Hydropic Abortion Research Articles

A prospective study of ultrasound screening for molar pregnancies in missed miscarriages

To examine the relationship between ultrasound and histological features in the screening for molar changes in missed miscarriage. A prospective cohort study was conducted on all missed miscarriages, with features suspicious of molar pregnancy, on transvaginal ultrasound and/or on histological examination over a 5-year period. All cases of molar pregnancy diagnosed histologically were examined and cross-referenced with cases diagnosed on ultrasound and with the supplementary report from the regional referral center. When available, maternal serum beta-human chorionic gonadotropin (hCG) levels were recorded. Fifty-one cases of suspected molar pregnancy were referred to the regional center for further histological opinion and follow-up, and five cases were subsequently excluded from the final analysis because of the diagnosis of hydropic abortion (HA). In 33 cases a molar pregnancy was suspected at the initial scan. Of these, 26 (78.8%) were confirmed on histology, resulting in a 56% detection rate using ultrasound alone. In 15 cases hCG results were available, of which nine were greater than two multiples of the median. The diagnosis of both complete (CHM) and partial (PHM) hydatidiform moles in first-trimester miscarriages is difficult. hCG is significantly higher in both CHM and PHM and, in conjunction with transvaginal ultrasound, could provide the screening test required to enable clinicians to counsel women more confidently towards non-surgical methods of management of their miscarriage, where histopathological examination is not available.

P57 KIP2 immunohistochemistry in early molar pregnancies: emphasis on its complementary role in the differential diagnosis of hydropic abortuses

Morphologic examination still forms the main diagnostic tool in the differential diagnosis of molar pregnancies. However, the criteria are subjective and show considerable interobserver variability among pathologists. Once a diagnosis of molar pregnancy is made, DNA ploidy studies help to differentiate a triploid partial mole from diploid complete mole (CM). However, with earlier diagnosis and therapeutic evacuation of molar pregnancies, the differentiation of molar pregnancies from early nonmolar placentation is becoming increasingly difficult. The p57(KIP2) gene ( CDKN1C ) is strongly paternally imprinted and expressed from the maternal allele. Because CM lacks a maternal genome, p57(KIP2) immunostaining is correspondingly absent, whereas hydropic abortuses and partial mole show positive staining. We compared the use of p57(KIP2) staining in the differential diagnosis of 68 morphologically challenging cases of early first-trimester hydropic placentas. Diagnosis based on p57(KIP2) staining was compared with the original diagnosis based on morphology and DNA ploidy analysis. Concordant results were obtained in 65 of 68 cases studied. In 2 of 3 cases with a discordant diagnosis, microsatellite DNA genotyping analysis agreed with the results of p57(KIP2) staining, confirming that positive p57(KIP2) staining is a highly sensitive and specific marker for excluding CM in this setting. In addition, p57(KIP2) staining has the advantage of differentiating hydropic abortuses from CMs, a distinction not made by ploidy analysis. p57(KIP2) staining can be used in concert with ploidy studies to refine the diagnosis of early molar pregnancies.

Persistent gestational trophoblastic disease is rarely, if ever, derived from non-molar first-trimester miscarriage

Traditional epidemiologic data suggest that persistent gestational trophoblastic disease (pGTD), may follow, and be derived from, either molar pregnancy, non-molar term pregnancy or first-trimester non-molar miscarriage. We examined a database of cases of possible or probable hydatidiform moles and proven pGTD derived from the Regional Trophoblastic Disease Unit, Charing Cross Hospital, London. There were 424 cases (6%), in whom the initial registered diagnosis was that of PHM or CHM but central histopathological review diagnosed a definite non-molar hydropic abortion (HA). In eight of the 424 (2%), although the histology of the most recent index pregnancy was that of non-molar miscarriage, there was a previous history of pregnancy affected by hydatidiform mole; two of these developed subsequent pGTD. Of a further 86 cases referred for a histopathological opinion prior to registration which demonstrated definite non-molar HA, none developed pGTD (zero of 510 (0%, 95% CI 0-0.7%)). During the same period there were 352 cases with pGTD requiring chemotherapy. In 31 cases, the only known pregnancy was the preceding apparent non-molar HA. However, of these, there were only three cases in whom the preceding histological products of conception had been centrally reviewed and were suggestive of non-molar pregnancy. However, in all three of these cases, the specimens were inadequate for definite exclusion of molar pregnancy. In one case in whom no material was available for review, molecular genetic analysis using restriction fragment length polymorphisms was carried out, and the choriocarcinoma was genetically derived from a previous molar pregnancy rather than the preceding HA. There were therefore no cases identified on the database of the trophoblastic disease unit of pGTD requiring treatment in whom the trophoblastic tumour could be genetically proven to have arisen from the preceding first trimester non-molar HA. We suggest that the risk of pGTD developing from a histologically confirmed non-molar HA is less than 1 in 50,000 and that the majority of pGTD cases previously reported to have been caused by a non-molar miscarriage probably represent disease due to an unrecognised early molar pregnancy.

