Placental Site Trophoblastic Tumour

Placental site trophoblastic tumour (PSTT) is a rare gestational trophoblastic neoplasm (under 1 to 2%) derived from intermediate trophoblast of the implantation site. Unlike choriocarcinoma it has few syncytiotrophoblast cells, so hCG is low (usually below 1,000 to 2,000 mIU/mL), while human placental lactogen (hPL) is positive on immunohistochemistry (with Mel-CAM, CD146).

It follows a term pregnancy in about two thirds and an abortion or mole in the rest, with a latency of months to years (average 3.4 years). It is relatively resistant to chemotherapy and spreads by local invasion and lymphatics rather than blood, so surgery is the cornerstone of treatment. Survival is about 80 to 90% for stage I disease and under 50% for metastatic disease.

• Abnormal uterine bleeding or amenorrhoea after a pregnancy event (commonest presentation)
• Enlarged uterus with low level raised hCG
• Rarely nephrotic syndrome (immune complex deposition), virilisation, polycythaemia
• Lung, liver, vaginal or lymph node metastases in advanced disease

• Serum hCG: low relative to tumour burden (usually under 1,000 IU/L), with a raised free beta-hCG fraction; hPL may be raised
• Pelvic ultrasound with Doppler and MRI: myometrial mass with intense vascularity
• Histology: sheets of monomorphic intermediate trophoblast infiltrating myometrium, positive for hPL, Mel-CAM, cytokeratin and inhibin; Ki-67 usually 10 to 30%; under 5% of cells express hCG
• CT or PET-CT staging of chest, abdomen and pelvis, and MRI brain if metastases are present; stage anatomically from I (uterus only) to IV (distant)
• Adverse prognostic factors: interval from the last pregnancy over 48 months, stage III or IV, more than 5 mitoses per 10 high power fields, and clear cytoplasm

• Stage I (localised): hysterectomy, ovaries preserved when appropriate (remission about 100% in stage I with low recurrence in low risk cases). Fertility sparing local resection (curettage or hysteroscopic resection with adjuvant chemotherapy) can be considered in carefully selected young women with focal disease
• Adjuvant chemotherapy after hysterectomy for poor prognostic features (interval above 4 years, high mitotic index, deep invasion)
• Metastatic or recurrent disease: etoposide cisplatin alternating with etoposide-methotrexate-actinomycin D (EP-EMA) is the preferred regimen, continued for 8 to 12 weeks after hCG normalises; alternatives are paclitaxel cisplatin alternating with paclitaxel etoposide, and high dose chemotherapy with stem cell rescue. Methotrexate or actinomycin D alone are generally ineffective
• Immunotherapy: pembrolizumab and other PD-1 or PD-L1 inhibitors are active in chemorefractory disease, since PD-L1 expression is high
• Surgical resection of residual metastases
• Follow up: hCG and hPL monthly for at least 2 years, with pelvic imaging because hCG is an insensitive marker, and prolonged surveillance for late recurrence