Choriocarcinoma

Choriocarcinoma is a highly malignant gestational trophoblastic neoplasm of sheets of abnormal cytotrophoblast and syncytiotrophoblast without chorionic villi, with extensive haemorrhage and necrosis. It arises after a complete mole in about 50%, after a term pregnancy in about 25%, and after a miscarriage or ectopic pregnancy in about 25%. It can also be a non-gestational germ cell tumour (ovarian or testicular).

Hallmarks: very high hCG, and spread by blood to lung, liver, brain, spleen and kidney, even when the uterine primary is small or undetectable. Before chemotherapy mortality exceeded 90%; cure is now 90 to 100% with methotrexate or multiagent regimens.

• Irregular or persistent vaginal bleeding after any pregnancy event, which may be months to years later
• Haemoptysis, dyspnoea and pulmonary embolic phenomena from lung metastases, pulmonary hypertension
• Neurological: headache, seizures, hemiparesis, intracerebral haemorrhage
• Abdominal pain and haemoperitoneum (liver or uterine rupture), haematuria, melaena or gastrointestinal bleeding
• Thyrotoxicosis, theca lutein cysts, anaemia
• Rarely, an infant with metastatic choriocarcinoma from the mother's tumour

• Serum quantitative hCG, often above 100,000 IU/L. The hook effect can give falsely low values, so dilute the sample when clinical suspicion is high
• Imaging: pelvic Doppler ultrasound and MRI, CT chest, abdomen and pelvis, MRI brain; PET can locate occult disease
• Tissue diagnosis is not required, and biopsy of metastases is hazardous because of haemorrhage; uterine specimens show biphasic sheets of trophoblast with haemorrhage
• Genotyping can separate gestational from non-gestational choriocarcinoma and identify the causative pregnancy
• Risk score (6 or less low risk, 7 or more high risk) and anatomical stage I to IV

• Low risk (score 6 or less): methotrexate 50 mg IM on days 1, 3, 5 and 7 with folinic acid 15 mg orally on days 2, 4, 6 and 8, every 2 weeks, or actinomycin D 1.25 mg/m2 IV every 2 weeks. About 10 to 20% need second line therapy
• High risk (score 7 or more): EMA-CO every 14 days. Day 1: etoposide 100 mg/m2 IV, actinomycin D 0.5 mg IV, methotrexate 300 mg/m2 IV over 12 hours. Day 2: etoposide 100 mg/m2, actinomycin D 0.5 mg, folinic acid 15 mg every 12 hours for 4 doses starting 24 hours after methotrexate began. Day 8: cyclophosphamide 600 mg/m2 and vincristine 1 mg/m2. Give 2 to 3 additional courses after hCG normalises. Primary remission is 80 to 90% and overall cure 90 to 95%
• Ultra-high-risk disease (score 13 or more, or extensive liver or brain metastases): induction with etoposide 100 mg/m2 and cisplatin 20 mg/m2 on days 1 and 2, weekly for 1 to 3 weeks, before EMA-CO, to reduce early haemorrhagic death
• Salvage: etoposide cisplatin alternating with EMA, paclitaxel cisplatin alternating with paclitaxel etoposide, high dose chemotherapy with stem cell support, and checkpoint inhibitors (pembrolizumab, avelumab, camrelizumab with apatinib)
• Adjuncts: resection of chemoresistant uterine or lung lesions, hysterectomy in refractory disease, embolisation, radiotherapy for brain metastases (whole brain 30 Gy) or radiosurgery, and G-CSF support
• Supportive: transfuse to keep haemoglobin above 8 g/dL, avoid biopsy of metastases, manage tumour lysis, and treat hyperthyroidism with beta blockers
• Follow up: weekly hCG until three normal values, then monthly for 12 months (low risk) or 24 months (high risk). Contraception during follow up. Later pregnancies are safe after surveillance, with early ultrasound and hCG 6 weeks postpartum