Single-nucleotide polymorphism array and fluorescence in situ hybridization analysis to decode the cytogenetic profile of atypical partial hydatidiform moles diagnosed by short tandem repeat polymorphism analysis.

Accurate diagnosis of partial hydatidiform moles (PHMs) is crucial for improving outcomes of gestational trophoblastic neoplasia. The use of short tandem repeat (STR) polymorphism analysis to distinguish between PHM and hydropic abortuses is instrumental; however, its diagnostic power has not been comprehensively assessed. Herein, we evaluated the diagnostic efficacy of STR in differentiating between PHM and hydropic abortus, thus providing an opportunity for early measurement of human chorionic gonadotropin for PHMs. We reviewed charts of STR polymorphism analysis performed on fresh villous specimens and patient blood samples using a commercial kit for 16 loci. The genetic classification of 79 PHMs was confirmed. STR was reliable in differentiating PHMs when at least 15 loci were available. Typically, PHMs are characterized by their triploidy, including two paternal and one maternal haploid contribution. In our sample, seven PHMs lacked the three-allelic loci, requiring fluorescence in situ hybridization (FISH) analysis to investigate imbalanced biparental conceptus and single-nucleotide polymorphism array analysis to reveal cytogenetic details. Of these PHMs, two, three, and one were identified as androgenetic/biparental mosaics (diploids), monospermic diandric monogynic triploids, and a typical dispermic diandric monogynic triploid, respectively. The remaining case was monospermic origin, but its ploidy details could not be available. Therefore, STR differentiated PHM from a biparental diploid abortus in most cases. However, PHM diagnosis may be compromised when STR is used as the sole method for cases displaying distinct cytogenetic patterns lacking the three-allelic loci, including androgenetic/biparental mosaicism. Therefore, FISH should be considered to confirm the diagnosis.

Spermatogonium-Derived Complete Hydatidiform Mole.

A complete hydatidiform mole (CHM) is a conceptus with only sperm-derived chromosomes. Here, we report on a CHM with genomic DNA identical to that of the paternal somatic cells. The CHM developed in a woman who had undergone intrauterine implantation of a blastocyst obtained through in vitro injection of a presumed round spermatid into one of her oocytes. The CHM was genetically identical to peripheral white cells of her husband and contained no maternally derived nuclear DNA. We hypothesize that a spermatogonium, rather than a round spermatid, was inadvertently selected for the procedure. The CHM developed into a gestational trophoblastic neoplasia, which resolved after chemotherapy. (Funded by the Japan Society for the Promotion of Science.).

Multiple pregnancy with complete hydatidiform mole and coexisting normal fetus in a retrospective cohort of 141 patients.

BACKGROUND: Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. OBJECTIVE: This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. STUDY DESIGN: This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January 2022. RESULTS: Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day 8. CONCLUSION: Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study.

Evaluation of Combined p57KIP2 Immunohistochemistry and Fluorescent in situ Hybridization Analysis for Hydatidiform Moles Compared with Genotyping Diagnosis.

Immunostaining with p57KIP2 is a widely used diagnostic technique to differentiate complete hydatidiform moles (CHMs) from partial hydatidiform moles (PHM) and non-molar hydropic abortion. However, distinguishing between PHMs and non-molar hydropic abortions using histopathology alone is often challenging. This study aimed to evaluate the technical validity and additional benefits of using fluorescence in situ hybridization (FISH) in combination with p57KIP2 immunostaining to diagnose molar and non-molar conceptuses. The study involved 80 specimens, which underwent genetic diagnosis using short tandem repeat analysis, including 44 androgenetic CHMs, 20 diandric monogynic PHMs, 14 biparental non-molar hydropic abortions, 1 monoandric digynic triploid abortion, and 1 vaginal specimen of gestational trophoblastic neoplasia. Two pathologists independently diagnosed the cases based on morphology and p57KIP2 immunostaining while the clinical information was masked. FISH analysis was performed using 3 probes (CEP17, CEPX, and CEPY), which revealed that all androgenetic CHM and biparental diploid non-molar hydropic abortion specimens were diploid. Among the 20 diandric monogynic PHM cases examined by analyzing short tandem repeat polymorphisms, 18 were triploid, and the remaining 2 were diploid. These two specimens were possibly androgenetic/biparental mosaics based on FISH analysis, where the three-signal ratios counting 50 cells were clearly within the diploid ranges. Eight of the 20 genetic PHMs and 2 of the 14 genetically confirmed non-molar hydropic abortions that were falsely diagnosed based on morphology and immunohistochemistry by at least 1 pathologist were correctly diagnosed as PHM and non-molar hydropic abortion, respectively, by FISH analysis. However, 1 monoandric digynic villus was classified as triploid by FISH analysis, leading to a false PHM diagnosis. In conclusion, the combination of FISH analysis with p57KIP2 immunostaining helps in diagnosing molar and non-molar conceptuses in numerous cases; nevertheless, exceptional cases should be considered.

Molecular Basis of Hydatidiform Moles-A Systematic Review.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Invasive and metastatic hydatidiform moles in Slovakia in 1993‒2022.

OBJECTIVE: A retrospective analysis of invasive and metastatic hydatidiform moles (HM) in the Slovak Republic (SR)‒epidemiology, patient characteristics and treatment outcomes. BACKROUND: Invasive and metastatic mole is a highly curable type of gestational trophoblastic neoplasia. Both invasive and metastatic HM may be cured by hysterectomy without adjuvant chemotherapy. METHODS: Nineteen cases of histopathologically confirmed HM (10 invasive and 9 metastatic) were treated in SR from 1993 to 2022. Patients were divided into two groups according to treatment modality (hysterectomy only ‒ 8; hysterectomy and chemotherapy ‒ 11). The parameters included in the analysis were patient age, antecedent pregnancy, human chorionic gonadotropin level, tumor size and time to remission. RESULTS: The incidence of invasive and metastatic HM in the SR was 1:121,253 pregnancies, or 1:86,589 live births. The overall cure rate was 100%, without recurrence. Hysterectomy was performed as first-line therapy in 14 patients, with a cure rate of 57.1%. 4 out of 8 patients (50%) with metastatic moles, who underwent first-line hysterectomy, were cured without chemotherapy. There was no statistically significant difference between the two groups in all selected parameters. CONCLUSION: First-line hysterectomy may lead to remission without adjuvant chemotherapy or reduce the number of chemotherapies in invasive and metastatic HM (Tab. 4, Fig. 2, Ref. 21).

Presentation, medical complications and development of gestational trophoblastic neoplasia of hydatidiform mole after intracytoplasmic sperm injection as compared to hydatidiform mole after spontaneous conception - a retrospective cohort study and literature review.

OBJECTIVE: To describe the natural history of hydatidiform mole (HM) after intracytoplasmic sperm injection (ICSI), emphasizing the clinical and oncological outcomes, as compared to patients who had HM after spontaneous conception (SC). STUDY DESIGN: Retrospective historical cohort study of patients with HM followed at the Rio de Janeiro Federal University, from January 1st 2000-December 31st 2020. RESULTS: Comparing singleton HM after SC to those following ICSI there were differences in terms of maternal age (24 vs 34 years, p < 0.01), gestational age at diagnosis (10 vs 7 weeks, p < 0.01), preevacuation human chorionic gonadotropin levels (200,000 vs 99,000 IU/L, p < 0.01), occurrence of genital bleeding (60.5 vs 26.9%, p < 0.01) and hyperemesis (23 vs 3.9%, p = 0.02) at presentation, and time to remission (12 vs 5 weeks, p < 0.01), respectively. There were no differences observed in the cases of twin mole, regardless of the form of fertilization that gave rise to HM, except molar histology with greater occurrence of partial hydatidiform mole (10.7 vs 40.0%, p = 0.01) following ICSI. Univariate logistic regression for occurrence of postmolar GTN after ICSI identified no predictor variable for this outcome. However, after adjusting for maternal age and complete hydatidiform mole histology, multivariable logistic regression showed the risk of GTN with HM after ICSI had an adjusted odds ratio of 0.22 (95%CI:0.05-0.93, p = 0.04), suggesting a possible protective effect when compared to HM after SC. CONCLUSIONS: Singleton HM after ICSI are diagnosed earlier in gestation, present with fewer medical complications, and may be less likely to develop GTN when compared with HM after SC.

