Choriocarcinoma with multiple lung metastases from complete hydatidiform mole with coexistent fetus during pregnancy.

Gestational trophoblastic neoplasm (GTN) is a serious morbidity of complete hydatidiform mole with coexistent fetus (CHMCF) and usually develops after termination of pregnancy. Here we report a case of choriocarcinoma derived from CHMCF during pregnancy. A 33-year-old multiparous woman with suspected CHMCF was admitted with a severe cough. Computed tomography revealed multiple lung metastases. Cesarean section and hysterectomy were performed at 31 weeks of gestation on diagnosis of high-risk GTN from International Federation of Gynecology and Obstetrics (FIGO) scoring. A live female infant weighing 1390 g was delivered. Choriocarcinoma was diagnosed from pathological findings. The patient received multi-agent chemotherapy and was discharged on the 40th postoperative day. In conclusion, CHMCF can result in high-risk GTN during pregnancy. For a suspected GTN, diagnosis from FIGO scoring should determine treatment strategy. If patients with CHMCF wish to continue their pregnancy, careful follow-up, including regular chest radiography and ultrasonography, is warranted.

Long-term outcome of patients with persistent low-level elevation of human chorionic gonadotrophin.

AIM: The aim of this study was to investigate a series of patients with sustained low-level elevated human chorionic gonadotrophin (hCG) and explore the management of these patients. METHODS: A total of 47 patients with persistent low levels of hCG were selected for analysis between January 2002 and January 2014 at the Women's Hospital of Zhejiang University, Hangzhou, China. Data were retrospectively reviewed for patient characteristics, therapeutic strategies, and follow-ups. We compared the characteristics of patients who were and were not eventually considered to have malignancies. RESULTS: Among the 47 patients, 17 with persistent low-level elevated hCG and no detectable lesions were considered to have no active malignancy. Fifteen of the 17 patients had hCG levels that returned to normal range by the end of follow-up, while the remaining two did not. The other 30 patients were eventually diagnosed as having active malignancies due to detected lesions or increasing elevation of hCG. A large proportion of these patients were diagnosed with placental site trophoblastic tumor or epithelioid trophoblastic tumor. CONCLUSION: For patients with persistent low-level elevated hCG, frequent follow-up rather than any therapy is recommended. Treatment was considered effective and safe once diagnosis of active malignancy was confirmed.

Uterine perforation associated with gestational trophoblastic disease and arteriovenous malformation: A case report.

This case report outlines the clinical course of a young woman who presented as haemodynamically unstable due to uterine perforation. She had undergone suction dilation and curettage three weeks prior and received a diagnosis of complete molar pregnancy. During her most recent acute presentation, an emergency laparotomy revealed a full-thickness fundal uterine rupture in a region of newly identified arteriovenous malformation. Haemostasis was achieved with the primary repair of the perforation. She was subsequently diagnosed with gestational trophoblastic neoplasm (GTN), a condition characterised by abnormal proliferation of trophoblastic tissue. She received three courses of methotrexate followed by a two-month course of dactinomycin. At one-year surveillance, she had made a complete recovery.

Uterine epithelioid trophoblastic tumor with the main manifestation of increased human chorionic gonadotropin: A case report.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding, abdominal pain, and increased human chorionic gonadotropin (hCG). This study reported a case of uterine ETT with the main manifestation being increased hCG. CASE SUMMARY: A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022, complaining of increased hCG levels for 1 month. Magnetic resonance imaging revealed gestational trophoblastic tumor, and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed. The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results. Total laparoscopic hysterectomy and bilateral salpingectomy were performed, and hCG levels returned to normal. The patient was without recurrence during the postoperative 3-month follow-up. CONCLUSION: This study reported a case of uterine ETT with the main manifestation being increased hCG, highlighting that ETT should be considered in the presence of abnormal hCG. A total laparoscopic hysterectomy is recommended.

Progress of immunotherapies in gestational trophoblastic neoplasms.

BACKGROUND: Different from other malignant gynecologic tumors, gestational trophoblastic neoplasms (GTNs) exhibit an exceptionally high cure rate primarily through chemotherapeutic interventions. However, there exists a small subset of refractory GTNs that do not respond to conventional chemotherapies. In such cases, the emergence of immunotherapies has demonstrated significant benefits in managing various challenging GTNs. PURPOSE: This article aims to provide a comprehensive and systematic review of the immune microenvironment and immunotherapeutic approaches for GTNs. The purpose is to identify potential biomarkers that could enhance disease management and summarize the available immunotherapies for ease of reference. METHODS: We reviewed the relevant literatures toward immunotherapies of GTNs from PubMed. CONCLUSION: Current immunotherapeutic strategies for GTNs mainly revolve around immune checkpoint inhibitors (ICIs) targeting programmed death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1). Prominent examples include avelumab, pembrolizumab, and camrelizumab. However, existing researches into the underlying mechanisms are still limited.

