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Horm Metab Res 2014; 46(13): 964-973
DOI: 10.1055/s-0034-1383581
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Genetics and the Clinical Approach to Paragangliomas

K.-M. Schulte
1   Department of Endocrine Surgery, King’s College Hospital, King’s Health Partners, London, UK
2   Department of Surgery, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia
,
N. Talat
1   Department of Endocrine Surgery, King’s College Hospital, King’s Health Partners, London, UK
,
G. Galata
1   Department of Endocrine Surgery, King’s College Hospital, King’s Health Partners, London, UK
,
S. Aylwin
3   Department of Endocrinology, King’s College Hospital, King’s Health ­Partners, London, UK
,
L. Izatt
4   Clinical Genetics Department, Guy’s Hospital, London, UK
,
G. Eisenhofer
5   Institute of Clinical Chemistry and Laboratory Medicine, University Hospital of Dresden, Dresden, Germany
6   Department of Medicine III, University Hospital of Dresden, Dresden, Germany
,
A. Barthel
6   Department of Medicine III, University Hospital of Dresden, Dresden, Germany
7   Endokrinologikum RUHR, Bochum, Germany
,
S. R. Bornstein
6   Department of Medicine III, University Hospital of Dresden, Dresden, Germany
8   Department of Diabetes and Endocrinology, King’s College London, ­London, UK
› Author Affiliations
Further Information

Publication History

received 19 February 2014

accepted 04 June 2014

Publication Date:
11 July 2014 (online)

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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.

Key words

paraganglioma - cancer - malignancy - germline mutations

Supporting Information

 

  • References

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