Pulmonary metastatic gestational choriocarcinoma following an uncomplicated term pregnancy: a case report.

BACKGROUND: Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest nongynecological symptoms owing to distant metastases. The incidence of choriocarcinoma after a term pregnancy is really rare (1/160,000 pregnancies). CASE PRESENTATION: We report a case of a 20-year-old Iranian woman, gravida 2 para 1 live 1 abortion 1, who was referred to our gynecology department with sudden onset dyspnea and pain in the left hemithorax the day after her labor. The index pregnancy was without any complications. After the initial workup, the elevation of ß-human chorionic gonadotropin (HCG) levels (> 1,000,000) along with the identification of clinical (vaginal lesions) and radiological evidence of distant metastases (bilateral pulmonary nodes) directed us toward pulmonary metastatic choriocarcinoma diagnosis. After the oncology consult, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy regimen was started for the patient. She responded well to the treatment and is currently continuing her chemotherapy process. CONCLUSION: The prognosis of choriocarcinoma is very good if the treatment is started on time. We suggest that clinicians should consider gestational trophoblastic neoplasia in their differential diagnosis of the post-natal period complications, especially after a term and nonmolar pregnancy.

Primary mediastinal choriocarcinoma in an 18-year-old male with pulmonary and brain metastasis: A case report.

Primary mediastinal choriocarcinoma, also known as non-pregnant choriocarcinoma, is a rare malignancy unrelated to pregnancy, with a higher incidence in males. And primary mediastinal choriocarcinoma is mostly associated with organ and lymph node metastasis, with rapid progression and poor prognosis. Here, we report an extremely rare case of the primary anterior mediastinal choriocarcinoma that occurred in an 18-year-old man with multiple metastases of the lung and brain.

Choriocarcinoma in a viable pregnancy with the rare presentation of intractable lower back pain.

OBJECTIVE: We present a case of choriocarcinoma in a viable pregnancy with the rare presentation of intractable lower back pain. CASE REPORT: The patient is a 34-year-old multiparous woman with her second pregnancy, and a history of scoliosis with spinal fixation. Her first pregnancy was uneventful, with a term vaginal delivery. She was hospitalized four times due to intractable back pain from 25 to 31 weeks, and terminated at 31 weeks. The placenta was unremarkable on gross examination. Postpartum, the patient developed obstructive ileus, requiring a rectosigmoid resection. She was diagnosed with metastatic choriocarcinoma to the liver, para-aortic lymph nodes, and mesentery. A week later, she developed micro-thrombosis of all limbs, massive ascites, pleural effusion. Patient refused chemotherapy and died on post-operative Day 15. CONCLUSION: Presentation of choriocarcinoma in pregnancy varies widely. Clinicians should consider the differential diagnosis of choriocarcinoma when faced with abnormal unexplained symptoms during pregnancy.

Complete remission of choriocarcinoma with pulmonary vein thrombosis in the third trimester of pregnancy treated with systemic chemotherapy and anticoagulation: A case report.

RATIONALE: Choriocarcinoma is a highly aggressive tumor. It occurs infrequently during pregnancy. The management of choriocarcinoma during pregnancy poses several challenges. PATIENT CONCERNS: At 34 weeks of gestation, a 21-year-old primigravida was transferred to the emergency room for cephalgia, reduced fetal movements, and left intra-atrial intracavitary thrombus. DIAGNOSIS: Choriocarcinoma in the third trimester with lung and brain metastases, pulmonary vein thrombosis (PVT), and systemic thrombosis. INTERVENTION: An emergency cesarean section was performed. Subsequently, low-molecular-weight heparin anticoagulation combined with multiagent chemotherapy was administered. OUTCOME: A 1.59 kg live female was born. Multiagent chemotherapy combined with anticoagulation led to complete regression of the cerebral and pulmonary lesions and the dissolution of pulmonary vein thrombus. At the 11-month follow-up, the patient remained in complete remission without complications, and her child was disease-free. LESSONS: This is the first case of gestational choriocarcinoma with PVT. Our case suggests that conservative therapy can be the first choice for small, asymptomatic PVT secondary to choriocarcinoma.

Reduction of pl-CSA through ChSy-2 knockout inhibits tumorigenesis and metastasis of choriocarcinoma in JEG3 cells.

