An 11.8-year-old girl presented with recent voice change and increased leg hair. She had a past history of pelvic rhabdomyosarcoma at age 2, with relapse and local metastasis at age 4. Prior to original tumour treatment, oophoropexy was performed, aiming to prevent radiation exposure.
Puberty commenced at age 10, with 6-months of increased leg hair growth plus voice deepening, with a gravelly quality. Examination revealed Tanner stage 2-3 breast tissue bilaterally and stage 4 pubic hair. She was pre-menarchal. Maternal family history of cancer did not suggest a genetic link. Androgen excess was confirmed, with testosterone 10.4 nmol/L (0.1-1.9), FSH 4.7 IU/L (0-10), LH 4.5 IU/L (1-3), oestradiol 107 pmol/L. MRI demonstrated a large (42 x 36 x 42 mm) pelvic mass, abutting the left external iliac vessels, uterine fundus and urinary bladder.
Histopathology was consistent with stage 1 ovarian Sertoli-Leydig cell tumour (SLCT), with resolution of androgen excess (testosterone <0.4nmol/l/). But there was clear evidence of primary ovarian failure with FSH 60.7 IU/L (1-10), LH 32.1 IU/L (1-3.5) and Oestradiol 19 pmol/L, in the prepubertal range. Oestrogen was commenced to continue normal feminization, remaining linear growth and bone mass accrual. Further genetic investigations have not demonstrated a DICER mutation.
This case demonstrates several important points. The enormous androgen levels due to SLCT mask past chemotherapy /radiotherapy related ovarian failure, only becoming evident after tumour removal and cessation of androgen excess. SLCT are rare sex-cord ovarian tumours, accounting for 1% of all childhood cancers and 10% of all ovarian tumours in paediatrics (1, 2). Up to 85% have associated virilisation (1-3) with up to 63% reported to be due to a DICER 1 gene mutation (2, 3). Association between the rhabdomyosarcoma, the commonest soft tissue sarcoma of childhood (3) and later SCLT may be linked with DICER mutation (1).