Postpartum choriocarcinoma - a rare cause of delayed postpartum hemorrhage: Four case reports and literature review.

BACKGROUND: Delayed postpartum hemorrhage is rare, with an incidence of 0.5% to 2.0% in all pregnancies. The most important causes are placental remnants, infections, and placental bed subinvolution. Postpartum choriocarcinoma, a highly malignant complication of pregnancy, is a rare condition that can be easily misdiagnosed as other common causes, such as gestational remnants, and delays the diagnosis. METHODS: Four patients visited our clinic complaining of delayed postpartum hemorrhage, combined with respiratory and neurological symptoms in 2 cases. Two cases were confirmed by histopathological examination and in addition, medical history, elevated human chorionic gonadotropin (hCG) level, and imaging findings help confirm the diagnosis of delayed postpartum hemorrhage caused by postpartum choriocarcinoma in other cases. Individualized combination chemotherapies were prescribed. In the light of massive cerebral metastasis in case 2, intrathecal methotrexate injection combined with whole-brain radiotherapy was prescribed. RESULTS: Due to the absence of routine monitoring of ß-hCG following full-term delivery, there was widespread metastasis at the time of diagnosis. Three patients got complete remission and there is no sign of recurrence. One patient had relapse and widespread metastasis and died at home 6 months after the last chemotherapy. CONCLUSION: It is important to be aware of the possibility of choriocarcinoma in patients with delayed postpartum hemorrhage. Clinicians should improve the recognition of choriocarcinoma following full-term delivery, emphasize the monitoring of ß-hCG, comprehensively analyze the general condition of patients, and conduct standardized and individualized chemotherapy protocols.

Post molar choriocarcinoma with solitary renal metastasis in the absence of primary uterine tumor: a case report and review of the literature.

BACKGROUND: Choriocarcinoma is a rare and highly malignant form of gestational trophoblastic disease that may develop following pregnancy, abortion, or a hydatiform mole. Renal metastatic involvement by post molar choriocarcinoma is even rarer. In this case report, we describe a unique case of post molar choriocarcinoma with a solitary renal metastasis in the absence of a primary uterine tumor and metastases in other sites, which presented with urological symptoms and spontaneous renal hemorrhage. CASE PRESENTATION: A 41-year-old Persian woman with history of complete hydatiform mole presented with severe flank pain, nausea, vomiting, gross hematuria, and vaginal bleeding. Laboratory tests demonstrated a serum beta human chorionic gonadotropin hormone level of 60,000 mIU/mL. Imaging studies showed a lesion at the lower pole of the left kidney with active bleeding surrounded by hematoma, as well as an empty uterine cavity. Additionally, bilateral pleural effusion was detected without any lesion within the lungs. Subsequently, the patient underwent laparotomy, partial nephrectomy, and left para-ovarian cystectomy. Endometrial curettage was also carried out. The histopathology report revealed choriocarcinoma renal metastasis with high expression of beta human chorionic gonadotropin, cytokeratin 7, and Ki 67. Moreover, there were no malignant cells in the endometrial curettage specimens, and a corpus luteum cyst was found within the para-ovarian cyst. Further investigations revealed that the pleural effusion was free of malignant cells, and there was no evidence of metastatic lesions in the brain. As a result, the patient was referred to the oncology department to receive chemotherapy, and the beta human chorionic gonadotropin levels dropped to 5 mIU/mL after receiving courses of a standard regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine/oncovin over 3 weeks. Finally, monthly measurements of beta human chorionic gonadotropin levels for 6 months indicated that levels have constantly remained within normal ranges, showing no evidence of recurrence or new metastasis. CONCLUSIONS: Urological symptoms such as hematuria or spontaneous renal hemorrhage might be the only presentation of post molar choriocarcinoma with renal involvement. Thus, it can be beneficial to measure serum beta human chorionic gonadotropin levels among females of childbearing age who present with unexplained urological symptoms, especially if there is a history of prior hydatiform mole.

