Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours.

BACKGROUND: Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors. METHODS: The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced. RESULTS: Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005). CONCLUSION: PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.

Primary Cystic Trophoblastic Tumor of the Testis: A Study of 14 Cases.

Cystic trophoblastic tumor (CTT) has been described in postchemotherapy retroperitoneal lymph node dissections of patients with testicular germ cell tumors. Prognostically, this lesion is similar to teratoma and no further treatment is required after surgery in the absence of other components. CTT has not, however, been reported in the testis. We identified 14 CTTs in the treated (4) and untreated (9; no information for 1 patient) testes of patients 15 to 43 years old (median, 25) with mixed germ cell tumors. The CTT was a minor component (<1% to 10%) and associated with teratoma (14), embryonal carcinoma (7), yolk sac tumor (7), seminoma (1), and choriocarcinoma (1). At follow-up, CTT and teratoma were also found in 2 subsequent resections (spermatic cord and pelvis mass) in 2 patients. The CTTs were not grossly distinct but on microscopic examination were cystic to partly solid, with cysts often containing fibrinoid material and lined by mononucleated squamoid cells with eosinophilic to pale, frequently vacuolated cytoplasm and having pleomorphic nuclei with dense, often smudged chromatin. Mitotic activity was inconspicuous. Immunostains for hCG (6/6), inhibin (6/6), and p63 (2/6) were focally positive. The pathogenesis of CTT is not completely understood. As untreated patients without choriocarcinoma may have CTT in the testis, it is suggested that testicular CTT represents a form of regressed choriocarcinoma or a late morphologic phase in the transformation of choriocarcinoma to teratoma.

Nonchoriocarcinomatous Trophoblastic Tumors of the Testis: The Widening Spectrum of Trophoblastic Neoplasia.

Tumors of trophoblastic derivation other than choriocarcinoma are very rare in the testis but have been reported on occasion in association with other germ cell tumors. Their morphologic spectrum is analogous to the trophoblastic tumors of the female genital tract including epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT). Herein we report our experience with 8 cases of trophoblastic tumors of testicular origin that lacked the features of choriocarcinoma; these included 4 ETTs, 1 PSTT, 1 unclassified trophoblastic tumor (UTT), 1 partially regressed choriocarcinoma with a monophasic morphology, and 1 hybrid tumor showing a mixture of adenocarcinoma and a UTT. All tumors occurred in young men 19 to 43 years old. Five arose de novo within the testis (2 ETTs, 1 UTT, 1 regressing choriocarcinoma, and the hybrid tumor) as a component of mixed germ cell tumors, and 3 (2 ETTs and 1 PSTT) were found in metastatic sites after chemotherapy. The trophoblastic component was minor (5% to 10%) in 6 tumors but was 95% of 1 metastatic tumor (ETT) and 50% of the hybrid tumor. Other germ cell tumor elements were identified in all cases, most commonly teratoma. The ETTs consisted of nodules and nests of squamoid trophoblast cells showing abundant eosinophilic cytoplasm, frequent apoptotic cells, extracellular fibrinoid material, and positivity for p63 and negativity for human placental lactogen (HPL). The PSTT showed sheets of discohesive, pleomorphic, mononucleated trophoblast cells that invaded blood vessels with fibrinoid change and were p63 negative and HPL positive. The UTT showed a spectrum of small and large trophoblast cells, some multinucleated but lacking distinct syncytiotrophoblasts, and was patchily positive for both p63 and HPL. The hybrid tumor had ETT-like and adenocarcinomatous areas that coexpressed inhibin and GATA3 but were negative for p63 and HPL, leading to classification of the trophoblastic component as UTT. Seven of the patients were alive and well on follow-up (8 to 96 mo; median, 39 mo), whereas the patient with the hybrid tumor died of liver metastases at 2 years. Our study verifies that trophoblastic neoplasms often having the features of nonchoriocarcinomatous gestational trophoblastic tumors may arise from the testis, occur either in the untreated primary tumor or in metastases after chemotherapy, and should be distinguished from choriocarcinoma given what appears to be a less aggressive clinical course.

Epithelioid trophoblastic tumor: an outcome-based literature review of 78 reported cases.

