Objective: The clinical-pathological picture, pathogenesis, biological behavior and therapy of epithelioid trophoblastic tumor (ETT) alias undifferentiated choriocarcinoma (CH-Ned). Design: A retrospective analysis. Setting: Trophoblastic Disease Center in the Czech Republic (TDC-CZ), Department of Gynecology and Obstetrics, 3rd Medical Faculty, Charles University, Institute for the Care of Mother and Child, Prague. Methods: The identifi cation of all tumors complying with histopathological criteria of ETT-CHNed among 372 malignant tumors of trophoblast (MTT), treated at TDC-CZ in the years 1955-2003. Their morphological analysis was done from the standpoint of formal pathogenesis, correlation with clinical picture, laboratory and therapeutic results. Results: Among 372 malignant tumors of trophoblast (MTT) we detected 25 ETT-CHNed. The size of the tumor was in the range of 15 to 45 mm except two cases. One tumor diffusely infiltrated thyroid gland and clinically imitated struma. In the other case a massive dissemination of ETT-CHNed in the lungs was supposed to be tuberculosis. The tumor in the uterus and metastases was predominantly of solid character, not infrequently with necroses and haemorrhages. The microscopic analysis revealed larger irregular cells with frequent mitoses, resembling eight-day orthologic trophoblast. There were also infrequent elements of cyto-intermediate and syncytium-trophoblastic character. The mitotic index (3-7), proliferation markers (20%), inhibitin alpha, hCG and PLAP with histological picture suggest a specific form of MTT or choriocarcinoma. The age of the female patients was in the range of 22 to 43 years. In 18 cases (72%) the tumor displayed gynecological symptomatology, in 7 cases (28%) a non-gynecological one (pulmonary 3 times, thyroid once, CNS once, GIT once, mamma once). In the case history there was delivery in 10 cases, abortion in eight, mola hydatiosa completa twice, anamnesis was uncertain once and extra-uterine pregnancy was suspected also once. The interval between pregnancy and established diagnosis was in the range of one to 64 months. The ETT-CHNed diagnosis was established 18 times from curretage of endometrium, six times from biopsies of organs considered as primary localization of the tumor and once during post mortem examination. The hCG values upon admission were in the range of 101 to 103 mIU/ml in connection with a small number of differentiated syncitium-trophoblastic cells. In the first period (1955-1963) before introduction of chemotherapy all five patients died (100%) in the range of 4 months to 3 years. In the second period (1964-1980), hysterectomy with subsequent monochemotherapy resulted in permanent remission (20 years) in four women out of nine (44%). In the third period (1981-2003), hysterectomy with subsequent polychemotherapy resulted in complete remission from two to 18 years in 9 out of 11 women (82%), while in two cases with absent ETT-CHNed in uterus the intervention was limited to tumor extirpation in the lung or mamma with subsequent treatment with chemotherapy. Conclusion: The revision of 372 MTT treated in TDC-CZ (1955-2003) uncovered 25 ETT-CHNed. Their clinical-pathological analysis revealed that ETT-CHNed is a malignant tumor, which is not less aggressive than choriocarcinoma (CH-NST). It becomes manifest by frequent metastases, often with absent demonstrable tumor in the uterus. It represents a less differentiated form of MTT, becoming manifest in a low production of hCG. It can be derived by formal pathogenetics from non-differentiated earliest orthologic trophoblast. There are differentiated transitions between ETT-CHNed and CH-NST, which are analogous to grading of other malignant epithelial tumors. Hysterectomy with subsequent intensive chemotherapy decreased the original 100% mortality in the years 1955-1963 to 18.1% in the years 1980-2003.

        Key words: epithelioid trophoblastic tumor, clinical-pathological picture, biological properties, therapy