Placental site trophoblastic tumor: a 17-year experience at the New England Trophoblastic Disease Center.

OBJECTIVE: We reviewed cases of placental site trophoblastic tumors from the New England Trophoblastic Disease Center (NETDC) database from 1982-1999 in an effort to identify prognostic factors for recurrent disease. METHODS: A chart review was performed utilizing patients identified from the NETDC database. Data obtained included patient age at diagnosis, antecedent pregnancy, duration and extent of disease, presenting symptoms, pre- and posttreatment hCG levels, diagnostic and therapeutic procedures, treatment and outcome of patients. Statistical analysis was performed using Student's t test and chi(2) test when appropriate. RESULTS: Thirteen patients were identified. All ultimately underwent hysterectomy although initial treatment of 1 patient was uterine resection. There were 5 recurrences (43%)--3 among the 9 patients who had no metastases on presentation (33%) and 2 of 3 patients who presented with metastases (66%). The 5 patients who recurred were among 8 who had received peri- or postoperative chemotherapy (62.5%). Treatment of recurrences included continued or alternate chemotherapy, radiotherapy, and/or excision of locally recurrent disease. Follow up time averaged 56.2 months (range 12-182 months). One of the 4 patients receiving chemotherapy < or =1 week after hysterectomy recurred, whereas all 4 patients who received chemotherapy 3 weeks or more after hysterectomy recurred. Uterine tumor volume was significantly greater, 154.1 cm(3), in patients with initial metastases versus 42.3 cm(3) in patients without initial metastases (P = 0.04). Mitotic index (P = 0.04) was significantly increased in patients who developed recurrent disease. CONCLUSION: High mitotic index appears to be an adverse prognostic indicator for recurrence. Hysterectomy remains the mainstay of treatment. Chemotherapy is indicated for patients with metastases and may be indicated when the mitotic index is >5 mitoses/10 HPF. Radiation treatment may play a role in recurrent disease but must be evaluated on a case-by-case basis.

Management of gestational trophoblastic diseases: subsequent pregnancy experience.

Patients with gestational trophoblastic disease (GTD) can usually achieve complete sustained remission while retaining their fertility even in the presence of wide-spread metastasis. Following complete and partial mole, our patients had 1,239 and 205 later pregnancies, respectively, which resulted in 68.6% and 74.1% term live births, respectively. Patients with either type of hydatidiform mole have, in general, a normal later pregnancy experience. After one molar pregnancy, the risk of a molar pregnancy in a later conception was about 1%. Our patients who received chemotherapy for persistent gestational trophoblastic tumor had 522 later pregnancies, which resulted in 358 (68.6%) term live births and only 10 (2.5%) major and minor congenital anomalies. Data from other centers involving 2,598 later pregnancies also indicate that after chemotherapy patients can generally anticipate a normal future reproductive outcome.

Sonographic appearance of first trimester complete hydatidiform moles.

OBJECTIVE: Complete hydatidiform moles are now being diagnosed earlier in gestation, thus the clinical presentation and pathologic findings of complete molar pregnancy have changed. We studied the sonographic appearance of first trimester moles and the ability of ultrasound to detect them. METHODS: We reviewed the sonographic interpretation and sonograms, when available, from all patients with first trimester complete moles diagnosed at our institution from January 1988 to March 1996. RESULTS: Of the 24 patients in our study, the mean gestational age at time of the sonogram was 8.7 +/- 2.0 weeks (mean +/- SD) with a range of 5.7-12.3 weeks. The initial sonographic interpretation was a complete mole in 17 (71%) cases, partial mole versus failed pregnancy in two (8%), and failed pregnancy in five (21%) cases. Of the 22 patients with sonograms available for review, interpretation on review of the images was a complete mole in 18 (82%) cases, partial mole versus failed pregnancy in one (5%), and failed pregnancy in three (14%) cases. The typical sonographic appearance of a first trimester complete mole was a complex, echogenic, intra-uterine mass containing many small cystic spaces. CONCLUSION: The majority of first trimester complete moles demonstrate a typical ultrasound appearance such that the diagnosis can be made with ultrasound in most cases.

Recent advances in gestational trophoblastic disease.

Recent advances have increased our understanding of gestational trophoblastic disease, and epidemiologic studies have demonstrated that there are important differences in risk factors for complete and partial mole. Complete moles are now increasingly being diagnosed in the first trimester, affecting their clinical presentation and pathologic characteristics. While important advances have been made in chemotherapy, it is now recognized that etoposide is associated with a risk of second tumors. Several studies have advanced understanding of the molecular biology of gestational trophoblastic disease, and this is important for the eventual development of new and innovative therapy.

Gestational trophoblastic disease.

