Relevance of germline mutation screening in both familial and sporadic head and neck paraganglioma for early diagnosis and clinical management

Background: Head and neck paraganglioma (PGL) are benign tumors that can cause important direct or surgery induced morbidity. Almost all familial and 11-29% of sporadic PGL are caused by inactivating germline mutations in succinate dehydrogenase (SDH) genes. Our aim was to screen for such mutations and to evaluate clinical parameters as predictors of germline mutation. Methods: Seventy-four PGL patients were analyzed for germline mutations and large deletions in SDH genes, VHL and RET. Results were correlated to clinical characteristics including gender, age, tumor localization and multifocality. The surgical approach was evaluated in terms of tumor origin, sequelae and subsequent evolution. Results: Mutations in SDHB and SDHD were identified in equal proportion in 13/13 (100%) of familial and in 15/61 (25%) of sporadic cases. Familiarity, age <= 50 years and male gender were predictors of any germline mutation, while multifocality and carotid/vagal localization were indicative of SDHD mutation in particular. Conclusion: In contrast to other series, this cohort of Spanish patients showed many SDHB mutations. Sporadic cases with germline mutation are frequent and underline the importance of mutational screening of all PGL patients, allowing the identification of relatives at risk and the early diagnosis of the disease, reducing or avoiding morbidity.