Risk Of Persistent Trophoblastic Disease Research Articles

Expression of p57 immunomarker in the classification and differential diagnosis of partial and complete hydatidiform moles.

BACKGROUND:Hydatidiform mole (HM) is characterized histologically by cystic swelling of the chorionic villi, accompanied by variable trophoblastic proliferation. The most important reason for the correct recognition of moles is that they are associated with an increased risk of persistent trophoblastic disease (invasive mole) or choriocarcinoma.AIMS AND OBJECTIVES:The aim of the study was to determine whether there is any role of p57 in differentiating partial and complete moles by immunohistochemical staining.MATERIALS AND METHODS:A prospective observational study was undertaken in which 40 cases of molar pregnancy included over a period of 2 years. Detailed clinical and family histories were obtained from each patient. Histopathological examination followed by immunohistochemical study with p57 done in each case. Ultrasonography findings and serial titers of serum beta-human chorionic gonadotropin were noted whenever necessary.RESULTS:Among the forty cases included, 25 (62%) had complete molar (CM) pregnancy, whereas the rest 15 (38%) had partial mole (PM). Both CM and PM were more pronounced in the age group of 20–25 years (44% and 60%, respectively), and among nulliparous women (68% and 70% respectively), 17 (42.5%) mothers had a prior history of abortion. In the histologically unequivocal cases of complete mole, 96% (24 of 25) did not express p57 and a single case was focal positive. In contrast, it was strongly and continuously expressed in both villous cytotrophoblast and stromal cells in all cases of PM (15 of 15).CONCLUSION:p57 immunomarker is very helpful to diagnose and differentiate complete and partial HM.

Molecular and histological characteristics of early triploid and partial molar pregnancies

Molar pregnancy has the highest incidence of all gestational trophoblastic diseases. This is a heterogeneous group of diseases, composed of precancerous lesions and gestational trophoblastic tumours. The hydatidiform mole is characterised by varying degrees of proliferation of syncytiotrophoblastic and cytotrophoblastic cells and stromal oedema. Based on established morphological and cytogenetic criteria, molar pregnancy is divided into partial and complete. The risk of persistent trophoblastic disease is higher in complete moles compared with partial moles. The aim of this study was to assess the importance of additional molecular methods as a conjunction to the standard histopathological analysis to accurately determine the type and origin of triploidy and to detect partial molar pregnancy. This study examined a total of 24 cases of triploidy. Apart from the detailed histomorphological analysis, a molecular analysis of the placental tissue and maternal DNA was also performed. Digynic triploidy was found in 15 cases, whereas diandric triploidy was found in nine of the cases. The results showed that due to the histomorphological overlap between partial molar pregnancy and hydropic abortions, concomitant histopathological analysis of the placental tissue and molecular analysis of the placental and maternal DNA can lead to correct diagnosis.

Circulating Tumor DNA: A Potential Novel Diagnostic Approach in Gestational Trophoblastic Neoplasia

Circulating Tumor DNA: A Potential Novel Diagnostic Approach in Gestational Trophoblastic Neoplasia

Rare Case of Twin Pregnancy with Complete Hydatidiform Mole and Coexisting Fetus (CHMF) following Infertility Treatment.

Twin pregnancy consisting of complete molar pregnancy and a coexisting fetus occurs with an estimated incidence of 1 per 22,000–100,000 pregnancies, and may be increasing due to the greater use of assisted reproductive techniques [1]. These pregnancies are associated with significant maternal and fetal complications including preeclampsia, thromboembolic disease, hyperemesis, hemorrhage, intrauterine demise, and an increased risk of persistent trophoblastic disease. In this study, we report the case of twin pregnancy with a complete hydatidiform mole (CHM) that was managed conservatively according to the patient’s request and circumstances.

