Yolk Sac Tumour of the Ovary

Yolk sac tumour (endodermal sinus tumour) is the second most common malignant ovarian germ cell tumour (about 15 to 20 percent). It occurs mostly in girls and young women (median age about 19 years). It is unilateral, large (15 to 20 cm), and rapidly growing.

It results from malignant transformation of primitive germ cells with extraembryonic differentiation, and secretes alpha fetoprotein (AFP) and alpha-1 antitrypsin.

Histology shows reticular, microcystic and festoon patterns. Schiller-Duval bodies (a central vessel surrounded by tumour cells) are present in about 50 to 75 percent. Intra- and extracellular hyaline globules are seen. Immunostaining is positive for AFP, glypican-3, SALL4 and cytokeratin, and negative for OCT3/4 and CD30.

It was once almost uniformly fatal. With surgery and combination chemotherapy, 5-year survival is now over 90 percent in early stage disease and about 70 to 85 percent in advanced stage.

• Rapidly progressive abdominal or pelvic pain (about 75 percent) and a palpable mass; abdominal distension; fever; symptoms often start within days to weeks.
• Acute abdomen from torsion, rupture or haemorrhage (about 10 percent).
• Ascites, pleural effusion, and nausea in advanced disease.
• Amenorrhoea is unusual because the tumour is unilateral, and menstruation often continues.
• Examination: a large solid pelvic mass (often over 15 cm), tender, with signs of peritonism in rupture.
• Metastases: peritoneum, omentum, lymph nodes, liver, and lung.

• Serum alpha fetoprotein is raised in nearly all cases (often over 1,000 ng/mL, sometimes above 10,000). This is diagnostic in a young woman with a solid pelvic mass.
• AFP is used to monitor response and relapse. Its half life is 5 to 7 days, and a slower fall indicates persistent disease. hCG and LDH are also measured to identify mixed germ cell tumours.
• Ultrasound: large solid heterogeneous mass with cystic areas and a rich vascular pattern. MRI or CT shows a solid cystic mass with intense enhancement and sometimes "bright dot" vessels, peritoneal deposits and nodal disease.
• CT chest, abdomen and pelvis for stage; PET scan is optional.
• Karyotype in adolescents with abnormal development.
• Histology by surgical specimen: yolk sac pattern with Schiller-Duval bodies and AFP-positive cells; mixed germ cell tumours, found in about 30 percent, must be separated.
• Baseline tests before chemotherapy: renal function, audiometry, lung function, and fertility counselling.

• Surgery: unilateral salpingo oophorectomy with complete staging (peritoneal washings, omentectomy, peritoneal biopsies, assessment of lymph nodes). Preserve the uterus and contralateral ovary, even in advanced disease, since chemotherapy is highly effective.
• Remove the tumour intact in a bag to avoid rupture. Perform cytoreduction of metastatic disease when feasible without morbidity; interval cytoreduction after chemotherapy.
• Adjuvant chemotherapy for all stages, including stage I: BEP for 3 to 4 cycles, every 21 days. Treat 3 cycles for completely resected disease and 4 cycles for residual or advanced disease.
• BEP doses: bleomycin 30 units on days 1, 8 and 15 (or 15 units/m2), etoposide 100 mg/m2 on days 1 to 5, cisplatin 20 mg/m2 on days 1 to 5.
• Granulocyte colony stimulating factor (filgrastim 5 micrograms/kg daily) is added when needed. Fluids, antiemetics (ondansetron 8 mg, dexamethasone 8 mg, aprepitant 125 mg on day 1 then 80 mg on days 2 and 3), and magnesium supplementation protect against toxicity.
• Monitoring: AFP weekly during treatment, with a decline at the expected rate and normalisation by cycle 3. Then every month for the first year, every 2 months for the second year, and every 3 to 6 months afterwards. CT or MRI as needed; lung function (with bleomycin), audiometry, creatinine clearance.
• Persistent AFP elevation or relapse: salvage chemotherapy with TIP (paclitaxel 175 mg/m2 on day 1, ifosfamide 1.2 g/m2 on days 1 to 5 with mesna, cisplatin 20 mg/m2 on days 1 to 5) or VeIP (vinblastine, ifosfamide, cisplatin) for 4 cycles. The alternative is high dose carboplatin and etoposide with autologous stem cell rescue.
• Surgically resect residual masses in relapse. Cure rates are about 50 percent.
• Residual mass after chemotherapy with normal AFP: resection to exclude mature teratoma (growing teratoma syndrome) or viable tumour.
• Fertility: normal ovarian function and fertility are preserved in most. Oocyte cryopreservation or GnRH agonist protection before chemotherapy is offered. Pregnancy is advised 1 to 2 years after finishing treatment.
• Late effects: ototoxicity, nephrotoxicity, neuropathy, pulmonary toxicity, secondary leukaemia (etoposide), and cardiovascular disease; long term follow up is needed.