title: Genetics and the clinical approach to paragangliomas.
abstract: This study analyses new information on gene mutations in paragangliomas and puts them into a clinical context. A suspicion of malignancy is critical to determine the workup and surgical approach in adrenal (A-PGL) and extra-adrenal (E-PGL) paragangliomas (PGLs). Malignancy rates vary with location, family history, and gene tests results. Currently there is no algorithm incorporating the above information for clinical use. A sum of 1,821 articles were retrieved from PubMed using the search terms "paraganglioma genetics". Thirty-seven articles were selected of which 9 were analyzed. It was found that 599/2,487 (24%) patients affected with paragangliomas had a germline mutation. Of these 30.2% were mutations in SDHB, 25% VHL, 19.4% RET, 18.4% SDHD, 5.0% NF1, and 2.0% SDHC genes. A family history was positive in 18.1-64.3% of patients. Adrenal PGLs accounted for 55.1% in mutation (+) and 81.0% in mutation (-) patients (RR 1.2, p < 0.0001). Bilateral A-PGLs accounted for 56.4% in mutation (+) and 3.2% in mutation (-) patients (RR 8.7, p < 0.0001). E-PGL were found in 33.6% of mut+ and 17.3% of mut- (RR 1.7, p < 0.0001). In mutation (+) patients PGLs malignancy varied with location, adrenal (6.4%) thoraco-abdominal E-PGL (38%), H & N E-PGL (10%). Malignancy rates were 8.2% in mutation (-) and lower in mutation (+) PGLs except for SDHB 36.5% and SDHC 8.3%. Exclusion of a mutation lowered the probability of malignancy significantly in E-PGL (RR 0.03 (95% CI 0.1-0.6); p < 0.001). Mutation analysis provides valuable preoperative information to assess the risk of malignancy in A-PG and E-PGLs and should be considered in the work up of all E-PGL lesions.
authors.affiliation: Department of Endocrine Surgery, King's College Hospital, King's Health Partners, London, UK.
authors.forename: K-M
authors.initials: KM
authors.lastname: Schulte
authors.affiliation: Department of Endocrine Surgery, King's College Hospital, King's Health Partners, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Talat
authors.affiliation: Department of Endocrine Surgery, King's College Hospital, King's Health Partners, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Galata
authors.affiliation: Department of Endocrinology, King's College Hospital, King's Health -Partners, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Aylwin
authors.affiliation: Clinical Genetics Department, Guy's Hospital, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Izatt
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Hospital of Dresden, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Eisenhofer
authors.affiliation: Department of Medicine III, University Hospital of Dresden, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Barthel
authors.affiliation: Department of Medicine III, University Hospital of Dresden, Dresden, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
mesh_terms: D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation / Q000235:genetics; D059645:Mutation Rate; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology*