[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.

Age of parents and risk of gestational trophoblastic disease.

The relationship of gestational trophoblastic disease (GTD) to parental age was evaluated in a case-control study of 132 women with hydatidiform mole (108) or choriocarcinoma (24) and 304 control subjects hospitalized for normal deliveries. Cases and controls were recruited in Lombardy (Northern Italy), and all were white and Italian. Compared to the risk of developing trophoblastic tumors in women 21-35 years old, the risk of developing trophoblastic tumors was elevated both in younger [less than or equal to 20 yr old, relative risk (RR) = 1.4, with 95% confidence interval (Cl) of 0.7-2.8] and in older subjects, RR being 1.2 (95% Cl 0.7-2.8) and 5.2 (95% Cl 2.2-12.3) for women 36-40 years old and over 40, respectively. The risk estimates for the last two categories were reduced to 0.7 (with 95% Cl of 0.3-1.9) and 2.5 (with 95% Cl of 0.7-8.9) when adjustment was made for paternal age by means of the Mantel-Haenszel procedure. Higher paternal age also was associated with GTD: Women whose husbands were 41-45 years old and over 45 had RR of 1.6 (with 95% Cl = 0.7-3.7) and 4.9 (with 95% Cl = 2.2-11.1), respectively, compared to women married to men less than 40 years old. These risk estimates were practically unchanged when adjustment was made for the woman's age. Examination of the effects of parental and maternal ages suggests that the highest risk estimate was observed when both parents were older. The findings of the present study were consistent with increased risk in the youngest maternal age group and confirm that older maternal age is associated with increased risk of GTD. Furthermore, showing a strong, independent effect of paternal age, they give epidemiologic support to the cytogenetic evidence of an androgenetic role in the origin of GTD.

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.

Trophoblastic tumors in Greenland.

From 1950 through 1974, 37 cases of hydatidiform mole not followed by malignancy and 11 cases of invasively growing trophoblastic tumors (IGTT) occurred among indigenous Greenlandic women. The overall incidence of benign mole was 1:850 births, only slightly higher than most incidences in low-risk areas like Western Europe, North America, Australia, and Israel. In contrast, the overall incidence of IGTT, 1:2861 births, and the minimum incidence of histologically confirmed choriocarcinoma, 1:5245 births, are among the highest population-based incidence on record. A marked increase in incidence of both hydatidiform mole and IGTT was found late in reproductive life. A recent high incidence of mole among teenagers increased the incidence with statistical significance during the latest 10 years, whereas maximum incidence of IGTT was found in 1960--64. A strong association existed between hydatidiform mole and IGTT. During the study period Greenlandic women with mole had a 20% risk of developing IGTT and 64% of IGTT cases were preceded by molar pregnancy. Four cases of benign mole, but no case of IGTT, occurred among the small group of Danish women living in Greeland. The incidence, 1 mole:685 births, was higher than among the indigenous population, although the latter had a lower socio-economic status. The reason for the high occurrence of IGTT among indigenous Greenlanders remains unknown. The predominating HL-A 9 antigen could conceivably reflect a genetic predisposition.

Persistent ectopic pregnancy.

From 1982-1986, 625 tubal ectopic pregnancies were treated at the University of Hawaii School of Medicine Affiliated Hospitals. The percentage of cases in which the involved tube was preserved increased from 7% in 1982 to 26% in 1986. The presence of persistent trophoblastic tissue was diagnosed by elevated serum levels of the beta subunit of human chorionic gonadotropin (beta-hCG) after conservative surgery in four patients. Three of the four patients developed intra-abdominal hemorrhage and required laparotomy. One patient remained asymptomatic despite elevated beta-hCG levels, which disappeared 60 days after surgery. Evaluation of histologic slides demonstrated persistent intraluminal trophoblastic tissue without invasion in two patients, and extraluminal invasion into the tubal wall in one patient. The use of postoperative serial beta-hCG titers might facilitate recognition of this complication in time to prevent further tubal damage and hemorrhage.

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)

Oral contraceptives and postmolar trophoblastic disease.

