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A 47-year-old woman was referred to the new patient diabetic clinic with typical symptoms of hyperglycaemia. On routine abdominal examination, a mass was found on the left side of the abdomen which was ballottable and bimanually palpable. There was a history of ‘benign retinal tumour’ several years ago which did not need active treatment. Further enquiry revealed this to have been a retinal angioma. Routine laboratory tests on blood and urine were unremarkable except for findings of diabetes mellitus. She went on to have ultrasound scan followed by computed tomography (CT) of the abdomen (figure).
- What is the main abnormality seen on the CT scan and what is the radiological diagnosis?
- What other abnormalities are present on the CT scan?
- What condition does the patient have?
- What other abnormalities may occur in this condition?
There is a large solid tumour arising anteriorly from the lower half of the left kidney, with a necrotic centre. There are two solid tumours of the right kidney, with the anterior tumour predominantly necrotic. These appearances are consistent with bilateral hypernephromas.
There are multiple bilateral simple renal cysts, multiple pancreatic cysts and a small left adrenal mass.
The combination of retinal angioma and bilateral hypernephromas indicates the diagnosis of von Hippel-Lindau syndrome.
von Hippel-Lindau syndrome is a rare genetic disorder with multi-organ involvement. The most common features are retinal angiomatosis (51%), haemangioblastoma of the central nervous system (46%), and renal lesions (33%).1 The pancreatic features of the condition include pancreatic cysts, endocrine deficiency,2 exocrine deficiency,3 metastatic islet cell tumour,4 and acute pancreatitis.5The other features are phaeochromocytomas (24%), epididymal cystadenomas and, rarely, carcinoid tumour of the bile duct6 and deafness due to bilateral endolymphatic sac tumours.7
von Hippel-Lindau syndrome is an autosomal dominant inherited disease with a prevalence of 1:40 000.1 The von Hippel-Lindau (VHL) gene has been localised and cloned at human chromosome 3p25-p26.8 The VHL gene product has been found to suppress growth of renal cell carcinoma lines in vitro.9 The association of von Hippel-Lindau disease with renal cell carcinoma may be explained either by mutation of or loss of both alleles of the VHL gene or by disturbance in the function of the VHL gene product.9 10
Although commonly referred to as cerebelloretinal haemangioblastomatosis, there are other significant clinical associations like renal cell carcinoma and phaeochromocytoma. Our patient was known to have retinal angiomas. Subsequent CT scan of the brain did not show evidence of intracranial haemangioblastoma. Both of the renal tumours were biopsied under CT guidance and histological examination showed adenocarcinoma. Urinary normetadrenaline screening for phaeochromocytoma was negative.
Although pancreatic cysts are common, pancreatic endocrine or exocrine deficiency is uncommon. Our patient presented with symptoms of diabetes mellitus which was treated by dietary means. There was no clinical suggestion of steatorrhoea. Central nervous system lesions in von Hippel-Lindau disease present as haemangioblastomas and metastatic renal carcinomas. The haemangioblastomas are mainly intracranial (74%), the rest being located in the spinal cord.11Retinal angiomatosis present as both capillary and cavernous haemangiomas. The renal lesions include renal angiomas, renal cysts and renal carcinomas. Renal carcinomas are frequently bilateral and, if not diagnosed early, tend to metastasize. Our patient went on to have bilateral nephrectomy and renal replacement therapy with chronic ambulatory peritoneal dialysis. Parenchymal sparing surgery is sometimes used in selected patients with renal carcinoma.12
The initial presentation of von Hippel-Lindau syndrome could be to a medical or surgical speciality but more awareness of the syndrome and its associations will lead to early diagnosis. The finding of retinal angiomas or CNS haemangioblastomas should lead to radiological assessment of the kidneys. Screening of first degree relatives will help in early identification of affected individuals.
Formal referral to a medical genetics service will help detailed screening of the patients and their relatives. Medical genetics clinics normally maintain computer registers of such families and are best placed to ensure their adequate prolonged follow-up.
von Hippel-Lindau syndrome.
We are grateful to Dr P Norburn for providing CT films.