Embryonal Carcinoma of the Testis

Embryonal carcinoma is a malignant germ cell tumour made of primitive undifferentiated cells resembling the embryo.

Pure embryonal carcinoma is uncommon, accounting for about 2 to 5% of testicular germ cell tumours, though embryonal elements are found in about 85% of mixed tumours.

It affects men aged 20 to 35. It is more aggressive than seminoma, with early vascular invasion and metastasis to lymph nodes, lung, liver and other sites.

Pathophysiology. The tumour arises from germ cell neoplasia in situ, carries the isochromosome 12p, and is composed of pleomorphic cells in glands, papillae and solid sheets, with necrosis and haemorrhage.

Cells are positive for CD30, OCT3/4, SOX2 and cytokeratin, and negative for CD117 and D2-40.

Vascular and lymphatic invasion is common, and a large share of stage I patients have lymphovascular invasion. This marks a high risk of relapse (about 40 to 50% without adjuvant treatment).

Tumour markers: AFP and beta-hCG may be normal or raised. A high AFP points to a yolk sac component, and a high hCG to a trophoblastic component.

Stage and risk group use TNM staging with serum tumour markers, and the good, intermediate and poor risk groups for nonseminomatous germ cell tumour, based on marker levels and visceral metastases.

A painless or painful testicular mass, often with a short history, and sometimes with a normal sized testis when the tumour is small. Metastatic features include back pain, cough, dyspnoea, abdominal or neck masses, and weight loss. Rarely, spontaneous haemorrhage or necrosis presents as acute pain mimicking infection.

• Scrotal ultrasound: a heterogeneous mass with ill defined margins, cystic areas and invasion of the tunica albuginea.
• AFP, beta-hCG and lactate dehydrogenase before orchidectomy, and repeated until normal after it.
• CT of chest, abdomen and pelvis with contrast. MRI of the brain when hCG is over 5000 IU/L or neurological symptoms are present.
• Pathology: pure embryonal carcinoma or mixed components, lymphovascular invasion, rete testis invasion and pT stage. CD30 positive immunostaining confirms the diagnosis and separates it from seminoma.
• Pre-treatment: semen analysis, testosterone, creatinine clearance, audiometry and lung function.

Differential diagnosis.

• Seminoma
• Yolk sac tumour
• Mixed germ cell tumour
• Testicular lymphoma
• Choriocarcinoma
• Epididymo orchitis or abscess
• Metastatic carcinoma

• Offer sperm banking before treatment.
• Radical inguinal orchidectomy with high ligation of the cord.
• Stage I:
  • With lymphovascular invasion (high risk, usual for embryonal carcinoma): adjuvant BEP for 1 cycle (relapse falls to about 2 to 3%), nerve sparing retroperitoneal lymph node dissection, or surveillance in men who accept a higher relapse risk.
  • Without lymphovascular invasion: surveillance.
• Stage IIA or IIB with normal markers: nerve sparing retroperitoneal lymph node dissection or BEP for 3 cycles. Stage II with raised markers, IIC and III: BEP for 3 cycles (good risk) or 4 cycles (intermediate and poor risk), or EP for 4 cycles when bleomycin is unsuitable.
  • 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. Neutropenic fever needs intravenous antibiotics within 60 minutes.
• 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 include cardiovascular disease, metabolic syndrome, hypogonadism, neuropathy, ototoxicity, bleomycin lung toxicity and second cancers. Offer sperm banking before treatment.

Monitoring. Clinical review with markers every 2 to 3 months in year 1, every 3 to 4 months in year 2, then every 6 months to year 5, with CT at about 3 and 12 months. After chemotherapy: markers and review every 1 to 3 months in year 1, then spaced out, and CT as directed.

Referral and escalation. Refer to urology and to a specialist oncology centre. Urgent referral for metastatic symptoms, marker rise or neutropenic fever.