ESPE Abstracts

An 11 year 8-month-old girl presented to her oncologist with recent voice change and increased leg hair growth. She had a past history of pelvic rhabdomyosarcoma in 2012, at age 2, with relapse and local metastasis at age 4. Prior to original tumour treatment, oophoropexy had been performed, aiming to prevent ovarian radiation exposure. At time of the new complaint, she was receiving a trial treatment. Puberty was reported to have commenced at age 10, with 6-months of increased leg hair growth plus voice deepening, with a gravelly quality, causing her to remain quiet in class. MRI demonstrated a large (42x 36x 42mm) pelvic mass, abutting but not encasing the left external iliac vessels, uterine fundus and urinary bladder. 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. Endocrinology consult revealed Tanner stage 2-3 breast tissue bilaterally, stage 4 pubic hair and a deep voice. She was pre-menarchal. A family history of cancer in maternal grandparents (salivary/parotid, thyroid cancer, breast cancer) did not suggest a specific genetic link. The pelvic mass was removed, histopathology consistent with stage 1 ovarian Sertoli-Leydig cell tumour (SLCT), with resolution of androgen excess (testosterone <0.4nmol/l/) but she had 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 will be commenced to continue normal feminization, remaining linear growth and bone mass accrual. Further genetic investigations to date have not demonstrated a DICER mutation. This case demonstrates several important points. The enormous androgen levels due to SLCT completely masked 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 paediatric patients, often adolescents (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, past possible radiation exposure or may be similar to a reported link between cervical sarcoma botryoides and ovarian SCLT in at least 19 patients, predominantly adults (3), where relapse within 3 years was common (1).