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Management of von Hippel–Lindau-associated kidney cancer

Nature Clinical Practice Urology volume 2, pages 248–255 (2005)Cite this article

Abstract

Von Hippel–Lindau disease (VHL) is an autosomal-dominant inherited condition that predisposes patients to develop renal cysts and tumors, most commonly in the second to fourth decades of life. Renal cysts and tumors have historically been a major cause of disease-related morbidity and mortality, so urologists are often called on to manage patients with VHL. Knowledge of the extrarenal manifestations of VHL (hemangioblastomas of the central nervous system and retina, endolymphatic sac tumors, pancreatic cysts, epididymal and broad-ligament cysts, and pheochromocytomas) and integration of nonurologic specialties into management teams for VHL patients will help to achieve successful outcomes. Screening for renal manifestations of VHL, by regular imaging of the abdomen, begins late in the second decade of life. Because renal tumors in VHL can be multifocal and bilateral, management can be complex. Radical nephrectomy removes all tissue at risk for forming renal tumors; however, this necessitates renal replacement therapy. In an effort to control cancer effectively while preserving native renal function and minimizing intervention, some researchers have proposed an observational strategy. Patients are screened until the largest tumor reaches 3 cm in diameter, at which time operative intervention is recommended. Nephron-sparing surgery is undertaken, whenever technically feasible, with the goal of removing all tumors in that renal unit. The role of minimally invasive technologies is currently being evaluated in selected patients with VHL renal masses. Elucidation of molecular pathways associated with VHL renal tumors may facilitate development of effective medical treatments for these lesions in the future.

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Figure 1: von Hippel–Lindau-associated renal tumors.
Figure 2: von Hippel–Lindau-associated renal tumors before and after nephron-sparing surgery.
Figure 3: Ultrasound during nephron-sparing surgery.
Figure 4: Mutation of the VHL gene is associated with increased stability of hypoxia-inducible factors (HIFs), resulting in HIF accumulation.

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Acknowledgements

Thanks to R Dreyfuss (Medical Arts and Photography Branch, National Institutes of Health) and L Errington (Urologic Oncology Branch, National Cancer Institute) for their assistance in the preparation of figures and text for this manuscript.

Author information

Authors and Affiliations

  1. Urologic Oncology at the Urologic Oncology Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD

    Robert L Grubb III, Peter L Choyke, Peter A Pinto, W Marston Linehan & McClellan M Walther

  2. Molecular Imaging Program,

    Robert L Grubb III, Peter L Choyke, Peter A Pinto, W Marston Linehan & McClellan M Walther

  3. Urologic Oncology,

    Robert L Grubb III, Peter L Choyke, Peter A Pinto, W Marston Linehan & McClellan M Walther

  4. Urologic Oncology,

    Robert L Grubb III, Peter L Choyke, Peter A Pinto, W Marston Linehan & McClellan M Walther

  5. Urologic Oncology,

    Robert L Grubb III, Peter L Choyke, Peter A Pinto, W Marston Linehan & McClellan M Walther

Authors
  1. Robert L Grubb III
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  2. Peter L Choyke
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  3. Peter A Pinto
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  4. W Marston Linehan
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  5. McClellan M Walther
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Corresponding author

Correspondence to W Marston Linehan.

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Competing interests

The authors declare no competing financial interests.

Glossary

HEMANGIOBLASTOMAS

Tumors, generally benign, made up of blood vessels, commonly located in the cerebellum and spinal cord

ANGIOMAS

Tumors composed primarily of lymphatic or blood vessels

PHEOCHROMOCYTOMAS

Tumors of the adrenal gland, derived from chromaffin cells, that cause excessive adrenaline production and hypertension

FUHRMAN GRADE

A 4-point scale that grades malignant potential of renal cancer cells based on the appearance of the nuclei

CRYOABLATION

Destruction of tissue by freezing with argon gas or liquid nitrogen (−140°C to −195°C) delivered via a cryoprobe; cell death occurs in two stages: immediate cellular necrosis from the freeze/thaw cycles followed by microcirculatory insufficiency and resultant ischemic necrosis

RADIOFREQUENCY ABLATION (RFA)

Heat-induced tissue destruction using an electrical current that is passed through a needle electrode placed directly into the tissue

HYPOXIA-INDUCIBLE FACTORS (HIF)

Proteins that activate transcription ('transcription factors') of genes involved in tumorigenesis; HIF degradation is regulated by the VHL gene product in an oxygen-dependent manner

HEAT-SHOCK PROTEIN 90 (HSP90)

A molecular chaperone that activates several protein kinases; inhibitors of HSP90 have antiproliferative and antitumor activities

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Grubb, R., Choyke, P., Pinto, P. et al. Management of von Hippel–Lindau-associated kidney cancer. Nat Rev Urol 2, 248–255 (2005). https://doi.org/10.1038/ncpuro0179

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