Immunohistochemical characterization of p57Kip2 expression in tetraploid hydropic placentas.

Because there are differences in the origin, morphology, and natural history of hydropic placental villous issues, it is important to identify and document rare specimens that deviate from the diploid complete hydatidiform mole (CM), triploid partial hydatidiform mole (PM), or diploid hydropic abortion (HA). Tetraploid hydropic placentas have rarely been studied. To evaluate the frequency of p57Kip2 protein (p57) expression in tetraploid hydropic placentas and to determine its clinicopathologic significance. Forty hydropic DNA tetraploid placental specimens were evaluated by immunohistochemistry of formalin-fixed tissues, using a monoclonal antibody against p57, a putative paternally imprinted inhibitor gene. DNA ploidy in all cases was analyzed by flow cytometry. Thirty cases were histologically diagnosed as CMs, 10 were HAs, and none were PMs. In all HAs, nuclear p57 was strongly expressed in cytotrophoblasts, intermediate trophoblasts, and villous stromal cells. In contrast, in CMs, p57 expression in cytotrophoblasts and villous stromal cells was either absent (26 cases) or very low (4 cases). Assuming that the degree of molar change roughly correlates with the proportion of paternal chromosomes present, all chromosomes might be paternally derived in all tetraploid CMs and the 10 HAs, including 2 that were karyotyped as 92,XXYY or 90,XXYY,-13,-14, which were presumably due to 2 sets of chromosomes each from paternal and maternal origin. Expression of p57 is aberrant in tetraploid CMs. This finding is in line with the hypothesis that the loss of p57 is involved in the abnormal development of androgenetic CMs. For the evaluation of a patient with trophoblastic disease, p57 immunostaining is an ancillary diagnostic method that may be used in concert with flow cytometry.

Immunohistochemical characterization of cyclin E and p27KIP1 expression in early hydatidiform moles.

The aim of this study is to evaluate whether the expression of p27 (p27) and cyclin E (cE) is related to the development of hydatidiform moles and whether their expressions are associated with prognosis in these lesions. Ten diploid voluntary artificial abortions (ABs), 20 diploid hydropic abortions (HAs), 20 triploid partial moles (PMs), and 44 diploid complete moles (CMs) (including 4 with persistent disease), all of which were in the first trimester, were evaluated by immunohistochemistry of formalin-fixed tissues using monoclonal antibodies against p27 and cE protein. DNA ploidy in all cases was analyzed by flow cytometry. In ABs, nuclear cE was expressed at low (1+) to moderate (2+) levels in cytotrophoblast (CT), intermediate trophoblast (IT) and occasionally in syncytiotrophoblast (ST). In all CMs, cE-positive nuclei of CT were observed at high levels (3+), and (1+) to (2+) levels in clusters of IT. On the other hand, all HAs and PMs showed cE levels comparable to those observed in ABs. There was a significant difference in cyclin E expression in CT between CMs and non CMs, but there was no significant difference of cE levels between CMs with and without persistent disease. In 3 of 10 ABs, nuclear p27 was expressed at (1+) levels in ST. Similar expression was observed in 27 (including 2 invasive lesions) of 44 CMs, 10 of 20 PMs, and 8 of 20 HAs. CT and IT were rarely positive (1+) for p27 in the cases examined. Decidual stromal cells provided a reliable positive internal control for p27 expression. These findings support the hypothesis that trophoblast proliferation is related to the balance between the positive cell cycle factors, such as cE, and the negative cell cycle inhibitors, such as p27. The overexpression of cE in the trophoblastic elements suggests that cE protein expression may be dysregulated in early CMs. Neither cE nor p27 expression is a prognostic indicator in CMs.

