Familial Cancer

, Volume 13, Issue 4, pp 637–644 | Cite as

Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment

  • Fred H. Menko
  • Eamonn R. Maher
  • Laura S. Schmidt
  • Lindsay A. Middelton
  • Kristiina Aittomäki
  • Ian Tomlinson
  • Stéphane Richard
  • W. Marston Linehan
Original Article


Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition in which susceptible individuals are at risk for the development of cutaneous leiomyomas, early onset multiple uterine leiomyomas and an aggressive form of type 2 papillary renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene which inactivate the enzyme and alters the function of the tricarboxylic acid (Krebs) cycle. Issues surrounding surveillance and treatment for HLRCC-associated renal cell cancer were considered as part of a recent international symposium on HLRCC. The management protocol proposed in this article is based on a literature review and a consensus meeting. The lifetime renal cancer risk for FH mutation carriers is estimated to be 15 %. In view of the potential for early onset of RCC in HLRCC, periodic renal imaging and, when available, predictive testing for a FH mutation is recommended from 8 to 10 years of age. However, the small risk of renal cell cancer in the 10–20 years age range and the potential drawbacks of screening should be carefully discussed on an individual basis. Surveillance preferably consists of annual abdominal MRI. Treatment of renal tumours should be prompt and generally consist of wide-margin surgical excision and consideration of retroperitoneal lymph node dissection. The choice for systemic treatment in metastatic disease should, if possible, be part of a clinical trial. Screening procedures in HLRCC families should preferably be evaluated in large cohorts of families.


Hereditary leiomyomatosis and renal cell cancer Fumarate hydratase Type 2 papillary renal cell cancer Tricarboxylic acid cycle Surveillance Nephrectomy Targeted therapy 



This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the Intramural Research Program of the NIH, Frederick National Laboratory, Center for Cancer Research. This project has been funded in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. The research was also supported by the Wellcome Trust Centre for Human Genetics, Grant Reference 090532/Z/09/Z. The Centre Expert National Cancers Rares PREDIR (S. Richard) is supported by grants from the French National Cancer Institute (INCa) and the French Department of Health.


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Fred H. Menko
    • 1
  • Eamonn R. Maher
    • 2
  • Laura S. Schmidt
    • 3
    • 7
  • Lindsay A. Middelton
    • 7
  • Kristiina Aittomäki
    • 4
  • Ian Tomlinson
    • 5
  • Stéphane Richard
    • 6
    • 8
  • W. Marston Linehan
    • 7
  1. 1.Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of Medical GeneticsUniversity of CambridgeCambridgeUK
  3. 3.Basic Science Program, Leidos Biomedical Research, Inc.Frederick National Laboratory for Cancer ResearchFrederickUSA
  4. 4.Department of Medical GeneticsUniversity of Helsinki and Helsinki University Central Hospital/HUSLABHelsinkiFinland
  5. 5.Molecular and Population Genetics Laboratory and National Institute for Health Research Biomedical Research Centre, Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
  6. 6.Centre Expert National Cancers Rares PREDIR, Service d’UrologieAP-HP, Hôpital BicêtreLe Kremlin-BicêtreFrance
  7. 7.Urologic Oncology Branch, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  8. 8.Génétique Oncologique EPHE, INSERM U753Faculté de Médecine Paris-Sud and Institut de cancérologie Gustave RoussyVillejuifFrance

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