Persistent Gestational Trophoblastic Tumor Research Articles

Complete hydatidiform mole and surviving coexistent twin.

Twin gestations consisting of a complete hydatidiform mole and coexisting fetus are rare and associated with an increased risk of persistent gestational trophoblastic tumor. Data were abstracted from 25 well-documented cases from the literature to which we added an additional case. Cases were then separated according to whether the pregnancy was evacuated before fetal viability (19 cases) or resulted in a surviving infant (7 cases). The previable and viable groups did not differ with respect to mean age, gravidity, parity, presenting symptoms, accuracy of sonographic diagnosis in identifying the molar component, uterine size at evacuation, or the presence of preeclampsia and theca lutein cysts. Statistically significant differences (P < .05) were detected between the previable and viable groups in estimated gestational age at evacuation (18.6 weeks vs. 33.0 weeks), the discrepancy between uterine size and estimated gestational age at evacuation (8.1 weeks vs. 1.0 weeks), and preevacuation serum hCG level (1,078,416 vs. 167,883 mIU/liter). Persistent GTT developed in 68.4 percent of the previable group patients and 28.6 percent of those in the viable group (P = .09). In patients with complete hydatidiform mole and coexistent fetus, fetal survival is associated with clinical characteristics suggestive of less exuberant molar growth. The advanced gestational age required to produce a viable, surviving fetus is not an independent risk factor for the development of persistent GTT.

Prevalence and Significance of Implantation Site Trophoblastic Atypia in Hydatidiform Moles and Spontaneous Abortions

The authors studied the prevalence and significance of implantation site trophoblastic atypia in hydatidiform moles and spontaneous abortions. Three pathologists independently categorized 99 early abortion specimens regarding diagnosis (spontaneous abortion, partial hydatidiform mole, complete hydatidiform mole); qualitative atypia of implantation site trophoblast (absent, mild, moderate-severe); and quantitative atypia of implantation site trophoblast (absent, focal, diffuse). Interobserver agreement was good to excellent regarding diagnosis (kappa 0.66-0.79) and poor to fair regarding qualitative atypia of implantation site trophoblast (kappa 0.20-0.43). By consensus diagnosis, implantation site trophoblastic atypia was mild and focal in 5% of 22 spontaneous abortions; predominantly focal in 40% of 30 partial moles (33% mild atypia; 7% moderate-severe atypia); and, predominantly diffuse in 87% of 47 complete moles (21% mild atypia; 66% moderate-severe atypia). Among hydatidiform moles, the subsequent development of persistent gestational trophoblastic tumor did not relate to the degree of implantation site trophoblastic atypia. The authors conclude that trophoblast of the implantation site exhibits focal, mild atypia in some partial hydatidiform moles,and diffuse marked atypia in most complete hydatidiform moles. Thus, implantation site trophoblastic atypia may be a useful pathologic guideline regarding the diagnosis and classification of hydatidiform moles.

Gestational trophoblastic disease.

Gestational trophoblastic disease consists of a group of interrelated diseases, including molar pregnancy, placental site trophoblastic tumor, and choriocarcinoma. Advances in the diagnosis and management of gestational trophoblastic diseases over the past 5 years were reviewed. Molar pregnancy is now categorized as complete or partial on the basis of gross and microscopic histopathologic and karyotypic findings. Early detection of persistent gestational trophoblastic tumor (GTT) depends on careful postmolar gonadotropin follow-up and consideration of the diagnosis for any woman of reproductive age with unexplained gynecologic and/or systemic symptoms. Triple therapy with methotrexate, actinomycin D, and cyclophosphamide was once the preferred treatment for patients with high risk metastatic GTT but induced remission in only about 50%. Treatment with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine is now the preferred regimen for treatment of high risk metastatic GTT and has been shown to induce remission in about 70% of patients. Important advances have been made in the diagnosis and treatment of patients with gestational trophoblastic disease, and patients can be reassured that they can anticipate normal reproductive functioning.