Immunohistochemical characterization of p57KIP2 expression in early hydatidiform moles

The differentiation of complete mole (CM), an aberrant androgenetic conceptus, from partial mole (PM) and hydropic abortion (HA) in early gestations is very important for patient management. In this study, 10 diploid voluntary artificial abortions (ABs), 20 diploid HAs, 20 triploid PMs, and 44 diploid CMs (including 4 persistent diseases), all of which were in the first trimester, were evaluated by immunohistochemistry of formalin-fixed tissues using a monoclonal antibody against p57KIP2 protein (p57), a putative paternally imprinted inhibitor gene. DNA ploidy in all cases was analyzed by flow cytometry. In all ABs, nuclear p57 was strongly expressed in cytotrophoblasts, intermediate trophoblasts, villous stromal cells, and decidual stromal cells but was absent in syncytiotrophoblast. In diploid CMs, p57 expression in cytotrophoblasts and villous stromal cells was either absent (37 cases) or very low (7 cases). Villous intermediate trophoblasts stained for p57 in 12 cases of CM. On the other hand, 16 HAs and 19 PMs showed p57 levels comparable to those observed in ABs. Decidual stromal cells provided a reliable internal control in all cases. These findings support the hypothesis that misexpression of p57 is involved in the abnormal development of androgenetic CMs. This immunohistochemical analysis is a useful tool for the differential diagnosis of CMs. HUM PATHOL 33:1188-1192. Copyright 2002, Elsevier Science (USA). All rights reserved.

Expression of cyclin E in gestational trophoblastic disease

Gestational trophoblastic disease represents a spectrum of lesions characterized by an abnormal proliferation of trophoblast, including partial mole, complete mole, invasive mole, choriocarcinoma, and placental site trophoblastic tumor, which have varying propensities for local uterine invasion and metastasis. Recent advances have demonstrated various clinicopathologic factors associated with gestational trohoblastic disease. But there are few reports on concerning factors related to persistence or malignant transformation in gestational trophoblastic disease. Increasing evidences have indicated that cyclin E is a nuclear protein essential for the G1-S phase transition and its overexpression has been reported to be correlated with certain cancers. To our knowledge, there has been no published study on the expression of cyclin E in gestational trophoblastic disease. The current study was conducted not only to examine the expression of cyclin E in a spectrum of gestational trophoblastic disease classified by the pathological diagnosis but also to determine whether there is any relationship between the cyclin E expression and clinical risk factors, such as patient's age, parity, initial serum -hCG, and its persistence. The immunohistochemical expression of cyclin E was determined in formalin-fixed paraffin-embedded sections of 3 hydropic abortions, 15 partial moles, 33 complete moles, 2 invasive moles and 3 choriocarcinomas. Cyclin E index was defined as the percentage of positively labeled nuclei per 1000 cells. Choriocarcinoma had a significantly higher cyclin E expression compared to hydropic chages(p=0.015); although there was a difference in cyclin E expression between complete mole and choriocarcinoma, this had no statistical significance(p=0.051). In contrast to our expectation, cyclin E expression was the lowest in invasive mole but numbers of cases were too small to draw any conclusion. comparison of cyclin E expression according to age, parity, initial serum -hCG, and persistence showed no significant difference. Our results suggest that expression of cyclin E may play an important role in malignant transformation of gestational trophoblastic disease. However, to examine the potential clinical value of cyclin E as a prognostic marker in gestational trophoblastic disease, prospective studies with a large number of cases are required.

Over-diagnosis of hydatidiform mole in early tubal ectopic pregnancy.

