[Atypical epithelioid trophoblastic lesions after a cesarean section with cyst and fistula formation:a clinicopathological analysis of 4 cases].

Objective: To elucidate the clinicopathologic characteristics of atypical epithelioid trophoblastic lesions with cyst and fistula formation after cesarean section. Methods: The clinical and pathological data of 4 cases of post-cesarean atypical epithelioid trophoblastic lesions with cyst and fistula formation diagnosed at Women's Hospital, School of Medicine, Zhejiang University during April 2007 to June 2018 were evaluated by hematoxylin and eosin stain and EnVision two-step immunohistochemical staining technique. Results: The age of the 4 patients ranged from 32 to 41 years, with a mean age of 36.5 years. Three patients recieved cystectomy and one underwent subtotal hysterectomy. Histologically, the lesions were well circumscribed and consisted of uniform cells of medium size, irregularly enlarged with hyperchromatic nuclei and 1 to 2 inconspicuous nucleoli embedded in abundant hyalinized matrix with fibrinoid material in the center. The cells exhibited immunohistochemical feature of chorionic-type intermediate trophoblastic cells (CK18+, p63+ and CD146-). All patients were alive without recurrence during follow-up of 1 to 40 months (mean=22 months). Conclusion: Atypical epithelioid trophoblastic lesion with cyst and fistula formation after cesarean section has unique histological features, and its biological behavior and prognosis are still unclear, which need further exploration.

Complete hydatidiform mole and a coexistent fetus following ovulation induction in a patient with Sheehan's syndrome: a first case report and review of literature.

Pregnancy in Sheehan's syndrome (SS) is extremely rare. We present the first reported case of twin pregnancy with complete hydatiform mole (CHM) and a coexistent fetus (CHCF) in a patient with SS. A 29-year-old Chinese patient with SS became pregnant following one cycle of ovulation induction with human menopausal gonadotropin after secondary infertility. A normal live fetus and a low echogenic mass suspected hydatidiform mole (HM) were detected by ultrasound examinations at gestational week 8. The couple highly desired to continue the pregnancy because it is very hard to get pregnant for the patients with SS. However, the pregnancy was terminated for the size of the HM component increased rapidly at gestational week 15. Histological examinations confirmed CHCF. Genetic studies showed that the CHM genome was derived from paternal diploidy, and the normal fetus was from biparental genomes. Furthermore, a literature review on these topics is included. This case highlighted that even in a patient with SS, twin pregnancy with CHCF can still occur after ovulation induction.

What do women with gestational trophoblastic disease understand about the condition?

INTRODUCTION: Little is known about patients' understanding of the causes, treatments, and implications of gestational trophoblastic disease (GTD). Clinical observation suggests that such health literacy is limited. We report on the perceptions of causes and treatment of GTD and its impact on fertility and reproductive outcomes. METHODS: Cross-sectional analysis of 176 Australian women previously diagnosed with GTD (no longer receiving follow-up/treatment) recruited from a state-wide registry. Participants comprised 149 (85%) women with GTD who did not require chemotherapy and 27 (15%) women who required chemotherapy for malignancy or persistent molar disease. Data were collected from medical records and via self-report questionnaire. RESULTS: Participants were 94 women (53%) with partial mole, 75 (43%) with complete mole, 4 (2%) with choriocarcinoma, and 3 (2%) with hydatidiform mole not otherwise specified. Mean (SD) age at diagnosis and time since diagnosis were 32.1 (6.3) and 4.7 (3.3) years, respectively. Chance/bad luck was the most endorsed cause (n = 146, 83%); 23 (13%) thought GTD was hereditary and 10 (6%) identified a chromosomal etiology. Between 24% and 32% were unsure of the role of alcohol/drugs, venereal diseases, smoking, pollution, contraceptives, and lowered immunity. Surgical/medical procedure (n = 127, 72%) and healthy diet (n = 53, 30%) were the most endorsed treatments. Between 18% and 23% were unsure of the treatment effectiveness of diet, vitamins, exercise, complementary therapy, and contraception. All women treated with chemotherapy understood the rationale thereof; 23 (85%) perceived chemotherapy to be successful, and 19 (70%) could name the agent. Few women perceived a negative impact on their fertility (n = 28, 16%); 52 (30%) were reluctant to conceive again and 100 (57%) questioned their ability to have healthy children. After diagnosis, 111 (63%) had at least 1 live birth. CONCLUSIONS: Notwithstanding limitations, this study is the largest of its type to date. These descriptive data enhance our understanding of patients' experience on GTD, highlight the scope of GTD health literacy, and may be useful for clinicians to adjust the content of their patient education.