Background: Placental-like chondroitin sulfate A (pl-CSA) is exclusively expressed in cancerous and placental tissues and is highly correlated with the degree of malignancy. However, the mechanism through which pl-CSA regulates tumorigenesis and metastasis in choriocarcinoma remains unclear. Methods: Stable transfectants of the JEG3 choriocarcinoma cell line, including a negative control (NC) line and a cell line with knockout of the biosynthetic enzyme CS synthase-2 (ChSy-2) (ChSy-2-/-), were obtained using CRISPR/Cas9 systems and identified by immunofluorescence, flow cytometry, western blots and enzyme-linked immunosorbent assays (ELISAs). The proliferation, migration, invasion and colony formation of the cells were determined by a cell counting kit, scratch-wound assays, transwell assays and soft agar colony formation assays in vitro, respectively. The tumorigenesis and metastasis of choriocarcinoma were also investigated through two xenograft models in vivo. Results: The ChSy-2 protein in the ChSy-2-/-group was below the detection threshold, which was accompanied a significant reduction in the pl-CSA level. Reducing pl-CSA through ChSy-2 knockout significantly inhibited cell proliferation, migration, invasion and colony formation in vitro and tumorigenesis and metastasis of choriocarcinoma, with deceases in tumor volume and metastatic foci and a high percent survival compared to the NC in vivo. Conclusion: pl-CSA, as a necessary component of JEG-3 cells, was efficiently reduced through ChSy-2 knockout, which significantly inhibited the tumorigenesis and metastasis of choriocarcinoma. ChSy-2/pl-CSA could be alternative targets for tumor therapy.

Extracorporeal Membrane Oxygenation Support as a Bridge to Recovery during Chemotherapy in a Young Patient with Metastatic Choriocarcinoma and Severe Acute Respiratory Distress Syndrome.

INTRODUCTION: A young woman presented at a local hospital with severe dyspnea directly after childbirth. She was di-agnosed with choriocarcinoma and massive pulmonary metastases. Shortly after administration of polychemotherapy she developed severe acute respiratory distress syndrome (ARDS). CASE PRESENTATION: The patient was transferred to the intensive care unit (ICU) and extracorporeal membrane oxygenation (ECMO) center of the university hospital. Venovenous ECMO support was implemented for 28 days while enabling continuous chemotherapy. After 49 days in the ICU, she was transferred to the oncology ward in a stable respiratory state. DISCUSSION/CONCLUSION: Although the survival rates of ARDS in the general ICU population have improved lately due to improved management of ARDS and ECMO support, the data on adult cancer patients receiving ECMO support are very limited. Only few small retrospective studies on ECMO support in adult cancer patients have been conducted. Unfortunately the survival rates of patients after allogenic hematopoietic stem cell transplantation and ECMO support were discouraging. Nevertheless, cancer patients with at least stable disease who are eligible for full-code ICU management may be potential candidates for ECMO in case of severe ARDS. Our case report not only shows that patients suffering from choriocarcinoma with pulmonary metastases may develop severe ARDS in the context of polychemotherapy, but also demonstrates that ECMO support enables chemotherapy continuation and complete remission of the underlying choriocarcinoma.

Demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma: a UK population study.

OBJECTIVE: To investigate the demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma. DESIGN: A retrospective national population-based study. SETTING: UK 1995-2015. POPULATION: A total of 234 women with a diagnosis of gestational choriocarcinoma, in the absence of a prior molar pregnancy, managed at the UKs two gestational trophoblast centres in London and Sheffield. METHODS: Retrospective review of the patient's demographic and clinical data. Comparison with contemporary UK birth and pregnancy statistics. MAIN OUTCOMES: Incidence statistics for non-molar choriocarcinoma across the maternal age groups. Cure rates for patients by FIGO prognostic score group. RESULTS: Over the 21-year study period, there were 234 cases of non-molar gestational choriocarcinoma, giving an incidence of 1:66 775 relative to live births and 1:84 226 to viable pregnancies. For women aged under 20, the incidence relative to viable pregnancies was 1:223 494, for ages 30-34, 1:80 227, and for ages 40-45, 1:41 718. Treatment outcomes indicated an overall 94.4% cure rate. Divided by FIGO prognostic groups, the cure rates were low-risk group 100%, high-risk group 96% and ultra-high-risk group 80.5%. CONCLUSIONS: Non-molar gestational choriocarcinoma is a very rare diagnosis with little prior detailed information on the demographics and natural history. The data in this study give age-related incidence data based on a large national population study. The results also demonstrated the widely varying natural history of this rare malignancy and the marked correlation of disease incidence with rising maternal age. TWEETABLE ABSTRACT: National gestational choriocarcinoma database indicates a close association between increasing maternal age and incidence.

