Sertoli-Leydig Cell Tumour

Sertoli-Leydig cell tumours are rare sex cord stromal tumours of the ovary. They are composed of Sertoli cells, Leydig cells and, in intermediate and poorly differentiated forms, primitive gonadal stroma with or without heterologous elements. They account for less than 0.5 percent of ovarian tumours.

They occur mainly in women under 30 years (mean age 25), though they can occur at any age. They are unilateral in over 98 percent, and stage I in about 90 percent.

About 50 percent secrete androgens (testosterone, androstenedione), causing virilisation. Others are hormonally silent or secrete oestrogen.

Grading:

• Well differentiated (about 11 percent; benign behaviour).
• Moderately differentiated (about 54 percent).
• Poorly differentiated (about 13 percent).
• Retiform and heterologous variants.

Prognosis relates to stage and differentiation. Malignancy occurs in about 10 to 20 percent overall, with intermediate and poorly differentiated types in 11 to 59 percent.

Over 60 percent of cases in younger women are associated with DICER1 mutations (germline in 60 percent). These are associated with pleuropulmonary blastoma, multinodular goitre and thyroid cancer, cystic nephroma, and embryonal rhabdomyosarcoma of the cervix, so germline testing is required.

• Virilisation in about one third to one half: oligomenorrhoea or amenorrhoea, defeminisation (breast atrophy), hirsutism, acne, temporal balding, voice deepening, clitoromegaly, and increased muscle mass. Onset is usually over months.
• Abdominal or pelvic mass, pain, bloating; acute abdomen from torsion or rupture (rupture occurs in about 10 to 15 percent).
• Oestrogenic effects (precocious puberty, endometrial hyperplasia) in a minority.
• Examination: unilateral, solid, mobile adnexal mass (mean size 13 to 16 cm).
• Features suggesting DICER1 syndrome: a personal or family history of thyroid disease, lung cysts, kidney cysts, or childhood tumours.

• Hormonal profile: total testosterone raised (often 5 to 20 nmol/L or more, usually above 6.9 nmol/L), androstenedione raised, SHBG low, LH and FSH low.
• DHEAS is normal or mildly raised (in contrast to adrenal tumours with markedly raised DHEAS).
• Alpha fetoprotein is raised in about 10 to 20 percent of tumours with heterologous elements, and inhibin may be raised.
• Pelvic ultrasound, MRI: solid mass with variable cystic areas and a hypervascular fibromatous component. CT of the chest, abdomen and pelvis to stage. Adrenal imaging to rule out an adrenal source when testosterone is high.
• Exclusion of other virilising causes: polycystic ovary syndrome (milder androgen elevation and bilateral polycystic ovaries), adrenal tumours, congenital adrenal hyperplasia (17-hydroxyprogesterone raised), steroid cell tumour, hilus cell tumour, luteoma of pregnancy.
• Selective venous sampling is rarely necessary in a postmenopausal woman with a normal imaging study.
• Histology: tubules lined by Sertoli cells with Leydig cells in the stroma; immunostaining for inhibin, calretinin, SF-1 and CD99; heterologous elements (mucinous glands, cartilage, skeletal muscle) in some.
• DICER1 germline testing, thyroid ultrasound and chest imaging in patients with the mutation.

• Surgery. Women who have completed childbearing, or with high risk disease: hysterectomy, bilateral salpingo oophorectomy and surgical staging (peritoneal washings, omentectomy, peritoneal biopsies; lymphadenectomy only if suspicious nodes).
• Young women with unilateral stage IA disease: fertility sparing unilateral salpingo oophorectomy with the uterus and contralateral ovary preserved, and staging. Remove intact in a retrieval bag, avoiding rupture (which increases stage to IC).
• Stage I well differentiated or moderately differentiated tumours: no adjuvant therapy.
• Adjuvant chemotherapy for stage IC, stage II to IV, poorly differentiated or heterologous elements or retiform pattern:
  • BEP (bleomycin 15 units/m2 weekly or on day 1 to 3, etoposide 100 mg/m2 on days 1 to 5, cisplatin 20 mg/m2 on days 1 to 5, every 21 days for 3 to 4 cycles).
  • Or carboplatin AUC 5 to 6 with paclitaxel 175 mg/m2 every 21 days for 4 to 6 cycles.
• Recurrence (usually within 5 years, often in the abdomen or pelvis): secondary cytoreduction when feasible and chemotherapy; response is variable.
• Surveillance: clinical review and testosterone every 3 months for 2 years, then every 6 months to 5 years, then annually. Image for rising levels or symptoms. Testosterone is a sensitive marker of recurrence.
• Virilising signs regress over months after surgery (hair growth and menses recover, though clitoromegaly and voice deepening may persist). Antiandrogens (spironolactone 100 to 200 mg daily) may be used for residual hirsutism.
• DICER1 syndrome: genetic counselling, cascade testing of relatives, and surveillance (thyroid ultrasound, chest imaging, renal imaging).
• Fertility after conservative surgery is good, and pregnancy is allowed after the surveillance period. Complete childbearing before prophylactic salpingo oophorectomy.