Trophoblastic Hyperplasia Research Articles

Enhancing Clinicopathological Diagnosis of Hydatidiform Mole Through the Combined Application of Histomorphologic Analysis, Immunohistochemical Analysis of p57 Expression, and Short Tandem Repeat Typing Method

This study aims to assess the early histomorphologic characteristics and investigate the role of the p57kip2 protein combined with STR genotyping for pathological diagnosis and typing of the hydatidiform mole (HM). A total of 73 induced abortion tissues were collected for pathological evaluation, including 14 cases with partial HM (PHM), 7 cases with complete HM (CHM), and 52 cases with non-molar pregnancies. Histopathological examination of moles was conducted using hematoxylin and eosin staining. DNA extraction from paraffin sections was performed using Fe3O4 nano-magnetic beads. Molecular diagnosis was performed using STR genotyping. Immunohistochemical analysis was used to determine the distribution and expression level of p57kip2 protein in HM. Significant differences were observed in the morphological indices of villous edema, cistern formation, trophoblastic inclusions, and trophoblastic hyperplasia between the PHM and CHM groups (P < 0.05). The central cistern formation and the trophoblast inclusion showed a significant difference between the HM and non-molar pregnancy (P < 0.05). Moreover, our findings revealed that p57kip2 expression contributed to distinguishing CHM from PHM. However, it could not distinguish PHM from non-mole pregnancy. Furthermore, the results of STR genotyping were consistent with pathological typing. In conclusion, the integration of pathomorphology, immunohistochemical staining, and molecular diagnostics holds great value for the diagnosis and classification of HM.

Gestational Trophoblastic Disease: Complete versus Partial Hydatidiform Moles.

Hydatidiform moles, including both complete and partial moles, constitute a subset of gestational trophoblastic diseases characterized by abnormal fertilization resulting in villous hydrops and trophoblastic hyperplasia with or without embryonic development. This involves chromosomal abnormalities, where one or two sperms fertilize an empty oocyte (complete hydatidiform mole (CHM); mostly 46,XX) or two sperms fertilize one oocyte (partial hydatidiform mole (PHM); mostly 69,XXY). Notably, recurrent occurrences are associated with abnormal genomic imprinting of maternal effect genes such as NLRP7 (chromosome 19q13.4) and KHDC3L (chromosome 6q1). Ongoing efforts to enhance identification methods have led to the identification of growth-specific markers, including p57 (cyclin-dependent kinase inhibitor 1C; CDKN1C), which shows intact nuclear expression in the villous cytotrophoblast and villous stromal cells in PHMs and loss of expression in CHMs. Treatment of hydatidiform moles includes dilation and curettage for uterine evacuation of the molar pregnancy followed by surveillance of human chorionic gonadotropin (HCG) levels to confirm disease resolution and rule out the development of any gestational trophoblastic neoplasia. In this review, we provide a synopsis of the existing literature on hydatidiform moles, their diagnosis, histopathologic features, and management.

Diandric triploid partial mole versus digynic nonmolar triploidy: is morphological assessment sufficient for the diagnostic distinction?

Diagnostic separation of diandric triploid gestation, i.e. partial mole from digynic triploid gestation, is clinically relevant, as the former may progress to postmolar gestational trophoblastic neoplasia. The aim of the study was to investigate if the combination of abnormal histology combined with ploidy analysis-based triploidy is sufficient to accurately diagnose partial mole. A genotype-phenotype correlation study was undertaken to reappraise histological parameters among 20 diandric triploid gestations and 22 digynic triploid gestations of comparable patient age, gestational weeks, and clinical presentations. Two villous populations, irregular villous contours, pseudoinclusions, and syncytiotrophoblast knuckles, were common in both groups. Villous size ≥2.5 mm, cistern formation, trophoblastic hyperplasia, and syncytiotrophoblast lacunae were significantly more common in the partial hydatidiform mole. Cistern formation had the highest positive predictive value (PPV) (93%) and highest specificity (96%) for diandric triploid gestation, although the sensitivity was 70%. Cistern formation combined with villous size ≥2.5 mm or trophoblast hyperplasia or syncytiotrophoblast lacunae had 100% specificity and PPV, but a marginal sensitivity of 60%-65%. A moderate interobserver agreement (Kappa = 0.57, Gwet's AC1 = 0.59) was achieved among four observers who assigned diagnosis of diandric triploid gestation or digynic triploidy solely based on histology. None of histological parameters are unique to either diandric triploid gestation or digynic triploid gestation. Cistern formation is the most powerful discriminator, with 93% PPV and 70% sensitivity for diandric triploid gestation. While cistern formation combined with either trophoblastic hyperplasia or villous size ≥2.5 mm or syncytiotrophoblast lacunae has 100% PPV and specificity for diandric triploid gestation, the sensitivity is only 60% to 65%. Therefore, in the presence of triploidy, histological assessment is unable to precisely classify 35% to 40% of diandric triploid gestations or partial moles.

