Williams, S.T., Chatzikyriakou, P., Carroll, P.V. et al. (34 more authors) (2022) SDHC phaeochromocytoma and paraganglioma: A UK‐wide case series. Clinical Endocrinology, 96 (4). pp. 499-512. ISSN 0300-0664
Abstract
Objective
Phaeochromocytomas and paragangliomas (PPGL) are rare, but strongly heritable tumours. Variants in succinate dehydrogenase (SDH) subunits are identified in approximately 25% of cases. However, clinical and genetic information of patients with SDHC variants are underreported.
Design
This retrospective case series collated data from 18 UK Genetics and Endocrinology departments.
Patients
Both asymptomatic and disease-affected patients with confirmed SDHC germline variants are included.
Measurements
Clinical data including tumour type and location, surveillance outcomes and interventions, SDHC genetic variant assessment, interpretation, and tumour risk calculation.
Results
We report 91 SDHC cases, 46 probands and 45 non-probands. Fifty-one cases were disease-affected. Median age at genetic diagnosis was 43 years (range: 11–79). Twenty-four SDHC germline variants were identified including six novel variants. Head and neck paraganglioma (HNPGL, n = 30, 65.2%), extra-adrenal paraganglioma (EAPGL, n = 13, 28.2%) and phaeochromocytomas (PCC) (n = 3, 6.5%) were present. One case had multiple PPGLs. Malignant disease was reported in 19.6% (9/46). Eight cases had non-PPGL SDHC-associated tumours, six gastrointestinal stromal tumours (GIST) and two renal cell cancers (RCC). Cumulative tumour risk (95% CI) at age 60 years was 0.94 (CI: 0.79–0.99) in probands, and 0.16 (CI: 0–0.31) in non-probands, respectively.
Conclusions
This study describes the largest cohort of 91 SDHC patients worldwide. We confirm disease-affected SDHC variant cases develop isolated HNPGL disease in nearly 2/3 of patients, EAPGL and PCC in 1/3, with an increased risk of GIST and RCC. One fifth developed malignant disease, requiring comprehensive lifelong tumour screening and surveillance.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 John Wiley & Sons Ltd. This is an author-produced version of a paper subsequently published in Clinical Endocrinology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | gastrointestinal tumour; paraganglioma; phaeochromocytoma; rare diseases; succinate dehydrogenase |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Nov 2021 16:51 |
Last Modified: | 24 Sep 2022 00:14 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/cen.14594 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:180578 |