Does diffusion weighted imaging have a prognostic value in differentiating gynecological diseases?

INTRODUCTION: Apparent diffusion coefficient (ADC) values are effective in the diagnosis of different gynecological lesions. METHODS: A retrospective evaluation was made of 12 patients with uterine cervix carcinoma and 151 patients with uterine lesions, comprising endometrial cancer, endometrial polyps, carcinosarcoma, submucous myoma, adenomyosis, endometrial hyperplasia, gestational trophoblastic neoplasm (GTN), and leiomyomas. As a control group, 20 healthy volunteers with normal endometrium and normal cervix were also evaluated. In three series, one-shot, spin echo, echo planar, b = 1000 s/mm2 value and diffusion-weighted imaging (DWI) were applied to all subjects and ADC values were obtained. RESULTS: The mean ADC values of Group 1 (Endometrial carcinoma) were lower than those of all the other groups (P < 0.001) and the mean ADC value of group 6 (GTN) was higher than that all other groups (P < 0.001). A statistically significant difference was found between the groups in terms of the lesion-myometrium ADC ratios (P < 0.001). CONCLUSION: There are few studies in literature related to ADC measurements in GTN. The ADC values of GTN were found to be significantly higher than the other uterine lesions. These results will aid in the design of future studies and might be used to guide management of patients with GTN. IMPLICATIONS FOR PRACTICE: Diffusion-weighted MRI seems to be a promising imaging technique in differentiating different uterine lesions.

An Extremely Rare Case of Splenic Rupture Secondary to Metastatic Gestational Choriocarcinoma.

Gestational choriocarcinoma (GC) is an uncommon malignant tumor consisting of trophoblastic cells. The lungs, liver, and central nervous system are the most common metastatic sites for this disease. However, splenic metastasis is unusual and might result in spontaneous rupture. Symptoms associated with splenic rupture may be the first presentation of malignancy. A thorough medical history and examination are necessary to detect the primary lesion. Herein, we present a case of a 23-year-old female who had splenic rupture secondary to choriocarcinoma metastasis. Although the emergency condition had been solved, the patient died 1 month after due to brain metastasis. The goal of this article was to report a new case of spontaneous splenic rupture caused by choriocarcinoma metastasis and to review the existing literature on splenic metastases associated with GC, including the epidemiology and etiology.

Core 2 ß1,6-N-acetylglucosaminyltransferases accelerate the escape of choriocarcinoma from natural killer cell immunity.

Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted from choriocarcinoma and contains a core2 O-glycan formed by core2 ß1,6-N-acetylglucosaminyl transferase (C2GnT). Choriocarcinoma is considered immunogenic as it is gestational and contains paternal chromosomal components. Here we examined the function of C2GnT in the evasion of choriocarcinoma cells from natural killer (NK) cell-mediating killing. We determined that C2GnT is highly expressed in malignant gestational trophoblastic neoplasms. C2GnT KO downregulates core2 O-glycan expression in choriocarcinoma cells, which are more efficiently killed by NK cells than control cells. C2GnT KO cell containing tumor necrosis factor-related apoptosis inducing ligand have lower viability than control cells. Additionally, poly-N-acetyllactosamine in core2 branched oligosaccharides on MHC class I-related chain A (MICA) and mucin1 (MUC1) is significantly reduced in C2GnT KO cells. Meanwhile, the cumulative survival rate of nude mice inoculated with C2GnT KO tumors was higher than that of the control group. These findings suggest that choriocarcinoma cells may escape NK cell-mediated killing via glycosylation of MICA and MUC1.

Gestational Trophoblastic Neoplasia With Urinary System Metastasis: A Single Center Experience.

Background: Gestational trophoblastic neoplasia (GTN) with urinary system metastasis is rare. There is limited information about this situation. This study aimed to analyze clinical features, prognostic factors, and survival outcomes of patients with metastasis to the urinary system arising from GTN. Methods: Medical records of 53 consecutive GTN patients with urinary system metastases and treated at Peking Union Medical College Hospital (PUMCH) between 1990 and 2018 were reviewed. The Kaplan-Meier survival analysis was used to describe the overall survival. Prognostic factors were identified using univariate and multivariate analyses. Results: Fifty-three GTN patients with urinary tract metastasis were identified in our institution. The mean age of patients was 30.8 years (range, 23-53 years). Thirty-six (67.9%) patients achieved complete remission (CR), and the remaining 17 (32.1%) showed progressive disease. The 5-year overall survival rate of the entire cohort was 78.4%. Age ≥ 40 years was an independent risk factor for prognosis (HR 12.353, 95% CI 2.203-69.261, P = 0.004). Previous failed chemotherapy history (P = 0.040) and the presence of brain and/or liver metastases (P = 0.024) significantly influenced the survival of GTN patients with urinary tract system metastasis. Conclusion: GTN with urinary tract metastasis is a rare condition. Patients with different metastatic sites have different CR rates and prognosis. Therefore, individualized strategies should be considered for patients with different metastatic sites. Urinary system metastasis is probably not a prognostic factor in GTN patients. Patients aged ≥40, those who had previous failed multidrug chemotherapy, and presented brain and/or liver metastases showed a significant adverse outcome.

