Diploid Hydatidiform Mole Research Articles

Co-existence of a diploid hydatidiform mole and a normal fetus: mysterious events at the pronuclear stage

Co-existence of a diploid hydatidiform mole and a normal fetus: mysterious events at the pronuclear stage

Twin pregnancies with diploid hydatidiform mole and co-existing normal fetus may originate from one oocyte

In twin pregnancies comprising a hydatidiform mole and a normal co-fetus, the ploidy of the mole is almost exclusively reported as diploid and very rarely as triploid. We aimed at understanding this unbalanced distribution of diploid and triploid moles in twin pregnancies by investigating the number of gametes involved. Using polymorphic DNA markers, we compared the alleles of seven moles with those of the normal co-fetuses and deduced the number of oocytes and spermatozoa represented in each twin pregnancy. The genomes of all seven moles were androgenetic diploid; six moles were homozygous in all loci analyzed and one mole was heterozygous in several loci. In one homozygous mole, the paternal alleles were identical to those of the normal co-fetus in 13 non-linked informative microsatellite loci, indicating the involvement of one spermatozoon only, and thus of one oocyte only. Duplications of the paternal genome followed by abnormal cell division can explain this observation. In six moles, the paternal alleles were different from those of the normal co-fetus suggesting involvement of two (or more) spermatozoa. Overfertilization of one oocyte followed by abnormal cell division is a possibility. It is possible that twin pregnancies comprising a diploid mole and a normal co-fetus most often derive from one single oocyte fertilized with one or more spermatozoa. This can explain why diploid moles are far more frequent than triploid moles in twin pregnancies.

Differences in Current Clinical Features of Diploid and Triploid Hydatidiform Mole

Hydatidiform mole (HM) complicates about 1 in 1000 pregnancies in the western world. Nearly all diploid moles have an androgenetic genome and are thought to result from fertilization of an anucleate egg with either 1 sperm, followed by endoreduplication of the haploid genome, or with 2 sperms. Rare diploid moles have a biparental genome. Triploid moles result from dispermy and have 2 paternal sets of chromosomes plus 1 maternal set. This study contrasted the clinical features of diploid and triploid molar pregnancies in 259 women diagnosed in the years 1986-2003 as having a molar pregnancy. Molar ploidy was determined by karyotyping, flow cytometry, and/or analysis of polymorphic DNA markers. The series included 154 women with diploid HM and 105 with triploid HM. For both groups, the median age at diagnosis was 27 years. Diploid HM was more frequent than triploid HM in women aged 40 years and older, and all 6 subjects aged 15 to 18 years had diploid moles. The median gestational age at diagnosis was 12 and 16 weeks, respectively, for women with diploid and triploid HM. Nearly two thirds of diploid HMs but just over one fifth of triploid HMs were diagnosed in the first trimester. Triploid HM was more often the result of assisted reproduction, but this difference was not significant. Multiple logistic regression analysis identified four factors that independently predicted diploid HM. They were an initial human chorionic gonadotropin level of at least 100,000 IU/liter; a first-trimester gestational age; vaginal bleeding; and maternal age of 40 or older. Women with a large uterus more often had a diploid than a triploid mole. Of women having triploid and diploid moles, 54% and 27%, respectively, were diagnosed before symptoms developed. Hyperemesis occurred more often in women with diploid mole, but not significantly so. These findings distinguish clinically between diploid and triploid HM. They suggest that the presenting clinical features of molar pregnancy can serve as an early predictor of molar ploidy, and, therefore, may have prognostic value.

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.

Metastatic trophoblastic disease after an initial diagnosis of partial hydatidiform mole: genotyping and chromosome in situ hybridization analysis.

Hydatidiform mole (HM) is classified into partial (PHM) and complete (CHM) subtypes according to histopathologic and genetic criteria. Traditionally, it is believed that PHM carries a better prognosis and rarely develops metastasis. However, making a distinction between PHM and CHM using histologic criteria alone may be difficult. The authors used fluorescent microsatellite genotyping following laser-capture microdissection and chromosome in situ hybridization (CISH) to perform a genetic analysis of six patients with histologically diagnosed PHM who subsequently developed metastatic gestational trophoblastic neoplasia. Patients ranged in age from 25 years to 44 years (mean, 33.2 years). The gestational age of the molar pregnancies varied from 6 weeks to 20 weeks. All six patients had pulmonary metastases, with additional liver metastasis in two patients. Among the six patients with histologically diagnosed PHM, it was found that four patients had a diploid karyotype and no maternal alleles; thus, their neoplasms actually were CHM. Maternal genome was detected in the remaining two patients consistent with a biparental origin, and these patients had a triploid karyotype. CISH findings in all patients correlated with the genotyping findings. Triploid HM had maternally derived alleles, whereas diploid HMs were purely androgenetic. In the current study, which may be the largest series of genetically analyzed metastatic PHMs to date, the difficulty of histologic distinction between PHM and CHM was confirmed. Molecular analysis may help to refine the classification of HM. Although the current findings support the belief that most aggressive trophoblastic diseases are derived from CHM, a small number of PHMs do progress to metastatic disease. Thus, the current study reaffirmed that all patients with HM should be followed closely irrespective of histologic subclassification.