Embarazo molar y feto vivo / Live fetus co-existent with a hydatiform mole

Se presenta un caso de mola hidatiforme con feto vivo diagnosticado mediante ecografía en la semana 20 de gestación, cuyo feto nació vivo a las 36 semanas. En raras ocasiones aparece una neoplasia trofoblástica compartiendo embarazo con un feto vivo, particularmente si finaliza con fetos vivos nacidos durante el segundo o tercer trimestre, generalmente los fetos mueren intraútero durante el primer trimestre del embarazo. En nuestro caso el embarazo se llevó a término sin complicaciones. De cualquier forma es preciso un control y vigilancia estricta de estas pacientes (AU)

Epithelioid trophoblastic tumor of the endocervix: a case report.

BACKGROUND: It is difficult to recognize epithelioid trophoblastic tumor (ETT) as a trophoblastic disease because of its rarity and growth pattern simulating a carcinoma. CASE REPORT: A 36-year-old woman with stage IB(1) squamous cell carcinoma of the uterine cervix and a high serum beta-human chorionic gonadotropin (beta-hCG) level underwent radical hysterectomy with pelvic and para-aortic lymphadenectomy. However, light microscopic findings and immunohistochemical studies with pan-cytokeratin, epithelial membrane antigen, inhibin-alpha, beta-hCG, and human placental lactogen revealed ETT of the endocervix. The patient is alive with no evidence of disease 12 months after surgery. CONCLUSION: Before the patient is resorted to radical surgical interventions for assumed cervical carcinoma, ETT should be ruled out in women of reproductive age with endocervical tumors and elevated serum beta-hCG levels.

[Gestational trophoblastic tumors and recent clinical information].

Recent clinical advances in the field of gestational trophoblastic diseases are described. WHO modified its risk factor scoring system. This change was proposed to combine both the basic FIGO anatomic staging with the modified WHO risk factor scoring system. Patients who score as low-risk are treated with single agent chemotherapy, such as methotrexate (MTX), and patients refractory to MTX are treated with a combination chemotherapy, EMA/CO. Patients who score as high-risk are treated with EMA/CO, and patients refractory to the first line chemotherapy may be successfully treated with EP/EMA. Recent epidemiological data showed that women with complete hydatidiform moles could anticipate normal reproduction in the future. Studies found that pregnancies after treatment of molar pregnancy resulted in 69% full-term, live births; 8% premature deliveries; 1% ectopic pregnancies, and 0.5% stillbirths. First-trimester spontaneous abortions occurred in 17% of pregnancies, and major and minor malformations were detected in 0.4% of infants. Patients with hydatidiform mole were at increased risk of developing molar pregnancy in subsequent conceptions. After having one molar pregnancy, the risk of having molar disease in a future gestation was about 1%. The risk of persistent gestational trophoblastic tumors was increased by long-term oral contraceptive use before conception. In a large, multicenter, case-control study, the risk was shown to be increased in women who had ever used oral contraceptives, but was highest for women taking oral contraceptives during the cycle in which they became pregnant. Partial hydatidiform moles were never previously proven to transform into choriocarcinoma; however, a recent study with molecular techniques clearly showed that partial moles could transform into choriocarcinoma. All patients with suspected partial moles should be reviewed centrally and require hCG follow-up.

Are fertility drugs a risk factor for persistent trophoblastic tumour?

BACKGROUND: The introduction of ovulation-inducing drugs has raised concern that women exposed to these therapies may be at increased risk of cancer. We assessed the potential association between exposure to fertility drugs and the risk of developing persistent trophoblastic tumour (PTT). METHODS: We conducted a systematic review of the English and non-English language literature using the National Library of Medicine's Medline to identify all observations of patients with hydatidiform mole (HM) after treatment with ovulation-inducers. RESULTS: Fifty-two cases were considered including 26 singleton molar pregnancies and 26 multiple molar pregnancies consisting of an HM and one or more co-existent fetus(es) (HM-and-CF). PTT occurred in 15% of patients with singleton HM and in 42% of patients with HM-and-CF, 15% of whom had a metastatic disease. Of those patients with HM-and-CF, 16 patients delivered at <24 weeks gestation, mostly because of vaginal haemorrhage. Ten patients delivered at > or = 24 weeks of gestation, six of whom (25%) had a normal live child. These results are similar to spontaneously conceived pregnancies. CONCLUSIONS: Although women having an HM after therapy with ovulation-inducing drugs seem to have no added risk of PTT, multiple pregnancies are more likely to occur, and the overall risk may be increased.

