Choriocarcinoma metastases complicated with cerebral venous sinus thrombosis in the third trimester of pregnancy: a case report and literature review

Choriocarcinoma metastases complicated with cerebral venous sinus thrombosis in the third trimester of pregnancy: a case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Choriocarcinoma metastases complicated with cerebral venous sinus thrombosis in the third trimester of pregnancy: a case report and literature review Sheng Wang, Changrong Wang, Feng You This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4472426/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 3 You are reading this latest preprint version Abstract Background Intracerebral hemorrhage (ICH) in younger females is usually attributed to ruptured aneurysms or cerebrovascular malformations. By contrast, metastatic brain tumors and complications stemming from intracranial venous sinus thrombosis (CVST)-associated hemorrhagic strokes are rare instigators of ICH in women of childbearing age. We report a case of choriocarcinoma metastasis with rapid progression of cerebral venous sinus thrombosis in a patient in the third trimester. Additionally, the literature review revealed only two cases where choriocarcinoma was complicated by CVST, and both were identified post-chemotherapy. Case presentation A case of a 33-year-old expectant woman, in her 32 + weeks of pregnancy, sought hospital admission owing to persistent blurred vision that had prevailed for over half a month. After her admission, she endured three instances of ICH within only one week, during which period digital subtraction angiography unveiled the presence of thrombosis within the superior sagittal sinus. Choriocarcinoma in the third trimester with lung and brain metastases, ICH, and CVST. The patient underwent an emergency caesarean section and delivered a premature baby girl. Catheter directed thrombolysis in the intracranial venous sinus and evacuation of the hematoma by craniotomy were subsequently performed. Eventually, this patient was diagnosed with choriocarcinoma with multiple metastases and received drug chemotherapy. Conclusions The symptoms and imaging findings of brain metastases with hemorrhage and CVST overlap with each other, resulting in delaying and confusing the diagnosis. Furthermore, early diagnostic interventions for choriocarcinoma coupled with intensive treatment strategies can potentially improve patient prognosis and help avoid life-threatening consequences. Gestational trophoblastic neoplasia Choriocarcinoma Cerebral venous sinus thrombosis Brain metastasis Intracerebral hemorrhages Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Gestational trophoblastic neoplasm (GTN) is a type of malignant tumor that arises in connection with pregnancy [1]. The primary manifestations of GTN include irregular vaginal bleeding and symptoms emanating from metastatic sites. Around 10–19% of individuals with GTN already exhibit distant metastases at the initial diagnosis, pulmonary metastases form the most prevalent pattern (76–87%), succeeded by vaginal (30%), liver (10%), and cerebral occurrences (10%) [2]. The onset of the disease marked by brain hemorrhage is an uncommon phenomenon. Notably, choriocarcinoma, a specific subtype of GTN, exhibits a high sensitivity to radiotherapy, making early diagnosis and intervention pivotal in enhancing patient survival rates. Concurrently, pregnancy-induced hypercoagulability alongside hemodynamic shifts imposes substantial thrombosis risks on women during the third trimester and in the early puerperium [3]. Cerebral venous sinus thrombosis (CVST), a distinct category of cerebrovascular disease, is characterized by escalated intracranial pressure, resulting from hindered cerebral venous reflux and disrupted cerebrospinal fluid absorption due to various etiological factors. It accounts for a small fraction, about 0.5%-1.0%, of all cerebrovascular diseases, with 27%-57% of strokes during pregnancy related to CVST primarily occurring in puerperal women [4]. The relationship between choriocarcinoma and CVST is unclear. To date, there are no published case reports of choriocarcinoma with pulmonary and cerebral metastases occurring during pregnancy associated with maternal CVST. In this report, we review the uncommon instance of a 33-year-old woman who, during her third trimester of pregnancy, experienced CVST and repeated intracerebral hemorrhage (ICH) and was subsequently diagnosed with choriocarcinoma, accompanied by pulmonary and cerebral metastases, following a cesarean section. Case presentation A 33-year-old female patient, at 32 + 4 weeks of gestation (G4P1), expected to deliver by December 2, 2021, was hospitalized on October 6, 2021, due to experiencing blurred vision persisting for over half a month. Initially, she was diagnosed with severe preeclampsia, gestational diabetes mellitus, a left ovarian teratoma, and a scarred uterus. She reported that regular blood glucose monitoring was manageable, and OGTT results illustrated a blood glucose profile of 5.14-8.98-9.8 mmol/L. Approximately two weeks prior, she noticed