OBJECTIVES: Epithelioid trophoblastic tumor (ETT) is very rare; and therefore, a substantially increased data set is unlikely to be obtained in the near future. This analysis aimed to assess the effects of current management on clinical outcomes and to identify potential prognostic indicators in ETT. METHODS: We applied a literature search using PubMed to analyze the clinical data of 78 published cases of ETT. RESULTS: Women with ETT present at reproductive age (mean ± SD, 37.1 ± 8.7 years) and have a slightly to moderately elevated serum ß-human chorionic gonadotropin (median, 665 IU/L). Epithelioid trophoblastic tumor is frequently present in the lower uterine segment/cervix (26/58 cases) and can be misdiagnosed as squamous cell carcinoma (6/26). Lung is the most common extrauterine site of ETT (5/11 with uterine ETT and 10/20 without uterine ETT). Kaplan-Meier analysis indicates that chemotherapy (surgery with postoperative chemotherapy vs surgery alone) is associated with increased ETT relapse (P = 0.005), even after stratification by International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.008); but FIGO stage remains the only significant prognostic indicator for ETT (P = 0.015). CONCLUSIONS: This analysis confirms the hypothetical chemotherapy resistance and prognostic value of FIGO staging in ETT. These findings remain tentative given the small data set available for analysis and the reporting bias from these published cases; however, they may confer a risk-adapted therapy. Finally, both gynecologists and pathologists should be alert to the potential misdiagnosis of squamous cell carcinoma when ETT is present in the lower uterine segment/cervix.

Analysis of clinicopathologic prognostic factors in 9 patients with epithelioid trophoblastic tumor.

OBJECTIVE: This study aimed to investigate the clinicopathologic features and prognostic factor in patients with epithelioid trophoblastic tumor (ETT). METHODS: From January 2002 to June 2010, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 9 patients with ETT were analyzed retrospectively in our institution. RESULTS: Of 9 patients, 8 (88.9%) had metastases. The histopathologic results of 7 patients (77.8%) with poor outcomes showed diffuse multifocal disease within the uterus, full-thickness myometrial invasion, uterine serosal involvement, and extensive necrosis. The size of the uterus exceeded 8 weeks of gestation in 7 patients. Two of them had poorly differentiated carcinoma. All patients were treated with multimodality treatment that combined with surgery and chemotherapy. After the initial treatments, 5 patients with International Federation of Gynecology and Obstetrics stage I achieved complete remission (CR), 1 patient achieved partial remission, and 3 patients (33.3%) had no response to treatments and died of progressive disease. After following up for 6 to 107 months (mean, 24 months), 4 (44.4%) of the 5 patients with initial CR had relapse: 3 of them achieved a second CR and the other 1 was under treatment. CONCLUSIONS: Epithelioid trophoblastic tumor is a rare and special type of intermediate trophoblastic tumor with a high degree of malignancy and poor prognosis. Multifocal lesions in bulky uterus, combined with full-thickness myometrial invasion and uterine serosal involvement, could be related to poor outcomes in patients with ETT. The prognosis of ETT could be improved by increasing diagnostic accuracy, identifying prognostic factor at an early stage, and providing early intensive multimodality treatment to patients with poor prognostic factors.

[Placental site trophoblastic tumor].

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD) that originates from the implantation site intermediate trophoblast. It accounts for about 1% of all GTDs, with an estimated incidence of 1 per 100,000 pregnancies. Most patients are in their thirties and the prevailing presenting symptom is abnormal vaginal bleeding. More than half of the patients present with disease limited to the uterus and the remainder present with disease extension beyond the uterus. The overall mortality rate is 25%. The most important adverse prognostic factor is disease extension beyond the uterus. Other adverse prognostic factors are interval from antecedent pregnancy > 2 years, mitotic count > 5 mitotic figures/10 high-power fields, and age > 40 years. Since PSTT is less sensitive to chemotherapy than GTDs originating from cytotrophoblast and syncytiotrophoblast (hydatidiform mole, invasive mole, and choriocarcinoma), hysterectomy is the mainstay of treatment. Systemic multi-agent chemotherapy is administered in the presence of disease extension beyond the uterus and considered in the presence of other adverse prognostic factors. The EP/EMA regimen seems to be the most effective chemotherapy available to date for PSTT. Although PSTT produces less human chorionic gonadotropin (hCG) than choriocarcinoma, beta-hCG is still the best available serum marker for monitoring the response to treatment and for follow-up.

Combination chemotherapy with 5-fluorouracil, methotrexate and etoposide for patients with high-risk gestational trophoblastic tumors: a report based on our 11-year clinical experiences.