Choriocarcinoma After Normal Vaginal Delivery; A Rare Entity.

Choriocarcinoma is a malignant gestational trophoblastic neoplasm with rare postpartum presentation. Its manifestation after full term delivery is very rare with paucity of data reported from Pakistan. We received a patient in the postpartum period with symptoms of distant metastasis. She was diagnosed with choriocarcinoma based on our workup and was referred for chemotherapy after management. Now she is receiving follow-up care.

Treatment results of the second-line chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia treated with 5-day methotrexate and 5-day etoposide.

OBJECTIVE: Highly effective chemotherapy for patients with low-risk gestational trophoblastic neoplasia (GTN) is associated with almost a 100% cure rate. However, 20%-30% of patients treated with chemotherapy need to change their regimens due to severe adverse events (SAEs) or drug resistance. We examined the treatment outcomes of second-line chemotherapy for patients with low-risk GTN. METHODS: Between 1980 and 2015, 281 patients with low-risk GTN were treated. Of these 281 patients, 178 patients were primarily treated with 5-day intramuscular methotrexate (MTX; n=114) or 5-day drip infusion etoposide (ETP; n=64). We examined the remission rates, the drug change rates, and the outcomes of second-line chemotherapy. RESULTS: The primary remission rates and drug resistant rates of 5-day ETP were significantly higher (p<0.001) and significantly lower (p=0.002) than those of 5-day MTX, respectively. Forty-seven patients (26.4%) required a change in their chemotherapy regimen due to the SAEs (n=16) and drug resistance (n=31), respectively. Of these 47 patients failed the first-line regimen, 39 patients (39/47, 82.9%) were re-treated with single-agent chemotherapy, and 35 patients (35/39, 89.7%) achieved remission. Four patients failed second-line, single-agent chemotherapy and eight patients (17.0%) who failed first-line regimens were treated with combined or multi-agent chemotherapy and achieved remission. CONCLUSIONS: Patients with low-risk GTN were usually treated with single-agent chemotherapy, while 20%-30% patients had to change their chemotherapy regimen due to SAEs or drug resistance. The second-line regimens of single-agent chemotherapy were effective; however, there were several patients who needed multiple agents and combined chemotherapy to achieve remission.

A pilot randomized controlled clinical trial of second uterine curettage versus usual care to determine the effect of re-curettage on patients' need for chemotherapy among women with low risk, nonmetastatic gestational trophoblastic neoplasm in Urmia, Iran.

OBJECTIVE: The objective of this study was to determine if second curettage was associated with a decreased need for the number of chemotherapy treatments compared to usual care. METHODS: A pilot randomized controlled clinical trial was designed at Motahhari Referral Hospital in 2014. Fifty-two patients with low risk, nonmetastatic gestational trophoblastic neoplasm were assigned randomly to two arms. The interventional arm included a repeat uterine curettage, and the control group received standard care (chemotherapy). All participants were followed periodically over 6 months. Primary outcome was defined as the number of chemotherapy courses in each arm. Student's t-test and receiver operator characteristics (ROC) curve were applied for statistical analysis as appropriate. RESULTS: Fifty percent of participants who underwent re-curettage did respond to intervention with no further chemotherapy after 6 months of follow-up. The intervention arm had higher number of remissions without chemotherapy compared to those who received usual care. In the subgroup analysis, the ROC curve could predict the re-curettage treatment response by beta human chorionic gonadotropin (BhCG) level significantly. No complications were reported in the intervention arm. CONCLUSION: Second curettage is an alternative effective procedure to decrease the need for chemotherapy among patients with low risk, nonmetastatic gestational trophoblastic neoplasm. Further clinical trials with larger sample size may be needed to determine the effective role of second curettage among patients.

Primary choriocarcinoma in mediastinum with multiple lung metastases in a male patient: A case report and a review of the literature.