Subsequent pregnancy outcome in patients with spontaneous resolution of HCG after evacuation of hydatidiform mole: comparison between complete and partial mole.

This study compared subsequent pregnancy outcome in patients with complete and partial hydatidiform moles. Among 1052 patients with molar pregnancy (complete mole, 801; partial mole, 251) monitored at Chiba University Hospital between 1981 and 1999, 891 patients (84.7%) had spontaneous resolution of human chorionic gonadotrophin (HCG) after mole evacuation, and 161 patients (15.3%) required chemotherapy. Of the 891 patients, 438 (49.2%) had 650 subsequent pregnancies. The pregnancy outcome was not significantly different in patients with complete and partial moles, and was comparable with that in the general Japanese population. The incidence of repeat molar pregnancy in patients with complete and partial mole (1.3 and 1.5% respectively) was 5-fold higher than that of the general population, while no increased risk of persistent gestational trophoblastic tumour (GTT) associated with later molar pregnancy was observed. During HCG follow-up, 10 patients (1.1%) developed secondary high-risk GTT between 14 and 54 months after mole evacuation. The incidence of high-risk GTT in patients with and without subsequent pregnancies was 0.46% (2/438) and 1.8% (8/453) respectively (P = 0.1243). In conclusion, patients with complete and partial mole can anticipate a normal future reproductive outcome, and pregnancies after experiencing hydatidiform mole may not affect the development of high-risk GTT.

Expression of nm23-H1 in hydatidiform mole and its relationship with the development of postmolar disease.

The aim of the present study was to investigate the expression of nm23-H1 in human placenta, hydatidiform mole and choriocarcinoma cells. Nm23-H1 protein was localized in the cytotrophoblast, but not in the syncytiotrophoblast. In the hydatidiform mole cases with subsequent spontaneous remission, nm23-H1 mRNA levels were significantly lower than those in first-trimester placentas. However, its levels were elevated in the hydatidiform mole cases that progressed to persistent gestational trophoblastic disease and were comparable to those of first-trimester placentas, and they were further elevated in choriocarcinoma cells. The present data suggest an association of nm23-H1 for the proliferation activity of trophoblast, and its increased expression may influence the development of persistent trophoblastic disease.

Twin pregnancy consisting of 46, XY heterozygous complete mole coexisting with a live fetus.

Complete hydatidiform mole and coexistent fetus (CMCF) is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic diseases. The aim of this study was to reveal a potential risk factor and to determine optimum management of CMCF cases. Molar tissues are cytogenetically divided into two types, homozygous and heterozygous. The molar tissue of our case showed a 46, XY heterozygous complete mole. Genomic DNA was analyzed by the polymerase chain reaction using sets of unlabelled forward and Cy-5-labelled reverse primers for DNA marker loci. The patient developed persistent trophoblastic disease (PTD) with lung metastasis. Since 1980 there have been 13 reports (including our case) that cytogenetically revealed CMCF and clarified the clinical outcome. Nine of the 16 CMCF cases before 21 weeks of gestation and seven of the 12 CMCF cases after 22 weeks of gestation developed PTD. The incidence of PTD from CMCF was not related to the gestational age at termination or delivery. There were 10 case reports that analyzed the zygosity of a mole, heterozygous or homozygous. Two of six homozygous and three of four heterozygous moles in CMCF cases developed PTD. A heterozygous mole is thought to be a high risk factor for the incidence of PTD. Cytogenetic study is clinically useful for the optimum management of CMCF cases.

Complete hydatidiform mole and a coexistent viable fetus: report of two cases and review of the literature.