OBJECTIVES: To evaluate the efficacy, toxicity, and survival of patients with high-risk gestational trophoblastic tumors (GTTs) treated with the 5-fluorouracil (5-FU), methotrexate (MTX) and etoposide (VP-16) regimen. METHODS: Between 1992 and 2003, 26 consecutive patients with FIGO-defined high-risk GTTs were treated with 5-FU, MTX and VP-16 regimen. Among them, 9 patients had received prior chemotherapy. Remission rate, causes of treatment failure, and toxicity were analyzed retrospectively. RESULTS: After treatment with 5-FU, MTX and VP-16 regimen, 21 of 26 gained complete respond (80.8%). Two patients were performed adjuvant hysterectomy and both cured ultimately. Five developed resistance (19.2%), and 1 died of widespread metastases (3.8%). All 5 patients who developed resistance were treated with multidrug regimen of etoposide, methotrexate, and actionmycin D alternating with cyclophosphamide and vincristine (the EMA/CO); 4 were salvaged and 1 died of refractory disease. No ones relapsed. WHO grade 4 leukocytopenia and thrombocytopenia with the 5-FU, MTX and VP-16 regimen occurred in 9.0% and 2.4%, respectively, of the total 167 cycles; other toxic effects were acceptable and manageable. With mean follow up of 37 months, neither relapse nor secondary tumor was observed. CONCLUSIONS: According to our 11 years of clinical observation, 5-FU, MTX and VP-16 chemotherapy is one of effective multiagent regimen for patients with high-risk GTTs. Its toxicity is mild and manageable. For patients with high-risk and refractory GTTs, this new triple salvage chemotherapy regimen may be an effective alternative.

[Assessment of staging and prognostic scoring system for malignant trophoblastic neoplasia].

OBJECTIVE: To assess malignant trophoblastic neoplasia with the standards of the clinical stage and prognostic factor scoring system. METHODS: Through assessing the high-risk factors except clinical stages for 223 patients before treatment according to International Federation of Gynecology and Obstetrics (FIGO) scoring system published in 2000, appropriate treatments were selected for the different patients. RESULTS: Forty-three of 78 cases of choriocarcinomas were with high-risk factors, the other 35 cases were with low-risk factors; 7 of 145 cases of invasive moles were with high-risk factors and the others were with low-risk factors. The primary chemotherapy principle was that one agent was used for those patients with low-risk factors and two or multiple-agents were used for those patients with high-risk factors. Among all patients, the one-year, three-year and five-year survival rates were 98.6%, 98.1% and 97.1% respectively. No patient died of drug toxicity or complication. CONCLUSION: Selection of treatment approaches according to the prognostic assessment of malignant trophoblastic neoplasia could lead to promising survival rate with no uncurable complication and toxic effects.

Central nervous system involvement in gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate characteristics of patients with central nervous system (CNS) lesions of gestational trophoblastic disease and determine prognostic and therapeutic implications applicable to management. METHODS: Nine patients among 56 cases of malignant gestational trophoblastic neoplasia (GTN) were analyzed prospectively in a single institution between the years 1990 and 1997 with at least two years of follow-up. Brain metastases were documented by physical exam and computed tomography scan or magnetic resonance imaging. In terms of therapy, all of the patients received an etoposide, methotraxate, actinomycin, cyclosphamide and vincristine (EMA-CO) regimen for 5 to 9 courses. To prevent unexpected intracranial hemorrhage, all patients received radiation therapy. No intrathecal chemotherapy was given. Remission was defined as three weekly beta-hCG levels below assay sensitivity (<5 mIU/ml). RESULTS: The mean age of the patients at diagnosis was 29.6 years. While two of the patients initially presented with symptoms related to cranial involvement, five were diagnosed during routine investigation for metastasis in malignant GTD and the remaining two developed cerebral metastases during the therapy. Besides central nervous system involvement, six had additional lung, two had hepatic and splenic and one had pelvic metastases. Overall survival was 66.6%. Two patients had a fulminant clinical course and were lost one month after initial diagnosis. CONCLUSION: Early diagnosis via computed tomography of the head and beta-hCG serum testing along with aggressive, multiagent intervention (EMA-CO) have greatly improved patient prognosis of this once highly fatal condition.

Survival of children with malignant germ cell, trophoblastic and other gonadal tumours in Europe.

