Mixed Gestational Trophoblastic Tumors-Challenging Clinicopathological Presentations

Mixed gestational trophoblastic tumors are exceptionally rare and have variable clinicopathological presentations. We report 3 such tumors with different combinations of choriocarcinoma (CC), placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). The patients' age ranged from 38 to 44 years. Mixed trophoblastic tumor was not considered at the initial diagnosis and all 3 tumors were proven of gestational origin by DNA genotyping. Patient #1 presented with serum human chorionic gonadotropin (hCG) of 97 mIU/mL and a 5.6-cm cervical mass that was initially interpreted as PSTT on biopsy. Hysterectomy revealed a mixed PSTT (60%) and ETT (40%) with extrauterine metastases of only the ETT component. The tumor recurred 15 months after a multiagent chemotherapy and was tested positive for programmed death-ligand 1. The patient received immune checkpoint inhibitor therapy and remained disease-free after 24 months. Patient #2 presented with vaginal bleeding and serum hCG of 46,458 mIU/mL. An endometrial biopsy was interpreted as CC. Recurrence developed in the uterus and lung after methotrexate-based chemotherapy. A mixed CC and ETT were eventually diagnosed upon consultation review. Patient #3 presented with a complete hydatidiform mole and serum hCG of 744,828 mIU/mL. Three months after methotrexate, followed by actinomycin D therapy, a uterine mass was found. Hysterectomy revealed a mixed CC and PSTT. In conclusion, the rarity, elusive presentation, and wide range of histology make the diagnosis of mixed trophoblastic tumors highly challenging. The clinical management and prognosis are dictated by each component of the tumor. CC component must be considered when the patient presents with a high serum hCG level.