Tubal ectopic hydatidiform moles are rare lesions, and only 40 cases have been reported in the world literature. We investigated the apparently high incidence of tubal ectopic hydatidiform moles in women referred for treatment to a Supraregional Trophoblastic Tumour Screening and Treatment Centre between 1986 and 1996. Of 4261 women referred during the study period, 25 (0.6%) had a suspected tubal ectopic hydatidiform mole and paraffin-embedded tissue was available in 20 (80%) of these. Each case was reviewed by two pathologists and DNA flow cytometric analysis was undertaken when the histological diagnosis was initially deemed equivocal or suggestive of hydatidiform mole. On review, 17 cases (85%) showed no evidence of hydatidiform mole (circumferential trophoblastic proliferation, hydrops, scalloped villi, and stromal karyorrhexis). Of these, 11 cases (65%) showed features of early placentation and six (35%) showed hydropic abortion. DNA flow cytometry was performed in 14 (82%) of these cases and revealed a diploid population in each case. Three cases of molar pregnancy (15%) were identified. Each of these cases had the histological features of an early complete hydatidiform mole. Sufficient tissue was available for DNA flow cytometric analysis in two of these cases and confirmed the presence of diploidy in each. Our results show that tubal ectopic hydatidiform mole is a rare entity and demonstrate that it is over-diagnosed. Polar trophoblastic proliferation and hydropic villi are features of early placentation and of hydropic abortion. Sheets of extravillous trophoblast may be particularly prominent in tubal ectopic gestation. In the absence of circumferential trophoblastic proliferation combined with hydropic change a diagnosis of gestational trophoblastic disease should be avoided.

Choriocarcinoma and partial hydatidiform moles

Partial hydatidiform moles (PMs) rarely require chemotherapy and have never previously been proven to transform into choriocarcinoma, the most malignant form of gestational trophoblastic disease (GTD). Consequently, some have questioned whether women with PMs need human chorionic gonadotropin (hCG) follow-up. Here, we investigate whether PMs can transform into choriocarcinomas. Patients with a PM who developed a subsequent choriocarcinoma were identified from our GTD database. The histology of both PM and ensuing choriocarcinoma was reviewed and flow cytometry used to verify the triploid status of the PMs. To determine whether the choriocarcinoma arose from the PM, DNA from the PM and choriocarcinoma in each patient was compared using microsatellite polymorphisms. Of the 3000 patients with PM, 15 required chemotherapy for persisting GTD. This was identified as choriocarcinoma in three cases. In one patient, the local pathologist could not differentiate between a PM or a hydropic abortion and neither central histological review nor hCG follow-up were obtained. This patient nearly died before the diagnosis of choriocarcinoma was made. Fortunately, the local pathologists correctly diagnosed PM in the two other patients who were then registered for hCG follow-up. Some months later, the hCG was rising and repeat uterine evacuation revealed choriocarcinoma. The PM was confirmed to be triploid in all three cases and genetic analysis showed that the subsequent choriocarcinomas contained identical single maternal and two paternal alleles at several independent loci. Our results show that PMs can transform into choriocarcinoma. All patients with suspected PM should be reviewed centrally and, if confirmed, need hCG follow-up.

Molecular genetic testing from paraffin-embedded tissue distinguishes nonmolar hydropic abortion from hydatidiform mole

Diagnosis of hydatidiform mole by histology and ploidy analysis is limited by overlap of criteria for nonmolar hydropic abortion, complete mole, and partial mole. With early presentation, diagnosis is difficult due to limited tissue and lack of clinical features. Accurate diagnosis of these entities is important for both prognosis and patient management. We assessed a polymerase chain reaction (PCR) assay for polymorphic short tandem repeats (STR) for discrimination between nonmolar hydropic abortion, complete mole, and partial mole based on the genetic composition of molar pregnancies. Seventeen cases of products of conception (POC) diagnosed by histology and flow cytometry ploidy analysis were studied retrospectively. PCR was performed using maternal and chorionic villus DNA extracted from microdissected, formalin-fixed, paraffin-embedded tissue sections. Allelic patterns for up to eight well-characterized polymorphic STR loci were determined using the GenePrint Fluorescent STR System (Promega Corporation, Madison, WI). The presence of three villus alleles at a single locus was interpreted as partial mole. Detection of only one allele in the villi, different from all maternal allele(s) at the same locus, was interpreted as a complete mole. This technique identified eight complete moles previously diagnosed as complete mole (3), hydatidiform mole, otherwise unspecified (1), hydropic villi (2), hydropic villi versus partial mole (1), and partial mole (1). The diagnoses of five partial moles by the molecular assay were consistent with the diagnoses by histology and flow cytometry. One nonmolar gestation was identified, which had been diagnosed previously as hydropic villi. In three cases, maternal DNA amplification was insufficient for definitive diagnosis. Molecular genetic testing of POC from paraffin-embedded tissue accurately distinguishes complete mole, partial mole, and nonmolar hydropic abortion. Identification of triploidy by flow cytometry can confirm a histological impression of partial mole. Histological and ploidy analysis of POC results in underdiagnosis of complete moles.