Mola hidatiforme parcial: a propósito de un caso

Gestational trophoblastic disease (GTD) is made up of a set of uncommon pathologies associated with pregnancy, ranging from benign to malignant; It has been described as several unusual benign and malignant processes, derived from an abnormal proliferation of the trophoblast of the human placenta, this groups a set of benign lesions such as hydatidiform mole and gestational trophoblastic neoplasia. Hydatidiform mole is a rare obstetric pathology, consisting of an abnormal pregnancy characterized by hydropic degeneration of the chorionic villi and trophoblastic hyperplasia, with a clinical presentation that warrants proper use of available diagnostic tests, especially ultrasound and Doppler , early in pregnancy, to establish its timely diagnosis, which will favorably improve the prognosis; In addition to performing histology, molecular genetic studies would be key to help in the diagnostic pathway. Its treatment of choice is uterine evacuation and strict monitoring with human chorionic gonadotropin (hCG), specifically of β-hCG levels, essential for early diagnosis of gestational trophoblastic neoplasia. High-risk trophoblastic disease (TGD) is treated with multidrug chemotherapy, with or without adjuvant surgery to remove resistant foci of disease, or radiation therapy for brain metastases.

Epidemiological and morphological pattern of complete hydatidiform mole in Aminu Kano Teaching Hospital, Kano Northwestern Nigeria

Background: Complete hydatidiform mole (CHM) is the most common form of non-neoplastic gestational trophoblastic diseases (GTD) that is associated with progression to choriocarcinoma without prompt intervention. The objectives of this study is to morphologically analyze all cases of complete hydatidiform mole in Aminu Kano Teaching Hospital using set down criteria, look at the epidemiological pattern and compare with similar studies in order to stimulate proper identification from other forms of moles, hence reduce morbidity and mortality associated with the known complication of progressing to deadly Choriocarcinoma. Material and Methods: This was a retrospective study of all molar specimens submitted to Histopathology Pathology Department of Aminu Kano Teaching Hospital, Kano between 1st January 2015 and 31st December 2016. Formalin-fixed paraffin-embedded tissue blocks and corresponding Haematoxylin and Eosin (H&E) stained slides were retrieved. Cases with final diagnosis of complete mole were selected for further detailed microscopic evaluations. The collected data were presented using simple frequency tables and figures including photomicrographs of representative lesions. Results: There were sixty-seven cases of complete hydatidiform mole during the study period out of the 61,780 deliveries, giving an approximate incidence of 1:1000 deliveries in Kano metropolis and its environs. The peak incidence was observed in women between 20- 24 years of age with majority presenting between 11-14weeks of pregnancy. The ratio of complete to partial mole was approximately 3:1. Constant morphologic features associated with CHM includes; villous enlargement, trophoblastic hyperplasia, round shape chorionic villi and fibromyxoid stroma. Least prominent feature of CHM is myxoid stromal type. Conclusion: Complete hydatidiform occurs commonly in the gestational ages of between eleven to fourteen weeks; need histopathologic evaluations and prompt intervention to avoid consequences of both immediate complication such as invasive mole and long-term complication of choriocarcinoma. Keywords: Hydatidiform Mole, Complete Mole, Choriocarcinoma

Twin/Multiple Gestations With a Hydatidiform Mole: Clinicopathologic Analysis of 21 Cases With Emphasis on Molecular Genotyping and Parental Contribution.

Complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) are abnormal gestations characterized by vesicular chorionic villi accompanied by variable trophoblastic hyperplasia, with or without embryonic development. CHMs are purely androgenetic (only paternal [P] chromosome complements), mostly homozygous/monospermic (~85%) but occasionally heterozygous/dispermic, whereas PHMs are overwhelmingly diandric triploid (2 paternal [P] and 1 maternal [M] chromosome complements) and heterozygous/dispermic (>95%). The presence of a fetus in a molar pregnancy usually indicates a PHM rather than a CHM; however, CHMs and PHMs rarely can be associated with a viable fetus or a nonmolar abortus in twin pregnancies and rare multiple gestation molar pregnancies have been reported. A "one-oocyte-model," with diploidization of dispermic triploid zygotes, has been proposed for twin CHM with coexisting fetus, and a "two-oocyte-model" has been proposed for twin PHM with coexisting fetus. Among 2447 products of conception specimens, we identified 21 cases of twin/multiple gestations with a molar component, including 20 CHMs (17 twins, 2 triplets, 1 quintuplet) and 1 PHM (twin). P57 immunohistochemistry was performed on all; DNA genotyping of molar and nonmolar components was performed on 9 twin CHMs, 1 triplet CHM, 1 quintuplet CHM, and 1 twin PHM. All CHM components were p57-negative and those genotyped were purely androgenetic. Twin CHMs had genotypes of P1M1+P2P2 in 5, P1M1+P1P1 in 1, and P1M1+P2P3 in 1, consistent with involvement of 1 oocyte and from 1 to 3 sperm-most commonly a homozygous CHM but involving 2 sperm in the whole conception-and compatible with a "one-oocyte-model." The triplet CHM was P1M1+P1P1+P2M2 and the quintuplet CHM was P1M1+P2M2+P2M2+P3M3+P4P4, consistent with involvement of 2 sperm and at least 2 oocytes for the triplet and 4 sperm and at least 3 oocytes for the quintuplet. The twin PHM had a P1M1+P2P3M2 genotype, consistent with involvement of 2 oocytes and 3 sperm. p57 immunohistochemistry is highly reliable for diagnosis of CHMs in twin/multiple gestations. Refined diagnosis of molar twin/multiple gestations is best accomplished by correlating morphology, p57 immunohistochemistry, and molecular genotyping, with the latter clarifying zygosity/parental chromosome complement contributions to these conceptions.

Audit of Partial and Complete Hydatidiform Moles in Tertiary Care Hospital JPMC, Karachi

Objective: This study aims to investigate the clinical presentation, frequency and histopathology of hydatidiform mole, as well as to determine the clinical significance of such histopathological examination. Material and method: This was a retrospective study undertaken at the Department of Pathology Bmsi Jpmc Karachi from January 1st, 2016 to November 31st, 2021.All molar pregnancy cases were thoroughly examined, taking into account their age, gestational age, signs and symptoms, clinical diagnosis where available and histopathology. Results: Total 73 cases of hydatidiform moles were obtained during study period. There were 64.3% partial hydatidiform moles and 35.6 % complete moles. The majority of the patients were between the ages of 21 and 35 years. Bleeding per vaginum was the most prevalent presenting symptom. The period of gestation in majority of patients (54.7%) was 2–5 months. Conclusion: We came to the conclusion that partial mole was more common than complete mole .Histopathlogical findings of PHM differ from CHM.The diagnosis of molar pregnancy is helped by histopathological study of products of conception (POC), that can be missed on clinical and ultrasound assessment. As a result, products of conception should be subjected to histological investigation on a regular basis to avoid missing the diagnosis of molar pregnancy. Keywords: Molar pregnancy,Trophoblastic hyperplasia, Hydatidiform mole,

Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia.