Primary choriocarcinoma is a rare malignant tumor, particularly in men. The tumor, mostly found in the gastrointestinal system and mediastinum, often metastasizes early with poor therapeutic effects and prognosis. Herein, we present a male patient with primary mediastinum choriocarcinoma and widespread lung metastases. The disease progressed rapidly with little therapeutic effect from chemotherapy. The patient died of this disease 75 days after initial symptom presentations. Literature review found only 41 cases of primary choriocarcinoma reported in the mediastinum. This case highlights the importance of keeping primary choriocarcinoma in the differentials for mediastinum tumors in young men. Sex hormone testing is helpful to confirm diagnosis. Early biopsy should be performed to confirm pathologic diagnose, and early surgery and chemotherapy should be considered to improve the cure rate of this disease.

Diagnostic challenges in cornual epithelioid trophoblastic tumor.

OBJECTIVE: We present a case of primary cornual epithelioid trophoblastic tumor (ETT) because of its rarity and diagnostic and therapeutic challenge. CASE REPORT: A 28-year-old woman, gravida 1, para 1, who missed menstruation for 3 months, had an elevated ß-human chorionic gonadotropin serum level of 2764 mIU/mL, an absence of intrauterine pregnancy, and the presence of an adnexal mass detected by transvaginal ultrasound. As an ectopic pregnancy was suspected, laparoscopic surgery was performed and showed a right corneal mass. Complete excision of the tumor was done through exploratory laparotomy. Frozen pathology favored the diagnosis of squamous cell carcinoma. Since there was no apparent tumor at other sites, no additional surgery was done. The final pathology showed ETT. Primary ETT is often misdiagnosed as an ectopic pregnancy, leading to delayed treatment, and poses a diagnostic challenge in distinguishing it from squamous cell carcinoma during pathological examination. CONCLUSION: Careful evaluation and avoidance of overtreatment are emphasized.

Placental site trophoblastic tumor: Immunohistochemistry algorithm key to diagnosis and review of literature.

•Histologic morphology is frequently equivocal for PSTTs.•Histology combined with immunohistochemical staining was necessary to make the diagnosis.•PSTT confined to the uterus was successfully treated with surgery alone.

Unilateral hydronephrosis caused by invasive mole: a case report.

Invasive mole belongs to gestational trophoblastic neoplasm, which is a highly curable group of pregnancy-related tumors. However, approximately 20% of gestational trophoblastic tumors will be resistant to or relapsed after initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. It is still unclear which regimens are the most effective and least toxic. Here, we report a case of unilateral hydronephrosis presenting 1 week after a history of curettage because of a hydatidiform mole. With the combination treatments of chemotherapy and surgery, the patient was cured.

Diagnosis and treatment of placental site trophoblastic tumor.

Here we report a case of a placental site trophoblastic tumor in a 36 year old Chinese woman, 31 months following a prior normal pregnancy. Her clinical presentation and ultrasound findings were uncharacteristic; and the final definitive diagnosis was established based on histological examination in conjunction with immunohistochemistry studies and a normal beta human chorionic gonadotropin level. The tumor exhibited high grade histological features with tumor necrosis, nuclear atypia and high mitosis. The patient was successfully treated with hysterectomy with pre- and post-operative chemotherapy.

Major surgeries performed for gestational trophoblastic neoplasms in a teaching hospital in Tehran, Iran.

OBJECTIVE: This study aim was to evaluate indications and outcomes of surgical interventions performed in patients with gestational trophoblastic neoplasm. METHODS: During January 1995 to December 2005, 110 patients with a diagnosis of persistent gestational trophoblastic neoplasm were treated in our Gynecologic Oncologic Department. Risk score calculation was carried out based on the revised FIGO 2000 scoring system for gestational trophoblastic neoplasm. Data from the patients' records and pathologic reports were analyzed by the chi-square and Fisher's exact tests and logistic regression. The Kaplan-Meier method including the log rank test was used to compare survival and recurrence. RESULTS: Eight patients did not complete their treatment and were excluded from the study. We evaluated treatment responses and outcomes in 102 patients. Seventy-nine patients (77.5%) responded fully to chemotherapy while 23 patients (22.5%) required surgery. Among 23 patients who underwent surgery, 10 cases (43.5%) had bleeding, and 13 cases (56.5%) had drug resistance. Several factors were found to be significantly different between the groups who responded to chemotherapy and those who needed surgery, including age (p=0.001), antecedent non-molar pregnancy (0.028), tumor stage (p=0.009), and pre-treatment risk scores (p=0.008). But, the total courses of chemotherapy (p=0.521), need to salvage chemotherapy (p=0.074), survival rates (p=0.714), and disease free survival rates (p=0.206) were not significantly different. CONCLUSION: The data suggest that age, antecedent non-molar pregnancy, tumor stage and the prognostic score are clinical predictors of need for surgery. But, it dose not seem that surgery have any effect on the total course of chemotherapy, need for salvage chemotherapy, and patient prognosis.