Pathology of Gestational Trophoblastic Disease (GTD).

Gestational trophoblastic disease (GTD), comprising hydatidiform moles (HM) and gestational trophoblastic tumors (GTT), is extremely rare. HM originate from villous trophoblast and are considered preneoplastic. GTT originate from the intermediate, largely extravillous trophoblast and includes choriocarcinoma, placental site trophoblastic tumor, epitheloid trophoblastic tumor, and mixed trophoblastic tumor. The abnormal (non-molar) villous lesions, non-malignant tumour-like conditions, and non-gestational tumors add to the diagnostic dilemma. The correct diagnosis and classification of these rare conditions are important. This review intends to provide an update on changes in the World Health Organization classification and focusses on the morphologic aspects in diagnosis of GTD.

Treatment of High-Risk Gestational Trophoblastic Neoplasia.

High-risk gestational trophoblastic neoplasia encompasses patients with high volumes of disease or diffuse metastatic involvement who are unlikely to achieve remission with single-agent chemotherapy. Etoposide-based multi-drug regimens form the core of high-risk therapy. Second-line therapy includes platinum-based regimens. Increasingly, third-line therapy uses immunotherapy. Surgical intervention may be required to resect foci of resistant disease or manage complications. Treatment should continue until the hCG is less that the reference range for normal, followed by at least 3 cycles of consolidation therapy. At least 2 years of hCG surveillance are advisable for most patients requiring multiagent therapy to encompass 95% of relapses.

Gestational Trophoblastic Neoplasia Rate and Its Related Factors in Women With a Partial Hydatidiform Mole at Tudu Hospital, Vietnam.

Background Minimal studies have been carried out on a partial hydatidiform mole (PHM) in Vietnam, so the treatment outcomes for patients with PHM are unknown. This study aimed to determine the occurrence rate of gestational trophoblastic neoplasia (GTN) and its related factors in women with PHM at Tu Du Hospital, Vietnam. Materials and methods This retrospective cohort study included 370 women with PHM diagnosed through a histopathological assessment following termination of pregnancy at Tu Du Hospital from January 2020 to December 2021. Survival analysis was used for GTN cumulative rate estimation and the Cox regression model for determining GTN-related factors. Results After a 1-year follow-up, 21 patients were found to have GTN, exhibiting a rate of 5.7% (95% confidence interval (CI): 3.5 - 8.4). GTN occurred 4.67±2.23 weeks following curettage with peaks at weeks 3-6. No cases of GTN were recorded eight weeks following termination by curettage. After multivariate analysis, the GTN rate was higher in patients with a history of miscarriage/termination (hazard ratio (HR)=2.84; 95% CI: 1.05-7.69). Conclusion The rate of GTN in PHM patients was 5.7%. Patients who had a history of miscarriage or termination were 2.84 times more likely to develop GTN than patients who did not.

A Case of Metastatic Vulvar Choriocarcinoma Misdiagnosed as Vulvar Abscess: A Case Report.

Background: Metastatic vulvar choriocarcinoma, a rare ectopic gestational trophoblastic neoplasia (GTN), often presents a diagnostic challenge due to its mimicry of other conditions, particularly in resource-limited settings. Its primary symptom is abnormal vaginal bleeding without a clear cause. Consequently, diagnosing and managing it poses difficulties for many low-resource health facilities, as evidenced by the current case. Case Presentation: We present the case of a 25-year-old, P2+2+2L2, who had a large painless, bleeding vulva mass for nearly 5 months. This followed a spontaneous abortion the month prior. The mass gradually increased in size and was accompanied by fever, pus discharge, and weight loss. Despite being treated at multiple health facilities for a vulvar abscess, there was no improvement. A diagnosis was finally made at a tertiary facility where elevated quantitative serum beta-human chorionic gonadotropin (hCG) (ß-hCG) was noted. Due to uncontrollable vulva bleeding, she was referred to another tertiary facility for emergency radiotherapy. Following stabilization, chemotherapy was administered using the EMA-CO protocol. Conclusion: The report highlights the difficulty in diagnosing vulvar choriocarcinoma, underscoring the importance of a high index of suspicion. Clinical tests such as serum (ß-hCG) and imaging studies are crucial for diagnosis. In resource-limited settings, a simple strip-based urine pregnancy test with serial dilutions can be sufficient for diagnosing and managing vulvar choriocarcinoma.

Non-gestational Choriocarcinoma of the Ovary: A Report of a Rare Case From Saudi Arabia.

Non-gestational choriocarcinoma of the ovary is extremely rare and presents diagnostic and therapeutic challenges. Early recognition, appropriate surgical intervention, and adjuvant chemotherapy are essential for successful management. This case underscores the importance of considering choriocarcinoma in the differential diagnosis of ovarian tumors, especially in perimenopausal women with vascular mass. We present the case of a 47-year-old sexually active woman with a history of pelvic pain, diagnosed with non-gestational choriocarcinoma of the ovary. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with successful management using the bleomycin, etoposide, and platinum (BEP) regimen. This case highlights the importance of early detection and appropriate management of this rare entity.

Tislelizumab for treatment of a pediatric patient with primary mediastinal choriocarcinoma: a case report.

