Chimeric Singleton Placenta Comprising Placental Mesenchymal Dysplasia and Complete Hydatidiform Mole with Live Birth and Postpartum Diagnosis of Gestational Trophoblastic Neoplasia.

INTRODUCTION: Placental mesenchymal dysplasia (PMD) is a benign lesion that is often misdiagnosed as complete (CHM) or partial hydatidiform mole. PMD usually results in live birth but can be associated with several fetal defects. Herein, we report PMD with CHM in a singleton placenta with live birth. CASE PRESENTATION: A 34-year-old gravida 2, para 1, living 1 (G2P1L1) woman was referred on suspicion of a molar pregnancy in the first trimester. Maternal serum human chorionic gonadotrophin levels were increased during early pregnancy, with multicystic lesions and placentomegaly observed on ultrasonography. Levels decreased to normal with no fetal structural abnormalities observed. A healthy male infant was delivered at 34 gestational weeks. Placental p57KIP2 immunostaining and short tandem repeat analysis revealed three distinct histologies and genetic features: normal infant and placenta, PMD, and CHM. Gestational trophoblastic neoplasia was diagnosed and up to fourth-line chemotherapy administered. CONCLUSION: Distinguishing PMD from hydatidiform moles is critical for avoiding unnecessary termination of pregnancy. CHM coexisting with a live fetus rarely occurs. This case is unique in that a healthy male infant was born from a singleton placenta with PMD and CHM.

A real-time computer-aided diagnosis method for hydatidiform mole recognition using deep neural network.

BACKGROUND AND OBJECTIVE: Hydatidiform mole (HM) is one of the most common gestational trophoblastic diseases with malignant potential. Histopathological examination is the primary method for diagnosing HM. However, due to the obscure and confusing pathology features of HM, significant observer variability exists among pathologists, leading to over- and misdiagnosis in clinical practice. Efficient feature extraction can significantly improve the accuracy and speed of the diagnostic process. Deep neural network (DNN) has been proven to have excellent feature extraction and segmentation capabilities, which is widely used in clinical practice for many other diseases. We constructed a deep learning-based CAD method to recognize HM hydrops lesions under the microscopic view in real-time. METHODS: To solve the challenge of lesion segmentation due to difficulties in extracting effective features from HM slide images, we proposed a hydrops lesion recognition module that employs DeepLabv3+ with our novel compound loss function and a stepwise training strategy to achieve great performance in recognizing hydrops lesions at both pixel and lesion level. Meanwhile, a Fourier transform-based image mosaic module and an edge extension module for image sequences were developed to make the recognition model more applicable to the case of moving slides in clinical practice. Such an approach also addresses the situation where the model has poor results for image edge recognition. RESULTS: We evaluated our method using widely adopted DNNs on an HM dataset and chose DeepLabv3+ with our compound loss function as the segmentation model. The comparison experiments show that the edge extension module is able to improve the model performance by at most 3.4% regarding pixel-level IoU and 9.0% regarding lesion-level IoU. As for the final result, our method is able to achieve a pixel-level IoU of 77.0%, a precision of 86.0%, and a lesion-level recall of 86.2% while having a response time of 82 ms per frame. Experiments show that our method is able to display the full microscopic view with accurately labeled HM hydrops lesions following the movement of slides in real-time. CONCLUSIONS: To the best of our knowledge, this is the first method to utilize deep neural networks in HM lesion recognition. This method provides a robust and accurate solution with powerful feature extraction and segmentation capabilities for auxiliary diagnosis of HM.

A complete hydatidiform mole and coexisting viable fetus in a twin pregnancy: a case report with literature review.

