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Case history

image A 44-year-old man presented to the hospital with left flank pain and haematuria. An abdominal CT scan showed masses in both kidneys that were suspected to be renal cell carcinoma (RCC). The patient underwent partial nephrectomy of the left kidney. Two months later, he underwent radical nephrectomy of the right kidney. Pathology of the samples showed clear cell RCC in both kidneys. At that time, the patient was also found to have haemangioblastoma in the right retina and the cerebellum and was diagnosed with von Hippel-Lindau (VHL) disease. His family history included VHL disease in his father and his older sister. He was married and had one son, aged 9 years.

The patient developed local recurrent RCC in the left kidney 2 years after nephrectomy, which was subsequently treated by radiofrequency ablation.

On surveillance chest CT, multiple lung and pleural metastases were found. The patient was treated with sunitinib (50 mg; 4 week treatment with a 2 week rest period) and achieved partial response, according to the response evaluation criteria in solid tumours, 6 months after treatment. Follow-up chest CT after 12 months showed disease progression; the patient's medication was therefore changed to everolimus. After 2 months of treatment with everolimus, response studies showed further disease progression and the patient managed with best supportive care without further chemotherapy due to his poor general condition.

What is VHL disease?

What is the function of the VHL gene and its importance in RCC?

What is the evidence base for this patient's treatment options?

How should the patient's family be managed?

What is VHL disease?

VHL disease is a rare, hereditary autosomal-dominant cancer syndrome characterized by the development of multiple vascular tumours. Most frequently, these include retinal and CNS haemangioblastomas, clear cell RCCs, phaeochromocytomas, pancreatic islet tumours, endolymphatic sac tumours and, additionally, renal and pancreatic cystadenomas, and epididymal cystadenomas in men.1

A VHL gene abnormality is present in approximately 1 in 36,000 individuals. The initial manifestations of disease can occur in childhood, adolescence or adulthood, with a mean age at initial presentation of about 26 years.2 In one large series, the mean age at onset of RCC was 44 years; it was estimated that 69% of patients surviving to age 60 would develop RCC.2 RCCs are often multicentric and bilateral, and can arise either in conjunction with cysts or de novo from non-cystic parenchyma.3

What is the function of the VHL gene and its importance in RCC?

VHL disease is associated with a mutation of both alleles of the VHL gene located on the short arm of chromosome 3. To date, over 150 mutations responsible for the development of VHL syndrome have been identified.4

The syndrome is caused by inactivation of the VHL protein, the product of the VHL gene. VHL protein is a tumour suppressor ...

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