A 26-year-old Caucasian female presented with nausea, intermittent abdominal pain and amenorrhoea of 3 months duration. She was known to have Von HippelLindau disease (Exon 3A/T 742 mutation) and had undergone surgery for cerebellar haemangioblastoma. She also had presumed dermoid cyst in right ovary which had been monitored by ultrasound. Ultrasound revealed an increase in size and vascularity of right ovarian cyst. MRI scan revealed it to be a 6.3 cm lobulated mass in close contact with uterus. Serum biochemistry showed normal gonadotrophins and serum testosterone of 22.1 nmol/l. Her tumour markers were negative. Urinary catecholamines were normal.
She underwent right ovarian cystectomy and her periods restarted after 11 months of amenorrhoea. Her postoperative serum testosterone level was 1.5 nmol/l.
Histology showed clear cell tumour and it was thought to be a renal cell carcinoma. There was no evidence of renal tumour on imaging. In view of high preoperative testosterone and return of periods review of histology suggested it to be a clear cell testosterone secreting tumour of ovary.
Von HippelLindau disease is autosomal dominant with age dependent penetrance. VHL gene is on chromosome 3p25-26. Systemic manifestations include: retinal and CNS haemangioblastomas; pheochromocytomas; cysts in pancreas and kidneys; renal cell carcinomas; epididymal cystadenoma and islet cell tumours. Papillary cystadenomas of epididymis are seen in 1026% of men and tend to be bilateral in VHL. Histologically indentical lesions can be found in the broad ligament but are exceedingly rare. Over-expression of hypoxia inducible factor-1α (HIF-1α) has been reported in clear cell carcinoma of ovary.
Conclusion: To our knowledge, this is the first case of steroid secreting clear cell ovarian tumour in association with VHL. The tumour was non- functioning but 4 years later transformed into a testosterone secreting tumour. We suggest that tumour transformation occurred because of inducible proteins secondary to over-expression of HIF-1α.