OBJECTIVE: The aim of this study was to report the clinical features, management, and outcome of two cases of complete hydatidiform mole with a coexisting viable fetus and to review the literature. PATIENTS: In this article, we report on the well-documented follow-up of 2 cases of twin pregnancies with complete hydatidiform mole and a viable fetus, both of which ended with the delivery of a normal infant at 41 and 26 weeks of gestation. It is of interest that both pregnancies were achieved following induction of ovulation with hMG/hCG. Since 1977, the year in which complete and partial moles were characterized as distinct pathologic entities, 15 cases (including our 2) have been reported. RESULTS: Persistent GTT developed in eight patients (53.3%) and four patients (27.7%) developed metastatic disease. Seventy-five percent patients with persistent GTT were treated with single-agent chemotherapy. The median gestational age of the patients with subsequent persistent GTT was 34.5 weeks compared to 38 weeks in the patients without persistent GTT. CONCLUSION: Complete hydatidiform mole and coexistent fetus is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic tumor. Based on currently available information, it seems that in the presence of a stable pregnancy, normal karyotype, and a normal sonogram it is reasonable to allow the pregnancy to continue.

Gestational trophoblastic disease following the evacuation of partial hydatidiform mole: a review of 66 cases.

OBJECTIVE: The current study was undertaken in order to identify the clinical characteristics and natural history, as well as methods of investigation and available therapy, of persistent gestational trophoblastic disease (GTD) following the evacuation of partial hydatidiform mole (PM). METHODS: Case reports of persistent GTD following the evacuation of partial mole, were searched using the Medline computerized retrieval system. There were 66 such cases (including 4 cases treated at our department), representing 2.9% of GTD following PM. RESULTS: The mean age of the women at diagnosis was 28.4 years and mean gravidity was 2.99. The mean gestational age at diagnosis was 15.5 weeks and the mean uterine size was 13.6 weeks. The most common presenting symptom was vaginal bleeding. In the majority of the patients, the pre-evacuation diagnosis was incomplete or missed abortion. CONCLUSIONS: Although the malignant potential of PM is low, persistent GTD may develop after PM and may even metastasize, it is usually responsive to single agent chemotherapy but may require combination chemotherapy. Therefore, after evacuation of PM, these women should be followed with serial serum b-hCG. Further research is needed to enable earlier identification of PM that eventually will develop persistent GTD.

Persistent gestational trophoblastic tumour with partial hydatidiform mole as the antecedent pregnancy.

OBJECTIVE: A 16 year review of persistent gestational trophoblastic tumour when the antecedent pregnancy was a partial hydatidiform mole. DESIGN: Cases of persistent gestational trophoblastic tumour with partial hydatidiform mole as the antecedent pregnancy were reviewed for the period 1976 to 1992. DNA ploidy was analysed by flow cytometry. SETTING: A University Hospital which is a reference centre for gestational trophoblastic tumour. SUBJECTS: The case notes of 207 women with persistent gestational trophoblastic tumour were reviewed. MAIN OUTCOME MEASURES: A rise (or failure to fall) of beta hCG titre, or sign of metastasis. RESULTS: Six (2.9%) women had partial hydatidiform mole as the antecedent pregnancy and all were initially judged to be low risk. However, two developed pulmonary metastasis; one woman developed persistent gestational trophoblastic tumour shortly after a hysterotomy, and none developed choriocarcinoma. The geometric mean of serum beta hCG concentrations at the initiation of chemotherapy was 868 mIU/ml (95% CI 114-1524). Of the six women, one achieved remission after total abdominal hysterectomy, and five after chemotherapy. The mean interval from starting treatment to remission was 68 days (95% CI 27.9-108.0). The initial beta hCG titre and interval were not statistically different from those found in cases of persistent gestational trophoblastic tumour when the antecedent pregnancy was not partial hydatidiform mole. Of the six, the DNA content was triploid in three and diploid in two. One of the two diploid cases required multiple courses of chemotherapy to achieve remission. CONCLUSION: Partial hydatidiform mole can have malignant sequelae and can develop very soon after treatment. Its DNA content can be either diploid or triploid, the lungs being the most common site of metastasis. After evacuation of partial hydatidiform mole, immediate chest X-ray and regular follow up of the serum beta hCG level is necessary.

Successful resolution of persistent trophoblastic disease after partial mole with the EMA-CO regimen.