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

Transient Thyrotoxicosis in Molar Pregnancy

Introduction: Thyroid function abnormalities commonly occur in pregnancy. Due to the structural homology between beta-human chorionic gonadotropin (beta-hCG) and thyrotropin (TSH), some of these changes may be physiologic, while others can be from pathologic causes. Molar pregnancies represent a unique etiology, as beta-hCG levels are often markedly elevated due to trophoblastic hyperplasia and can cause hyperthyroidism. Case Description: A 20-year-old pregnant female presented at 18 weeks estimated gestational age for persistent nausea and vomiting, which had worsened over the past one to two weeks. She also noted palpitations and heat intolerance. On initial presentation, her heart rate was 145 beats per minute, blood pressure was 135/86 mmHg, oxygen saturation was 98% on room air, and temperature was 98.3 F. Exam was notable for sinus tachycardia; no thyromegaly, palpable thyroid nodules, lower extremity edema, or tremors were appreciated. Transvaginal ultrasound was performed, and an approximately 17-week fetus with no cardiac activity was identified; an enlarged and hydropic placenta and bilateral theca lutein cysts were also seen on imaging, concerning for a partial molar pregnancy. Laboratory data revealed plasma beta-hCG >1,000,000 mIU/mL. Due to her symptoms and tachycardia that were refractory to intravenous hydration, thyroid function tests (TFTs) were assessed: TSH of 0.01 uIU/mL and free T4 (FT4) 6.85 ng/dL. She was started on methimazole and beta blockade in the pre-operative period. She received mifepristone and underwent dilatation and evacuation. Histopathology was consistent with a partial mole, given the presence of fetal somatic differentiation. Beta-hCG and FT4 levels rapidly trended down in the post-operative setting, and methimazole was discontinued. Levels were monitored closely after discharge. Atenolol was stopped when her TFTs normalized. Approximately six weeks after surgery, her TSH was 0.523 uIU/mL and FT4 was 0.70 ng/dL. Three months after surgery, the beta-hCG level had decreased to 4 mIU/mL. Discussion: In North America, the incidence of hydatidiform moles is approximately 100 per 100,000 pregnancies. Hydatidiform moles compromise two distinct entities: complete moles and partial moles, which are distinguishable based on karyotype and histopathological features. In molar pregnancies, the trophoblastic tissues, which produce hCG, are hyperplastic; thus, markedly elevated hCG levels can be seen. Due to its structural similarity to TSH, beta-hCG can activate TSH receptors and drive production of thyroid hormone, which can subsequently result in a thyrotoxic state. Surgical management of the mole is key, as the hyperthyroidism usually resolves with uterine evacuation, though hCG levels must be monitored closely afterwards to ensure gestational trophoblastic neoplasia does not develop.

Case Series of Placental Mesenchymal Dysplasia with Live Birth

Objective: Placental mesenchymal dysplasia (PDM) is a rare disease, the cause is unknown, some are called mesenchymal stem hyperplasia, and some are called pseudo-vesicular block or vascular malformation. The aim is to report the clinical and pathologic characteristics of three cases of placental mesenchymal dysplasia (PMD). Method: Pathologic and clinical data were retrieved from the electronic medical records. The data were reviewed and summarized by the same pathologist. Results: Maternal age was respective 36 years, 31 years and 33 years. Cesarean section was performed at 39 weeks, 37 weeks and 38 weeks, respectively. The newborns were born with birth weight of 1790, 2370 and 3150 grams, respectively, with placenta weight of 590, 579 and 510 grams respectively. Placenta for pathological examination was performed macroscopically thick-walled vessels. Microscopic observation showed that the part of the stem villus was saclikely dilated, the blood vessels were thickened in the villi, the blood vessel wall was thickened, the villus interstitial was loose, and the mucus was changed. Part of the villus edema and degeneration, no trophoblastic hyperplasia, the final villus structure is normal. Conclusion: The size of the lesions in the Placental mesenchymal dysplasia and the location of the lesion is closely related to the birth weight of the newborn. Detailed histology is necessary for diagnosis and differential diagnosis.

Diagnosis and Management of Placental Mesenchymal Disease. A Review of the Literature.