Interphase cytogenetic and AgNOR analyses of hydatidiform moles.

AIM: To determine the potential value of interphase cytogenetic and argyrophilic nucleolar organiser region (AgNOR) analyses in the diagnosis and classification of hydatidiform moles. METHODS: Serial tissue sections from 37...

The diagnosis and prognosis of molar pregnancy: The experience of the National Referral Centre in London

Since 1973, hCG follow up and treatment of patients with hydatidiform moles in the UK has been centralised. Registrations of moles have increased from 475 to 1248 in 2 years but histological review shows that first trimester non-molar hydropic abortions (HAs) and complete moles (CMs) are often called partial moles (PMs) by pathologists. The introduction and widespread acceptance of the term PM in 1977, coincided with improvements in ultrasound which brought forward 6 weeks the average time of evacuation of CMs, when hydrops is not yet complete but partial and when vessels are present in most CMs, leading to erroneous diagnoses of PM. Many true PMs are dismissed as HAs and often, HAs are called PMs. Valid diagnostic criteria for younger CMs and for PMs have been available for over 10 years and when used, PM is overwhelmingly associated with triploidy. Reported diploid PMs are partly explained by misdiagnosed HAs, rare cases of Beckwith-Widemann syndrome, CMs with partially developed hydrops, twin pregnancies and rare androgenetic CMs with fetal red cells in villi. A rare mole with “normal” diploid biparental karyotype probably exists but morphologically resembles CM. CM and PM have widely different prognosis but the present diagnostic confusion means much of the published epidemiological, clinical and genetic information on PM based on suspect diagnostic criteria ia also suspect.

The role of deoxyribonucleic acid image cytometric and interphase cytogenetic analyses in the differential diagnosis, prognosis, and clinical follow-up of hydatidiform moles: A report from the central molar registration in the Netherlands

Objectives: To assess the value of deoxyribonucleic acid ploidy in the differential diagnosis and clinical follow-up of hydatidiform moles, the histopathologic features, deoxyribonucleic acid ploidy, and clinical follow-up were compared in 347 cases: 143 complete moles, 52 partial moles, and 152 abortions, of which 56 cases were hydropic abortions with histologic features of triploidy but lacked trophoblastic hyperplasia. Study Design: In all cases deoxyribonucleic acid image cytometry was performed, and in 85 of these cases interphase cytogenetics was also performed. Results: With use of deoxyribonucleic acid image cytometry and interphase cytogenetics, a bimodal polyploid deoxyribonucleic acid pattern was present in 97% of complete moles, 27% of partial moles, and 4% of abortions. All these cases of partial mole were reclassified to complete mole on the basis of this deoxyribonucleic acid pattern and the histopathologic features in spite of the presence of fetal blood cells, amnion, or yolk sac. Deoxyribonucleic acid triploidy was found in 95% of the remaining partial moles, in 77% of hydropic abortions with histologic features of triploidy, and in 14% of the remaining abortions. Reliable differentiation between deoxyribonucleic acid triploid partial moles and hydropic abortions with histologic features of triploidy was not possible on basis of the histopathologic features (trophoblastic hyperplasia) or 3.5c exceeding rates. Deoxyribonucleic acid diploidy was found in 1% of complete moles, 23% of hydropic abortions with features of triploidy, and 78% of the remaining abortions. Deoxyribonucleic acid tetraploidy was rarely found (1% of complete moles, 2% of partial moles, 1% of abortions). Persistent gestational trophoblastic disease developed in 33% of the bimodal deoxyribonucleic acid polyploid cases (all complete moles), in 1% of the diploid cases (concerning one of the two diploid complete moles), and in 1% of the triploid cases (partial moles). Conclusion: Deoxyribonucleic acid analysis is essential in the diagnosis of hydatidiform moles to decide on clinical follow-up.

P53 PCNA, and Ki-67 in hydropic molar and nonmolar placentas: an immunohistochemical study.

