Cancer Risks

VHL is associated (https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1440) with a variety of diseases, many of which are rare. See the sidebar for incidence rates of known association. The presence of one or more of those diseases, especially as a major feature, or a family member with a known pathogenic VHL variant, should trigger referral to a genetics professional for further evaluation. Because screening begins in infancy, testing for a known familial pathogenic variant is done at birth.

Prevention and Early Detection

People with VHL require lifelong screening, ideally with a team of specialists that is familiar with its symptoms and management, to detect problems when they are most easily treated. Screening recommendations (https://www.ncbi.nlm.nih.gov/books/NBK1463/) change as patients age:

• Beginning at one year:
  • Annual evaluation for neurologic symptoms, hearing changes, nystagmus, strabismus, and white pupils
  • Annual blood pressure monitoring
• Beginning at five years:
  • Continue one-year screening.
  • Annual plasma analysis or 24-hour urine collection for fractionated metanephrines
  • Audiology assessment every two to three years
  • Thin-slice magnetic resonance imaging (MRI) with contrast of the internal auditory canal for repeated ear infections
  • Dilated eye and retinal examination with indirect ophthalmoscope
• Beginning at 16 years:
  • Continue five-year screening.
  • Annual abdominal ultrasound
  • MRI of the abdomen, focusing on kidneys, pancreas, and adrenal glands
  • MRI of the brain and total spine every two years

In addition to identifying patients for germline biomarker testing, nurses can provide patients and families with education about prevention and detection, including (https://rarediseases.org/rare-diseases/von-hippel-lindau-disease/):

• Avoid tobacco use and chemical exposure.
• Avoid contact sports for patients with adrenal or pancreatic lesions.
• Report the following symptoms:
  • High or variable blood pressure, especially spiking blood pressure
  • Irregular or rapid heartbeat
  • Increased headache frequency or intensity
  • Increased sweating
  • Feelings of a panic attack, fear, or anxiety
  • Loss of balance or coordination
  • Loss of bowel or bladder function
  • Hearing loss
  • Pain (including abdominal) with unknown cause

Treatment Options

Large or malignant tumors typically require surgery or radiotherapy. Kidney tumor resection, ideally nephron-sparing surgery or partial nephrectomy to preserve kidney function, is generally considered (https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1440) when the largest tumor reaches 3 cm. 

In August 2021, the U.S. Food and Drug Administration approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-cancers-associated-von-hippel-lindau-disease) belzutifan as first-line therapy for VHL-associated renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors not requiring immediate surgery. Belzutifan is an inhibitor that targets hypoxia-inducible factor 2-alpha, which drives growth of malignant and benign VHL tumors.