SDHC phaeochromocytoma and paraganglioma: A UK-wide case series
| Autor: | Anand Velusamy, Angela F. Brady, Joseph Carlow, Huw Dorkins, Rebecca Igbokwe, Benjamin Whitelaw, Teng-Teng Chung, Rachel Harrison, Fiona Lalloo, Paul Brennan, Louise Izatt, Schaida Schirwani, Alan Kelsall, Barbara McGowan, Sophie T Williams, Rosemarie Davidson, Paul V. Carroll, Nicola Tufton, Patrick J. Morrison, Soo-Mi Park, Christopher Bowles, John Newell-Price, Julian Adlard, Monika Kosicka-Slawinska, Eamonn R. Maher, Richard M. Martin, Lara Hawkes, Rebecca Dyer, Scott Akker, Rupert Obholzer, Florian Wernig, Tricia Tan, Ruth T Casey, Prodromos Chatzikyriakou, Gemma White, Anna L. Mitchell, Mary Porteous |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
Proband Male medicine.medical_specialty Gastrointestinal Stromal Tumors Endocrinology Diabetes and Metabolism Adrenal Gland Neoplasms Disease Pheochromocytoma Asymptomatic Malignant disease Germline Paraganglioma Endocrinology Internal medicine Medicine Humans Carcinoma Renal Cell Germ-Line Mutation Retrospective Studies GiST business.industry Membrane Proteins Middle Aged medicine.disease Kidney Neoplasms United Kingdom Succinate Dehydrogenase Cohort Female medicine.symptom business |
| Zdroj: | Clinical endocrinologyREFERENCES. 96(4) |
| ISSN: | 1365-2265 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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