Trophoblastic Disease Research Articles

Epithelioid Trophoblastic Tumor Predominant Mixed Germ Cell Tumor of the Testis: A Case Report and Review of the Literature.

An epithelioid trophoblastic tumor is a rare form of gestational trophoblastic neoplasia that mostly affects the uterus and endocervix in female patients of the reproductive age group. The tumor is believed to arise from chorion leave-type intermediate trophoblast. The epithelioid trophoblastic tumor in men is extremely rare and mostly described in association with mixed germ cell tumors of the testis. It is more commonly identified at the metastatic sites than in the testis. The epithelioid trophoblastic tumor should be differentiated from placental site trophoblastic tumor and squamous cell carcinoma. The distinctive morphology and characteristic immunohistochemical staining pattern help differentiate epithelioid trophoblastic tumors from other neoplasms. Only 7 male patients with epithelioid trophoblastic tumors have been described to date. Of these 7 patients, 4 were in metastatic sites, 2 in the testis, and 1 in the lung without the involvement of the testis or retroperitoneum. The proportion of epithelioid trophoblastic tumors was only 5% in the 2 patients with testis involvement. Here, we report the third patient with a primary testicular epithelioid trophoblastic tumor in a young man. Further, this is the first report to document epithelioid trophoblastic tumor as dominant histology in a testicular germ cell tumor.

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, β-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.Graphical abstract

Dissecting the microenvironment of gestational trophoblastic disease through deconvolution of bulk RNA-seq data

Dissecting the microenvironment of gestational trophoblastic disease through deconvolution of bulk RNA-seq data

Androgenetic/biparental mosaic/chimeric gestation: A case report

Introduction: Androgenetic/biparental mosaic/chimeric (ABMC) conceptions are a rare group of gestational trophoblastic disease (GTD) that arise as a result of mosaicism or chimerism and are characterized by hydropically enlarged and variably sized villi. Currently, there are very few reports describing ABMC conceptions; there are 13 total in the literature, and even more rare are those with a molar component. Case Report: A 27-year-old female patient at 6+4wga presented to the clinic with a complaint of new vaginal bleeding and was diagnosed with a pregnancy of unknown location. The patient re-presented to the clinic at 8+4wga by last menstrual period (LMP) for a follow-up ultrasound. A serum human chorionic gonadotropin (hCG) was ordered and returned at 424,008 mIU/mL. A transvaginal ultrasound demonstrated a heterogeneous “snowstorm” appearance throughout uterine cavity, with a concern for complete mole in the setting of a significantly elevated beta hCG. The patient underwent a suction dilation and curettage with ultrasound guidance. Pathology returned the following report: The specimen was sent to pathology and DNA ploidy returned as diploid; however, p57 demonstrated a discordant staining pattern characterized by expression in villous cytotrophoblast but the absence in villous stromal cells was characteristic of androgenetic/biparental mosaic/chimeric gestation. No fetal parts were identified in gross examination of the specimen. Conclusion: Androgenetic/biparental mosaic/chimeric (ABMC) conceptions are important to accurately diagnose because the molar form carries an increased risk for persistent gestational trophoblastic diseases. There are few case reports published regarding ABMC cases. We present this case to provide additional data to the field and emphasize the utility for p57 immunohistochemistry and genetic testing to be performed.

Pseudo-myometrial thinning in placental site trophoblastic tumors: a case series with multiparametric MRI.

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasm with few previous imaging case reports. We report multiparametric MRI findings in four cases of PSTT with special emphasis on the "pseudo-myometrial thinning" underlying the tumor. We reviewed multiparametric MRI and pathologic findings in four cases of PSTT from four institutions. Signal intensity, enhancement pattern, margins, and location of the tumors were evaluated, and myometrial thickness underlying the tumor and normal myometrial thickness contralateral to the tumor were measured on MRI. The myometrial thickness underlying the tumor was also measured in the resected specimen and compared with the myometrial thickness measured on MRI using the Friedman test. All tumors showed heterogeneous signal intensity on T1-weighted imaging, T2-weighted imaging (T2WI), and diffusion-weighted imaging. Three of the four tumors had a hypervascular area on dynamic contrast-enhanced (DCE) MRI. A hypointense rim on T2WI and DCE-MRI was seen in all tumors. All tumors protruded into the uterine cavity to varying degrees and extended into the myometrium close to the serosa. The myometrial thickness underlying the tumor measured on MRI (median thickness, 1.2mm) was significantly thinner than that measured on pathology (median thickness, 9.5mm) and normal myometrial thickness contralateral to the tumor on MRI (median thickness, 10.3mm) (P = 0.02), and there was no significant difference between the latter two. The thickness of the myometrium underlying the tumor on MRI was approximately one tenth of the thickness on pathology. Thus, the tumors appeared to have almost transmural invasion even when pathologically located within the superficial myometrium. This "pseudo-thinning" of the underlying myometrium and the hypointense rim on MRI could be caused by focal compression of the myometrium by the tumor, possibly due to the fragility of the myometrium at the placental site.