One hundred patients, managed for molar pregnancy at the New England Trophoblastic Disease Center, were selected at random to determine if the contraceptive method following molar evacuation influenced the incidence of postmolar trophoblastic disease. Following molar evacuation, 58 (58%) patients used oral contraceptives and 42 (42%) patients used barrier methods (foam, condom, and/or diaphragm). Postmolar trophoblastic disease developed in 11 (18.9%) patients using oral contraceptives and in 6 (14.3%) patients using barrier methods (P greater than .10). The mean human chorionic gonadotropin (hCG) regression time after molar evacuation was 7.0 weeks in patients using oral contraceptives and 7.2 weeks in patients using barrier methods. The 2 groups of patients were comparable in age, gravidity, molar histology, pretreatment hCG titers, and exposure to prophylactic chemotherapy. Oral contraceptives do not appear to increase the risk of postmolar trophoblastic tumors and therefore may be safely prescribed after molar evacuation during the entire interval of gonadotropin monitoring.

Hydatidiform mole: a vascular congenital anomaly.

The thesis is advanced that a critical time for development of embryonic blood vessels in the placenta is 13 to 21 days after conception, especially during days 18 to 21. Dietary requirements at this time are specific and demanding for nutritional precursors of thymidine which is an important constituent of DNA. Folic acid and histidine are specifically essential for thymidine synthesis. These are reviewed with respect to cultures and socioeconomon levels in societies where occurrence of hydatidiform mole is endemic. Specific nutritional deficiencies are discussed in relation to kinds of diets and ways of food preparation. When specific dietary requirements are lacking at a time of high need, embryo death, abnormality, and/or avascularity of trophoblastic placental villi may be the earliest pathogenic signs of hydatidiform mole.

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.

Partial hydatidiform mole with subsequent trophoblastic tumor; a case report.

A case of partial hydatidiform mole revealed by genetic marker analysis one maternal and two paternal chromosome complements. Levels of serum human chorionic gonadotropin were persistently elevated during follow-up. Avillous curettage specimens prior to chemotherapy were morphologically suspicious for gestational choriocarcinoma. It is still uncertain whether the risk for gestational choriocarcinoma preceded by partial mole exceeds the risk related to non-molar abortions. Careful follow-up with serial serum human chorionic gonadotropin levels is required to detect persistent disease.

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.

Post-molar trophoblastic disease following coexisting molar pregnancy and living fetus subsequent to clomiphene citrate therapy.

A case of the combination of a complete hydatidiform mole and a coexisting, living fetus arising from a twin pregnancy, subsequent to clomiphene citrate therapy for ovulation induction, is presented. The diagnostic problems of this combination as well as the incidence of molar pregnancy following the use of ovulation inducers are discussed.

Herpes type-2 viruses and gynaecological malignancies.

Numerous sero-epidemiologic studies have noted an association between Herpes Type 2 (HT-2) virus and carcinoma of the cervix. In a study to evaluate the role of this virus, if any, on the etiology of extra cervical pelvic malignancies in Ibadan, the prevalence of HT-2 virus antibodies was found not to be significantly different in patients with extra cervical pelvic malignancies (carcinoma of the vulva and malignant trophoblastic disease) and cases of chronic cervicitis when compared with healthy controls. It was therefore concluded that no association could be found between HT-2 virus and extra cervical pelvic malignancies.

Hydatidiform mole: clinicopathologic associations with the development of postevacuation trophoblastic disease.

Clinical information and histopathologic material for 165 patients with hydatidiform mole referred to the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School during one year were reviewed in order to identify characteristics more likely to be associated with the development of gestational trophoblastic tumors. Twenty-nine patients (18%) required chemotherapy for invasive mole or choriocarcinoma. Patients with uterine enlargement beyond that expected for dates and patients with ovarian theca-lutein cysts were much more likely to require treatment after molar evacuation (47% vs. 18% and 40% vs. 16%, respectively). There was no correlation between the initial human chorionic gonadotropin level, gestational age, uterine size per se, maternal age or gravidity and the subsequent clinical course. Histologically, the following factors were associated with an increased incidence of postmolar gestational trophoblastic tumor: (1) progressive nuclear atypia (26.7% if atypia present vs. 40% if absent); (2) necrosis and hemorrhage (39.1% if extensive vs. 12.8% if limited); (3) decreased trophoblast maturation (48% if less than 20% mature vs. 8.7% if greater than or equal to 20% mature); (4) trophoblast proliferation (50% if marked vs. 13.9% if limited); (5) increased ratio of cytotrophoblast to syncytium (33.3% if greater than 1 vs. 6.4% if less than 1); and (6) absence of Nitabuch's layer (21.4% if absent vs. 11.6% if present). Hydatidiform moles which demonstrate clinical or histopathologic evidence of excessively abnormal proliferative activity, as indicated by these features, are more likely to develop invasive mole or choriocarcinoma and should be considered for prophylactic chemotherapy.