Sixty molar and nonmolar placentas with hydropic features [23 complete moles, 14 partial moles, 8 moles-not further classified, and 15 hydropic, nonmolar placentas] were evaluated immunohistochemically for expression of Ki-67, proliferating cell nuclear antigen (PCNA), and p53, and the results were compared with DNA ploidy and S-phase fractions derived from flow cytometric analysis. The data were evaluated to determine if proliferation marker staining could aid in distinguishing mole from non-mole and partial from complete mole. PCNA and p53 expression did not discriminate between moles and non-moles. However, the percentage of rimming villous cytotrophoblast nuclei reactive for Ki-67 differed significantly between moles and non-moles (p < 0.001). All molar specimens contained at least one medium-sized villus with > 70% Ki-67-positive cells, whereas the maximum percentage of reactive cells in hydropic abortuses was 22%. These results suggest that percentage Ki-67 positivity in rimming cytotrophoblast nuclei may aid in distinguishing a mole from a nonmolar, hydropic abortion.

A clinical, histopathological and flow cytometric study of 149 complete moles, 146 partial moles and 107 non-molar hydropic abortions.

We have compared the clinical and histological features of 149 complete moles with 146 triploid partial moles and 107 diploid non-molar hydropic abortions initially registered as moles for human chorionic gonadotrophin (hCG) follow-up. Forty-one patients with complete moles, five with partial moles and one with hydropic abortion received chemotherapy for hCG elevations interpreted as persistent trophoblastic disease. Complete moles were aborted or were evacuated significantly earlier than partial moles (means of 12.1 and 15.4 weeks; P < 0.001) and hydropic abortions significantly earlier than complete moles (mean 10.7 weeks; P < 0.005). The means of the highest recorded hCG were higher in complete moles (184,056 i.v.) than in partial moles (66,259 i.v.) and hydropic abortion (7942 i.v.). When hCG became normal without chemotherapy, this occurred earlier in patients with hydropic abortion than in those with partial moles (means of 46.7 days and 62.8 days; P < 0.001) and earlier in partial moles than in complete moles (mean 78.3 days; P < 0.005). The incidence of partial moles was comparable throughout fertile years but rose to 1.9 times the average after 40 years. Complete moles were commoner between 14 and 25 years and after 35 years, reaching 4.8 times the average after 40 years. Hydropic abortions were rare before 25 years and increased with age to 12 times the average after 40 years. Stromal karyorrhexis and shape of villi, before they become hydropic, discriminate well between complete and partial mole. Hydrops increased and vascularity decreased with molar age and the presence of non-hydropic villi or vessels did not discriminate between partial mole and the younger complete moles evacuated nowadays.

Incidence of hydatidiform mole in a Tokyo hospital: A 5-year (1989 to 1993) prospective, morphological, and flow cytometric study

This prospective study reports the incidence of hydatidiform mole (HM) in a population of 13,510 pregnancies in a Tokyo hospital over a 5-year period between 1989 and 1993. During this period all “products of conception” from first- and second-trimester abortions were histologically reviewed, and 76 hydropic placentas were retrieved and analyzed by flow cytometry (FCM). Of 23 specimens originally diagnosed as complete hydatidiform mole (CM), 21 were diploid, and two were aneuploid (nontriploid/tetraploid). Of 22 partial hydatidiform moles (PMs), 20 were triploid, and two were diploid. Of 31 hydropic abortions (HAs), 20 were diploid, nine were triploid, one was tetraploid, and one was aneuploid. As to the correlation between morphology and data of FCM, two PMs were reclassified as HA, and eight HAs as PM, giving a ratio of 1 CM to 1.22 PM (23:28 cases). The incidence of HM was 1:265 pregnancies, (CM, 1:587; PM, 1:483). Only one case (3.6%) of PM was suspected clinically. One specimen of persistent disease occurred following a diploid CM. In our retrospective histological and FCM study in which 172 cases diagnosed as HM were retrieved from surgical pathology files between 1981 and 1991, there were 129 CMs and 43 PMs (CMs: PMs = 3: 1). These findings indicate that PM is a common but underdiagnosed condition. Almost all studies in the literature may have severely underreportred the incidence of PM. It is suggested that during routine delivery and pathology examination only the most florid PMs are recognized, whereas most with subtler changes go undiagnosed. Through detailed pathological examination and data of FCM, an underdiagnosis of PM can be surely avoided. The recent elucidation of HM by FCM should lead to a complete reappraisal of the epidemiology of gestational trophoblastic disease.

Ploidy analysis of products of conception by image and flow cytometry with cytogenetic correlation.

