[Malignant trophoblastic tumors (MTT) treated in the years 1955-2004 in trophoblastic disease center in the Czech Republic (TDC-CZ): clinical-pathological features, curability, typing, pathogenesis].
OBJECTIVE
Clinical- pathological features, typing, curability and pathogenesis of malignant tumors of trophoblast (MTT).


METHODS
A retrospective analysis.


METHODS
Trophoblastic Disease Center in the Czech Republic (TDC-CZ), Mother and Child Care Institute, 3rd Medical Faculty, Charles University, Prague.


METHODS
Revision of 379 MITT cases treated at TDC-CZ and comparison of their histological picture with developmental stages of orthologic trophoblast from the standpoint of MTT typing and pathogenesis. The determination of curability of different histological types and risk stages (RS) used in TDC-CZ and a comparison with RS axccording to FIGO, WHO and NIH. Differentiation of undifferentiated choriocarcinoma (CH-Und) alias Epitheloid Trophoblastic Tumor (ETT) from the given cohort of MIT and establishment of its clinical and biological properties, curability and formal pathogenesis.


RESULTS
Three hundred and seventy nine MTT cases were classified into 5 histological types onthe basis of analogy with developmental stages of 7 to 14 days old trophoblast. 1: typical "classical" choriocarcinoma - No Special Type (CH-NST), which forms more than 80% of MTT. Moreover, the degree of differentiation of tumorous trophoblast and its prevailing (cytological) type made it possible to define other 4 types, i.e.: 2: CH-syncytio-trophoblastic (CH-Syn), representing 3.8%; 3: CH-cytotrophoblastic CH-Cyt with 3.3%; 4: CH-dissociated (CH-Dis), representing 6%; 5: CH-undifferentiated (CH-Und) with 6.8%. Mortality due to MIT of all mentioned types reached 94% until 1963, decreased to 43% until 1980 and has been 5.8% in the period of 1981-2004. In the latter period of time (1981-2004), mortality due to CH-Cyt proved to be 40%, that due to CH-Dis being 11%, and CH-Und 18%, though. Mortality of s.c. Placental Site Trophoblastic Tumor, which includes our CH-Cyt and CH-Dis therefore forms 21.4%. We have been using four RS in TDC-CZ. The following outline includes only the main features: 1st RT includes CH-NST < 30mm limited to uterus in connection with mole. 2nd RS includes CH-NST > 30mm after birth. 3rd RS includes CH-NST with multiple metastases outside GIT and CNS and MTT with the CH-Cyt, Dis, Und component < 75%. 4th RS includes CH-NST with metastases in CNS or GIT. MTT with CH-Cyt Dis, Ned component < 75% with metasteses and MTT with the same components > 75% In the last 23 years 1st RS and 2nd RS includes 85 % of all MTT in the TDC-CZ and curability is 100%. In the 3rd RS curability decreases to 64.3% and decreases to 55.6% in the 4th RS. According to FIGO classification the 1st RS forms 48%, 2nd RT represents 17% and 100% curability applies for both of them. 3rd a RS includes 20% of 100% curability, 3rd bc RS forms 10% with 67% curability and 4th abc RS includes 5 % with 50% curability. In using the WHO classification with four RS, their percentage representation is similar to our classification with similar curability; nevertheless the 1st RS and 2nd RS did not detect almost 8% of MTT, which ended with exitus. 3rd RS according to FIGO is overestimated in view of 100% curability and the abc degree in 1st and 2nd RS are only of theoretical significance and irrelevant for the choice of treatment. The closest results comparable with our classification were those of NIH. A very careful clinical-pathological analysis of 25 CH-Und-ETT, detected among 379 MTT revealed that CH-Und-ETT is anaggressive malignant form of CH, which is best derived from undifferentiated 7-8 days old trophoblast. It is insidious for its seemingly primary extragenital symptomatology in seven out of 25 cases, low hCG values and poor sensitivity to chemotherapy.


CONCLUSIONS
1) The comparison of histological pictures of 379 MTT with developmental stages of orthologic trophoblast of 7-14 days old embryo was the basis for classification of 5 types of choriocarcinoma (CH): 1. Differentiated CH "No Special Type" (CH-NST), 2. Syncytiotrophoblastic CH (CH-Syn), 3. Cytotrophoblastic CH (CH-Cyt), 4. Dissociated CH (CH-Dis), and 5. Non-differentiated CH (CH-Und); 2) We have determined their percentual (and absolute) occurrence in the group of 379 MTT treated in CTN in the years 1955-2004. 3) We have described biological properties of individual types of CH and established the way they influence curability. 4) Four degrees of risk (RS) were specified in relation to 7 types of risk factors observed (1. size of tumor, 2. type of preceding pregnancy, 3. interval from pregnancy to the diagnosis, 4. histological type of CH, 5. number of metastases, 6. localization of metastases, 7. values of hCG). It has become obvious how RS influenced curability of CH (1st and 2nd RS forms 85% of all CH's and their curability is 100% (!), 3rd and 4th RS are represented in 15% and their curability is 64% in the 3rd RS and 55% in the 4th RS. 6) The curability reached in CTN was compared with that determined according to FIGO, WHO and NIH, respectively. The results proved to be similar, but in case of FIGO the 3rd degree was overestimated and the degrees abc in the 1st and 2nd RS were of theoretical importance only, therefore being of no values for the choice of treatment. Low and medium score according to WHO did not detect 8% of women who had died. The CH curability according to RS, having been recommended by NIH and used in the American Centers was virtually the same as our results. 7) It has been proved that the histological type of CH significantly influenced the determination of RS in the given patient. 8) CH-Und-ETT represents the least differentiated form of MTT, in other words choriocarcinoma. This is associated with a low production of HCG, mostly between 10(1) and 10(3) mIU/ml. 9) Pathogenesis of CH-Und ETT-ETT we derive from the earliest, undifferentiated stage of orthological trophoblast. The origin from the differentiated intermediate trophoblast chorion leeve we considerei improbable. 10) There are continuous transitions from CH-Und-ETT and PSTT to CH-NST, representing an analogy to grading in other malignant epithelial tumors.
Zavadil
M
M
Centrum pro trofoblastickou nemoc v CR (CTN-CR), 3. LF UK, Praha. zavadilctn@upmd.cz
Feyereisl
J
J
Safár
P
P
Pán
M
M
D002822:Choriocarcinoma / Q000145:classification / Q000473:pathology* / Q000628:therapy; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000145:classification / Q000473:pathology* / Q000628:therapy; D006801:Humans; D011247:Pregnancy; D014594:Uterine Neoplasms / Q000145:classification / Q000473:pathology* / Q000628:therapy