A 29-year-old nullipara with partial hydatidiform mole at 8 weeks had pre-evacuation hCG levels of 275,000 mIU/ml. Free beta-hCG levels were measured as 3% (normal value below 4%). The patient developed persistent gestational trophoblastic disease, failed to respond to methotrexate and actinomycin D, but has responded to combination chemotherapy with EMA-CO. Such a response to EMA-CO was not reported previously.

Etiology, epidemiology, risk and prognostic factors, screening, and imaging of gynecologic cancers.

This review presents some of the articles published over the past year pertaining to the etiology, epidemiology, risk and prognostic factors, screening, and imaging techniques of gynecologic cancer. The most significant advances in this period were made in the area of the genetics of gynecologic cancers and the factors that control tumor growth. New technologies are being developed in this area, which may eventually produce therapies aimed at controlling gynecologic cancers at the genetic or cellular level. Research continues for ideal screening tests for noncervical gynecologic cancers. Continuing advances were made in imaging techniques, eg, magnetic resonance imaging, which can now display very high-resolution pictures of cancers in vivo, but this technology is limited by both cost and insufficient studies proving its value.

Identification of patients with persistent trophoblastic disease by means of a normal human chorionic gonadotropin regression curve.

OBJECTIVE: Data from the Dutch Central Registry of Hydatidiform Mole were used to establish a reference human chorionic gonadotropin regression curve after molar pregnancy. STUDY DESIGN: A normal serum human chorionic gonadotropin regression corridor was constructed after fitting data from 130 patients with uneventful human chorionic gonadotropin regression after evacuation of a complete hydatidiform mole. Retrospectively, data from 77 patients with persistent trophoblastic disease were analyzed by means of this normal corridor. Measurements were performed with a radioimmunoassay for both native and free human chorionic gonadotropin beta-subunits. RESULTS: Human chorionic gonadotropin disappearance curves showed a biphasic decline with median serum half-lives of 1.8 and 12.8 days. Median time until normalization was 74 days (range 28 to 430). With the 95th percentile line, 71 of 77 patients (92%) with persistent trophoblastic disease could be identified. In > 50% of cases this could be achieved within 6 weeks from evacuation. CONCLUSION: The normal regression corridor allows identification of patients with persistent trophoblastic disease and an expectant attitude within the limits of the corridor.

Genetic evidence that placental site trophoblastic tumours can originate from a hydatidiform mole or a normal conceptus.

The genetic origin of two placental site trophoblastic tumours was established using a Y chromosome-specific and locus-specific minisatellite probes. A gestational origin was confirmed for both tumours. In one case the origin of the tumour was consistent with derivation from a normal female conceptus while the other was shown to arise from a homozygous complete hydatidiform mole, an abnormal conceptus more usually associated with the development of choriocarcinoma.

The role of contraception in the development of postmolar gestational trophoblastic tumor.

From January 1974 to June 1988, 299 evaluable patients were referred to the John I. Brewer Trophoblastic Disease Center of Northwestern University Cancer Center for treatment and/or follow-up of a hydatidiform mole (N = 162) or postmolar gestational trophoblastic tumor (N = 137). The type of contraception and other prognostic factors before and after evacuation were correlated with the development of gestational trophoblastic tumor using both univariate and multivariate analysis. There was no relationship between pre-hydatidiform mole contraception and the development of gestational trophoblastic tumor. Oral contraceptives (OCs) were used by 139 patients (46%), barrier methods by 141 patients (47%), intrauterine devices (IUDs) by two patients (1%), and no contraception by 17 patients (6%). The risk of developing gestational trophoblastic tumor was compared between patients using versus not using: OCs--33 versus 57% (P less than .001), barrier methods--53 versus 40% (P = .30), IUD--100 versus 46% (P = .21), and any contraceptive method--43 versus 88% (P less than .001). The dose of estrogens could be determined in 75 patients taking OCs; 14 of 49 (29%) of the patients taking less than 50 micrograms versus nine of 26 (35%) taking 50 micrograms or more developed gestational trophoblastic tumor (P = .78). Stepwise logistic regression analysis demonstrated that the type of contraceptive used was the most important prognostic factor in gestational trophoblastic tumor development (P less than .0001), followed by the occurrence of theca-lutein cysts (P less than .0001), Asian maternal race (P = .02), lesser time from the last menstrual period (P = .005), and greater maternal age (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)