The Presence of the Autophagic Markers LC3B and Sequestosome 1/p62 in the Hydatidiform Mole.

Autophagy is implicated in normal pregnancy and various pathologic pregnancy conditions. Its presence in hydatidiform moles (HM) is unknown. We immunohistochemically studied 36 HM for LC3B and p62 to precisely determine their expression in the decidua, endometrium, and villi. Nineteen nonmolar pregnancies were also studied. LC3B was found in almost half of the villi and p62 was found in almost all villi. LC3B expression was significantly higher in complete HM than in partial HM. LC3B showed different expression patterns in trophoblast layers. LC3B and p62 expression was higher in molar than nonmolar pregnancies. Autophagic markers are present in HM and their expression differs between complete and partial moles.

Gestational Trophoblastic Disease with Coexisting Progressing Pregnancy: Personalised Treatment Modalities.

Purpose: Gestational trophoblastic disease (GTD) coexisting with a steadily progressing pregnancy is an extremely rare condition presented in the literature as a single case or case series of successful delivery. The purpose of this study was to describe five cases of GTD and present possible management strategies for such patients. Methods: Clinical data of five pregnancies with coexisting GTD were identified within the Almazov National Medical Research Centre from 2018 to 2021. Results: Three cases of multiple pregnancies with complete hydatidiform moles and two cases of singleton pregnancies with intraplacental choriocarcinoma and invasive hydatidiform moles were identified. Three pregnancies were prolonged and ended with preterm deliveries. Malignant transformation of the GTD accounted for 60% of the cases. The condition of newborns was based on the level of prematurity and functional immaturity, and in all cases, it was aggravated by anemia. Conclusion: GTD coexisting with progressing pregnancy is threatened by the risks of preterm delivery, miscarriage, hemorrhage, and disease progression and requires monitoring in a multidisciplinary clinic experienced in the management of patients with malignant tumors during pregnancy. In cases of prolonged pregnancy against the background of GTD, we suggest the following monitoring during pregnancy: pelvic, abdominal ultrasound/MRI (without contrast), prenatal invasive fetal karyotype testing in cases of singleton pregnancy, lung X-ray/CT with uterine shielding, weekly assessment of ß-hCG levels, and dynamic monitoring of the fetus. The following postnatal monitoring should be performed: morphological examination of the placenta, weekly assessment of ß-hCG levels up to normalization, then monthly assessment up to six months, and control of ß-hCG level of the newborn.

Combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios for early prediction of postmolar gestational trophoblastic neoplasia.

PURPOSE: To investigate factors predicting postmolar gestational trophoblastic neoplasia (GTN) by combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios. METHODS: This retrospective study enrolled patients with histopathologically proven molar pregnancy. Patients lost to follow-up before remission or developing postmolar GTN were excluded. Demographic and clinical characteristics and hCG data obtained before and after molar evacuation were collected. Area under the receiver operating characteristic curve (AUC) analysis was used to identify the hCG and hCG ratio cutoff values that predict postmolar GTN. Multivariate analysis was employed to identify independent predictors of GTN. RESULTS: There were 113 complete moles, 11 partial moles, and 52 unspecified moles included in the final analysis. Of the 176 cases, 90 achieved remission and 86 developed post-molar GTN. The incidence of postmolar GTN was 48.9%, with a median time to GTN development of 5 weeks. Univariate analysis showed age, molar evacuation performed elsewhere, pre-evacuation hCG, hCG at 2nd week post-evacuation, and ratio of hCG at 2nd week post-evacuation to post-evacuation hCG significantly predict GTN. Multivariate analysis revealed an hCG value ≥ 1400 IU/L at 2nd week post-evacuation (AUC: 0.92, aOR: 6.51, 95% CI 1.28-33.16; p = 0.024) and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 (AUC: 0.88, aOR: 12.27, 95% CI 2.15-70.13; p = 0.005) to independently predict GTN. CONCLUSIONS: An hCG value ≥ 1400 IU/L at 2nd week post-evacuation and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 independently and reliably predict postmolar GTN.