The changing clinical presentation of complete molar pregnancy

To determine if the clinical presentation of complete hydatidiform mole has changed in recent years compared with historic controls (1965-1975). Chart review of all 74 patients referred to the New England Trophoblastic Disease Center for the primary management of complete hydatidiform mole during 1988-1993 was performed and comparison made to historic controls (1965-1975). Vaginal bleeding remained the most common presenting symptom, occurring in 62 of 74 (84%) current patients, compared with 297 of 306 (97%) controls (P = .001). However, anemia was present in only four of 74 (5%) current patients, compared with 165 of 306 (54%) controls (P = .001). Excessive uterine size, preeclampsia, and hyperemesis occurred in only 21 of 74 (28%), one of 74 (1.3%), and six of 74 (8%) current patients, respectively, compared with 156 of 306 (51%), 83 of 306 (27%), and 80 of 306 (26%), respectively, of historic controls (P = .001). No cases of clinical hyperthyroidism or respiratory distress were found in recent years. Ultrasound diagnosed complete hydatidiform mole before the onset of clinical symptoms in seven of 69 (10%) current patients. Among patients not receiving chemoprophylaxis, persistent gestational trophoblastic tumor developed in 23% of current patients and 18.6% of historic controls. Fewer current patients with complete hydatidiform mole present with the traditional symptoms of complete hydatidiform mole (excessive uterine size, anemia, preeclampsia, hyperthyroidism, or hyperemesis) when compared with historic controls. However, there has been no statistically significant change in the development of persistent gestational trophoblastic tumor in current patients compared with historic controls.

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

To investigate the clinical features and natural history of twin conceptions consisting of complete hydatidiform mole and a coexisting fetus.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.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.Our findings indicate that patients with complete hydatidiform mole and coexisting fetus are at high risk for developing persistent gestational trophoblastic tumor.

Subsequent Pregnancy Experience in Patients With Gestational Trophoblastic Disease

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.

The correlation of spiral arteries morphology with uterine artery doppler velocimetry

Objective.The goal of this work was to study the expression of epidermal growth factor receptor (EGFR) and c-erbB-3 and c-erbB-4 oncogenes in gestational trophoblastic diseases and normal first-trimester placenta.Study design. Paraffin sections of 16 cases of partial mole, 25 cases of complete mole, 10 cases of gestational choriocarcinoma, and 11 cases of therapeutic abortion were studied immunohistochemically for EGFR, c-erbB-3, and c-erbB-4 proteins. The presence of EGFR mRNA was studied using in situ hybridization.Results. Staining for EGFR was detected immunohistochemically in all cell types in gestational trophoblastic diseases and normal placenta. In situ hybridization for EGFR mRNA correlated with immunostaining for EGFR in all tissues studied. All 10 cases of choriocarcinoma exhibited strong immunoreactivity for EGFR. The levels of expression of EGFR in choriocarcinoma and syncytiotrophoblasts and cytotrophoblasts in complete mole were significantly greater than those in syncytiotrophoblasts and cytotrophoblasts in both normal placenta and partial mole (P < 0.01, P < 0.01). Expression of c-erbB-3 did not significantly differ among placental and gestational trophoblastic disease tissues and trophoblastic cell types except for significantly increased expression in choriocarcinoma as compared with cytotrophoblasts of partial mole (P = 0.02). The placenta, complete and partial mole, and choriocarcinoma tissues demonstrated similar immunoreactivity for c-erbB-4. Strong immunostaining for EGFR (P = 0.02) and c-erbB-3 (P < 0.01) in extravillous trophoblasts of complete mole was found to be significantly correlated with the development of persistent postmolar gestational trophoblastic tumor.Conclusion. The EGFR-related family of oncogenes may be important in the pathogenesis of gestational trophoblastic diseases. The increased expression of EGFR and c-erbB-3 in complete mole may also influence the development of persistent gestational trophoblastic tumor.