Cesarean scar choriocarcinoma following a cesarean scar molar pregnancy: A case report

Gestational choriocarcinoma, a rare variant of gestational trophoblastic disease, typically arises from abnormal trophoblastic cell proliferation post-pregnancy, often associated with a hydatidiform mole. While most choriocarcinoma cases develop within the uterine cavity, an exceedingly rare manifestation occurs within a previous cesarean section scar. In our study, a 31-year-old woman with a history of hydatidiform mole presented with amenorrhea and spotting. Initial assessments revealed elevated beta-human chorionic gonadotropin (βhCG) levels and a heteroechoic mass at her prior cesarean section scar in sonographic examination. Histopathologic findings and the metastatic workup categorized the patient as FIGO stage I, indicating no metastasis. Due to the absence of metastasis, adjuvant chemotherapy was omitted. Total abdominal hysterectomy confirmed choriocarcinoma. Post-surgery, βhCG levels notably decreased, remaining negative during the two-year follow-up with no reported symptoms. Our findings suggest that surgical resection and meticulous βhCG monitoring may be a promising treatment strategy for non-metastatic choriocarcinoma.

Diagnosis and management of a case of gestational trophoblastic neoplasia with lumbosacral metastases.

Gestational trophoblastic neoplasia (GTN) with spinal metastasis is rare with few documented cases worldwide. Few studies have explored chemotherapy combined with radiotherapy in the treatment of such cases. However, because of its rarity, there is still no standardized treatment regimen. A 34-year-old Gravida 1 Para 0 (0010) was diagnosed with GTN with metastasis to the lumbosacral spine, resulting in conus medullaris syndrome with lumbar radiculopathy. She presented with a 14-month history of amenorrhea, left lower extremity pain, and urinary and bowel retention. On examination, there was a 10.0 × 7.0 cm lumbosacral mass and atrophy of the left lower extremity. Transvaginal ultrasound showed a cul de sac mass, and diluted β-human chorionic gonadotropin (β-hCG) titer was markedly elevated at more than 1000 000 mIU/mL. Magnetic resonance imaging (MRI) of the lumbosacral spine showed an ill-defined sacral mass measuring 13.3 × 11.5 × 6.3 cm with spinal canal, bone, muscle, and nerve root involvement. She was treated with 10 cycles of EMACO and palliative radiotherapy with 10 sessions of 30 Gy of external beam radiation therapy directed toward the lumbosacral mass. Repeat MRI showed a decrease in size of the mass to 6.6 × 8.2 × 4.1 cm with concurrent decrease in β-hCG to 1.30 mIU/ml, and resolution of leg pain and urinary and bowel symptoms. She was declared to be in remission 3 months after the last cycle of EMACO.

Epithelioid Trophoblastic Tumor—A Challenge to Manage due to Its Rare Existence: A Case Report with Review of Literature

AbstractEpithelioid trophoblastic tumor (ETT) is the rarest type of gestational trophoblastic neoplasia. It has variable presentations and is an aggressive tumor. Because of its rarity, it is difficult to establish an appropriate diagnosis, management, and follow-up. A woman of age 45 years postmenopausal status with an antecedent term pregnancy 13 years back was diagnosed to have ETT in the hysterectomy specimen. She had come with urinary retention as the tumor was infiltrating the bladder. Beta-human chorionic gonadotropin levels were normal. Immunohistochemistry confirmed the diagnosis. Though metastatic workup was normal, adjuvant multiagent chemotherapy was given as the bladder flap margin was not free of tumor cells and antecedent pregnancy was > 4 years. Every new case of ETT needs to be reported to bring about more awareness of the unusual presentations, and it may help come to a consensus for appropriate management.

