Makindo Medical Notes

Renal cell carcinoma is the leading cause of death in patients with von Hippel-Lindau disease, which also causes retinal, cerebellar, and spinal haemangioblastomas.

About Von Hippel-Lindau Disease

• Von Hippel-Lindau (VHL) disease is a rare autosomal dominant genetic condition that predisposes individuals to develop tumours and cysts in multiple organs.
• The disease is characterized by the development of both benign and malignant tumours, particularly in the kidneys, adrenal glands, central nervous system (CNS), and pancreas.
• The prevalence of VHL disease is estimated to be approximately 1 in 36,000 individuals worldwide.

Aetiology

• VHL is caused by mutations in the VHL gene, a tumour suppressor gene located on chromosome 3 (3p26-p25).
• The VHL gene encodes the VHL protein, which plays a crucial role in regulating cellular responses to hypoxia by targeting hypoxia-inducible factors (HIFs) for degradation.
• In patients with VHL disease, mutations in this gene lead to abnormal cellular responses to hypoxia, resulting in tumour formation and growth in various tissues.

Clinical Features

• Polycythaemia: Due to erythropoietin (EPO) secretion by EPO-producing renal or cerebellar haemangioblastomas, resulting in increased red blood cell count.
• Renal Cell Carcinoma: Often presents as a renal mass, potentially with haematuria, pain, or a palpable lump. It is a significant cause of morbidity and mortality in VHL patients.
• Phaeochromocytomas: Catecholamine-secreting tumours that can lead to hypertensive crises, palpitations, and sweating.
• Multiple Cysts: Cysts may occur in the kidneys, liver, and pancreas, often asymptomatic but occasionally causing abdominal discomfort or pain due to cyst enlargement.
• CNS Haemangioblastomas: Frequently found in the cerebellum, brainstem, and spinal cord, causing symptoms such as headaches, ataxia, and weakness. They may lead to complications if untreated.
• Retinal Haemangioblastomas: May present with vision changes and can lead to vision loss if untreated; can be visualized on ophthalmoscopic examination.

Investigations

• Full Blood Count (FBC): Assesses for polycythaemia, which can occur secondary to EPO-secreting tumours such as renal cysts or cerebellar haemangioblastomas.
• Gadolinium-enhanced MRI: The preferred imaging modality for detecting CNS haemangioblastomas. MRI allows for high-resolution imaging of brain and spinal cord structures.
• Ultrasound or CT Imaging: Useful for detecting renal masses, cysts in the liver or pancreas, and other abdominal pathology.
• Urinalysis: Screens for haematuria, which may indicate renal malignancy, and malignant cells in cases of advanced renal carcinoma.
• Plasma Metanephrines and Catecholamines: These are tested to detect the presence of phaeochromocytomas, especially in patients with hypertension or symptoms suggestive of catecholamine excess.
• Genetic Testing: Confirmation of VHL gene mutation can aid in diagnosis, family screening, and counselling, as well as early detection in relatives at risk.

Management

• Surveillance: Regular screening and surveillance are essential to monitor tumour development and progression, enabling early intervention. This may include regular MRI scans, abdominal imaging, and ophthalmoscopic examinations.
• Surgical Management: Surgical resection is the main treatment for symptomatic or malignant tumours, including renal cell carcinoma and symptomatic CNS haemangioblastomas.
• Renal Tumours: Nephron-sparing surgery is preferred for renal cell carcinoma to preserve kidney function. For larger tumours, partial or total nephrectomy may be necessary.
• Phaeochromocytomas: Surgical excision is recommended to prevent hypertensive crises. Patients may require preoperative alpha- and beta-blockade to control blood pressure.
• Retinal Haemangioblastomas: Laser photocoagulation or cryotherapy is often used to prevent vision loss.
• Genetic Counselling: Important for individuals with VHL and their families, as VHL is an autosomal dominant condition with a 50% risk of transmission to offspring.