The utility of molecular and immunohistochemical techniques in diagnosing molar pregnancies

Based on established morphological and cytogenetic criteria, molar pregnancy is divided into partial and complete. The risk of persistent trophoblastic disease is higher in complete moles. The aim of this study was to assess the importance of additional molecular and immunohistochemical methods to accurately determine the presence and type of molar pregnancy. This study examined 30 cases of hydropic abortion and molar pregnancies, which were also analyzed with immunohistochemical methods using p57 and p63 antibodies. Molecular analysis of the placental tissue was done in 25 of the cases. The results showed that chromosomal abnormalities were found in 82% of the cases. Of these, 27.3% showed triploidy, whereas maternal tissue was not found in one analyzed case of complete mole. Trisomy was found in 40% and 9% were consistent with Turner syndrome. The immunohistochemical analysis revealed absence of p57 positivity in both cases of complete mole, but there was no difference in p63 positivity between the different molecular groups. In order to obtain accurate and clinically relevant diagnosis of molar pregnancy, the products of conception should be analyzed by an experienced pathologist, using additional immunohistochemical and molecular analyses.

15. A twin with a mole! A case report of an extremely rare condition of molar pregnancy with a coexisting fetus progressing to a viable infant

<h3>Introduction</h3> Molar pregnancy with a coexisting twin fetus is an extreme rarity. The incidence of such an occurrence ranges from 1 in 10,000 to 100,000 pregnancies and this may increase with the greater use of assisted reproductive techniques. The management of these pregnancies is difficult due to complications such as fetal death, vaginal bleeding, pre-eclampsia and an increase risk for persistent trophoblastic disease. Delivery of a viable term normal infant from this combination is even rarer. <h3>Case report</h3> We report a case of molar pregnancy in a 36-year-old woman with a coexisting twin fetus which progressed to delivery of a viable healthy infant at term gestation. The submitted specimen was a twin placenta comprising two separate discs joined by a dividing membrane. One of the discs was pale yellow and small. Vesicles were not evident macroscopically. Microscopic examination showed a dichorionic diamniotic twin gestation. The placenta of the viable term gestation showed no significant abnormality while the separate yellow disc showed changes of hydatidiform mole with extensive infarct-like necrosis. <h3>Discussion</h3> Molar pregnancy with a coexisting twin fetus progressing to a healthy infant is an extremely rare entity. The management guidelines for decision making are limited as there are only a few published reports in the literature. We present this case report to highlight the existence of this extremely rare entity. In addition, it demonstrates that, despite the presence of a coexisting molar gestation, the non-molar gestation may progress to delivery of a normal healthy term infant.

Placental mesenchymal dysplasia - a case report and review of literature

CaseThis 32 year old primigravida with no risk factors had ultrasound scan at 15 weeks which showed abnormally thick placenta with cystic spaces suggestive of partial molar pregnancy with normal...

Twin pregnancy with a complete hydatidiform mole and co-existent live fetus: two case reports and review of the literature

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. In this article, we report on the well-documented follow-up of two cases of twin pregnancies with complete hydatidiform mole and a normal fetus. Genetic amniocentesis showed normal fetal karyotype in both of two cases. In the first case, a live male infant was delivered by a cesarean section because of severe maternal bleeding at 29 weeks of gestation. In the second case, termination of pregnancy was performed due to early onset of severe preeclampsia and vaginal hemorrhage. The chances of a live birth have been estimated between 30 and 35% and the risk of persistent trophoblastic disease is similar to singleton molar pregnancies in complete mole with coexisting fetus pregnancy. Therefore, in these pregnancies, expectant management instead of termination of pregnancy can be suggested.

Evaluation of the risk of persistent trophoblastic disease after twin pregnancy with diploid hydatidiform mole and coexisting normal fetus

This study was undertaken to evaluate the risk of persistent trophoblastic disease and obstetric complications related to a multiple pregnancy comprising a diploid hydatidiform mole and normal cofetus(es). From a database of 270 consecutively collected hydatidiform moles, 8 multiple and 154 singleton molar pregnancies were identified. Molar and fetal ploidy was determined, and data on clinical features and chemotherapy were collected. Differences between groups were assessed with Fisher's exact or Mann-Whitney test. The molar component in all 8 multiple pregnancies was diploid. Five patients with diploid mole and coexisting fetus pregnancy chose to terminate their pregnancy, 2 aborted spontaneously, and 1 patient delivered a healthy child. Two diploid mole and coexisting fetus pregnancies (25%) and 17% of the singleton molar pregnancies were followed by persistent trophoblastic disease (P = .63). The risk of persistent trophoblastic disease after a diploid mole with coexisting fetus pregnancy is similar to that after a singleton molar pregnancy, and expectant management instead of therapeutic abortion can be pursued.

