thirty cases were included. The mean age at diagnosis was 36.8 years (±15.4 years) and 53.3% were females. Remission was observed in 33.3% and stable disease (including partial responses) in 53.0%. SDHC and SDHD patients were prone to develop single and multiple head and neck paragangliomas, respectively. SDHB patients carried an increased risk of malignancy. Deletions in SDHB exon-1 and in SDHD exon-4 were the most common genetic findings. SDHB patients and head and neck paragangliomas had the worse prognosis, the former related to malignancy, and the latter to cranial nerve deficits, unresectable disease, and multimodality interventions. Peptide receptor radionuclide therapy and radioactive iodine MIBG therapy proved to be ineffective. Radiotherapy represented a good alternative in unresectable head and neck paragangliomas and in bone metastases. Conclusion This single center study is the most complete Portuguese cohort in the literature and helps to understand the behavior of tumors based on their genotype and anatomical location.