Background: Primary mediastinal choriocarcinoma (PCC) is a rare, highly vascular invasive, and prognostically unfavorable malignant tumor. When occurring outside the gonads, primary choriocarcinoma is commonly found in midline locations such as the mediastinum or retroperitoneum. Currently, there is no standardized treatment strategy for PCC. In the case reported herein, we employed tislelizumab and chemotherapy in the treatment of a patient with PCC, and as in March 2024, the patient remained survive. Case Description: A 15-year-old boy who presented with symptoms of fever and cough for a year. Chest computed tomography (CT) scan showed a relatively large soft tissue shadow in the right upper anterior mediastinum, measuring approximately 5.4 cm × 3.8 cm. The patient's soft tissue exhibited unclear demarcation from surrounding mediastinal structures and was accompanied by lung metastasis. The patient underwent a fine needle aspiration biopsy for a mediastinal mass, and the pathology results indicated a germ cell tumor with solid malignant components in the mediastinum, along with pulmonary metastasis of the solid malignancy. The patient's serum levels of beta-human chorionic gonadotropin (ß-HCG) were elevated at 125,554 mIU/mL (normal range: <5 mIU/mL), and alpha-fetoprotein (AFP) was 75.8 ng/mL (normal range, 0.605-7 ng/mL). The patient's cranial magnetic resonance imaging (MRI) plain scan indicated multiple scattered abnormal signals in both cerebral hemispheres. Subsequently, the patient was transferred to Children's Hospital of Nanjing Medical University for his further treatment. During the treatment period, we employed various therapeutic approaches, including chemotherapy, radiotherapy and tislelizumab therapy. After five cycles of tislelizumab treatment, the patient's symptoms of cerebral edema significantly improved, ß-HCG levels decreased. Brain MRI of the patient revealed multiple abnormal signals within the skull, with some lesions showing reduction in size and significant improvement in the surrounding edema zones. The clinical symptoms of the patient improved and he achieved partial remission (PR). At the moment, the patient is living with the disease. Conclusions: The effectiveness of chemotherapy for PCC is limited. Tislelizumab may potentially serve as salvage treatment options for PCC.

Equol exerts anti-tumor effects on choriocarcinoma cells by promoting TRIM21-mediated ubiquitination of ANXA2.

Choriocarcinoma is a malignant cancer that belongs to gestational trophoblastic neoplasia (GTN). Herein, serum metabolomic analysis was performed on 29 GTN patients and 30 healthy individuals to characterize the metabolic variations during GTN progression. Ultimately 24 differential metabolites (DMs) were identified, of which, Equol was down-regulated in GTN patients, whose VIP score is the 3rd highest among the 24 DMs. As an intestinal metabolite of daidzein, the anticancer potential of Equol has been demonstrated in multiple cancers, but not choriocarcinoma. Hence, human choriocarcinoma cell lines JEG-3 and Bewo were used and JEG-3-derived subcutaneous xenograft models were developed to assess the effect of Equol on choriocarcinoma. The results suggested that Equol treatment effectively suppressed choriocarcinoma cell proliferation, induced cell apoptosis, and reduced tumorigenesis. Label-free quantitative proteomics showed that 136 proteins were significantly affected by Equol and 20 proteins were enriched in Gene Ontology terms linked to protein degradation. Tripartite motif containing 21 (TRIM21), a E3 ubiquitin ligase, was up-regulated by Equol. Equol-induced effects on choriocarcinoma cells could be reversed by TRIM21 inhibition. Annexin A2 (ANXA2) interacted with TRIM21 and its ubiquitination was modulated by TRIM21. We found that TRIM21 was responsible for proteasome-mediated degradation of ANXA2 induced by Equol, and the inhibitory effects of Equol on the malignant behaviors of choriocarcinoma cells were realized by TRIM21-mediated down-regulation of ANXA2. Moreover, ß-catenin activation was inhibited by Equol, which also depended on TRIM21-mediated down-regulation of ANXA2. Taken together, Equol may be a novel candidate for the treatment for choriocarcinoma.

Epidemiology of Gestational Trophoblastic Disease.

Worldwide incidence rates of gestational trophoblastic disease (GTD) are difficult to estimate and compare due to large methodological differences within and between countries. Asia has generally reported higher incidence rates than Europe and North America, but modern reports have demonstrated a temporal decrease of GTD incidence rates in Asia and an increase in some European countries and North America. The main risk factors for hydatidiform mole are maternal age and previous molar events. Future studies on the epidemiology of GTD should include gestational trophoblastic neoplasia and international collaborative studies on this rare disease should be encouraged.

Surgical Management of Gestational Trophoblastic Neoplasia.

Gestational trophoblastic neoplasia (GTN) is primarily treated with chemotherapy, but surgery plays a key role at different steps in disease management, including initial diagnosis, primary therapy, and salvage options. Initial diagnosis is usually made by electric or manual vacuum aspiration for molar pregancy or uterine curettage for other forms of GTN. Excisional procedures of localized disease, whether second curettage or hysterectomy, can obviate chemotherapy, but patients still require monitoring for relapse. Resection remains a useful adjunct for either the management of isolated foci of chemoresistant disease or the management of bleeding complications.

Metastatic choriocarcinoma presenting as upper gastrointestinal bleeding: A case report.

Choriocarcinoma is a type of gestational trophoblastic disease that occurs as a complication of pregnancy-related events. The gestational trophoblastic disease includes both benign and malignant conditions including complete and partial mole, invasive mole, choriocarcinoma, and placental site trophoblastic disease. Choriocarcinoma generally presents with pervaginal bleeding, symptoms of anemia, and symptoms of its metastatic lesion. The common sites of metastasis are the lung, vagina, brain, and liver. The gastrointestinal (GI) tract is an uncommon site of metastasis occurring in <5% of patients. Upper GI bleeding as presenting complaints without pervaginal bleeding is also very rare with only a few reported cases. Here we present a case of 29 years young female who presented in our emergency department with complaints of hematemesis and altered sensorium where clinical suspicion was peptic ulcer disease but imaging modality with computed tomography showed hypervascular lesions in the brain with suspicion of choriocarcinoma. With further imaging and laboratory tests, confirmatory diagnosis of choriocarcinoma was made. This case highlights the importance of imaging in the diagnosis of choriocarcinoma where the history of the patient is misleading.