Analysis of 309 cases after hydatidiform mole: different follow-up program according to biologic behavior.

Between 1976 and 1985, at the Obstetrics and Gynecology Department of Milan University, a total of 309 cases of hydatidiform mole, 223 complete moles and 86 partial moles, were monitored with the assay of beta-human chorionic gonadotropin, following a postmolar biochemical surveillance program. Spontaneous remission of the disease occurred in 287 (92.9%) patients. Marker levels were undetectable in 80.4% of cases within 60 days after evacuation of the mole and in 19.6% between 61 and 140 days. There were 22 (7.1%) patients diagnosed as having gestational trophoblastic tumors (GTT) and treated with chemotherapy: 20 were complete moles and 2 partial moles. Considering these data, the authors suggest different follow-up times for partial and complete moles and confirm the necessity of selection criteria in a diagnosis of GTT.

Pathologic features of sharp curettings in complete hydatidiform mole. Predictors of persistent gestational trophoblastic disease.

The medical records and pathologic specimens were reviewed from 33 patients with complete molar pregnancy at Brigham and Women's Hospital between 1980 and 1989. Two pathologists (D.R.G. and R.W.R.) reviewed all slides from the original sharp curettage to identify pathologic features that may be associated with persistent gestational trophoblastic tumor (GTT). The pathologic features evaluated were implantation site, presence of myometrium, presence of villi, presence and degree of atypia in cytotrophoblast, syncytiotrophoblast and intermediate trophoblast, presence of fibrinoid, presence of implantation site inflammatory cells, volume of tissue and area of trophoblastic tissue. Only one pathologic feature, fibrinoid deposits, identified in sharp curettings was associated with the development of persistent GTT. While 12 (48%) of 25 patients who attained remission without chemotherapy had fibrinoid deposits, only 1 (12.5%) of 8 patients who developed persistent GTT had them (P less than .10).

The risk factors in the development of persistent trophoblastic disease following hydatidiform mole.

Hydatidiform mole (HM) is not uncommon in our country. Its dangerous sequalae is the fatal persistent trophoblastic disease (PTD). The prognostic risk factors for the development of PTD were analyzed in 108 cases of HM treated in Ramathibodi Hospital from 1978 to 1986. Statistical univariate analysis was by calculation of relative risk (RR) and chi-square test. The incidence of PTD was 27.8 per cent. The significant risk factors were the presence of theca-lutein cyst, gestational age of less than 16 weeks, "large for date" uterus, and patients' age of 40 years or more. Their RR were 4.25, 3.11, 3.00 and 2.68 respectively. These findings were comparable with previous reports. The use of prophylactic chemotherapy in patients with these risk factors was suggested.

[Malignant cyto-trophoblastic tumors following the abortion of a mole. Their treatment with methotrexate alone or in conjunction with surgery].

We report six case histories of malignant tumours following abortion of moles. In three cases their surgical removal allowed us to control them by histology: two of these were destruens chorio-adenomata, one case only was a choriocarcinoma. In the three other cases the cure was obtained by the sole use of anti-mitotic drugs. This treatment was undertaken on bioclinical evidence of malignancy which is certainly not foolproof, but which is practical in use, when one appreciates how difficult it is to diagnose some of these post-mole tumours histologically. There is a place for the surgical treatment of these cases in spite of the usefulness of Methotrexate. This place varies according to the age of the patients and the resistance of the tumours to treatment with anti-mitotic drugs.