The risk of persistent trophoblastic disease after hydatidiform mole classified by morphology and ploidy

Hydatidiform mole can be classified by histopathologic characteristics and by genetic constitutions and most complete moles are diploid, whereas most partial moles are triploid. We investigated the concordance between these two classifications, characterized moles with conflicting classifications, and compared the ability of the two classifications to discriminate between patients with and without a substantial risk of persistent trophoblastic disease. 294 cases of consecutively collected hydropic placentas clinically suspected of hydatidiform mole made the basis of this retrospective study. We determined the ploidy and reviewed the original histopathologic material in all cases. Data on possible chemotherapy were collected for each patient. 270 of the conceptuses were histopathologically classified as hydatidiform mole. Among the 24 conceptuses classified as non-molar miscarriage, 20 were triploids, 2 were diploid androgenetic and 2 were diploid biparental. In 23% of the conceptuses, the histopathologic and genetic classifications were conflicting. 5% of the patients with hydropic placentas classified as partial mole encountered persistent trophoblastic disease; however, the genome was diploid in all these moles. None of 131 patients with a triploid hydropic gestation encountered persistent trophoblastic disease. As full concordance between the histopathologic and the genetic classifications was not found, we believe that features beyond the genetic constitution influence the development of morphologic features in hydatidiform moles. We recommend that gestations suspected of hydatidiform mole are subjected to histopathologic examination. If hydatidiform change and trophoblastic hyperplasia are identified, the ploidy should be used to identify patients with a high risk of persistent trophoblastic disease.

Predictors of Low Risk of Persistent Trophoblastic Disease in Molar Pregnancies

To search for predictive factors for low risk of persistent trophoblastic disease in patients with molar pregnancies. A total of 270 consecutively collected, histologically confirmed hydatidiform moles were classified by ploidy using karyotyping and flow cytometry. The parental origin of the genome was determined by analysis of microsatellite polymorphisms. Data on clinical features and pathology reports were collected for each patient. The observed frequency of persistent trophoblastic disease in patients with triploid moles was 0 of 105, (95% confidence interval 0-2.8%), whereas 28 of 162 patients with diploid molar pregnancies developed persistent trophoblastic disease (P < .001). Patients with a diploid mole and an initial hCG level lower than 49,000 units per liter did not develop persistent trophoblastic disease (P = .03). The risk of persistent trophoblastic disease after a triploid mole is very low. By combining the present data with data from published studies with valid ploidy assessment, the frequency of persistent trophoblastic disease in patients with triploid moles is 0 of 196 (95% confidence interval 0-1.5%). We suggest that the surveillance program for patients with triploid molar pregnancies is shortened. Initial hCG less than 49,000 units per liter is a possible predictor of low risk of persistent trophoblastic disease in women with diploid molar pregnancies, but this observation needs confirmation in larger studies.

Second-Trimester Maternal Serum Markers in Twin Pregnancy with Complete Mole: Report of 2 Cases

We present second-trimester serum marker levels in cases of twin pregnancy with complete hydatidiform mole and a coexistent fetus (CHMCF). Second-trimester inhibin A (InhA) levels have not been previously reported in such cases. Second-trimester maternal serum screening, alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and InhA measurements combined with maternal age to estimate a patient's risk of Down syndrome during pregnancy was performed as a routine prenatal test in 2 cases of CHMCF. Hospital records containing serum marker data, patient history, pathology reports, and pregnancy outcome were reviewed. In cases of CHMCF, maternal serum AFP and uE3 levels were similar to those of a normal singleton pregnancy, whereas hCG and InhA levels were markedly increased. Second-trimester maternal serum marker profiles in cases of CHMCF are a composite of normal singleton and molar tissue secretions. We have found, for the first time, that second-trimester InhA levels are markedly increased in these cases. Serum marker levels may be useful in diagnosis of CHMCF, prenatal counseling, and evaluation of risk for persistent trophoblastic disease.