Patients diagnosed with molar pregnancy are treated by either suction curettage or hysterectomy, depending on their desire to preserve fertility. We use single-agent chemotherapy, preferably methotrexate, to treat low- or moderate-risk persistent trophoblastic tumors. High-risk patients who have metastatic disease are treated primarily with combination chemotherapy and, as indicated, adjuvant radiotherapy or surgery. We perform a hysterectomy in all cases of placental-site trophoblastic tumors; combination chemotherapy is used if there is evidence of metastatic disease.

Outcome of pregnancies occurring within 1 year of hydatidiform mole.

OBJECTIVE: To determine the outcome of subsequent pregnancies in patients with partial or complete molar pregnancy who conceive before completing the recommended hCG follow-up of at least 6 months. METHODS: Retrospective record review of patients with partial or complete mole who conceived before the standard gonadotropin follow-up of 6 months was completed during 1980-1998. RESULTS: Sixty-seven patients with molar pregnancy who conceived before completion of hCG follow-up were identified. Thirty-five (52.2%) patients had a prior partial mole, and 32 (47.8%) had a prior complete mole. The mean interval from first achieving undetectable hCG level to new pregnancy was 3.1 and 3.4 months in patients with partial and complete mole, respectively. Eleven patients underwent elective termination, and 12 were lost to follow-up. Of the remaining 44 patients, 33 (75.0%) had live births, 10 had spontaneous abortions, and one had an ectopic pregnancy. A viable pregnancy outcome was achieved in 20 (83.3%) of 24 patients with partial mole and 13 (65.0%) of 20 patients with complete mole. None of the patients developed any evidence of postmolar persistent gestational trophoblastic tumor. None of the live births had any detectable fetal anomalies. CONCLUSION: The risk of persistent tumor is low and reproductive outcome is favorable once undetectable hCG levels are achieved. Pregnancies occurring before the completion of recommended hCG follow-up may be allowed to continue under careful surveillance.

Repetitive hydatidiform mole with different male partners.

OBJECTIVE: The aim of this study was to determine the role of parental factors that may relate to the pathogenesis of molar pregnancy. METHODS: A retrospective review of six patients who had a molar pregnancy with at least two different partners at New England Trophoblastic Disease Center between 1965 and March 1999 was performed. RESULTS: A total of 34 pregnancies with 20 different partners were observed in 6 patients. These pregnancies resulted in 15 (44.1%) hydatidiform moles, 8 (23.5%) term live births, 7 (20.6%) therapeutic abortions, 3 (8.8%) spontaneous abortions, and 1 preterm delivery. While 5 patients had a molar pregnancy with 2 different partners, 1 patient had a molar pregnancy with 3 different partners. Two patients developed persistent postmolar gestational trophoblastic tumor in 3 (20.0%) of the 15 episodes of molar pregnancy. Three of the male partners reported a total of 7 healthy children from prior relationships. CONCLUSION: The experience in these six patients suggests that a primary oocyte problem may contribute to the development of molar pregnancy.

Outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients with persistent gestational trophoblastic tumor.

OBJECTIVE: To determine the outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients treated with chemotherapy for gestational trophoblastic tumor. METHODS: Retrospective record review of patients with gestational trophoblastic tumor who conceived before standard hCG follow-up was completed during 1973-1998. RESULTS: Forty-three patients treated for gestational trophoblastic tumors conceived before human chorionic gonadotropin follow-up was completed. The antecedent pregnancy was complete mole in 31 (72.1%) and partial mole in 12 (27. 9%) patients. Of the 43 patients, 39 (90.7%) had stage I, 1 had stage II, and 3 had stage III disease. The mean interval from human chorionic gonadotropin remission to new pregnancy was 6.3 months (range 1-11 months). Ten patients underwent elective termination and four patients were lost to follow-up. Of the remaining 29 patients, 22 (75.9%) had term live births, 3 (10.3%) had preterm delivery, 3 had spontaneous abortion, and 1 (3.5%) had a repeat mole. Two cases of fetal anomalies were detected; one was inherited polydactyly and the other was hydronephrosis. One patient developed choriocarcinoma with lung involvement and underwent cesarean section at 28 weeks; a normal fetus was delivered and no choriocarcinoma was detected in the placenta. CONCLUSION: Pregnancies occurring in patients treated for gestational trophoblastic tumor before standard human chorionic gonadotropin follow-up is completed may continue under close clinical surveillance since the majority have a favorable outcome. However, patients should also be advised of the low but important risk of delayed diagnosis in case tumor relapse develops during early subsequent pregnancy.

Revised FIGO staging system for gestational trophoblastic tumors. Recommendations regarding therapy.