Evolution of Treatment Strategies for Gestational Trophoblastic Neoplasia: Chemotherapy, Immunotherapy, and Molecular Targeted Therapy.

In addressing Gestational Trophoblastic Neoplasia (GTN), it is imperative to acknowledge the evolving landscape of treatment options, especially in light of the challenges posed by traditional methods. While historically, surgical interventions, radiation therapy, and chemotherapeutic agents have been the mainstays, the emergence of resistance and high-risk scenarios necessitates a reevaluation of our therapeutic approaches. Our review highlights the promising advancements in immunotherapy and molecular targeted therapy as viable alternatives for GTN management. The introduction of immune checkpoint inhibitors and kinase inhibitors offers a paradigm shift, particularly for patients resistant to conventional chemotherapy regimens. These novel therapies not only exhibit efficacy but also demonstrate manageable toxicity profiles, particularly in high-risk cases. However, integrating these innovative treatments into established international guidelines presents a formidable task. As we move forward, it is imperative that future research not only prioritizes fertility preservation but also rigorously evaluates long-term toxicity implications. International collaboration becomes pivotal in addressing the nuances of this rare and complex disease. In conclusion, our review underscores the need for a nuanced approach to GTN treatment, one that prioritizes reduced toxicity and improved quality of life. By embracing the advancements in immunotherapy and molecular targeted therapy, we can pave the way for more effective and patient-centered care in the management of GTN.

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 estimationand 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.

Gestational Trophoblastic Choriocarcinoma with Lung Metastasis: A Case Report

Background: The choriocarcinomais rare highly aggressive malignant tumor of gestational trophoblastic neoplasia with increasing rate of hematogenous spread to distant organ particularly to the lung. The mortality rate of chroiocarcinoma before chemotherapy management was 90% but advanced chemotherapy approach had contributed to favorable prognostic outcome and more than 90% curative rate.

Presenting Features and Outcomes of Gestational Trophoblastic Neoplasia: A Case Series from a Single Institution

Presenting Features and Outcomes of Gestational Trophoblastic Neoplasia: A Case Series from a Single Institution

Relationship Between Risk Factors and The Incidence of Gestational Trophoblastic Neoplasia at RSUP Dr. M. Djamil Padang Year 2019-2021

Relationship Between Risk Factors and The Incidence of Gestational Trophoblastic Neoplasia at RSUP Dr. M. Djamil Padang Year 2019-2021

The Role of Methotrexate Chemotherapy in Impeding Rupture - Low-Risk Gestational Trophoblastic Neoplasia Management: A Case Report

The Role of Methotrexate Chemotherapy in Impeding Rupture - Low-Risk Gestational Trophoblastic Neoplasia Management: A Case Report

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.

Atypical Presentation of Gestational Trophoblastic Neoplasia Imparting Lesson: A Case Series and Review of Literature

Atypical Presentation of Gestational Trophoblastic Neoplasia Imparting Lesson: A Case Series and Review of Literature

Epithelioid trophoblastic tumor with lung metastasis: A case report and literature review.

Epithelioid trophoblastic tumor (ETT) is an extremely rare variant of gestational trophoblastic neoplasms (GTNs). The biological behavior and therapeutic schedule of ETT remains to be defined which frequently poses diagnostic and therapeutic challenges. Although ETT is a relatively indolent malignancy tumor, the therapeutic efficacy and survival rate decrease significantly when presented with metastases. The lung is the most common site of ETT metastasis. A 39-year-old female patient presented with irregular vaginal bleeding and slight distention pain in lower abdomen. The patient was diagnosed ETT with lung metastasis after surgery and immunohistochemical staining. A total abdominal hysterectomy plus bilateral salpingectomy and histopathology were performed. The patient received 3 cycles of etoposide, methotrexate, actinomycin-D/etoposide, cisplatin (EMA/EP) regimen chemotherapy after surgery. Due to the presence of lung metastasis, she received pulmonary lesion resection and another cycle of postoperative chemotherapy. The patients showed a good response to treatment initially. However, the patient did not complete the full initial treatment for family reasons and had signs of recurrence after 2.5 months. The serum β-hCG level gradually elevated and the lung imaging showed that the lesion area gradually expanded. After 15 months of follow-up, the patient declined further treatment due to a lack of presenting symptoms. The diagnosis of ETT should be taken into consideration in patients with abnormal vaginal bleeding and low levels of β-hCG. Patients with metastatic disease should be treated with complete surgical resection and intensive combination chemotherapy to maximize the opportunity for cure. Targeted biological agents might be potential therapeutic strategies for chemotherapy-resistant or recurrent patients.