Intrauterine hydatidiform mole complicated with tubal ectopic pregnancy: a case report.

Heterotopic pregnancies are rare pathological pregnancy disorders in clinical practice. However, the number of cases has increased with the widespread use of ovulation induction drugs in recent years. The clinical manifestations of heterotrophic pregnancies are diverse and easy to missed or misdiagnosed. A 33-year-old married Gravida1 Para 0 + 0 patient was admitted on December 8, 2020 with intermittent abdominal pain 18 days after uterine curettage for complete hydatidiform mole of 8 weeks gestation. She had ovulation-promoting drugs prior to the index pregnancy. Hysteroscopic-directed endometrial biopsy and laparoscopic left tubal surgery were offered to her; and she is being followed up with serial pelvic ultrasounds and ß-Human Chorionic Gonadotrophin (ßHCG) assays. This case study presents a case of intrauterine hydatidiform mole complicated with tubal pregnancy to highlight the problems associated with its diagnosis and treatment.

DNA analysis of partial hydatidiform mole revealing triandric monogynic tetraploidy.

The authors present a case of a partial hydatidiform mole where DNA analysis (STR - short tandem repeat genotyping) showed a triandric monogynic tetraploid genome composition with a XXXY gonosomal complement. This genetic finding clinicopathologically correlates with a partial hydatidiform mole, although it is rare in comparison with the typical, diandric monogynic triploid partial moles. The genetic analysis definitively confirmed the suspected diagnosis of a partial mole. To exclude the possibility that molar pregnancy represented retained products of conception after elective pregnancy termination, STR profiles from molar pregnancy and previous products of conception were compared. Short tandem repeats genotyping is a useful molecular genetic method in the differential diagnosis of partial hydatidiform moles, where clinical-pathological findings are frequently ambiguous.

Hydatidiform mole.

Hydatidiform mole is the most common form of gestational trophoblastic disease. It is an abnormally formed placental tissue with characteristic changes in karyotype, arising in fertilization disorders. The presence of abundant paternal genetic information plays a key role in the pathogenesis of complete and partial hydatidiform moles. These lesions are characterized by a relatively wide spectrum of morphological changes that may not be fully expressed, especially in the early stages of pregnancy. In addition, some changes can be observed in non-molar gravidities, which, unlike hydatidiform moles, lack any risk of malignant transformation. Although conventional histological examination still plays a key role in the diagnosis, it should be supplemented by other methods that reliably differentiate individual lesions. Accurate diagnosis of molar gravidities is important not only for determining the correct therapeutic approach, but the obtained data may also contribute to further research of these pathological entities.

Molecular diagnosis of complete and partial hydatidiform moles.

Complete and partial hydatidiform moles are abnormal products of conception that can be identified by clinical, ultrasonographic, morphologic, histologic, and genetic methods. The diagnosis is usually confirmed only by histological examination. However, accurate diagnosis based on morphological criteria is difficult and some studies have shown that misclassifications are common, even when analysed by highly experienced pathologists. Misdiagnosis may mean that women are either not included in adequate ß-hCG follow-up with the risk that the hydatidiform mole progresses to choriocarcinoma or, conversely, are included in follow-up unnecessarily. A reliable complementary method to pathological interpretation may be genetic analysis of the conceptus to eliminate the diagnostic dilemma by distinguishing non-molar spontaneous abortions from hydatidiform moles and defining the type of hydatidiform mole. The aim of our short paper is to introduce the routine molecular analysis used in our laboratory to a wider range of clinical pathologists.