Collaborators of the EUROCARE study had provided records on 1263 cases of germ cell, trophoblastic and other gonadal neoplasms, registered in 34 cancer registries in 16 European countries over the period 1978--1992 and followed-up until the end of 1994. Observed 5-year actuarial survival for 490 cases diagnosed in 1985-1989 was 80% (95% confidence interval (CI)=(76, 83)). The corresponding figures were calculated for the intracranial and intraspinal germ cell tumours (68%, 95% CI=(57, 76)), other non-gonadal germ cell tumours (76%, 95% CI=(68, 82)), gonadal germ-cell tumours (89%, 95% CI=(85, 93)) and gonadal carcinomas (50%, CI=(24, 76)). Relatively large differences in survival were observed between age-sex subgroups, which also differed with histology, with extremely poor survival of young children with intracranial and intraspinal germ cell tumours. Lower survival was observed in the countries with formerly socialist economies. Time trends in survival were examined for the entire study period, including only the cases registered in the large contributing registries. For all germ cell tumours, the risk ratios calculated in the Cox regression analysis were markedly lowered for the years after the reference period of 1978--1981. The improved outcome is attributed to treatment advances.

[Gestational trophoblastic disease: the epidemiological analysis of 342 cases]. / Rozrosty i nowotwory trofoblastu--analiza epidemiologiczna 342 chorych.

Between 1987-1996 dates were collected to assess frequency and risk factors for gestational trophoblastic disease in a case-control study of 342 women with trophoblastic tumors and 342 pregnant women admitted for deliveries or spontaneous abortion to University Hospitals in Poznan, Poland. Were analyzed the age of women obstetric history, place of live and repeat appearance of hydatidiform mole. The risk of trophoblastic disease increased with increase in maternal age and above third pregnancy. The risk independent of living in town or in the country. The second and more incident of hydatidiform mole was associated with greater risk of malignant sequele. The study of the pregnancy of gestational trophoblastic disease was led in Great Poland in the support on the date from all pathologic centres in this region and public demographic office. The frequently of hydatidiform mole was between 1987-1996 2.32 per 100,000 women, and 0.76 for 1000 live birth (1 HM for 1315 live birth). The frequently of choriocarcinoma was 0.08 per 100,000 women (and 0.38 per 10,000 live birth (1 CHA per 26,315 live birth).

Gestational trophoblastic disease: the significance of vaginal metastases.

PURPOSE: To evaluate patients with vaginal lesions in gestational trophoblastic disease and determine prognostic and therapeutic implications applicable to management. METHODS: Twelve patients among 75 cases of gestational trophoblastic neoplasia were analyzed retrospectively between 1990 and 1997. Vaginal metastases were documented by physical examination and biopsy. Two patients received MAC III regimen (5 and 7 courses), 4 patients received EMA-CO regimen for 2 to 11 courses, while 6 were administered methotrexate alone. Remission was defined as 3 weekly beta hCG levels below assay sensitivity (<5 mIU/ml). RESULTS: The mean age of the patients was 25.4 years. While 10 of the patients presented initially with hemorrhage and bloody leukorrhea, the remaining 2 were diagnosed during a routine study of hydatidiform mole. The sites of involvement were almost always the anterior distal vaginal wall. Five cases had additional lung and 1 case had lung, liver, spleen and brain metastases. Three of the patients who received methotrexate as monotherapy did not respond to therapy and were switched to EMA-CO. Overall survival was 91.6%. One patient died in the first month of the initial therapy. CONCLUSION: The presence of large vaginal metastases should be classified as a high-risk factor and these patients must be treated by multiple agent chemotherapy.

The management of high-risk gestational trophoblastic tumours (GTT).

Between 1979 and 1995 we have treated 272 consecutive women with high-risk (GTT including 121 previously treated patients who were treated with the weekly EMA/CO (etoposide, methotrexate, actinomycin D alternating with cyclophosphamide and vincristine). The median follow-up is 4.5 years (range 1-16 years). The cumulative 5 year survival is 86.2% (95% confidence interval 81.9-90.5%). No deaths from GTT occurred later than 2 years after starting EMA/CO. In a multivariate analysis, adverse prognostic factors were the presence of liver metastases (p < 0.0001), interval from antecedent pregnancy > 24 months (p < 0.0001), brain metastases (p=0.0008) and term delivery of antecedent pregnancy (p=0.045). There were 11 (4%) early deaths while 213 (78%) achieved complete remission. 47 (17%) developed drug resistance to EMA/CO of whom 33 (70%) were salvaged by further cisplatinum based chemotherapy and surgery. 2 women developed acute myeloid leukaemia after treatment with EMA/CO. 56% of women who have been in remission for at least 2 years and had fertility conserving surgery have achieved pregnancy since completing EMA/CO and there have been 112 live births including 3 babies with congenital abnormalities. EMA/CO is an effective, easy to administer and well tolerated regimen for treating patient with high-risk GTT. More than half of these women will retain their fertility. However, there is a small but significant increase in second malignancies.