INTRODUCTION: A twin pregnancy involving a hydatidiform mole (HM) coexisting with a developing fetus is an extremely rare obstetric complication, which typically presents as a complete hydatidiform mole with a coexisting fetus (CHMCF) or a partial hydatidiform mole with a coexisting fetus (PHMCF). CASE PRESENTATION: A 26-year-old woman was admitted to our hospital due to a small volume of vaginal bleeding during the 31st week of pregnancy. The patient was previously healthy, and an intrauterine singleton pregnancy was detected by ultrasound on day 46 of gestation; however, bunch-of-grapes sign was observed in the uterine cavity at 24 weeks. The patient was subsequently diagnosed with CHMCF. As the patient insisted on continuing her pregnancy, she underwent hospital monitoring. Vaginal bleeding occurred in the 33rd week again and received a course of betamethasone, then continued pregnancy after bleeding stopped spontaneously. In the 37th week, a male infant weighing 3090 g was delivered by cesarean section, with an Apgar score of 10 at 1 min and a karyotype of 46XY. Placental pathology confirmed the diagnosis of a complete hydatid tumor. CONCLUSION: In this report, a case of CHMCF was maintained by monitoring of blood pressure, thyroid function, human chorionic gonadotrophin, and fetal condition during pregnancy. A live newborn was delivered by cesarean section. CHMCF is a clinically rare disease with high risks; thus, it should be diagnosed carefully using several tools, including ultrasound, magnetic resonance imaging, and karyotype analysis and dynamically monitored if the patient decides to continue the pregnancy.

Complete hydatidiform mole with a coexisting foetus of term pregnancy: A case report and review of the literature.

A case of a complete mole with a full term live foetus misdiagnosed as placental mesenchymal dysplasia prenatally is being reported here. The infant was delivered at term, and the placenta was accompanied with molar changes. Both the mother and baby were healthy with no complications at one-year follow-up. This report systematically summarises identification methods to reduce the rate of misdiagnosis for better pregnancy outcomes.

Predictive value of B-human chorionic gonadotropin for progression of molar pregnancy to persistent gestational trophoblastic neoplasm.

BACKGROUND: This study aimed to assess the predictive value of B-human chorionic gonadotropin (B-hCG) for progression of molar pregnancy to persistent gestational trophoblastic neoplasm (GTN). METHODS: This cohort study evaluated 126 patients with molar pregnancy. The patients were selected among those presenting to Yas Hospital in 2016-2017. All female patients with molar pregnancy hospitalized in this hospital who underwent evacuation were enrolled. After evacuation, the patients underwent ultrasound examination to measure their endometrial thickness. Also, presence of complete or partial mole was pathologically assessed. The B-hCG titers were measured before and at 48 h, 1 week, 2 weeks, and 3 weeks after the evacuation. The follow-up was continued until the B-hCG titer was negative or the patient was classified as a case of GTN according to the FIGO classification. Data were analyzed by the independent t-test, Mann-Whitney Test, χ2 test, receiver operating characteristic (ROC) curve, and linear regression. RESULTS: Of 126 patients with molar pregnancy, 13 developed GTN. The mean ratio of pre-evacuation B-hCG titer to the value at 3 weeks after evacuation was 0.02±0.005 in the full recovery and 0.06±0.04 in the GTN group, indicating an area under the curve (AUC) of 0.904. CONCLUSIONS: The ratio of pre-evacuation B-hCG titer to the value at 3 weeks after the evacuation of mole can serve as an excellent predictor for development of GTN.

Advances in diagnostics and management of gestational trophoblastic disease.

BACKGROUND: Gestational trophoblastic disease (GTD) is a heterogeneous group of rare tumours characterised by abnormal proliferation of trophoblastic tissue. It consists of benign or premalignant conditions, such as complete and partial molar pregnancy and variants of malignant diseases. The malignant tumours specifically are commonly referred to as gestational trophoblastic neoplasia (GTN). They consist of invasive mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). CONCLUSIONS: Patients with GTD are often asymptomatic, although vaginal bleeding is a common presenting symptom. With the advances in ultrasound imaging in early pregnancy, the diagnosis of molar pregnancy is most commonly made in the first trimester of pregnancy. Sometimes, additional imaging such as chest X-ray, CT or MRI can help detect metastatic disease. Most women can be cured, and their reproductive function can be preserved. In this review, we focus on the advances in management strategies for gestational trophoblastic disease as well as possible future research directions.

The diagnostic value and accuracy of ultrasound in diagnosing hydatidiform mole: A systematic review and meta-analysis of the literature.

