Placental-site trophoblastic tumour and epithelioid trophoblastic tumour

Placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT) arise from the intermediate trophoblast of the implantation site and the chorion laeve respectively, cell types that produce human placental lactogen rather than large amounts of hCG. Both present, usually in women in their thirties, with abnormal bleeding or amenorrhoea months or years after a normal pregnancy, miscarriage or mole, with serum hCG only mildly raised or even normal and often with a high proportion of hCG-free beta subunit; ETT can sit in the cervix or lower uterine segment and mimic squamous cell carcinoma. Unlike choriocarcinoma, they infiltrate the myometrium slowly, spread by lymphatics as well as blood, and are relatively resistant to chemotherapy, so hCG cannot be relied on to track them and imaging matters more. The FIGO score does not apply; the prognostic factors are stage, an interval of more than four years since the causative pregnancy, deep myometrial invasion, high mitotic count and, for PSTT, the presence of metastases, with the long interval the single strongest predictor of death.

Hysterectomy is the treatment for disease confined to the uterus and cures the great majority; fertility-sparing resection is attempted only in exceptional cases with small, localised tumours and carries a risk of recurrence. Metastatic disease and tumours arising more than four years after the antecedent pregnancy are treated with multi-agent platinum-containing chemotherapy, most often EP-EMA or TP/TE, with surgical removal of residual disease, and high-dose chemotherapy with autologous stem cell rescue has been used for resistant cases; EMA-CO alone is inadequate. Because response is measured by imaging as much as by hCG, FDG-PET is used to define residual disease before and after surgery. Immune checkpoint inhibitors are being tried in resistant intermediate trophoblastic tumours because, like other trophoblastic tumours, they express PD-L1, and pembrolizumab has produced responses in case reports. Registration with a national trophoblastic disease centre is recommended for every case because expert pathology is needed to separate PSTT and ETT from exaggerated placental site reaction, placental site nodule and choriocarcinoma, each of which is managed differently.