Successful diagnosis of asymptomatic choriocarcinoma by ultrasonography during a viable pregnancy: A rare case report.

BACKGROUND: Gestational choriocarcinoma occurs very rare in conjunction with pregnancy and it is camouflage for diagnosis. METHODS: We present a rare case of asymptomatic choriocarcinoma in a viable pregnancy that was successfully diagnosed by ultrasonography and had timely treatment. RESULTS: According to the ultrasonography, early diagnosis and treatment monitoring of choriocarcinoma during a viable pregnancy was administered and the newborn was discharged. CONCLUSION: Choriocarcinoma in pregnancy is camouflaged, and its clinical presentation varies widely. Despite an asymptomatic status, metastasis can occur, and ultrasonography is important for early diagnosis and treatment monitoring.

Chemotherapy is not needed when complete evacuation of gestational choriocarcinoma leads to hCG normalization.

BACKGROUND: The standard treatment for gestational choriocarcinoma is chemotherapy. OBJECTIVE: To describe the risk of recurrence with expectant management of gestational choriocarcinoma that has reached a normal human chorionic gonadotropin level after tumor removal without adjuvant chemotherapy. METHODS: A retrospective multicenter international cohort study was conducted from 1981 to 2017 involving 11 gestational trophoblastic disease reference centers with patient's follow-up extended until 2023. Clinical and biological data of included patients were extracted from each center's database. The inclusion criteria were i) histological diagnosis of gestational choriocarcinoma in any kind of placental tissue retrieved, ii) spontaneous normalization of human chorionic gonadotropin level following choriocarcinoma retrieval, iii) patient did not receive any oncological treatment for the choriocarcinoma, iv) and at least 6 months of follow-up after the first human chorionic gonadotropin level normalization. RESULTS: Among 80 patients with retrieved gestational choriocarcinoma and whose human chorionic gonadotropin level normalized without any other oncological therapy, none had a recurrence of choriocarcinoma after a median follow-up of 50 months. The median interval between choriocarcinoma excision and human chorionic gonadotropin level normalization was 48 days. The International Federation of Gynecology and Obstetrics/World Health Organization risk score was ≤6 in 93.7% of the cases. CONCLUSIONS: This multicenter international study reports that selected patients with gestational choriocarcinoma managed in gestational trophoblastic disease reference centers did not experience any relapse when the initial tumor evacuation is followed by human chorionic gonadotropin level normalization without any additional treatment. Expectant management may be a safe approach for highly selected patients.

Intracardiac metastasis of gestational choriocarcinoma: a case report and literature review.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) with intracardiac metastasis is rare, and here we reported a patient with intracardiac metastasis of high-risk and refractory gestational choriocarcinoma and reviewed relevant literatures. CASE PRESENTATION: A 37-year-old woman presented with vaginal bleeding and high level of ß-human chorionic gonadotropin (ß-hCG) at 199,060 (mIU/mL). It was clinically diagnosed with gestational choriocarcinoma. The patient initially received eight cycles of chemotherapy but unsatisfactory response was observed, and the level of ß-hCG still ranged between 5000 and 10,000. Then there was found intracardiac masses in the right atrium (2.6*1.7 cm), anterior chordae tendineae of the tricuspid valve (1.4*0.7 cm) and the right ventricle (4.1*2.9 cm) by ultrasonic cardiogram (UCG). PET/CT highly suspected the intracardiac metastasis of choriocarcinoma (SUVmax = 9.3) and no disease was found in the lung and pelvis. The patient undertook complete intracardiac masses resection. The pathology confirmed the intracardiac metastasis of disease. After a week of operation, the UCG found a 5.4*4.2 cm mass in the right atrium again. Considering the poor prognosis, the patient received palliative care and eventually died of disease progression. CONCLUSION: Intracardiac metastasis of GTN is an aggressive sign of disease. Patients can benefit from chemotherapy and surgery. Future investigation of PD-1 immunotherapy combines with chemotherapy are expected to improve the prognosis in this group of patients.