To review what is currently known about placental mesenchymal dysplasia (PMD) including imaging techniques for diagnosis and differentiation from a molar pregnancy, genetics, maternal/fetal effects, and management. A literature search by research librarians at 2 universities was undertaken using the search engines PubMed and Web of Science. The search terms used were "etiology" OR "cause" OR "risk" OR "risks" OR "epidemiology" OR "diagnosis" OR "therapy" OR "prognosis" OR "management" AND "placental mesenchymal dysplasia" OR "placenta" AND "mesenchymal dysplasia." No limit was put on the number of years searched. The etiology of PMD remains uncertain, although there are a number of theories on causation. An elevated maternal serum α-fetoprotein level, slightly elevated human chorionic gonadotropin level, normal karyotype, multicystic lesions on ultrasound, and varying degrees of flow within cysts using color Doppler (stained-glass appearance) are helpful in making the diagnosis. On pathologic examination of the placenta, PMD is differentiated from molar pregnancy by the absence of trophoblastic hyperplasia. Fetal complications of PMD include hematologic disorders, Beckwith-Wiedemann syndrome, liver tumors, fetal growth restriction, preterm delivery, and intrauterine fetal demise. Maternal complications include gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver function tests, low platelets) syndrome, and eclampsia. Accurate diagnosis of PMD is imperative for appropriate management and surveillance to minimize adverse maternal and fetal outcomes. The importance of a correct diagnosis of PMD is important because it can be misdiagnosed as a partial molar pregnancy or a complete mole with coexisting normal fetus, and this can result in inappropriate management.

Genome-wide single nucleotide polymorphism array analysis unveils the origin of heterozygous androgenetic complete moles

Hydatidiform moles are abnormal pregnancies, which show trophoblastic hyperplasia. Most often, the nuclear genome in complete hydatidiform moles (CHMs) is composed of only paternal chromosomes. Diploid androgenetic conceptuses can be divided into homozygous and heterozygous CHMs. Heterozygous CHMs originate from two sperms or a diploid sperm, the distinction of which has not been established. Here, we assessed the origin of heterozygous CHMs using single nucleotide polymorphism (SNP) array. Thirteen heterozygous CHMs were analysed using B allele frequency (BAF) plotting to determine the centromeric zygosity status of all chromosomes. One case was from the duplication of a single sperm with an XY chromosome. In the other twelve cases, centromeric zygosity was random, i.e. mixed status. Thus, the twelve heterozygous CHMs were considered to be of dispermic origin but not diploid sperm origin. BAF plotting of SNP array can be a powerful tool to estimate the type of hydatidiform moles.

Histological Study of Molar Pregnancy by using some of the Special Stains

Background: Molar pregnancy (hydatidiform mole HM) is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and will fail to come to term. A molar pregnancy is a gestational trophoblastic disease which grows into a mass in the uterus that has swollen chorionic villi. These villi grow in clusters that resemble grapes. A molar pregnancy can develop when a fertilized egg does not contain an original maternal nucleus. The diagnosis of HM is based on its morphology. In classic cases, the abnormally large villi have a vesicular or a grape like appearance. Histologically, HM presents variable degrees of circumferential trophoblastic hyperplasia and epithelial atypia. Distinguish between complete mole (CM) and partial mole (PM) is difficult especially with early diagnosis and evacuation of molar pregnancies, however, the criteria are subjective and show considerable inter-observer variability. Unfortunately in our country the histological diagnosis is depend only on routine stain (H&E) which is not giving a clear results in some cases because of that, the study design to find the similarities and differences between the two types of molar pregnancy by using some of special stains which surely distinguish between complete and partial moles samples using immunohistochemical marker P57KIP2. Objective: To detecting if the special stain can be helpful to distinguish between the two types of molar pregnancy also to find the accuracy of the routine diagnosis of hydatidiform mole comparing with P57 immunohistochemistry stain. Patients and Methods: The study conducted at the maternal teaching hospital in Erbil city. Thirty cases of Molar Pregnancy diagnosed, 15 of them were complete and the others were partial mole. All the samples studied histologically using H&E and some of special stains including: PAS stain, Congo red, and Trichrom, to describe the morphological differences between the two types of mole. Also immunohistological P57 stain was used in this study to confirm the type of mole. Results: The study result shows the morphological variation between complete and partial hydatidiform through using the routine H&E stain and special stains. The complete hydatidiform mole sections showed vesicular swelling of chorionic villi and circumferential trophoblastic hyperplasia, the trophoblastic proliferation grade varying in complete samples, most samples showed grade II (46.6%) of trophoblastic proliferation, while few of samples showed grade III (13.3%). The cases of partial hydatidiform mole showed scattered hydropic villi with irregular scalloped villous outlines and mild trophoblastic hyperplasia, trophoblastic distribution elucidate that the majority (60%) of samples show zonal distribution and high percentage (73.3%) of focal trophoblastic proliferation. The vessels in the villous stroma of most of partial molar samples (80%) was obviously seen also the cistern appear clearly in 73.33% of the samples and all partial molar pregnancy samples showed presence of fetal part in contrast to complete mole. The PAS stain show no different between the two types of molar pregnancy samples while the Congo red stained the partial molar samples intensely comparing with complete samples opposite to the trichrome stain which showed highly color intensity in complete than in partial samples. In this study the most important noticed results was high percentage (26.66) of positive result of P57 in complete diagnosed sample by routine way. Conclusion: The special stains can be helpful in diagnosis of hydatidiform mole and The study of p57 immunohistochemistry stain indicate present of misread in routine diagnoses of complete hydatidiform due to mimic morphological characters.

Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection

Zika virus (ZIKV) infection during human pregnancy may cause diverse and serious congenital defects in the developing fetus. Previous efforts to generate animal models of human ZIKV infection and clinical symptoms often involved manipulating mice to impair their Type I interferon (IFN) signaling, thereby allowing enhanced infection and vertical transmission of virus to the embryo. Here, we show that even pregnant mice competent to generate Type I IFN responses that can limit ZIKV infection nonetheless develop profound placental pathology and high frequency of fetal demise. We consistently found that maternal ZIKV exposure led to placental pathology and that ZIKV RNA levels measured in maternal, placental or embryonic tissues were not predictive of the pathological effects seen in the embryos. Placental pathology included trophoblast hyperplasia in the labyrinth, trophoblast giant cell necrosis in the junctional zone, and loss of embryonic vessels. Our findings suggest that, in this context of limited infection, placental pathology rather than embryonic/fetal viral infection may be a stronger contributor to adverse pregnancy outcomes in mice. Our finding demonstrates that in immunocompetent mice, direct viral infection of the embryo is not essential for fetal demise. Our immunologically unmanipulated pregnancy mouse model provides a consistent and easily measurable congenital abnormality readout to assess fetal outcome, and may serve as an additional model to test prophylactic and therapeutic interventions to protect the fetus during pregnancy, and for studying the mechanisms of ZIKV congenital immunopathogenesis.

Morts maternelles par maladies trophoblastiques gestationnelles. Résultats de l’enquête confidentielle française sur la mortalité maternelle, 2010–2012

Gestational trophoblastic diseases (GTD) correspond to several entities which all have a common pattern: hypersecretion of human chorionic gondotrophin by trophoblastic hyperplasia. Between 2010 and 2012, there were 4 maternal deaths due to GTD (choriocarcinoma). The ratio of maternal death caused by GTD was 0,16/100,000 living births which was similar to the rate from the 2007–2009 period. These deaths represented 1.6% from the whole maternal mortality and 3.3% of the direct maternal mortality. These four deaths occurred after delivery and the diagnosis of GTD was made between 60 and 180 days in the postpartum period. Two cases seemed to be potentially avoidable. The main causes of suboptimal management were linked to delay either in diagnosis of GTD or in initiating the appropriate treatment. The analysis of these maternal deaths gave the opportunity to stress some major lessons to optimize medical management of GTD. Therefore, a patient presenting with persistent bleedings more than six weeks after delivery needs some specific exams such as plasma human chorionic gondotrophin measurement and histopathologic examination to affirm GTD and start early specific treatments generally leading to complete recovery.

