MicroRNA Expression Profiling in Hydatidiform Mole for the Prediction of Postmolar GTN

Objectives: The primary aim of the study was to identify miRNAs that were differentially expressed between complete hydatidiform moles (CHMs) that turned out to be gestational trophoblastic neoplasia (GTN) [GTN moles] and CHMs that regressed spontaneously after evacuation [remission moles]. The secondary aim was to study the profiles of miRNA expressions in CHMs. Methods: A case-control study was conducted on GTN moles and remission moles. We quantitatively assessed the expression of 800 human miRNAs from molar tissues using Nanostring nCounter. Results: From a pilot study, 21 miRNAs were significantly downregulated in GTN moles compared to the remission moles. Five of them (miR-566, miR-608, miR-1226-3p, miR-548ar-3p and miR-514a-3p) were downregulated for >4 folds. MiR-608 was selected as a candidate for further analysis on 18 CHMs (9 remission moles and 9 GTN moles) due to its striking association with malignant formation. MiR-608 expression was slightly lower in GTN moles compared to the remission moles, that is, 2.22 folds change [p = 0.063]. Conclusion: We identified 21 miRNAs that were differentially expressed between GTN moles and remission moles suggesting that miRNA profiles can distinguish between the two groups. Although not reaching statistically significant, miR-608 expression was slightly lower in GTN moles compared to remission moles.

Cervical Hydatidiform Moles Pregnancy: Diagnosis and Treatment

Cervical partial hydatidiform mole is a rare condition and difficult to diagnose. A 39-year-old Balinese woman from Sanglah General Hospital, Bali, Indonesia complained vaginal bleeding with abdominal pain. The patient was diagnosed with a partial hydatidiform mole based on physical examination, ultrasound, beta HCG levels and pathology examinations. Mass evacuation surgery followed by arterial ligation to stop the bleeding and periodically examination of beta HCG levels was carried out until the 14th week after the procedure. Beta HCG decreased gradually to normal level and indicate no risk of trophoblastic malignancy. Establishing the early diagnosis significantly affects the outcome of patient. Keywords: partial cervical hydatidiform mole, blighted ovum, pregnancy, diagnosis, therapy.

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

ObjectiveTo 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.MethodsBetween 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.ResultsIn 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.ConclusionsA 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.

Transcriptomic Characterization of Postmolar Gestational Choriocarcinoma

The human placenta shares properties with solid tumors, such as rapid growth, tissue invasion, cell migration, angiogenesis, and immune evasion. However, the mechanisms that drive the evolution from premalignant proliferative placental diseases—called hydatidiform moles—to their malignant counterparts, gestational choriocarcinoma, as well as the factors underlying the increased aggressiveness of choriocarcinoma arising after term delivery compared to those developing from hydatidiform moles, are unknown. Using a 730-gene panel covering 13 cancer-associated canonical pathways, we compared the transcriptomic profiles of complete moles to those of postmolar choriocarcinoma samples and those of postmolar to post-term delivery choriocarcinoma. We identified 33 genes differentially expressed between complete moles and postmolar choriocarcinoma, which revealed TGF-β pathway dysregulation. We found the strong expression of SALL4, an upstream regulator of TGF-β, in postmolar choriocarcinoma, compared to moles, in which its expression was almost null. Finally, there were no differentially expressed genes between postmolar and post-term delivery choriocarcinoma samples. To conclude, the TGF-β pathway appears to be a crucial step in the progression of placental malignancies. Further studies should investigate the value of TGF- β family members as biomarkers and new therapeutic targets.

When a vesicular placenta meets a live fetus: case report of twin pregnancy with a partial hydatidiform mole

Background Hydatidiform moles exhibit a distinctive gross appearance of multiple vesicles in the placenta. The advances in cytogenetic technologies have helped uncover novel entities of hydatidiform moles and enabled elaborate diagnoses. However, management of a vesicular placenta with a coexistent live fetus poses a bigger challenge beyond hydatidiform moles. Case presentation A 33-year-old woman was referred to our department for suspected hydatidiform mole coexistent with a live fetus at 24 weeks’ gestation. The patient had conceived through double embryo transplantation, and first-trimester ultrasonography displayed a single sac. Mid-trimester imaging findings of normal placenta parenchyma admixed with multiple vesicles and a single amniotic cavity with a fetus led to suspicion of a singleton partial molar pregnancy. After confirmation of a normal diploid by amniocentesis and close surveillance, the patient delivered a healthy neonate. Preliminary microscopic examination of the placenta failed to clarify the diagnosis until fluorescence in situ hybridization showed a majority of XXY sex chromosomes. The patient developed suspected choriocarcinoma and achieved remission for 5 months after chemotherapy, but relapsed with suspected intermediate trophoblastic tumor. Conclusion We report a rare case of twin pregnancy comprising a partial mole and a normal fetus that resembled a singleton partial molar pregnancy. Individualized care is important in conditions where a vesicular placenta coexists with a fetus. We strongly recommend ancillary examinations in addition to traditional morphologic assessment in such cases.

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.

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 &gt;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.