Effects of multiagent chemotherapy and independent risk factors in the treatment of high-risk GTT--25 years experiences of KRI-TRD.

UNLABELLED: A retrospective and comparative study of high-risk gestational trophoblastic tumor (GTT) treated with different chemoregimen from 1971 to 1995 was performed and to find most effective chemotherapy regimen and independent risk factors. Three hundred seven patients in scoring over 8 points in WHO classification were categorized into high-risk group among 802 GTT cases received chemotherapy in the 2,418 GTD patients registered at KRI-TRD (Korean Research Institute for Gestational Trophoblastic Disease), Catholic University Medical College in Korea. Study groups of multiagent combination chemotherapy in 227 patients of the high-risk GTT were divided such as 49 cases of combination chemotherapy with MTX + folinic acid and Act-D, 40 cases of MAC regimen, 42 cases of CHAMOCA regimen, and 96 cases of EMA/CO. Initial tumor response according to hCG titer decrease was found in good response (log fall) 69.8%, of EMA /CO regimen group. On the other hand, good response was shown in only 24.5% of MTX + ACT-D, 32.5% of MAC regimen, and 52.4%, of CHAMOCA regimen respectively. Remission rate of EMA/CO regimen was 90.6% (87/96) and courses of chemotherapy until remission was 8.5+/-2.2. However, remission rate of other regimens of MTX + Act-D, MAC, and CHAMOCA were 63.3%, (31/49) 67.5% (27/40) and 76.2% (32/45) respectively, with 10.0+/-4.0, 10.7+/-4.3, 9.1+/-3.9 chemotherapy courses respectively until remission. Therefore, EMA/CO regimen groups were found to have low drug toxicity, early remission and a low failure rate. In the study of independent risk factors in the 165 cases of high-risk gestational trophoblastic tumor patients received EMA/CO regimen, stepwise Coxs proportional hazard's regression of prognostic factors using multivariate analysis revealed tumor age, number of metastatic organs, metastatic site and inadequate previous chemotherapy. According to the performance of fitted logistic regression model, the prediction rate of death and survival was 80.5%. CONCLUSIONS: The most effective chemotherapy to high-risk GTT was EMA/CO regimen than other regimens. The following factors showed poor prognosis; 1) Tumor age is over 12 month, 2) more than 2 organs had metastatic lesion, 3) inadequate previous therapy that includes unplanned operation and inadequate previous chemotherapy.

Risk factors for the prediction of treatment failure in gestational trophoblastic tumors treated with EMA/CO regimen.

OBJECTIVE: The purpose of this study was to determine the independent risk factors for resistance to EMA/CO chemotherapy in gestational trophoblastic tumor (GTT), to develop a more accurate scoring system for the evaluation of high-risk GTT patients. METHODS: We performed a retrospective study and reviewed 165 GTT patients who received the EMA/CO regimen. Among these patients, 27 showed resistance to EMA/CO. RESULTS: According to the univariate analysis of risk factors, tumor age, initial human chorionic gonadotropin level, metastatic site, number of metastatic organs, unplanned operation, gravidity, and inadequate previous chemotherapy all showed statistical significance. However, the results of the stepwise-Cox proportional hazards regression of prognostic factors using multivariate analysis showed statistical significance for tumor age, number of metastatic organs, metastatic site, and previously inadequate chemotherapy. The results of the stepwise logistic regression of prognostic factors showed tumor age and number of metastatic organs as significant. According to the performance of the fitted logistic regression model, the accuracy of predicted death and survival was 80.5%. CONCLUSIONS: We determined that the following factors indicate a poor prognosis: (1) tumor age greater than 12 months, (2) number of metastatic organs greater 2, (3) incomplete previous treatment, including unplanned operation and inadequate chemotherapy. In patients with two and three of these factors, the death rates were 17.7 and 56.6%, respectively.