A Rare Case Report of Molar Pregnancy with Coexisting Fetus

Abstract Aim: Here we report a molar pregnancy with a coexisting fetus progressing to a viable, healthy infant which is an extreme rarity, with the incidence of 0.005–0.01% of all the pregnancies. Background: Partial mole is defined as excessive trophoblastic proliferation with normal and hydropic villi and presence of a fetus or a fetal circulation with nucleated cells. Partial molar pregnancy with a singleton live fetes is a rare condition. it is commonly seen with twin gestation and it is rare with singleton pregnancy Case report: A 30 years old primigravida, referred from a private hospital at 38 weeks of gestation delivered a phenotypically normal and healthy infant 2200 gm in weight by caesarean section. The placenta weighed 500 gms and on sectioning revealed widespread, grape-like vesicles. Light microscopy revealed normal villi coexisting with villi showing hydropic change and cistern formation and diffuse circumferential trophoblastic hyperplasia consistent with molar change. A diagnosis of partial molar pregnancy with normal fetus was made. Conclusion: Very few twin pregnancies with a hydatidiform mole and a foetus continue to term as they often have spontaneous or induced terminations for maternal complications Management of molar changes associated with normal appearing fetus still remains challenging as not many studies have been done due to rarity of this disorder. Clinical significance: Though the general trend is to terminate pregnancy in foetus with coexistent mole in anticipation of complications, under close surveillance, optimal outcomes can be achieved. Monitoring of serum β-hCG, serial ultrasound for fetal growth, size of molar component, and theca lutein cysts can help to predict good patient outcomes.

P57 and Ki-67 expression in hydropic abortion and molar pregnancy

Background The histopathological diagnosis and differentiation between partial mole (PM) and complete mole (CM) bears difficulties. Hence, additional methods rather than morphology can be useful to reach the proper diagnosis. Immunohistochemical (IHC) analysis using antibodies such as p57 and Ki-67 can be used to solve this problem. This study was done to investigate the role of p57 and Ki-67 IHC in distinguishing between CM, PM, and hydropic abortion (HA). Patients and methods Twenty cases of molar pregnancies – 10 (CM) and 10 (PM) – and 10 HA diagnosed on histopathological criteria were studied histopathologically along with IHC using antibodies against p57 and Ki-67. The cases were collected in a retrospective manner from Pathology Lab, Faculty of Medicine, Mansoura University from January 2015 to December 2015. Results We found that CM demonstrated enlarged villi with circumferential trophoblastic hyperplasia. Villous stromal cells and cytotrophoblast were negative for p57. PM demonstrated hydropic, irregularly shaped villi with scalloped contours, trophoblastic inclusions, and mild circumferential trophoblastic hyperplasia. Villous stromal cells and cytotrophoblast were diffusely positive for p57. In all 10 CM cases, the Ki-67 proliferation index was relatively high (>26% of cells) with complete absence of p57 immunostaining in the cytotrophoblasts and villous stromal cells in comparison with PM cases with statistical significance (P Conclusion Our study further confirms the valuable role of p57 in the diagnosis of CM augmented by the traditional histopathological criteria. Ki-67 has a limited value in differentiating between some cases of PM and CM. The best possible use of Ki-67 is to differentiate between molar and nonmolar pregnancy along with other histological parameters, especially trophoblastic proliferation and villous enlargement.

Morts maternelles par maladies trophoblastiques gestationnelles. Résultats de l’enquête confidentielle française sur la mortalité maternelle, 2010–2012

Gestational trophoblastic diseases (GTD) correspond to several entities which all have a common pattern: hypersecretion of human chorionic gondotrophin by trophoblastic hyperplasia. Between 2010 and 2012, there were 4 maternal deaths due to GTD (choriocarcinoma). The ratio of maternal death caused by GTD was 0,16/100,000 living births which was similar to the rate from the 2007–2009 period. These deaths represented 1.6% from the whole maternal mortality and 3.3% of the direct maternal mortality. These four deaths occurred after delivery and the diagnosis of GTD was made between 60 and 180 days in the postpartum period. Two cases seemed to be potentially avoidable. The main causes of suboptimal management were linked to delay either in diagnosis of GTD or in initiating the appropriate treatment. The analysis of these maternal deaths gave the opportunity to stress some major lessons to optimize medical management of GTD. Therefore, a patient presenting with persistent bleedings more than six weeks after delivery needs some specific exams such as plasma human chorionic gondotrophin measurement and histopathologic examination to affirm GTD and start early specific treatments generally leading to complete recovery.