INTRODUCTION: Hydatidiform moles are the most common type of gestational trophoblastic disease. Internationally the incidence of hydatidiform moles is 1-2:1000 pregnancies. Early detection of women with hydatidiform moles is preferential, as these women are at a higher risk of developing other gestational trophoblastic disease. Despite Ultrasound being the most common modality used to diagnose hydatidiform moles, its diagnostic value and accuracy throughout all trimesters remains uncertain. Thus, the aim of this review was to explore and evaluate the diagnostic value and accuracy of Ultrasound in diagnosing hydatidiform mole throughout all trimesters of pregnancy. METHODS: The databases MEDLINE and CINAHL were searched between 2004 and 2021. Included studies were quality assessed using the Mixed Methods Appraisal Tool. RESULTS: A total of 8 studies were included. The narrative synthesis identified four themes: Misdiagnosis, Complete and Partial molar pregnancy, Operator dependency and Gestational age. The meta-analysis highlighted although the sensitivity of ultrasound for diagnosing hydatidiform moles is relatively low at 52.2%, the specificity was high at 92.6%. CONCLUSION: While histological examination remains the gold standard for detecting hydatidiform moles, our review made evident that ultrasound is a beneficial diagnostic tool in the detection of Hydatidiform moles, especially alongside other diagnostic investigations. This review has highlighted and collated the main barriers and facilitators to diagnosing hydatidiform moles using ultrasound. IMPLICATION FOR PRACTICE: Findings suggest that although sonographic detection of hydatidiform moles remains a diagnostic challenge, seeking a second opinion or repeating scans before making a final diagnosis should be embedded into clinical practice.

Changes in diagnostic sensitivity, incidence and presentation of complete and partial hydatidiform mole over the years.

OBJECTIVE: Molar pregnancy is the most common type of gestational trophoblastic disease. Several recent reports have described changes in the clinical representation, the incidence and the diagnostic sensitivity of molar pregnancy. These changes could be due to widespread use of transvaginal ultrasound and beta-hCG testing in the management of routine first-trimester investigations. STUDY DESIGN: This is a retrospective study of 144 women diagnosed with partial or complete mole at a regional medical center during 2007-2020. Incidence, demographics, clinical features and diagnostic sensitivity were compared between 2007 and 2014 and 2015-2020, and attempts were made to understand the bases of the changes between the time periods. RESULTS: Sixty-two moles were diagnosed during 2007-2014 and 82 during 2015-2020. The proportions of complete moles in the respective periods were 65% (40) and 18% (15). From the earlier to the later period, the incidence and proportion of complete moles decreased, and of partial moles, increased. The median gestational age at diagnosis of molar pregnancy was 9.3 weeks. In the later period, women presented less frequently with vaginal bleeding, though this remained the most common presenting symptom. The proportion of women who underwent surgical evacuation of the uterus due to suspected molar pregnancy decreased, as did the proportion of moles that was suspected in ultrasound evaluation (P < 0.001). CONCLUSION: The proportion of complete moles decreased between the periods examined. Gestational age at diagnosis was similar to data from 1994 to 2013. Some typical presenting symptoms of molar pregnancy decreased. However, earlier diagnosis of missed abortion can miss diagnoses of molar pregnancy.

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.

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.

Placental spectrum features between mesenchymal dysplasia and partial hydatidiform mole coexisting with a live fetus.

We report a case of a singleton hydrops pregnancy with placental gross and microscopic features between partial hydatidiform mole (PHM) and placental mesenchymal dysplasia (PMD) in a diploid live fetus. Pregnancy was complicated by early onset of growth restriction and pre-eclampsia. A female newborn was born at 29 weeks with no congenital malformations. Histology of the placenta revealed mixed phenotype of PMD and PHM, and genetic test results were normal.

Thyrotoxicosis: a rare presentation of molar pregnancy.

