Yolk Sac Tumour of the Testis

Yolk sac tumour is a malignant germ cell tumour with differentiation toward extra-embryonic yolk sac structures, and it secretes AFP. It is the commonest testicular tumour in infants and young boys, accounting for about 80% of prepubertal testicular tumours, with a median age of about 16 to 24 months.

In adults pure yolk sac tumour is rare (under 2%), but yolk sac elements occur in about 40% of mixed germ cell tumours. Prepubertal disease behaves differently: most boys present at stage I and are cured, and spread is by blood to the lungs.

Pathophysiology. Prepubertal tumours are not associated with germ cell neoplasia in situ or isochromosome 12p. Postpubertal tumours are, and behave like other nonseminomatous germ cell tumours.

Histology: reticular, microcystic, solid and glandular patterns, with Schiller-Duval bodies and hyaline globules. Immunostaining is positive for AFP, glypican-3, SALL4 and cytokeratin.

AFP is produced by the tumour, with a half life of 5 to 7 days. Normal infant AFP is high at birth and falls to adult levels (under about 10 to 15 ng/mL) by 8 to 12 months, so an age specific range is needed.

Boys: a painless scrotal mass, firm and often non-tender, noticed by a parent. Adults: a testicular mass with or without metastatic features such as back pain and cough. Blood borne spread causes lung metastases in children, and retroperitoneal or lung disease in adults. Rarely, rupture or haemorrhage gives pain.

• Scrotal ultrasound: a heterogeneous, vascular mass.
• AFP (age specific range in infants), beta-hCG and lactate dehydrogenase before orchidectomy, and repeated after it until normal.
• CT or MRI of the abdomen and pelvis, and CT of the chest, for staging. MRI of the brain only for symptoms.
• Histology after inguinal orchidectomy, with immunostaining for AFP, glypican-3 and SALL4.
• Adults: semen analysis, testosterone, creatinine clearance, audiometry and lung function before chemotherapy.

Differential diagnosis.

• Mixed germ cell tumour
• Teratoma
• Embryonal carcinoma
• Juvenile granulosa cell tumour
• Epidermoid cyst
• Hydrocele, hernia or torsion in boys
• Testicular lymphoma and leukaemic infiltration

• Offer sperm banking in postpubertal males before surgery and chemotherapy.
• Radical inguinal orchidectomy with high ligation of the cord. Never biopsy through the scrotum.
• Children, stage I (confined to the testis, markers normalising): surveillance after orchidectomy, with AFP, clinical review and ultrasound at regular intervals, and chest imaging. Relapse occurs in about 15 to 20%, and nearly all are cured with chemotherapy.
• Children with metastatic disease or persistent markers: platinum based chemotherapy within paediatric oncology, with doses by body surface area. Cure is about 90% or more overall.
• Adults (postpubertal):
  • Stage I: high risk (lymphovascular invasion) adjuvant BEP for 1 cycle or surveillance. Low risk: surveillance.
  • Stage IIA or IIB with normal markers: nerve sparing retroperitoneal lymph node dissection or BEP for 3 cycles. Raised markers, IIC and III: BEP for 3 cycles (good risk) or 4 cycles (intermediate and poor risk).
  • BEP is repeated every 21 days: bleomycin 30 units intravenously on days 1, 8 and 15, etoposide 100 mg/m2 on days 1 to 5, and cisplatin 20 mg/m2 on days 1 to 5 with hydration (1 to 2 L of saline before and after, plus magnesium and potassium).
  • Antiemetics for high emetic risk: ondansetron 8 mg, dexamethasone 12 mg and aprepitant 125 mg on day 1, then aprepitant 80 mg on days 2 and 3 with dexamethasone 8 mg on days 2 to 4.
  • Cisplatin needs creatinine clearance over 60 mL/min. Stop bleomycin for lung toxicity.
• Residual masses over 1 cm after chemotherapy with normal markers: surgical resection.
• Relapse: salvage chemotherapy (TIP or VeIP) or high dose carboplatin and etoposide with stem cell rescue at a specialist centre.
• Late effects: hearing loss, neuropathy, kidney impairment, secondary cancers and infertility. Children need long term follow up for hearing, fertility and growth.

Special groups. Children need paediatric oncology and surgeon care, with testis sparing surgery only for clearly benign lesions. Prepubertal boys with persistently high AFP after surgery need staging.

Monitoring. AFP every 1 to 3 months for the first 1 to 2 years, then every 3 to 6 months. Chest imaging and abdominal ultrasound or CT at intervals set by oncology, usually every 3 to 6 months in year 1 and 2. In adults, use the nonseminomatous germ cell tumour schedule of markers and imaging set by oncology.

Referral and escalation. Refer to paediatric surgery or urology and paediatric oncology for children, and to urology and a specialist oncology centre for adults. Urgent referral for rising AFP, metastases or neutropenic fever.