Ploidy analysis of hydropic placentas is used in conjunction with morphology and clinical data to classify hydatidiform moles and hydropic abortuses. In most studies, ploidy has been assessed by flow cytometry (FCM). To validate image cytometry (ICM) as a method to determine ploidy in this setting, the authors used both FCM and ICM to study 19 hydropic placentas in which cytogenetic analysis was available. Nuclear suspensions from paraffin-embedded tissue were used for both ICM and FCM. Image cytometry of tissue sections was performed in some cases. Image cytometry and FCM were concordant in all 19 cases, but discordant with cytogenetics in 2 of 19 cases. Two hydropic abortuses (HA) with a diploid karyotype were triploid and tetraploid, respectively, by both ICM and FCM, which suggested that the cultured tissue was not representative. DNA indices were most accurate when an internal diploid control was used as the reference. In ICM, higher resolution was achieved by analyzing cell suspensions rather than tissue sections. This study shows that ICM is a valid method of determining ploidy of hydropic placentas and partial hydatidiform moles in archival tissue.

Is There a Correlation Between Histology and Karyotype in Early Spontaneous Abortion?

The value of histologic evaluation of placental tissue in spontaneous abortions remains undefined. We analyzed 90 placentas from early spontaneous abortions to ascertain if morphologic features were predictive of karyotype. Normal karyotypes were observed in 40 cases, and abnormal karyotypes were found in 50. There were 25 trisomies, 6 triploidies, 2 tetraploidies, one 45, × 0, and 16 other abnormalities, such as mosaic and chimera. All 6 triploid placentas were partial moles. The pres ence of intravillous cistern formation and focal trophoblastic hyperplasia was seen more frequently in cases with abnormal karyotypes. The triploid cases, however, contributed the majority of cases with these villous changes. Hydropic abortion was observed approximately equally in both chromosomally normal and abnormal cases, and its incidence was high in cases of trisomy 16 and tetraploid placenta. Mild edema and regressive changes, such as stromal fibrosis, hypovascular stroma, and attenuated trophoblastic layers, were often found and none showed any specific chromosomal abnormalities. These results indicate that histology can provide only a suggestion as to the likelihood of triploidy and that histologic examination of spontaneous abortions is not useful as a method for predicting chromosomal abnor mality. Int J Surg Pathol 2(4):295-300, 1995

Comparison of villous trophoblast proliferation rate in hydatidiform mole and non-molar abortion by assessment of proliferating cell nuclear antigen expression

This study examines the proliferative activity of trophoblast in hydatidiform mole, non-molar hydropic abortion and non-molar spontaneous abortion. Nine cases of complete mole, 10 cases of partial mole, eight cases of non-molar hydropic abortion and six cases of non-hydropic second trimester abortion were examined by routine histopathology and the rate of cell proliferation was assessed by immunoreactivity for proliferating cell nuclear antigen (PCNA). Hydropic abortion showed a significantly lower PCNA index than complete mole and partial mole. There was no significant difference in PCNA index between partial mole and non-hydropic abortion. The trophoblast of partial hydatidiform mole demonstrates significant cell proliferation but this, although higher than that of hydropic abortion, is no higher than that of non-hydropic abortion of a similar gestational age. The role of partial mole as a precursor of persistent gestational trophoblastis disease remains unclear.

Histopathologic study of partial hydatidiform moles and DNA triploid placentas.

Sixty-two placentas with a triploid DNA content, which were analyzed by flow cytometry using paraffin-embedded tissues, were histologically investigated. These placentas were histologically classified as follows: 51 partial hydatidiform moles (PM), two hydropic abortuses and nine non-hydropic placentas. The DNA indices of the triploid peaks were between 1.41 and 1.60. Histologically, two populations of normal and edematous villi, vesicular villous edema with cistern formation, focal syncytiotrophoblastic hyperplasia with vacuolation, and villous scalloping with trophoblastic inclusion were almost always observed in the PM, but no single pathologic feature was specific for PM. The two entities, PM and triploid placenta, overlapped. Not all triploid gestations are PM and not all PM moles are triploid as shown in previously reported diploid or tetraploid PM. Although no patient with triploid PM developed persistent disease in this series, follow up of triploid PM is required as long as its true biological potential remains unclear. Flow cytometry is a reliable aid in the diagnosis of PM.