Twin Pregnancy Coexisting with Partial Mole and Normal Fetus: A Case Report

This case report highlights the rare occurrence of a twin pregnancy coexisting with a partial mole, presenting a unique set of challenges in management and outcome. A 20-year-old woman with primary subfertility conceived twins following ovulation induction, experiencing hyperemesis gravidarum and subsequently developing severe preeclampsia. Despite efforts to control her condition, termination of the pregnancy was necessary due to maternal safety concerns. Both twins, without anomalies, succumbed to early neonatal death. Histopathological examination revealed a partial mole. The case emphasizes the importance of vigilant monitoring and individualized treatment in such complex pregnancies, with a focus on maternal well-being. Continued follow-up is crucial to detect and manage potential gestational trophoblastic disease. This report underscores the need for informed decision-making and patient-centered care in managing twin pregnancies coexisting with molar tissue.

Molar pregnancy: a qualitative study of personal experiences and societal narratives of loss

Background/Aims Molar pregnancy is a rare complication of pregnancy. Patients face surgery, human chorionic gonadotropin monitoring and potentially systemic treatment, resulting in unique support needs. This study's aim was to explore the impacts of gestational trophoblastic disease on embodied and emotional experience. Methods This qualitative study considered stories of molar pregnancy from 20 women in the UK, US, Canada and Australia. These were drawn from 18 publicly available online blogs and eight semi-structured interviews, and analysed thematically. Results Three themes were developed: ‘loss’, describing women's responses to their pregnancy ending; ‘isolation’, comprising ‘rarity’, ‘lack of awareness’ and support seeking; and ‘alienation’, capturing the unfamiliarity of diagnosis, ‘failure’ and barriers to ‘moving forward’. Conclusions Experiences are shaped by wider narratives of ‘typical’ pregnancy. Patient care requires an individualised and responsive approach, and non-specialist practitioners should feel confident in discussing molar pregnancy and have access to up-to-date guidance.

A study on histomorphological analysis of gestational trophoblastic disease

Abstract Background: Gestational trophoblastic disease (GTD) represents a diverse group of conditions characterized by abnormal trophoblastic proliferation within the placenta. GTD includes benign and malignant lesions, ranging from complete and partial hydatidiform moles to more severe forms like invasive moles, choriocarcinoma, placental site trophoblastic tumors (PSTTs), and epithelioid trophoblastic tumors. Given that neoplastic GTD lesions respond remarkably well to chemotherapy, early and accurate histopathological diagnosis is crucial as it directly influences treatment and prognosis. Aim and Objectives: This study examined the histomorphological features of various types of GTD alongside key clinical factors such as age, parity, and gestational period. Materials and Methods: The study was conducted in the Department of Pathology over the course of10 years, from January 2014 to January 2024. All cases of GTD confirmed through histopathological examination of hematoxylin and eosin-stained slides were included in the analysis. Results: Out of 60 diagnosed cases of GTD, 34 (56.66%) were complete hydatidiform moles, 22 (36.67%) were partial hydatidiform moles, 1 (1.67%) was an invasive mole, 1 (1.67%) was choriocarcinoma, and 2 (3.33%) were PSTTs. The age of the affected patients ranged from 18 to 45 years, with the highest incidence observed in the 20–25 year age group (30 cases, 50%). Most cases (33, 55%) occurred during the first trimester, with a predominance among primigravida patients (28 cases, 46.66%). The most common clinical presentation was per vaginal bleeding, reported in 56 cases (93.33%). Conclusion: Although GTD can lead to serious complications, including metastasis, it is treatable. In this study, the complete hydatidiform mole was the most frequently encountered lesion and is associated with a higher risk of severe complications such as persistent GTD, invasive moles, and choriocarcinoma. Thus, early and accurate histopathological diagnosis is vital for the timely initiation of therapy, ultimately reducing the mortality rate. This study highlights the various categories and histomorphological features of GTD, emphasizing the importance of understanding its clinical presentation to mitigate disease burden and complications.