Von Hippel-Lindau disease
Updates to Article Attributes
Von Hippel-Lindau (vHL) disease is characterised by the development of numerous benign and malignant tumours in different organs (at least 40 types 1) due to mutation in VHL tumour suppressor gene on chromosome 3.
Epidemiology
The disease is rare with an estimated prevalence of 1:35,000-50,000.
Pathology
Distribution
Patients may develop some or all of the various lesions which include:
Abdominopelvic
- renal lesions
-
renal cell carcinoma(s) (RCCs): usually of the clear cell type 7
- 70% lifetime risk 9
- RCCs present at an earlier age in those with vHL
-
renal cysts
- can occur in up to 75% of cases 5
- often tend to be bilateral and multiple
- renal angiomyolipoma(s)
-
renal cell carcinoma(s) (RCCs): usually of the clear cell type 7
- pheochromocytoma(s)
- numerous pancreatic lesions (may be the earliest manifestation 3)
- pancreatic cysts
- pancreatic endocrine tumours: usually non-functional 9
- pancreatic serous cystadenoma
- pancreatic adenocarcinoma (rare)
- liver cysts
- papillary cystadenoma(s) of the epididymis
- paraganglioma (rare) 8
CNS
-
CNS haemangioblastoma(s): occur in ~70% 9
- cerebellar (~75%)
- spinal (~25%)
- choroid plexus papilloma (CPP)
Head and neck
-
retinal haemangioblastoma(s)
- most common presenting feature 9
- vision loss in 35-55% of patients 9
-
endolymphatic sac tumours (ELST)
- bilateral ELSTs considered pathognomonic for vHL 9
Features can be remembered by the neumonic HIPPEL:
- Haemangioblastoma
- Increased risk of RCC
- Phaeochromocytoma
- Pancreatic lesions (cysts, cystadenomas, cystadenocarcinomas)
- Eye dysfunction (retinal haemangioblastomas)
- Liver, renal and pancreatic cysts
Genetics
The disease carries an autosomal dominant inheritance with high expression and variable penetrance. It classically results from an inactivation of a tumour suppressor gene located on chromosome 3p25.5. However, no mutation has been identified in up to 30% of cases.
Radiographic features
Please refer to articles on individual lesions for specific imaging characteristics.
Treatment and prognosis
Most lesions with vHL are treatable and screening is recommended. Some experts advocate routine screening starting in adolescence. Prognosis is poor, with an median survival of ~50 years, with the most common cause of death being RCC and cerebellar haemangioblastomas 1.
History and etymology
Eugen von Hippel (1867-1939) was a German ophthalmologist that had described a rare disorder of the retina in 1904 and seven years later reported the basis of this disease, named as "angiomatosis of the retina".
Arvid Vilhelm Lindau (1892-1958) was a Swedish pathologist and bacteriologist that described the association between angiomatosis of the retina with hemangioblastomas of the cerebellum and other CNS parts and other visceral components of a disease so called as "angiomatosis of the central nervous system".
In 1964 the disease was renamed to “Von Hippel-Lindau disease”.
- +</ul><p>Features can be remembered by the neumonic HIPPEL:</p><ul>
- +<li>
- +<strong>H</strong>aemangioblastoma</li>
- +<li>
- +<strong>I</strong>ncreased risk of RCC</li>
- +<li>
- +<strong>P</strong>haeochromocytoma</li>
- +<li>
- +<strong>P</strong>ancreatic lesions (cysts, cystadenomas, cystadenocarcinomas)</li>
- +<li>
- +<strong>E</strong>ye dysfunction (retinal haemangioblastomas)</li>
- +<li>
- +<strong>L</strong>iver, renal and pancreatic cysts</li>
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