ESPE Abstracts

Background: Secondary amenorrhoea occurs in approximately 8% of adolescent females. Ovarian and adrenal tumours are rare causes of secondary amenorrhoea. Ovarian Sertoli-Leydig cell tumours (SLCT) are rare sex-cord stromal tumours of the ovary, accounting for <0.5% of all primary ovarian neoplasms. SLCTs affect all age groups, 75% detected in second and third decade of life (mean age 25 years) and <10% detected following menopause. Testicular-like tumour cell types (Sertoli and Leydig cells) produce androgens and present clinically due to androgenic effects. Prognosis depends on tumour differentiation. DICER1 predisposing variants account for about 60% of ovarian SLCTs. DICER1 syndrome is a familial tumour susceptibility syndrome associated with pleuropulmonary blastoma; ovarian sex cord-stromal tumours; cystic nephroma; thyroid gland neoplasia; and other rare tumours.

Case report: A 15-year-old girl presented with secondary amenorrhoea for 10 months with no significant other medical history. Body mass index 19.41 kg/m2, (Z=-0.42). Deepening of voice, coarse hair over the abdomen and clitoromegaly were noted on examination. Initial biochemistry showed elevated Testosterone concentration 18.4 nmol//L (0–1.8 nmol/L), and Androstenedione 33.2 nmol/L (0.0-10.1 nmol/L). 17 hydroxy progesterone was moderately elevated, 15.3 (0-4nmol/L). Cortisol, ACTH, DHEAS, thyroid functions, gonadotrophins oestradiol and tumour markers were within normal range. Urine steroid profile showed disproportionately elevated adrenal androgens compared to cortisol metabolites. Gynaecological transabdominal ultrasound scan identified a cystic and solid lesion in right ovary measuring 5.4 × 5.4 × 4.3 cm, located along the right pelvic sidewall without evidence of metastasis. Laparoscopic right salphingo-oophorectomy with omental and peritoneal biopsies performed. Histology consistent with moderately to poorly differentiated SLCT with focal retiform pattern without heterologous elements, normal background ovarian tissue and no malignant cells in peritoneal washing. Tumour staged as G2-3 Sertoli-Leydig cell tumour stage1. Immunohistochemistry positive for Calretinin, inhibin and WT1. Melan A highlighted clusters of Leydig cells. Vimentin and AE1/AE3 are positive in Sertoli cells. CT thorax revealed a left pulmonary nodule measuring 5.7 × 4.2 mm and several nodes in left lobe of thyroid gland. Genetic analysis confirmed two pathogenic variants in DICER1 gene; D1709N (RNase IIIb domain hotspot variant) and E292* (nonsense variant) at 44.4% VAF and 55.1% VAF respectively. Post operatively, testosterone normalised and resumed menstruation. Follow up arranged for tumour surveillance.

Conclusion: Secondary amenorrhoea and high testosterone levels narrow down the diagnosis towards ovarian tumours including SLCT. Genetic confirmation of DICER-1 germline mutation is important in view of individual and familial risk of associated neoplasms.