Association of Placental Mesenchymal Dysplasia With a Live Female Fetus and Complete Hydatidiform Mole: Report of a Challenging Case Confirmed by Molecular Genotyping Analysis.

Placental mesenchymal dysplasia (PMD) and complete hydatidiform mole (CHM) with a coexisting fetus are 2 rare placental abnormalities characterized by lacunar placenta and presence of an embryo on ultrasound examination. We report the case of a 34-yr-old woman referred at 32.6 weeks of gestation because of a multicystic placenta. A caesarean section was performed at 39.1 weeks of gestation giving birth to a 2905 g normal female infant. Pathological examination revealed macroscopic and microscopic morphological, and immunohistological features of PMD in the main placenta, and features of CHM in a separate placental mass. Fluorescent in situ hybridization and molecular genotyping analyses showed diandric diploidy in the CHM component and androgenetic/biparental mosaicism in the PMD component, confirming the association of PMD and CHM with a live infant. There was no progression to gestational trophoblastic neoplasia during follow-up for the mother, or any sign of Beckwith-Wiedemann syndrome or hepatic tumor in the child.

Rare Complete Hydatidiform Mole With p57 Expression in Villous Mesenchyme: Case Report and Review of Discordant p57 Expression in Hydatidiform Moles.

Complete hydatidiform mole (CHM) is a premalignant proliferative disease of the placenta characterized by misexpression of imprinted gene products, most notably p57. The majority of CHM exhibit immunohistochemical absence of p57 protein in villous mesenchyme (VM) and cytotrophoblast (CT) and are thus p57 VM/CT concordant. However, some gestations show loss of p57 in only VM or CT, either in all chorionic villi or a subset thereof (VM/CT discordant). Here, we present a rare case of a p57 VM/CT-discordant CHM with diffuse retention of p57 expression in VM but complete absence in CT. Histologically, the case exhibited typical features of CHM including trophoblast hyperplasia and severe nuclear atypia, but was unusual in the presence of gestational membranes identified ultrasonographically and histologically. Ploidy determination by FISH and genotyping by short tandem repeat analyses showed that this was a diploid gestation with variable allelic ratios and with an androgenetic lineage, similar to previously reported p57 VM/CT-discordant cases.

Centralized surveillance of hydatidiform mole: 7-year experience from a regional hospital in China.

OBJECTIVE: To assess the strategy and value of centralized surveillance of hydatidiform mole at a regional hospital in China and to investigate the necessity of prophylactic chemotherapy for high-risk complete hydatidiform mole. METHODS: Between February 2013 and February 2020, all women with hydatidiform mole in Dalian Women's and Children's Medical Center (Group) were registered for surveillance and treatment when indicated. Women with complete hydatidiform mole were categorized into low-risk and high-risk groups according to the criteria from Song Hongzhao's trophoblastic neoplasia. Outcomes and treatments were analyzed retrospectively. RESULTS: In total, 703 women with hydatidiform mole were registered for surveillance with a follow-up rate of 97.9% (688/703). 680 women were enrolled and 52 (7.6%) developed post-molar gestational trophoblastic neoplasia, all with low-risk International Federation of Gynecology and Obstetrics (FIGO) scores 0-5. Post-molar gestational trophoblastic neoplasia was diagnosed in 12.3% (51/413) of patients with complete hydatidiform moles and 0.4% (1/263) of patients were diagnosed with partial hydatidiform moles (χ2=32.415, p<0.001). Post-molar gestational trophoblastic neoplasia was diagnosed in 27.7% (28/101) of the high-risk complete hydatidiform mole group and in 7.4% (23/312) of the low-risk complete hydatidiform mole group (χ2=29.196, p<0.001). No difference in the pre-treatment assessments of patients with post-molar gestational trophoblastic neoplasia was found between the low-risk and high-risk complete hydatidiform mole groups (all p>0.05). All 52 patients with post-molar gestational trophoblastic neoplasia were cured, with a complete response rate of 61.2% (30/49) with first-line single-agent chemotherapy. CONCLUSIONS: A centralized hydatidiform mole surveillance program is feasible and effective and may improve the prognosis of patients with post-molar gestational trophoblastic neoplasia. Prophylactic chemotherapy is not recommended for women with high-risk complete hydatidiform mole with adequate surveillance.