High-risk gestational trophoblastic disease: analysis of clinical prognoses.

PURPOSE OF INVESTIGATION: An attempt to better define factors leading to patient survival in the high-risk group of malignant gestational trophoblastic disease (GTD). METHODS: From January 1, 1997 to December 31, 1995 25 cases of malignant high-risk GTD were retrospectively collected to evaluate prognostic factors by univariate and multivariate analysis. RESULTS: We identified the presence of liver metastases and/or brain metastases and the presence of intestinal metastases as significant by using univariate analysis. However, only the presence of liver metastases of brain metastases was significant by multivariate analysis (p=0.009). CONCLUSIONS: Although a high-risk group of GTD can be identified according to the modified World Health Organization (WHO) prognostic scoring system, liver metastases were not emphasized (only two points) in this scoring system. We suggested that these risk factors, including brain metastases and liver metastases, should be weighted more than other risk factors.

[Role of surgical interventions in the treatment of patients with trophoblastic tumor resistant to chemotherapy]. / Rol' khirurgicheskogo vmeshatel'stva pri lechenii bol'nykh trofoblasticheskoi opukhol'iu, rezistentnoi k khimioterapii.

A retrospective evaluation of 85 case histories of chemotherapy-resistant trophoblastic disease treated at the Center's clinic (1975-1996) was carried out. Both therapy efficacy and survival rates were lower in patients operated on prior to chemotherapy and during medication. However, excision of resistant foci of trophoblastic tumor contributed to the effectiveness of chemotherapy.

[Screening for transitional cell carcinoma of the bladder with trophoblastic differentiation in Upper Galilee].

Urinary bladder carcinoma with trophoblastic differentiation (TD) is a variant of urothelial (transitional cell) carcinoma (TCC) which secretes placental proteins, predominantly beta-human chorionic gonadotropin (HCG). An aggressive clinical course and a poor prognosis are characteristic of this tumor. We evaluated the frequency and clinical and pathological appearance of TCC-TD in the Upper Galilee and Golan Heights between 1988 and 1995 inclusive. Beta HCG, human placental lactogen (HPL), pregnancy specific beta-1 glycoprotein (SP-1) and placental alkaline phosphatase were determined immunohistochemically in paraffin-embedded TCC of urinary bladder. Tumor grade, stage and patient survival were also determined. There was beta-HCG immunostaining in 13 of 62 cases (20.9%). TD was correlated with higher grades of TCC and with advanced stages of disease. No cases of TCC-TD were found in grade 1, stage 0. Co-expression of beta-HCG and HPL was displayed in 2 cases, beta-HCG and SP-1 in 9, and beta-HCG, HPL and SP-1 in 2. Disease-free survival and overall survival were shorter in TCC-TD.

Gestational trophoblastic disease metastatic to the brain.

PURPOSE: To evaluate clinical characteristics, treatment technique, and results in patients with gestational trophoblastic disease metastatic to the brain. MATERIALS AND METHODS: From 1962 to 1994, 26 (4.1%) of 631 patients who underwent treatment for trophoblastic disease had or developed evidence of brain metastases (patients were aged 14-43 years). All patients received multiagent systemic chemotherapy and whole-brain irradiation. Total doses of radiation were 2,386-4,000 cGy (200-300 cGy per fraction). No patient received intrathecal chemotherapy. Patients were divided into three groups: group A, symptomatic brain metastases at presentation; group B, asymptomatic or minimally symptomatic brain disease at presentation; and group C, development of brain metastases during systemic chemotherapy. RESULTS: The overall 5-year actuarial survival rate was 51%. Multivariate analysis findings indicated that age, preceding pregnancy event, human chorionic gonadotropin level, World Health Organization score, performance of craniotomy, and number of brain metastases did not influence survival. The difference in the 5-year overall survival rates between groups A (39%) and B (100%) was significant (P = .03). CONCLUSION: Gestational trophoblastic disease metastatic to the brain is curable with systemic chemotherapy and whole-brain irradiation. The authors suggest treatment with steroids, chemotherapy (etoposide, high-dose methotrexate [1 g/m2], dactinomycin, cyclophosphamide, and vincristine sulfate), and concurrent whole-brain irradiation (3,000 cGy in 200-cGy fractions).