Male primary mediastinal choriocarcinoma with diffuse metastases: A case report.

RATIONALE: Choriocarcinoma is a rare and highly invasive gestational trophoblastic tumor that secretes high levels of human chorionic gonadotropin (hCG). As one of the uncommon non-gestational choriocarcinoma, primary mediastinal choriocarcinoma is an exceeding rare, and aggressive malignancy with poor prognosis. PATIENT CONCERNS: A 26-year-old man was admitted to the hospital with cough, shortness of breath, and occasional hemoptysis. DIAGNOSES AND INTERVENTION: Imaging examinations revealed a large mediastinal mass, diffuse nodular opacities with blurred edges in both lungs, and multiple brain lesions. Laboratory tests showed an astonishing increase of serum ß-hCG. A diagnosis of primary mediastinal choriocarcinoma with advanced lung and brain metastases was finally made after 3 biopsies and immunohistochemical analyses. Surgery and radiotherapy were not applicable at the time of diagnosis, and both targeted therapy and immunotherapy were unavailable. During the first 4 cycles of trophoblastic tumor-based chemotherapy, the patient improved clinically with fewer symptoms, decreased ß-hCG and reduced lesions. However, drug resistance quickly emerged, forcing an alternative chemotherapy regimen that also failed. OUTCOMES: The patient finally endured symptoms including headache, dizziness and vomiting, and subsequently succumbed after an overall survival time of six and half months. LESSONS: Male primary choriocarcinoma is an extremely rare type of malignancy. Greater awareness, earlier diagnosis and novel treatments are urgently needed to benefit patients.

Unusual Imaging Findings Associated with Germ Cell Tumors.

Germ cell tumors, because they contain immature and mature elements, can differentiate into different tissue types. They can exhibit unusual imaging features or manifest in a syndromic fashion. The authors describe these features and assign them to one of the following categories: (a) unusual manifestations of metastatic disease (growing teratoma syndrome, choriocarcinoma syndrome, ossified metastases, and gliomatosis peritonei); (b) autoimmune manifestations (sarcoidlike reaction and paraneoplastic syndromes); (c) endocrine syndromes (sex hormone production, struma ovarii, and struma carcinoid); or (d) miscellaneous conditions (ruptured dermoid cyst, squamous cell carcinoma arising from a mature teratoma, Currarino triad, fetus in fetu, pseudo-Meigs syndrome, and pancreatitis). Rare conditions associated with germ cell tumors demonstrate characteristic imaging findings that can help lead to the appropriate diagnosis and management recommendations. When evaluating for potential metastatic disease, alternative benign diagnoses should be considered (eg, growing teratoma syndrome, ossified metastases, ruptured dermoid cyst, gliomatosis peritonei, and sarcoidlike reaction), which may impact management. Germ cell tumors may also lead to life-threatening complications such as extensive hemorrhage from choriocarcinoma metastases or the rupture of mature teratomas, cases in which timely diagnosis is crucial. Autoimmune and endocrine manifestations such as paraneoplastic encephalitis, autoimmune hemolytic anemia, and hyperthyroidism may occur owing to the presence of germ cell tumors and can create a diagnostic dilemma for clinicians. Knowledge of the syndromic and unusual imaging findings associated with germ cell tumors helps guide appropriate management. ©RSNA, 2019.

Precision genotyping diagnosis of lung tumors with trophoblastic morphology in young women.

