Von Hippel-Lindau disease

Last revised by Mohammadtaghi Niknejad on 17 May 2023

Von Hippel-Lindau (vHL) disease is characterized by the development of numerous benign and malignant tumors in different organs (at least 40 types 1) due to mutations in the VHL tumor suppressor gene on chromosome 3.

The disease is rare with an estimated prevalence of 1:35,000-50,000. Most patients are diagnosed with their first tumor in early adulthood (mean age at diagnosis of initial tumor is 26) 10.

Clinical presentation is varied, depending on the site of disease manifestation (see below). Most commonly these are either within the abdominal cavity or affect the central nervous system. 

Patients may develop some or all of the various lesions which include:

A mnemonic to help remember the features of vHL is HIPPEL.

VHL can be classified according to clinical phenotypes, and the classification correlates with particular genotypes 10:

  • type 1: low-risk for pheochromocytoma but higher-risk for CNS hemangioblastoma, renal cell carcinoma, pancreatic cyst, and pancreatic neuroendocrine tumor

  • type 2A: high-risk for pheochromocytoma; low-risk for renal cell carcinoma

  • type 2B: high-risk for pheochromocytoma and renal cell carcinoma

  • type 2C: high-risk for pheochromocytoma only

The disease carries an autosomal dominant inheritance with high expression and penetrance; ~80% of cases occur via this pathway with ~20% arising de novo 10. It results from the inactivation of VHL, a tumor suppressor gene located on chromosome 3p25.5. However, no mutation is identified in up to 30% of cases.

Please refer to articles on individual lesions for specific imaging characteristics.

Most lesions from vHL are treatable and surveillance is recommended with various regional guidelines 10. Some experts advocate routine screening starting in adolescence. Prognosis is poor, with a median survival of ~50 years, with the most common cause of death being renal cell carcinoma and cerebellar hemangioblastoma 1

Eugen von Hippel (1867-1939) was a German ophthalmologist who had described a rare disorder of the retina in 1904 and seven years later reported the basis of this disease, named "angiomatosis of the retina". 

Arvid Vilhelm Lindau (1892-1958) was a Swedish pathologist and bacteriologist who described the association between angiomatosis of the retina and hemangioblastomas of the cerebellum and other parts of the CNS and other visceral components of a disease, calling it "angiomatosis of the central nervous system".

In 1964 the disease was renamed Von Hippel-Lindau disease.

ADVERTISEMENT: Supporters see fewer/no ads

Cases and figures

  • Case 1: with cerebellar hemangioblastoma
    Drag here to reorder.
  • Case 2: with spinal hemangioblastoma
    Drag here to reorder.
  • Case 3: pancreatic cysts - T2 fat sat
    Drag here to reorder.
  • Case 4
    Drag here to reorder.
  • Case 6
    Drag here to reorder.
  • Case 7
    Drag here to reorder.
  • Case 8: pancreatic cysts in vHL
    Drag here to reorder.
  • Case 10
    Drag here to reorder.
  • Case 11
    Drag here to reorder.
  • Case 12
    Drag here to reorder.
  • Case 13
    Drag here to reorder.
  • Case 14: bilateral pheochromocytomas
    Drag here to reorder.
  • Case 15: hemangioblastomas and angiomyolipomas
    Drag here to reorder.
  • Case 16
    Drag here to reorder.
  • Case 17
    Drag here to reorder.