Familial Cancer

, Volume 8, Issue 3, pp 257–260 | Cite as

SDHB-associated renal oncocytoma suggests a broadening of the renal phenotype in hereditary paragangliomatosis

  • Alex Henderson
  • F. Douglas
  • P. Perros
  • C. Morgan
  • E. R. Maher


Mutations in SDHB are one of the causes of hereditary paraganglioma syndrome. Germline mutations in SDHB predispose to the development of head and neck paragangliomas and phaeochromocytomas. Renal tumours are also increasingly being reported as component tumours in hereditary paragangliomatosis associated with mutations in SDHB. We present the first reported case of a family in whom an individual shown to carry a mutation in SDHB developed a renal oncocytoma. We review other reports of renal tumours associated with SDHB-associated hereditary paragangliomatosis and suggest that various histological subtypes of renal tumours are part of this condition. This observation indicates that SDHB-associated hereditary paragangliomatosis is unlike most tumour predisposition syndromes associated with the development of renal tumours which are usually associated with specific histological sub-types. The increasing recognition of the involvement of renal tumours in SDHB mutation carriers suggests that renal screening is likely to be valuable for these patients. SDHB mutations should also be considered in the context of genetic testing when renal tumours, regardless of histopathology, present in families with other tumours consistent hereditary paraganglioma syndrome.


Hereditary paragangliomatosis Oncocytoma Renal cancer SDHB 



Fumarate hydratase


Hereditary leiomyomatosis and renal cancer


Magnetic resonance imaging


Renal cell carcinoma


Succinate dehydrogenase subunit B


von Hippel Lindau syndrome


  1. 1.
    Kovacs G, Akhtar M, Beckwith BJ et al (1997) Heidelberg classification of renal cell tumours. J Pathol 183:131–133. doi:10.1002/(SICI)1096-9896(199710)183:2<131::AID-PATH931>3.0.CO;2-G PubMedCrossRefGoogle Scholar
  2. 2.
    Pavlovich CP, Schmidt LS (2004) Searching for the hereditary causes of renal-cell cancer. Nat Rev Cancer 4:381–393. doi:10.1038/nrc1364 PubMedCrossRefGoogle Scholar
  3. 3.
    Maxwell P, Wiesener M, Chang G-W et al (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275. doi:10.1038/20459 PubMedCrossRefGoogle Scholar
  4. 4.
    Mandriota SJ, Turner KJ, Davies DR et al (2002) HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron. Cancer Cell 1(5):459–468. doi:10.1016/S1535-6108(02)00071-5 PubMedCrossRefGoogle Scholar
  5. 5.
    Pollard PJ, El-Bahrawy M, Poulsom R et al (2006) Expression of HIF-1α, HIF-2α (EPAS1), and their target genes in paraganglioma and pheochromocytoma with VHL and SDH mutations. J Clin Endocrinol Metab 91(11):4593–4598. doi:10.1210/jc.2006-0920 PubMedCrossRefGoogle Scholar
  6. 6.
    Ricketts C, Woodward ER, Killick P et al (2008) Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst 100(17):1260–1262. doi:10.1093/jnci/djn254 PubMedCrossRefGoogle Scholar
  7. 7.
    Vanharanta S, Buchta M, McWhinney SR et al (2004) Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma. Am J Hum Genet 74(1):153–159. doi:10.1086/381054 PubMedCrossRefGoogle Scholar
  8. 8.
    Neumann HPH, Pawlu C, Peczkowska M et al (2004) Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 292:943–951. doi:10.1001/jama.292.8.943 PubMedCrossRefGoogle Scholar
  9. 9.
    Drucker AM, Houlden RL (2006) A case of familial paraganglioma syndrome type 4 caused by a mutation in the SDHB gene. Nat Clin Pract Endocrinol Metab 2(12):702–706. doi:10.1038/ncpendmet0342 PubMedCrossRefGoogle Scholar
  10. 10.
    Timmers HJLM, Kozupa A, Eisenhofer G et al (2007) Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with Succinate Dehydrogenase Subunit B-associated pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 92(3):779–786. doi:10.1210/jc.2006-2315 PubMedCrossRefGoogle Scholar
  11. 11.
    Klein RD, Jin L, Rumilla K et al (2008) Germline SDHB mutations are common in patients with apparently sporadic sympathetic paragangliomas. Diagn Mol Pathol 17(2):94–100. doi:10.1097/PDM.0b013e318150d67c PubMedCrossRefGoogle Scholar
  12. 12.
    Maher ER, Kaelin WG (1997) von Hippel–Lindau disease. Medicine 76:381–391. doi:10.1097/00005792-199711000-00001 PubMedCrossRefGoogle Scholar
  13. 13.
    Srirangalingam U, Walker L, Khoo B et al (2008) Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B gene mutation carriers. Clin Endocrinol 69(4):587–596CrossRefGoogle Scholar
  14. 14.
    Heimdal K, Silye A, Ariansen S (2007) A germline SDHB start codon mutation in a patient with abdominal paraganglioma and two renal cancers. American Society of Human Genetics, San Diego (October 2007)Google Scholar
  15. 15.
    Schmidt LS, Nickerson ML, Warren MB et al (2005) Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt–Hogg–Dubé syndrome. Am J Hum Genet 76(6):1023–1033. doi:10.1086/430842 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Alex Henderson
    • 1
  • F. Douglas
    • 1
  • P. Perros
    • 1
  • C. Morgan
    • 2
  • E. R. Maher
    • 3
  1. 1.Newcastle upon Tyne Hospitals NHS Foundation TrustNewcastle Upon TyneUK
  2. 2.Molecular Genetics Laboratory, Regional Genetics DepartmentBirmingham Women’s NHS Foundation TrustBirminghamUK
  3. 3.Cancer Research UK Renal Molecular Oncology GroupUniversity of BirminghamBirminghamUK

Personalised recommendations