Gestational Trophoblastic Disease

A middle-aged woman presented with vaginal bleeding leading to the identification of a uterine mass and serum hCG level of more than 700,000 mIU/mL. Imaging revealed no evidence of a gestational sac or fetal pole. She underwent hysterectomy. The photograph is of a bisected uterus containing a network of vesicular villi connected by fibrous strands historically referred to as resembling a “cluster of grapes.” Which of the following type of gestational trophoblastic disease does this patient most likely have?a.Nonmolar gestation with hydropic degenerationb.Partial hydatidiform molec.Complete hydatidiform mole (CHM)d.Choriocarcinoma Answer: c. Complete hydatidiform mole Complete hydatidiform mole is a form of gestational trophoblastic disease that results from fertilization of an abnormal empty ovum by 2 sperms or 1 sperm that replicates.1Di Cintio E. Parazzini F. Rosa C. Chatenoud L. Benzi G. The epidemiology of gestational trophoblastic disease.Gen Diagn Pathol. 1997; 143: 103-108PubMed Google Scholar, 2Lindor N.M. Ney J.A. Gaffey T.A. Jenkins R.B. Thibodeau S.N. Dewald G.W. A genetic review of complete and partial hydatidiform moles and nonmolar triploidy.Mayo Clin Proc. 1992; 67: 791-799Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar It is estimated to occur at a rate of 1 per 1000 pregnancies in the United States.1Di Cintio E. Parazzini F. Rosa C. Chatenoud L. Benzi G. The epidemiology of gestational trophoblastic disease.Gen Diagn Pathol. 1997; 143: 103-108PubMed Google Scholar Most CHMs are diploid, with 46,XX being the most common karyotype.1Di Cintio E. Parazzini F. Rosa C. Chatenoud L. Benzi G. The epidemiology of gestational trophoblastic disease.Gen Diagn Pathol. 1997; 143: 103-108PubMed Google Scholar, 2Lindor N.M. Ney J.A. Gaffey T.A. Jenkins R.B. Thibodeau S.N. Dewald G.W. A genetic review of complete and partial hydatidiform moles and nonmolar triploidy.Mayo Clin Proc. 1992; 67: 791-799Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar No fetus develops, but the placental tissue develops as a mass of vesicular villi, each about 1 cm, that fills the uterine cavity. Microscopy shows enlarged villi with central cisterns, stromal karyorrhexis, and a circumferential pattern of mixed trophoblastic hyperplasia (arrow). Complete evacuation is often sufficient treatment, and serum hCG is serially followed until it returns to 0. Because of increased risk (2%-3%) of choriocarcinoma in CHM, hysterectomy is often performed in patients older than 40 years.

EP15.11: Partial hydatiform mole: a case report

Partial hydatidiform mole is a histopathologic entity characterised by focal trophoblastic hyperplasia with villous hydrops together with identifiable fetal tissue. 90% of partial moles are due to diandric triploidy. In Type I placenta is modified; in type II placenta is normal. We report a case of PHM type I with increased fetal NT and other fetal anomalies (Dandy-Walker complex and tetralogy of Fallot). A 32 year old woman (gravida 2, para 0 with a miscarriage) was referred to Fetal Medicine AOUI Verona Centre for an increased fetal NT (4.6 mm) and vacuole formations in the placenta diagnosed at I trimester US scan. An expert US scan which reported nuchal edema (5.2 mm), vacuole formations in the placenta and heart anomalies was performed at 15+2 weeks. Amniocentesis showed a 69 XXY fetal karyotype. US scan at 18 weeks showed a IUGR, Dandy-Walker Complex, Tetralogy of Fallot, molar changes of placenta and ovaries enlarged with multiple bilateral theca lutein cysts. The patient had no clinical symptoms of molar pregnancy. BHCG was 1.255.660 UI/L. Pregnancy was terminated at 19+4 weeks by induction of labour with intravaginal Gemeprost. A fetus with molar placenta was delivered; suction and curettage were performed. Histopathologic analysis and immunohistochemistry confirmed the diagnosis of partial hydatiform mole. Cytogenetic analysis showed a triploid kariotype. Fetal autopsy wasn't done under request of the patient. Chest-X- ray was negative. BHCG levels were checked every 2 weeks until the values were within the normal range. A closed follow up is still being performed. Definitive diagnosis of partial mole by ultrasound is often difficult especially in the early scan. It might be confused with missed abortions or blighted ovum. Triploidy is usually incompatible with life. In this case the fetus survived up to the second trimester with IUGR and a major anomaly of the heart. Molar pregnancies generally have severe outcomes. Serial follow up of HCG levels after termination of pregnancy is necessary. Cytogenetic pattern has to be correlated with histopathological diagnosis.