Clinical features of gestational choriocarcinoma: A retrospective bicentric study.

OBJECTIVE: To investigate the clinicopathological features, prognostic factors, treatment, clinical response, and outcome of gestational choriocarcinoma (GCC). MATERIALS AND METHODS: A retrospective review was made of the clinicopathological and survival data of 13 patients who were diagnosed and treated for GCC in two referral centers in Turkey between 1992 and 2020. RESULTS: The median age of patients was 36 years (range, 27-54 years), and seven were ≤39 years. The antecedent pregnancy was a term in nine (69.2%) cases, and the risk score was ≥7 in 11 (84.6%). According to the International Federation of Gynecology and Obstetrics 2009 staging, eight cases were in stage I, two in stage III, and three in stage IV. With the exception of one patient, all the others received combination chemotherapy (CT), and two of those were also treated with radiotherapy. Chemoresistance developed in 50% (6/12), and second-line CT was given to four of these. The overall complete response rate was 69.2%. Four patients died of chemoresistance and disease progression, all of them were with antecedent-term pregnancy, had high scores ≥7, and had metastases. CONCLUSION: GCC is a unique subtype of gestational trophoblastic neoplasia, which differs from others in terms of poor prognosis, a frequent tendency to early metastasis, and resistance to treatment. To be able to achieve the most efficient therapy and prognosis, histopathology-based risk models should be developed.

Fertility-Sparing Treatment in Gestational Choriocarcinoma: Evaluating Oncological and Obstetrical Outcomes in Young Patients.

BACKGROUND Gestational choriocarcinoma (GC) is an uncommon neoplasia that occurs in women who may not have completed a procreation plan. The aim of this study was to evaluate oncological and obstetrical outcomes in young patients with GC after fertility-sparing treatment. MATERIAL AND METHODS The eligibility criteria for the study were histopathological diagnosis of GC, age ≤40 years, and treatment with systemic chemotherapy. Patients who underwent upfront hysterectomy were excluded. The response to treatment was assessed according to beta-human chorionic gonadotropin (beta-hCG) serum measurement. Complete response and progression were considered if the beta-hCG dropped to a normal range and increased (or reached a plateau), respectively. The birth rate was calculated as the number of women who gave birth after treatment divided by the total number of patients. RESULTS A total of 18 patients fulfilled the study's eligibility criteria. A complete response and progression to first-line chemotherapy were found in 13 (72.22%) and 5 (27.78%) patients, respectively. Salvage treatment was administered to patients with progression. Overall, 16 (88.88%) patients achieved complete response after treatment and 2 (11.12%) died. GC relapse was diagnosed in 1 patient 62 months after treatment. The birth rate was 22.22%, and a total of 6 children were born. All pregnancies ended in term delivery. No congenital abnormalities were detected in the newborns. CONCLUSIONS GC is a life-threatening form of gestational trophoblastic neoplasia, mainly due to its rapid course and resistance to chemotherapy. Most patients with GC will not be able to bear children after treatment.

A case of complete remission of intractable gestational choriocarcinoma with subsequent chemotherapy after pembrolizumab.

OBJECTIVE: Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) that originates from abnormal trophoblast proliferation. Although chemotherapy is effective for choriocarcinoma, personalized treatment becomes essential when patients develop chemoresistance. Here, we present the clinical course of a case of intractable choriocarcinoma that achieved complete remission with pembrolizumab following cytotoxic chemotherapy. CASE REPORT: A 38-year-old woman was initially diagnosed with low-risk GTN and treated with single- and multi-agent chemotherapy. She underwent a hysterectomy and was diagnosed with pathological choriocarcinoma with high-risk GTN. She was treated with multiple courses of several chemotherapy regimens. However, she did not achieve remission. Her choriocarcinoma showed high microsatellite instability; therefore, she took ten courses of pembrolizumab, but her hCG value increased. Subsequently, she underwent eight courses of paclitaxel and carboplatin alternating with paclitaxel and etoposide and achieved remission. CONCLUSION: This case suggests that pembrolizumab may improve the efficacy of subsequent chemotherapy.