Choriocarcinoma following a partial hydatidiform mole: A case report

Hydatidiform moles are classified as partial or complete by histologic criteria (Am J Obstet Gynecol 131:665–671, 1978 and Am J Obstet Gynecol 132:20–27, 1978). While persistent gestational trophoblastic tumors follow both types, there remains controversy as to whether the malignant extreme of gestational trophoblastic tumors, choriocarcinoma, can follow a partial hydatidiform mole (Am J Obstet Gynecol 127:167–170, 1977 and Arch Gynecol 234:161–166, 1984). In this instance, a 37-year-old woman presented with a partial hydatidiform mole that persisted and was treated with one course of chemotherapy. She attained a remission for 10 months, when a routine follow-up examination revealed an asymptomatic rise in serum betahuman chorionic gonadotropin from baseline to 14,600 mIU/mL. Dilatation and curettage revealed abundant avillous cytotrophoblast and syncytiotrophoblast with marked atypia, diagnostic of choriocarcinoma. Flow cytometry of paraffin blocks of both specimens showed the partial hydatidiform mole to be triploid and the choriocarcinoma diploid. The patient had no evidence of metastatic disease and was successfully treated with multiple-agent chemotherapy.

Flow cytometric analysis of DNA content in partial hydatidiform moles (PHM) with persistent gestational trophoblastic tumor (GTT)

Flow cytometric analysis of DNA content in partial hydatidiform moles (PHM) with persistent gestational trophoblastic tumor (GTT)

Persistent gestational trophoblastic tumor after partial hydatidiform mole

The current study investigates the clinical characteristics of patients with partial molar pregnancy who developed persistent gestational trophoblastic tumor (GTT). Between January 1979 and January 1989, 16 of 240 (6.6%) patients, who were followed for partial mole, developed persistent GTT. Fifteen (94%) patients were diagnosed as having a missed abortion before evacuation and only 1 patient presented with excessive uterine size and theca lutein ovarian cysts and was felt to have molar disease. No patient presented with toxemia, hyperemesis, or hyperthyroidism. All 16 patients developed nonmetastatic GTT. Fifteen patients achieved complete remission with methotrexate-citrovorum factor and only 1 patient required combination chemotherapy to attain remission. None of the patients had histologic evidence of choriocarcinoma. Patients with partial mole who developed persistent GTT did not have clinical or pathological characteristics that distinguished them from other patients with partial mole. All patients with partial mole should be followed with measurement of hCG levels to assure gonadotropin remission.

Hepatic scintigraphic changes associated with gestational trophoblastic disease

We reviewed the results of radionuclide liver imaging in 70 patients newly referred for evaluation and treatment of persistent gestational trophoblastic tumors. Some 58 patients (83%) had abnormal liver scans but no focal defects and no discernible hepatic malignancy. These diffusely abnormal scans may reflect chemotherapeutic and/or hormonal effects on the liver and should not be interpreted as indicative of metastases.

Persistence of Partial Mole

Between January 1979 and August 1984, 8 of 81 patients with partial molar pregnancy who were followed at the New England Trophoblastic Disease Center had persistent trophoblastic tumor develop. No significant clinical differences were noted between such patients and others whose partial moles did not persist. On microscopic examination, none of the initial molar specimens manifested an unusual degree of trophoblastic proliferation or atypia. In six patients, curettage immediately preceding the initiation of treatment for persistent disease revealed viable molar tissue. In four, this was associated with trophoblastic hyperplasia and atypia. All patients who had persistent gestational trophoblastic tumor achieved remission with single-agent chemotherapy. Monitoring of serum human chorionic gonadotropin levels after partial molar pregnancy is recommended to detect persistent disease and effect prompt therapy.

Persistence of partial mole.

Between January 1979 and August 1984, 8 of 81 patients with partial molar pregnancy who were followed at the New England Trophoblastic Disease Center had persistent trophoblastic tumor develop. No significant clinical differences were noted between such patients and others whose partial moles did not persist. On microscopic examination, none of the initial molar specimens manifested an unusual degree of trophoblastic proliferation or atypia. In six patients, curettage immediately preceding the initiation of treatment for persistent disease revealed viable molar tissue. In four, this was associated with trophoblastic hyperplasia and atypia. All patients who had persistent gestational trophoblastic tumor achieved remission with single-agent chemotherapy. Monitoring of serum human chorionic gonadotropin levels after partial molar pregnancy is recommended to detect persistent disease and effect prompt therapy.