Molar pregnancy with a coexisting living fetus: a case series.

BACKGROUND: Coexistence of molar pregnancy with living fetus represents a challenge in diagnosis and treatment. The objective of this study to present the outcome of molar pregnancy with a coexisting living fetus who were managed in our University Hospital in the last 5 years. METHODS: We performed a retrospective analysis of patients who presented with molar pregnancy with a coexisting living fetus to our Gestational Trophoblastic Clinic, Mansoura University, Egypt from September, 2015 to August, 2020. Clinical characteristics of the patients, maternal complications as well as fetal outcome were recorded. The patients and their living babies were also followed up at least 6 months after delivery. RESULTS: Twelve pregnancies were analyzed. The mean maternal age was 26.0 (SD 4.1) years and the median parity was 1.0 (range 0-3). Duration of the pregnancies ranged from 14 to 36 weeks. The median serum hCG was 165,210.0 U/L (range 7662-1,200,000). Three fetuses survived outside the uterus (25%), one of them died after 5 months because of congenital malformations. Histologic diagnosis was available for 10 of 12 cases and revealed complete mole associated with a normal placenta in 6 cases (60%) and partial mole in 4 cases (40%). Maternal complications occurred in 6 cases (50%) with the most common was severe vaginal bleeding in 4 cases (33.3%). There was no significant association between B-hCG levels and maternal complications (P = 0.3). CONCLUSION: Maternal and fetal outcomes of molar pregnancy with a living fetus are poor. Counseling the patients for termination of pregnancy may be required. TRIAL REGISTRATION: The study was approved by Institutional Research Board (IRB), Faculty of Medicine, Mansoura University (number: R.21.10.1492).

Gestational trophoblastic disease- rare, sometimes dramatic, and what we know so far.

Gestational trophoblastic disease (GTD) is a heterogeneous group of lesions that are characterized by the abnormal proliferation of the trophoblast. Morphology, behavior and clinical significance vary tremendously and range from benign, non-neoplastic lesions that cause sometimes dysfunctional uterine bleeding to aggressive, highly, malignant tumors. The recently updated 2020 World Health Organization (WHO) Classification of Female Genital Tumors divides GTD in molar pregnancies/ hydatidiform moles, gestational trophoblastic neoplasms, tumor-like lesions and abnormal (nonmolar) villous lesions. In this article we review the typical clinical presentations of GTDs, their histopathologic features, contributing immunohistochemical stains and current diagnostic criteria. We discuss novel insights in the proposed pathogenesis, newly proposed entities and advances in ancillary diagnostic techniques and their relevance to the histopathologic diagnosis of GTD. Additionally we briefly review current treatment options, prognosis and prognostic factors of GTDs.

Genetic screening of Chinese patients with hydatidiform mole by whole-exome sequencing and comprehensive analysis.

PURPOSE: We aim to explore if there are any other candidate genetic variants in patients with a history of at least one hydatidiform mole (HM) besides the well-known variants in NLRP7 and KHDC3L. METHODS: The diagnosis of HM type was based on histopathology, and available HM tissues were collected for short tandem repeat (STR) genotyping to verify the diagnosis. DNA extracted from blood samples or decidual tissues of the 78 patients was subjected to whole-exome sequencing (WES). RESULTS: We identified five novel variants in NLRP7, two novel variants in KHDC3L, and a chromosome abnormality covering the KHDC3L locus among patients with HM. We found that patients with HM who carried heterozygous variants in KHDC3L had a chance of normal pregnancy. We also detected four novel genetic variants in candidate genes that may be associated with HM. CONCLUSION: Our study enriched the spectrum of variants in NLRP7 and KHDC3L in Chinese HM patients and provided a new outlook on the effects of heterozygous variants in KHDC3L. The novel candidate genetic variants associated with HMs reported in this study will also contribute to further research on HMs.