Analysis of gestational trophoblastic disease by genotyping and chromosome in situ hybridization

Hydatidiform mole is classified into partial and complete subtypes according to histopathological and genetic criteria. Distinction between the two by histology alone may be difficult. Genetically, a complete mole is diploid without maternal contribution, whereas a partial mole is triploid with a maternal chromosome complement. To assess the accuracy of histological diagnosis by correlating with the genetic composition, we performed fluorescent microsatellite genotyping to detect the presence or absence of maternal genome in a hydatidiform mole and carried out chromosome in situ hybridization to analyze the ploidy. For genotyping analysis, paraffin sections of 36 complete and nine partial moles, diagnosed according to histological criteria, were microdissected and DNA was separately extracted from the decidua and molar villi. Six pairs of primers that flank polymorphic microsatellite repeat sequences on five different chromosomes were used. In all, 34 cases, including 31 complete moles and three partial moles diagnosed histologically, showed no maternal contribution by genotyping; thus these could be genetically considered as complete mole. The other 11 cases (five complete moles and six partial moles previously diagnosed by histology) showed the presence of maternal contribution and were genetically diagnosed as partial moles. The genotyping results correlated with histological evaluation in 88% (37/45) of hydatidiform mole and correlated with chromosome in situ hybridization findings in all the cases, that is, triploid hydatidiform moles had maternal-derived alleles, while diploid hydatidiform moles were purely androgenetic. Compared with genetic diagnosis, histological evaluation was more reliable for the diagnosis of a complete mole (91%, 31/34) than that of a partial mole (55%, 6/11) (P=0.0033). Seven complete moles and three partial moles diagnosed genetically developed gestational trophoblastic neoplasia. To conclude, genotyping and chromosome in situ hybridization can provide reliable adjunct to histology for the classification of a hydatidiform mole, especially in cases with difficult histological evaluation and early gestational age. As a partial mole still carries a risk of developing gestational trophoblastic neoplasia, follow-up is considered necessary for both complete and partial moles.

Diploid hydatidiform moles with fetal red blood cells in molar villi. 2--Genetics.

The purpose of this study was to determine the genetic origin of a series of seven diploid hydatidiform moles with fetal red blood cells in the molar villi, normally a characteristic feature of triploid, partial hydatidiform moles. DNA was prepared from formalin-fixed, paraffin-embedded blocks of molar tissue and blood from the patient and her partner. The genetic origin of molar tissue was determined by comparing microsatellite polymorphisms in molar and parental tissue following polymerase chain reaction (PCR) amplification of DNA. In six cases, the hydatidiform mole was shown to be androgenetic in origin and therefore genetically to be a complete hydatidiform mole. In one case, the hydatidiform mole was of biparental origin, having both a maternal and a paternal contribution to the genome. We conclude that fetal red blood cells may be observed in the villi of complete hydatidiform moles. In cases where the degree of trophoblastic hyperplasia and ploidy is suggestive of a complete hydatidiform mole, the presence of fetal red blood cells alone should not be considered indicative of a diagnosis of partial hydatidiform mole.

Diploid hydatidiform moles with fetal red blood cells in molar villi. 1--Pathology, incidence, and prognosis.

It is believed that fetal development does not occur in complete mole (CM); when present, it is usually interpreted as proof of partial mole (PM), in most cases a triploid conception with a low incidence of persistent trophoblastic disease (PTD). However, histological examination of 3180 moles in 8 years showed 60 moles (1.8 per cent) with features of CM and either embryonic tissues or amnion in the sample. Flow cytometry (FC) in 40 showed diploid complement in all. In ten of the 40, there was evidence of a twin; in 17, there was only amnion, which could belong to a twin; in the remaining 13, there was no evidence of a twin and nucleated fetal red blood cells (FRCs) were seen within molar vessels in ten (0.3 per cent). Seven of the 40 patients (17.5 per cent) and one of the ten with FRCs in villi (10 per cent) developed PTD, an incidence comparable to that of CM. Genetic studies in seven of these tea are reported separately. Finding fetal tissues with a mole or FRCs in molar vessels is not enough to classify it as PM, since it can be a CM with a twin, fetal development CM, or possibly a third type of mole. These rare diploid moles with fetal tissues have histological appearances and prognosis similar to those of CM.