Recurrent choriocarcinoma complicated with leprosy during chemotherapy: A case report and literature review.

RATIONALE: The global prevalence of leprosy has decreased substantially, and cases of leprosy infection are extremely rare in China. In this report, we present a case of recurrent choriocarcinoma complicated by leprosy infection during chemotherapy. PATIENT CONCERNS: A 24-year-old Chinese woman (gravida 3, para 2) presented to a local hospital with vaginal bleeding. Her medical history included a previous diagnosis of hydatidiform mole. DIAGNOSES, INTERVENTIONS AND OUTCOMES: The patient was diagnosed with choriocarcinoma and received chemotherapy in 6 cycles. Shortly after the initial treatment was completed, the disease recurred twice with resistance to multiple chemotherapeutic agents. In her second recurrence of choriocarcinoma, she was diagnosed with leprosy with many cutaneous nodules throughout her entire body. The patient was administered chemical treatment for leprosy with the multidrug therapy regimen after being diagnosed. To prevent exacerbating the infection, no immunotherapy was utilized to treat cancer, and the infection was well-controlled at the conclusion of anticancer therapy. LESSONS: Because of immunological reduction, cancer patients are susceptible to a variety of infections. For patients with cancer, prevention and early detection of rare infectious diseases should receive special attention. Immunotherapy must be used with caution when treating patients with cancer and infections.

Metastatic choriocarcinoma of the kidney in the absence of existing primary uterine tumor: A rare presentation.

Gestational choriocarcinomas are malignant neoplasms generally arising in the uterus in women of childbearing age. These are aggressive tumors with a high incidence of metastasis to vascular organs such as the lung, liver, and brain. Renal metastasis is extremely rare with low incidence rate and very few cases have been reported in literature. Hereby, we report a rare case of metastatic choriocarcinoma to the kidney in a 29-year-old female 10 years after resection of a hydatidiform mole. The histopathological diagnosis was made on a nephrectomy specimen. Pelvic and abdominal scan did not show any abnormal radiological findings. She was started on first-line chemotherapy and showed a complete response. In conclusion, gestational or primary nongestational choriocarcinomas should always be considered as a differential diagnosis in young females of reproductive age group presenting with flank abdominal pain, unexplained hematuria, and atypical renal tumor histology.

Pure testicular choriocarcinoma with gastrointestinal metastasis and paraneoplastic symptoms: a case report.

BACKGROUND: Pure testicular choriocarcinoma is a rare type of non-seminomatous germ cell tumor extremely poor prognostic with the tendency to bleed at the metastatic site. At the time of the diagnosis, 70% of patients have metastatic lesions. Depending on the site of the metastasis, symptoms vary. Gastrointestinal involvement is seen in less than 5% of cases, mostly in the duodenum. CASE PRESENTATION: We present a 47 years old male with testicular choriocarcinoma involving the jejunum, lung, liver, and kidney presenting with acute abdominal pain, melena, and dyspnea with some paraneoplastic symptoms. The patient had increased, severe and constant pain in the right lower quadrant for the previous four days. Additionally, he was complaining of nausea, vomiting, anorexia, and a history of melena for the last 10 days. Dyspnea on exertion, hemoptysis, and dry cough were the symptoms he was suffering from, for almost one year. The patient's general appearance was pale, ill, and thin with 10 kg of weight loss during the last some months. The computed tomography (CT) scan reported multiple metastatic lesions in both liver lobes and the left kidney. Pathologic study of the samples of small bowel lesions showed metastatic choriocarcinoma. Following the patient had been referred to an oncologist to start the chemotherapy regime. Finally, the patient has expired after 40 days of his first admission. CONCLUSIONS: Testicular choriocarcinoma is a rare but fatal malignancy among young men. Gastrointestinal metastases are infrequent involvement represented by melena and acute abdominal pain, obstruction, and mass. Physicians should consider it as a differential diagnosis for acute abdomen and gastrointestinal bleeding causation.

