Genetics and the Clinical Approach to Paragangliomas

TY - JOUR

T1 - Genetics and the Clinical Approach to Paragangliomas

AU - Schulte, K. -M.

AU - Talat, N.

AU - Galata, G.

AU - Aylwin, S.

AU - Izatt, L.

AU - Eisenhofer, G.

AU - Barthel, A.

AU - Bornstein, S. R.

N1 - © Georg Thieme Verlag KG Stuttgart · New York.

PY - 2014/12

Y1 - 2014/12

N2 - 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.

AB - 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.

KW - Family

KW - Genetic Predisposition to Disease

KW - Humans

KW - Mutation/genetics

KW - Mutation Rate

KW - Paraganglioma/genetics

U2 - 10.1055/s-0034-1383581

DO - 10.1055/s-0034-1383581

M3 - Article

C2 - 25014332

SN - 0018-5043

VL - 46

SP - 964

EP - 973

JO - Hormone and Metabolic Research

JF - Hormone and Metabolic Research

IS - 13

ER -