Epithelioid Trophoblastic Tumour

Epithelioid trophoblastic tumour (ETT) is the rarest form of GTN, derived from chorionic type intermediate trophoblast, histologically resembling carcinoma (nests and cords of epithelioid cells with eosinophilic or clear cytoplasm, geographic necrosis and hyalinised matrix). It typically occurs in the reproductive age group, 1 to 25 years (mean about 6 years) after a term pregnancy, and less frequently after an abortion or mole.

It may involve the lower uterine segment and cervix, mimicking squamous cell carcinoma. hCG levels are usually low (below 2,500 IU/L), with p63 and cyclin E positive and hPL weak or focal (unlike PSTT).

• Abnormal vaginal bleeding is the commonest presentation; amenorrhoea
• Uterine or cervical mass (cervical lesion may be mistaken for cervical cancer)
• Metastases in lung (25 to 30% at presentation), and less often liver, brain and other sites
• Rarely asymptomatic, found incidentally after a pregnancy event

• Serum hCG: modest elevation (mean about 2,500 IU/L), and may be normal
• Ultrasound and MRI show a solid or cystic, haemorrhagic mass in uterine fundus, lower uterine segment or cervix
• Histology is essential: nodular tumour of uniform epithelioid cells with eosinophilic or clear cytoplasm, geographic necrosis with hyaline material; immunohistochemistry positive for p63 (a key feature differentiating from PSTT), cytokeratin AE1/AE3, inhibin, and GATA3; weak or focal hCG and hPL; Ki-67 10 to 25%
• Differential diagnosis: squamous cell carcinoma of the cervix (p16 positive in carcinoma; ETT is p16 variable and p63 positive), PSTT (diffuse hPL and Mel-CAM positive), and choriocarcinoma
• Staging by CT chest, abdomen and pelvis, with MRI brain if indicated

• Surgery is the mainstay: total hysterectomy (with bilateral salpingectomy, ovaries conserved when normal) for stage I disease, with 5-year survival of about 90 to 100%; fertility preserving local resection has been reported in carefully selected patients, but recurrence is possible.
• Chemotherapy is recommended for metastatic disease or adjuvant therapy for high risk features: EP-EMA, TP/TE (paclitaxel/cisplatin alternating with paclitaxel/etoposide) and EMA-CO; these tumours are relatively chemoresistant, and 5-year survival with metastatic disease is about 50 to 65%.
• Immunotherapy: pembrolizumab, avelumab and other PD-1/PD-L1 inhibitors have shown promising activity in resistant cases.
• Resection of isolated recurrences or metastases, particularly pulmonary.
• Follow up: hCG monitoring is less reliable, so combine hCG every 3 months for 2 years with imaging (MRI pelvis, CT chest) at 3 to 6 month intervals for 2 to 5 years, then annually. Counsel regarding future pregnancy only after at least 12 months of remission.