Choriocarcinoma masquerading as lumbar spinal tumor: Case report and literature review.

RATIONALE: Choriocarcinoma is a highly invasive gestational trophoblastic neoplasm, usually metastasis to lung and brain, but occurrence of choriocarcinoma following spontaneous abortion presenting as a vertebral tumor is extremely rare, to the best of our knowledge. Because of the poor diagnosis and high malignancy, the low progression-free survival follows up. PATIENT CONCERNS: We here are reporting a case of choriocarcinoma that presented with vertebral tumor induced paralysis of limbs and incontinence of urine. DIAGNOSIS: Combined with the childbearing history, high ß-human chorionic gonadotrophinin levels, and imaging examination, a clinical diagnosis was made exactly. Till the pathological results after the operation of lumbar spinal canal tumorectomy, the diagnosis was exactly clear. INTERVENTIONS: After performing the laminectomy, the fierce bleeding follows up, just did the temporary limited decompression. Because of the vertebral artery embolization, lumbar spinal canal tumorectomy, spinal canal and root canal decompression, subdural decompression and hematoma removal were performed. OUTCOMES: After performing the operation and chemotherapy timely and positively, the patient lost consciousness and died due to the pulmonary embolism at last. LESSONS: This is the first case report describing choriocarcinoma with metastases to the spine amongst Chinese population as well. Early metastasis is one of the marked tendencies of choriocarcinoma, but spine metastasis and the related spinal oppressional symptoms were found instead of vaginal bleeding in this case, which is indeed rare.

Primary cesarean scar choriocarcinoma: A case series and literature review.

OBJECTIVES: To provide clinical guidance for early diagnosis and effective management of primary cesarean scar choriocarcinoma, which is an extremely rare but highly malignant trophoblastic tumor. METHODS: This retrospective case series summarized the clinical courses of seven patients diagnosed with cesarean scar choriocarcinoma. RESULTS: We identified two patients in our institution with cesarean scar choriocarcinoma. In addition, details of the previous five patients were extracted from databases and analyzed to provide more clinical information. The seven patients had an average age of 31.14 years, their tumor sizes ranged from 2.0 to 6.5 cm, and their pretreatment serum ß-human chorionic gonadotropin (ß-hCG) levels ranged from 3664 to 312 468 mIU/mL. All the patients were categorized as having FIGO Stage I disease, with four patients at low risk and three at high risk. Six of the seven were misdiagnosed with ectopic pregnancy before pathologic examination. CONCLUSIONS: Clinicians should pay attention to masses in cesarean scar and to continuous elevation of serum ß-hCG levels after treatment. When cesarean scar choriocarcinoma is suspected, diagnostic surgery can be chosen for tentative treatment and pathologic sampling. Salvage EMA-CO chemotherapy (etoposide, actinomycin D, methotrexate, cyclophosphamide and vincristine) should be performed as early as possible to prevent metastasis and recurrence after pathologic diagnosis.

Metformin regulates autophagy via LGMN to inhibit choriocarcinoma.

Choriocarcinoma has the problem of chemotherapy insensitivity and recurrence. Metformin may be a promising candidate to restrict choriocarcinoma progress because of its indirect and direct beneficial role on inhabitations of cancer cells without severe adverse side effects. In this study, metformin pressed the proliferation and invasion of choriocarcinoma JAR cells in vitro and the growth of the JAR subcutaneous xenografts in vivo. The high throughput sequencing and bioinformatics technology identified the low expression of legumain (LGMN) in lysosomal pathway caused by metformin, which was upregulated in human choriocarcinoma tissues compared with the early pregnancy tissues. As elevating metformin concentration and treatment time, the mRNA and protein expression of LGMN both depressed in two choriocarcinoma cell lines (JAR and JEG-3). LGMN was involved in metformin-mediated inhibition of cell proliferation and invasion. Furthermore, metformin induced autophagy via inhibiting LGMN through AKT/mTOR/LC3II signaling pathway of choriocarcinoma. Autophagy inhibitor could depress metformin-induced autophagy and improve cell proliferation and invasion ability dropped by metformin, while autophagy inducer could partially reverse the change of cell proliferation and invasion modulated by combination of metformin and LGMN overexpression. These results indicated that metformin inhibited cell proliferation and invasion ability by inducing autophagy in a LGMN-dependent manner so as to play a role in the treatment of choriocarcinoma.

Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma.

BACKGROUND: Choriocarcinoma is a rare and aggressive gynecological malignancy. The standard treatment is systemic chemotherapy as choriocarcinoma exhibits high chemosensitivity. However, refractory choriocarcinoma exhibits chemoresistance; thus, the prognosis remains very poor. This study aimed to identify novel therapeutic agents for choriocarcinoma by utilizing a drug repositioning strategy. METHODS: Three choriocarcinoma cell lines (JAR, JEG-3, and BeWo) and a human extravillous trophoblast cell line (HTR-8/SVneo) were used for the analyses. The growth inhibitory effects of 1,271 FDA-approved compounds were evaluated in vitro screening assays and selected drugs were tested in tumor-bearing mice. Functional analyses of drug effects were performed based on RNA sequencing. RESULTS: Muti-step screening identified vorinostat, camptothecin (S, +), topotecan, proscillaridin A, and digoxin as exhibiting an anti-cancer effect in choriocarcinoma cells. Vorinostat, a histone deacetylase inhibitor, was selected as a promising candidate for validation and the IC50 values for choriocarcinoma cells were approximately 1 µM. RNA sequencing and subsequent pathway analysis revealed that the ferroptosis pathway was likely implicated, and key ferroptosis-related genes (i.e., GPX4, NRF2, and SLC3A2) were downregulated following vorinostat treatment. Furthermore, vorinostat repressed tumor growth and downregulated the expression of GPX4 and NRF2 in JAR cell-bearing mice model. CONCLUSION: Vorinostat, a clinically approved drug for the treatment of advanced primary cutaneous T-cell lymphoma, showed a remarkable anticancer effect both in vitro and in vivo by regulating the expression of ferroptosis-related genes. Therefore, vorinostat may be an effective therapeutic candidate for patients with choriocarcinoma.

Recurrent Metastatic Choriocarcinoma Responsive to Etoposide and Cisplatin with Etoposide, Methotrexate, and Dactinomycin: A Case Report.

Choriocarcinoma is a malignant trophoblastic tumour usually of placental origin. It is characterized by early metastasis to the brain and lungs. With early detection, it has a better prognosis with treatment. We report a case of 18 years female at 26 weeks of gestation in her third pregnancy who had a history of treatment for metastatic gestational trophoblastic neoplasm with chemotherapy and radiotherapy two years back. Therefore, she was managed as a case of recurrent choriocarcinoma with brain metastasis with chemotherapy (etoposide and cisplatin with etoposide, methotrexate, and dactinomycin) and was responsive. Her symptoms resolved and ß-human chorionic gonadotropin dropped to normal value (<2.39 mIU/ml) which has shown that timely diagnosis and management can be vital for the successful treatment of brain metastasis. Keywords: chemotherapy; choriocarcinoma; metastasis; recurrence.

Primary non-gestational mediastinal choriocarcinoma metastatic to the brainstem.

Choriocarcinoma is a highly malignant tumour emerging from the syncytiotrophoblast divided into gestational and non-gestational presentations. Primary choriocarcinoma of the mediastinum is rare. Metastases to the brain often occur; however, brainstem involvement has not been reported for non-gestational choriocarcinoma. We described a middle-aged man who developed a complete left oculomotor nerve paralysis secondary to a brainstem tumour at the midbrain. The workup for the primary source of the brainstem tumour included a chest CT scan, which revealed a mediastinal mass. A mediastinal mass needle biopsy confirmed the diagnosis of primary mediastinal choriocarcinoma. Despite aggressive chemotherapy, the patient died 6 months after the initial presentation from neurological complications and multiorgan failure.