Nediferencované choriokarcinomy –epitelioidní trofoblastické tumoryléčené v Centru pro trofoblastickounemoc v ČR (CTN) v letech 1955 - 2003

Undifferentiated Choriocarcinomas – EpithelioidTrophoblastic Tumors Treated in Trophoblastic DiseaseCenter in the Czech Republic (TDC-CZ) in theYears 1955 – 2003

Objective:
The clinical-pathological picture, pathogenesis, biological behavior and therapy ofepithelioid trophoblastic tumor (ETT) alias undifferentiated choriocarcinoma (CH-Ned).Design: A retrospective analysis.Setting: Trophoblastic Disease Center in the Czech Republic (TDC-CZ), Department of Gynecologyand Obstetrics, 3rd Medical Faculty, Charles University, Institute for the Care of Mother andChild, Prague.Methods: The identifi cation of all tumors complying with histopathological criteria of ETT-CHNedamong 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, correlationwith 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 diffuselyinfiltrated thyroid gland and clinically imitated struma. In the other case a massivedissemination of ETT-CHNed in the lungs was supposed to be tuberculosis. The tumor inthe uterus and metastases was predominantly of solid character, not infrequently withnecroses and haemorrhages. The microscopic analysis revealed larger irregular cells withfrequent mitoses, resembling eight-day orthologic trophoblast. There were also infrequentelements of cyto-intermediate and syncytium-trophoblastic character. The mitotic index(3-7), proliferation markers (20%), inhibitin alpha, hCG and PLAP with histological picturesuggest a specific form of MTT or choriocarcinoma. The age of the female patients was in therange 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 ineight, mola hydatiosa completa twice, anamnesis was uncertain once and extra-uterinepregnancy was suspected also once. The interval between pregnancy and establisheddiagnosis was in the range of one to 64 months. The ETT-CHNed diagnosis was established18 times from curretage of endometrium, six times from biopsies of organs considered asprimary localization of the tumor and once during post mortem examination. The hCGvalues upon admission were in the range of 101 to 103 mIU/ml in connection with a smallnumber of differentiated syncitium-trophoblastic cells. In the first period (1955-1963) beforeintroduction of chemotherapy all five patients died (100%) in the range of 4 months to 3years. In the second period (1964-1980), hysterectomy with subsequent monochemotherapyresulted in permanent remission (20 years) in four women out of nine (44%). In the thirdperiod (1981-2003), hysterectomy with subsequent polychemotherapy resulted in completeremission from two to 18 years in 9 out of 11 women (82%), while in two cases with absentETT-CHNed in uterus the intervention was limited to tumor extirpation in the lung ormamma 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, whichis not less aggressive than choriocarcinoma (CH-NST). It becomes manifest by frequentmetastases, often with absent demonstrable tumor in the uterus. It represents a lessdifferentiated form of MTT, becoming manifest in a low production of hCG. It can be derivedby formal pathogenetics from non-differentiated earliest orthologic trophoblast. There aredifferentiated transitions between ETT-CHNed and CH-NST, which are analogous to grading of other malignant epithelial tumors. Hysterectomy with subsequent intensive chemotherapydecreased 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