Trophoblastic differentiation has been previously described in somatic carcinomas at different primary sites, including the lung. Lung carcinomas with trophoblastic morphology presenting in women during the reproductive years pose a unique diagnostic challenge due to their overlapping microscopical and immunophenotypical features with metastatic choriocarcinoma of gestational origin. Distinction between the two entities is paramount as they require different chemotherapeutic regimens and have a markedly different prognostic outlook. Here we report a series of three female patients (ages 37-48 years) presenting with lung masses. Two of the three patients were noted to have elevated serum beta-hCG levels at the time of their presentation, while serum beta-hCG was not evaluated preoperatively in the third patient. None of them had a clinical history of molar pregnancy or gestational trophoblastic neoplasia. Core biopsies of the lung masses were performed in two patients and one patient underwent a wedge resection, showing poorly differentiated carcinoma in all cases with scattered multinucleated giant cells, hemorrhage, and necrosis. Beta-hCG immunostain was performed in two cases and showed diffuse immunoreactivity. Clinical history and imaging studies were not conclusive in any of the cases to rule out a gestational origin. Short tandem repeat genotyping analysis was performed to compare the allelic patterns between tumor and normal tissues and revealed identical profiles in one case, consistent with somatic origin, and unique paternal alleles in two cases, confirming metastatic gestational choriocarcinoma. The patient with primary somatic lung carcinoma died of disease within 15 months despite chemotherapy, while both patients with gestational choriocarcinoma responded well to chemotherapy and are alive without evidence of disease. Our cases illustrate the diagnostic pitfalls of lung tumors with trophoblastic differentiation in young women. Genotyping analysis offers precise diagnostic distinction between primary lung carcinoma and gestational choriocarcinoma with major therapeutic and prognostic implications for the patients.

Short Tandem Repeats Define a Gestational Origin for Metastatic Choriocarcinoma.

This report presents the case of an apparently healthy female patient with a history of placenta accreta who was transferred from an outside hospital with the chief complaint of shortness of breath and a large spontaneous hemothorax requiring surgical exploration. Resection of a large, bleeding lower lobe mass identified metastatic gestational choriocarcinoma, a previously unreported cause of spontaneous hemothorax and an equally rare consequence of placenta accreta. The identification of novel genomic features associated with gestational choriocarcinoma allowed for confirmation of this subtype, which has clinical implications for surveillance and prognosis after treatment with adjuvant therapy.

Stage IV Gestational Choriocarcinoma Diagnosed in the Third Trimester.

BACKGROUND: Gestational trophoblastic neoplasia rarely occurs in term pregnancies. Stage IV choriocarcinoma treated with conventional chemotherapy can result in death as a result of hemorrhagic sequelae at tumor sites. CASE: A 30-year-old woman at 34 weeks of gestation presented with a persistent cough, worsening dyspnea, and vaginal bleeding. Chest radiograph demonstrated innumerable lung nodules, and quantitative ß-hcg concentration exceeded 1.3 million milli-international units/mL. Cesarean delivery was performed for presumed abruption. Placental pathology demonstrated choriocarcinoma, and imaging confirmed stage IV disease with a World Health Organization score of 14. Remission was achieved after two courses of low-dose induction chemotherapy followed by 10 cycles of combination chemotherapy. CONCLUSION: Gestational trophoblastic neoplasia should be considered in a pregnant or postpartum woman presenting with atypical vaginal bleeding. Coexistent pulmonary or neurologic findings may suggest advanced disease.

Metastatic Choriocarcinoma Masquerading as a Congenital Glabellar Hemangioma.

Infantile choriocarcinoma (ICC) is a rare, highly malignant form of gestational trophoblastic neoplasia. Rapid diagnosis and initiation of treatment are paramount in reaching a successful outcome. Patients with these tumors typically present with a triad of anemia, hepatomegaly, and precocious puberty. Cutaneous manifestations of ICC are extraordinarily rare with few documented cases. Here, we describe a male neonate who presented to our Dermatology clinic with a rapidly growing, markedly vascular glabellar mass associated with abnormal laboratory values suggestive of Kasabach-Merritt phenomenon. The initial clinical impression of infantile hemangioma led to an initial treatment with propranolol. However, the mass continued to enlarge and a biopsy was obtained. Histology revealed a high-grade, poorly differentiated carcinoma. A robust immunohistochemical battery demonstrated tumor reactivity with Glut-1, GATA3, Glypican-3, CAM5.2, and ß-hCG establishing the diagnosis of metastatic choriocarcinoma. The diagnosis was further supported by the elevated serum ß-hCG. In addition to the glabellar mass, imaging demonstrated tumor foci in the liver and lung. Clinical investigation of the mother revealed no evidence of disease.