Diagnosis and outcome of complete hydatidiform mole coexisting with a live twin fetus

Objective: The aim of this study was to highlight the outcome of complete hydatidiform mole (CHM) coexisting with a live co-twin. Methods: We investigated four cases of such pregnancy by ultrasound, pathological, cytogenetic, and molecular techniques. Information on clinical follow-up and outcome was also available. Results: All four pregnancies were spontaneous: two ended with the delivery of a live-born baby, while the other two were terminated because of signs of serious maternal pathology or intrauterine fetal death. The criteria for carrying on with the pregnancy are reviewed. The immediate outcome depends on the maternal criteria of serious pathology and on the likelihood of intrauterine fetal death. The risk of persistent trophoblastic disease (PTD) is the same as in the case of a singleton complete mole and also seems to be correlated with the zygosity mechanism identified by molecular analysis. Conclusion: Hydatiform mole with a live co-twin fetus is a rare obstetric occurrence. In the case of a normal fetal karyotype, it is justifiable to await developments in the absence of maternal complications. However, treatment criteria still need improvement and diligent maternal follow-up is always warranted in the postpartum period.

Genomic Imprinting in Gestational Trophoblastic Disease—A Review

The abnormal pregnancy hydatidiform mole (HM) can be classified as complete (CHM) or partial (PHM) on the basis of both morphology and genetic origin. PHM are diandric triploids while almost all CHM are androgenetic. Thus the characteristic trophoblastic hyperplasia seen in both CHM and PHM is usually associated with the presence of two paternal genomes. Very occasionally CHM may be diploid, but biparental, in origin. These rare BiCHM are found in patients with recurrent HM and appear to be associated with an autosomal recessive condition predisposing to molar pregnancies. Since they are pathologically indistinguishable from androgenetic CHM, BiCHM are also likely to result from defects in genomic imprinting. There is evidence that the gene mutated in this condition, provisionally mapped to 19q13.3–13.4, may be important in setting the maternal imprint in the ovum. Women with BiCHM have a much higher risk of recurrent HM than women with AnCHM and an appreciable risk of persistent trophoblastic disease. Investigation of these unusual BiCHM and isolation of the defective gene will lead to a greater understanding of the function of genomic imprinting in early development.

Medical induction prior to surgical evacuation of hydatidiform mole: is there a greater risk of persistent trophoblastic disease?

A retrospective study was undertaken to assess whether stimulation of uterine contractility prior to surgical evacuation of a molar pregnancy will lead to an increased frequency of persistent trophoblastic disease. Forty-seven patients treated with chemotherapy for persistent trophoblastic disease after a hydatidiform mole between 1971 and 1988 were evaluated. The use of medical methods in this study group was compared to a control group of 219 patients with hydatidiform mole not requiring further treatment. A medical method, mainly treatment with prostaglandins, was used in 61.7% in the study group compared to 35.2% in the control group. This difference was, however, due to different stage distribution in the groups. Persistent disease was significantly correlated to uterine size and medical methods were mainly used in patients where uterine size corresponded to 15 weeks gestation or more. In this subset of patients, a medical method was used in the same frequency in both groups. Thus, large uterine size seems to be an independent risk factor. We conclude that stimulation of uterine contractility, which in Sweden is frequently used before surgical evacuation of the uterus in patients with hydatidiform mole and large uteri, carries no additional risk.

The problem of identification of prognostic factors for persistent trophoblastic disease

The role of anamnestic and clinical factors in defining the high group at risk of developing persistent trophoblastic disease (PTD) has been analyzed in 301 cases of hydatidiform mole. Patients age 40 or more years with AB blood, and a previous history of molar pregnancy had an elevated risk of developing PTD. The presence of various risk factors increased the frequency of PTD. However, with discriminant analysis, correct classification of outcome was obtained for only 69% of cases. Despite the magnitude of risk of PTD for women with three or more risk factors, the clinical relevance of prognostic variables in the prediction of outcome was limited by the low proportion of women classified in the low- and high-risk groups, making the identification at diagnosis of the women who could benefit of prophylactic chemotherapy extremely difficult and hence of little clinical importance.