OBJECTIVE: To evaluate the revised International Federation of Gynecology and Obstetrics (FIGO) staging system for gestational trophoblastic tumors (GTT) and to recommend therapy. STUDY DESIGN: Review of the literature regarding the development of the FIGO staging system, the World Health Organization (WHO) prognostic scoring system and Hammond's clinical classification for GTT plus analysis of response to single-agent chemotherapy in 546 patients treated at the New England Trophoblastic Disease Center. RESULTS: The revised FIGO staging system appears to successfully combine anatomic staging and a prognostic clinical classification. The revised FIGO staging system reliably predicts treatment outcome and therefore can be used to help select optimal treatment protocols. CONCLUSION: The revised FIGO staging system is capable of predicting patients who respond poorly to single-agent chemotherapy, appears to reliably predict outcome and therefore can be used to help select appropriate treatment protocols.

Natural history of postterm choriocarcinoma.

OBJECTIVE: To review the 32-year experience of the New England Trophoblastic Disease Center (NETDC) with choriocarcinoma occurring after a term gestation and to evaluate potential prognostic factors using the World Health Organization (WHO) prognostic score. STUDY DESIGN: The charts of 44 women who were treated for postterm choriocarcinoma at the NETDC from August 1964 to January 1996 were retrospectively reviewed. Demographic data and details of the clinical course were determined. Potential risk factors, including disease duration, pretreatment human chorionic gonadotropin (hCG) level, sites of metastases and stage, as well as data regarding the infants and previous and subsequent pregnancies, were evaluated. RESULTS: Five (11%) of the infants suffered significant complications secondary to maternal choriocarcinoma. The time interval from delivery to diagnosis, pretreatment hCG level and sites of metastatic disease were all significant risk factors in predicting outcome. All 31 patients with a WHO score < or = 8 survived, and 6/13 (46%) patients with a WHO score > 8 died. CONCLUSION: Disease duration greater than four months from delivery, pretreatment hCG level > 100,000 mIU/mL, presence of liver or brain metastases, and a WHO score > 8 were all important predictors of outcome in patients with postterm choriocarcinoma.

Gestational trophoblastic disease. Subsequent pregnancy outcome, including repeat molar pregnancy.

OBJECTIVE: To determine subsequent reproductive outcomes in patients treated for partial molar pregnancy, complete molar pregnancy and persistent gestational trophoblastic tumors at the New England Trophoblastic Disease Center (NETDC) between June 1, 1965, and December 31, 1996. STUDY DESIGN: Questionnaires were mailed to all patients followed at the NETDC to assess subsequent pregnancy experience. All patients and their referring physicians were also requested to inform the NETDC about later pregnancies. RESULTS: Following partial mole, complete mole and persistent gestational trophoblastic tumor, our patients had 195, 1,234 and 504 later pregnancies, respectively. These patients had a later pregnancy experience comparable to that of the general population. However, after having one molar pregnancy, the risk of molar pregnancy in a later conception was about 1%. Twenty-nine of our patients had at least two episodes of molar pregnancy; following two episodes of molar pregnancy, 6 (23.1%) of 26 later conceptions resulted in another molar gestation. CONCLUSION: Patients with partial mole, complete mole and persistent gestational trophoblastic tumor can be reassured that in general they can anticipate a normal future reproductive outcome.

The management of gestational trophoblastic tumors with etoposide, methotrexate, and actinomycin D.

OBJECTIVE: To evaluate the efficacy and safety of etoposide, methotrexate, and actinomycin D (EMA) as primary and secondary therapy for gestational trophoblastic tumor (GTT). METHODS: In a retrospective study, the medical records of all patients with middle-risk metastatic GTT or nonmetastatic choriocarcinoma receiving primary EMA and patients with GTT resistant to single-agent regimens treated with secondary EMA were reviewed. Hematologic toxicity was graded using WHO criteria. RESULTS: Seven patients received primary EMA with 5 (67%) achieving remission. Twenty-two patients with resistance to single-agent regimens received secondary EMA with 21 (95%) achieving remission. The most acute hematologic toxicity was grade 1 or 2. Only 2 of 90 EMA cycles were associated with grade 4 toxicity requiring hospital admission. CONCLUSION: Although EMA effectively induces remission with minimal acute hematologic toxicity in the primary and secondary therapy of GTT, recently published data regarding secondary tumors associated with etoposide exposure should restrict its use to patients who absolutely require etoposide to achieve remission.

Progressive angiomyolipoma with inferior vena cava tumor thrombus.

A 45-year-old man presented with an incidentally discovered benign renal angiomyolipoma. This lesion initially demonstrated renal vein involvement. On referral to our institution 3 years later, there was interval progression of tumor thrombus to the intrahepatic inferior vena cava. Intravascular extension of benign angiomyolipoma, though rare, has been reported. We present a new example and review the literature concerning this unusual complication of a common renal neoplasm.