A 49-year-old woman, G8P7, presented with 1 week of worsening vaginal bleeding and abdominal cramps in the setting of a recently discovered unplanned pregnancy. Vaginal ultrasound findings and a significantly elevated human chorionic gonadotropin (hCG) level were concerning for molar pregnancy. She developed signs of hyperthyroidism on the night of admission, for which the endocrinology team was consulted. Laboratory data were consistent with hyperthyroidism. The patient was believed to have thyrotoxicosis secondary to molar pregnancy with concern for impending thyroid storm. Her mental health disorder and bacteraemia made taking care of her further challenging. She was started on a beta-blocker, antithyroid agent and intravenous corticosteroids. She underwent an uncomplicated suction dilation and curettage (D&C), with resolution of her symptoms a few days after. At a follow-up appointment, the patient continued to be asymptomatic and was feeling well.

Invasive mole presenting as a heavily bleeding vaginal lesion 3 weeks after uterine evacuation.

Gestational trophoblastic disease occurs in 1-3:1000 gestations worldwide. Up to one-fifth of complete hydatidiform moles undergo malignant transformation, with 2%-4% manifesting as metastatic disease. Of these, a third present with vaginal metastases, which can cause bleeding and discharge. We describe the case of a 49-year-old primiparous woman presenting with syncope and intense bleeding from an anterior vaginal lesion, 3 weeks after uterine evacuation for a presumed spontaneous abortion. A vaginal metastatic nodule was suspected; haemostasis was achieved with vaginal packing, precluding the need for surgical intervention. The patient was ultimately diagnosed with invasive mole with vaginal and lung metastases (stage III high-risk gestational trophoblastic neoplasia (GTN)) and started on multiple-agent chemotherapy. Two months later the lesion had regressed completely, and remission was reached 2 weeks later. Clinicians should consider the possibility of metastatic GTN with vaginal involvement whenever heavy vaginal bleeding follows a recent history of failed pregnancy.

Three atypical presentations of choriocarcinoma, occurring during and shortly after a coexistent viable pregnancy.

Gestational choriocarcinoma is a malignant tumour originating from the trophoblastic tissue that can arise during or after any type of pregnancy, but most of the time follows a molar pregnancy. Characteristic for this tumour is its rapid haematogenous spread to various organs, causing atypical presentations often attributable to metastatic disease. We review three cases that occurred during and shortly after a coexistent intrauterine pregnancy. The patient of Case 1 presented with neurological symptoms due to hypercalcaemia, in Case 2 there was initially suspicion of appendicitis and the third patient presented with acute respiratory insufficiency. This case series illustrates that, although highly effective chemotherapy is available, choriocarcinoma can be life-threatening and accurate diagnosis is challenging but critical.

Histopathological examination of the curettage material in nonviable pregnancies and evaluation of the frequency of hydatidiform mole.

AIM: The study aimed to determine the frequency of possible missed diagnosis of gestational trophoblastic disease in nonviable pregnancies and to evaluate the importance of histopathological examination. METHODS: In this retrospective study, the results of the histopathological assessment of patients undergoing uterine surgery with a diagnosis of nonviable pregnancy were analyzed before 14 weeks of gestation. Nonviable pregnancy was defined as anembryonic pregnancy and intrauterine exitus (IU-ex) based on ultrasound findings. The frequency and sonographic characteristics of molar pregnancy in nonviable pregnancy were analyzed. RESULTS: Molar pregnancy was detected in 24 (1.62%) of 1481 patients diagnosed with nonviable pregnancy on ultrasound. One thousand one hundred and twenty-one of the cases were IU-ex (75.69%) and the remaining were anembryonic pregnancy (24.31%). The mean crown-rump length of pregnancies in the IU-ex group was 16.7 mm and the mean gestational age was 8 weeks. The average gestational sac diameter was found to be 26 mm in anembryonic pregnancy patients. The hydatidiform mole ratio was significantly higher in anembryonic pregnancy patients (3.06%) than in IU-ex patients (1.16%) (p = 0.013). CONCLUSIONS: The appearance of early molar pregnancy on ultrasound evaluation may mimic anembryonic pregnancies. Therefore, histopathological examination of anembryonic pregnancies may be useful in early diagnosis and for the treatment of gestational trophoblastic neoplasia.