Case-control study of risk factors for partial molar pregnancy.

OBJECTIVE: The purpose of our study was to identify risk factors for partial molar pregnancy from a woman's general, reproductive, and dietary history. STUDY DESIGN: Sixty-five women with pathologically confirmed partial molar pregnancy were interviewed, and their experiences were compared with those of 130 age-matched control women who had successfully completed a pregnancy with delivery of a live infant at the same hospital during the same calendar period. RESULTS: Multivariate analysis revealed that exposures which independently and significantly predicted increased risk for partial molar pregnancy included irregular cycles, pregnancy histories including only male infants among prior live births, and oral contraceptive use for > 4 years. Dietary factors previously postulated for complete molar pregnancy including protein, fat, vitamin A, or carotene were found not to be related to risk for partial molar pregnancy. CONCLUSION: Epidemiologic patterns for complete and partial molar pregnancies appear to differ somewhat; risk for partial mole is associated with reproductive history but not dietary factors.

Clinical features of multiple conception with partial or complete molar pregnancy and coexisting fetuses.

The estimated incidence of twin pregnancy consisting of hydatidiform mole and a coexisting fetus is 1 per 22,000-100,000 pregnancies. Since 1965, nine patients with this entity have been treated at the New England Trophoblastic Disease Center (NETDC), Boston. One patient had a partial hydatidiform mole coexisting with a normal placenta and fetus. The other eight patients had twin pregnancies with a complete hydatidiform mole (CHM) and coexisting fetus. We compared the clinical outcomes in these 8 patients and 14 additional published case reports of multiple gestations composed of CHM and coexisting fetuses with a group of 71 patients with singleton CHM treated at NETDC. Twelve of the 22 patients (55%) with CHM and coexisting fetuses developed persistent gestational trophoblastic tumor, requiring chemotherapy. Five of these patients developed metastases requiring multiple cycles of chemotherapy to achieve remission. The presenting symptoms of multiple conception with CHM and coexisting fetuses were similar to those in patients with a singleton conception and complete mole. However, as compared to singleton CHM, patients having a multiple conception with CHM and coexisting fetuses were diagnosed at a later gestational age, had higher preevacuation beta-human chorionic gonadotropin levels and had a greater propensity to develop persistent tumor. These data indicate that patients with multiple conceptions consisting of CHM and coexisting fetuses are at high risk of developing persistent gestational trophoblastic tumor.

Psychological, social and sexual effects of gestational trophoblastic disease on patients and their partners.

The psychological, social and sexual effects of gestational trophoblastic disease in both patients and their partners are reviewed. The results suggest that despite the favorable prognosis of this disease, mood disturbances, sexual disturbances and fertility concerns can persist in both patients and their partners. Recommendations are made concerning providing supportive care to meet the needs of patients and their partners.

Subsequent pregnancy experience in patients with gestational trophoblastic disease. New England Trophoblastic Disease Center, 1965-1992.

We reviewed the subsequent pregnancy outcome in patients with partial mole, complete mole and persistent gestational trophoblastic tumor treated at the New England Trophoblastic Disease Center from June 1, 1965, to December 31, 1992. Such patients can be assured that they can anticipate a normal future reproductive outcome. However, when a patient has had a molar pregnancy, she is at increased risk (1%) of developing molar disease in a subsequent conception.

Natural history of twin pregnancy with complete hydatidiform mole and coexisting fetus.

OBJECTIVE: To investigate the clinical features and natural history of twin conceptions consisting of complete hydatidiform mole and a coexisting fetus. METHODS: Since 1973, eight well-documented cases of twin pregnancy with complete hydatidiform mole and coexisting fetus have been treated at the New England Trophoblastic Disease Center (NETDC). The clinical features of these eight patients were compared to 71 patients with singleton complete hydatidiform mole treated at the NETDC and with the published experience of other investigators. Flow cytometric analysis of DNA content was performed in addition to histologic inspection to assist in confirming the diagnosis of twin pregnancy with complete hydatidiform mole and coexisting fetus. RESULTS: Five of the eight patients in this series developed persistent gestational trophoblastic tumor requiring chemotherapy. Three of these five patients developed metastases requiring multi-agent chemotherapy to achieve remission. The presenting symptoms of twin pregnancy with complete hydatidiform mole and coexisting fetus were similar to those in patients with a singleton complete mole. However, compared to singleton complete molar gestation, a twin pregnancy with complete mole and coexisting fetus was diagnosed at a later gestational age, had higher preevacuation beta-hCG levels, and had a greater propensity to develop persistent gestational trophoblastic tumor. CONCLUSION: Our findings indicate that patients with complete hydatidiform mole and coexisting fetus are at high risk for developing persistent gestational trophoblastic tumor.