blurred vision, yet didn't experience headaches, dizziness, anxiety, or chest tightness. She consulted the local hospital's ophthalmology department, which didn't find any significant abnormalities, thus no specialized treatment was administered. However, four days ago, she revisited the hospital after experiencing a headache accompanied by vomiting. Examination by the Otorhinolaryngological department revealed papilloedema in the fundus associated with bleeding. At this time, her blood pressure had surged to 147/73 mmHg and she had proteinuria (++). Therapeutic interventions included oral administration of Amlodipine besylate tablets, intravenous magnesium sulfate for symptomatic relief, and intramuscular dexamethasone injections to promote fetal lung maturity. She exhibited fluctuating postprandial blood glucose levels between 7.4–9.4 mmol/L and fasting levels between 4.9–6.2 mmol/L. Currently, she still experiences blurred vision but no other discomforts, such as vaginal bleeding. Considering her relatively early stage of pregnancy, we advised further treatment and facilitated her transfer to our facility for comprehensive care. Upon admission, her vital signs were noted as follows: temperature 36.9℃, pulse 78 beats/min, respiration rate 20 breaths/min, and blood pressure 140/80 mmHg. Obstetric examination revealed a uterine fundal height of 31 cm, an abdominal circumference of 97 cm, and an estimated fetal weight of 2.0 kg. Auxiliary examination on 2021.10.05 obstetric ultrasound (local hospital) showed intrauterine pregnancy, single live fetus. The next day post-admission, the patient encountered a severe headache. An urgent head magnetic resonance imaging (MRI) displayed an ICH in the right occipital lobe and a subarachnoid hemorrhage (Fig. 1 A-B). After the consultation with the neurosurgery department, this patient was advised to transfer to the neurosurgery department for further treatment after the termination of pregnancy. Consequently, she underwent a cesarean section and left ovarian cyst removal on October 8, 2021. During this procedure, the peritoneum was notably adherent to the anterior uterine wall, necessitating adhesion separation and an 8-month-sized uterus with an undeveloped lower segment was noted. A female infant, weighing 2123 g, was delivered with Apgar scores of 8, 9, and 9 at 1, 5, and 10 minutes post-delivery, respectively. The placenta was situated on the posterior wall of the uterus, showing complete and autonomous delivery with unbroken fetal membranes. There was a cyst on the left ovary, which was removed and pathological evaluation identified the cyst as a mature teratoma. Considering that the patient was a pregnant woman with hypercoagulable blood, it was necessary to exclude post-thrombotic hemorrhage of venous sinus, and there was an indication for cerebral digital subtraction angiography (DSA). Subsequently, on the afternoon of October 10, 2021, she exhibited symptoms of disoriented speech and numbness in her right upper limb. Emergency computed tomography (CT) scan (Fig. 1 D) revealed a new hemorrhagic area in the left frontal lobe, and a repeated CT scan (Fig. 1 E) later that night indicated an escalating hemorrhage in the left frontal-parietal region. Emergency cranial DSA (Fig. 2 ) at night showed bilateral internal carotid arterial system shows no significant abnormality, slow intracranial venous drainage, poor visualization of the superior sagittal sinus, part of the draining vein was seen in the right cortex, and the draining vein disappeared from the left central sulcus area, and the current diagnosis was intracranial venous sinus with cortical venous thrombosis, and intracranial venous sinus cannulae thrombolytic surgery was performed after the family's consent was solicited. The patient's consciousness deteriorated, and craniotomy was performed immediately after DSA to remove the hematoma. During this operation, the left cortical vein appeared darkened and purple, displaying poor reflux and a ruptured cortical hematoma. Following bilateral hematoma removal, she was transferred to the ICU. On October 11, 2021, a follow-up head CT (Fig. 1 F) exhibited alterations post-hematoma evacuation, indicating a reduced size of the left frontal hematoma. Chest CT (Fig. 3 A-B) revealed sporadic lesions in the right lower lobe of the lung, considering the possibility of inflammatory lesions, along with exudative alterations in the dorsal portions of both lower lungs. Ultrasound evaluations did not detect any notable irregularities in the liver, gallbladder, pancreas, spleen, uterus, or bilateral ovaries. Regrettably, on October 12, 2021, a subsequent head CT revealed an elevated hematoma density within the left frontal lobe (Fig. 1 G). Laboratory assessments showed a D-dimer level of 1890 ug/L and a C-reactive protein level of 163 mg/L. On October 15, 2021, cranial MRV examination (Fig. 3 C) showed stenosis at the junction of bilateral transverse sinus and sigmoid sinus. On October 16, 2021, the patient experienced a worsening headache, and a CT reevaluation highlighted a fresh hematoma in the right occipital lobe (Fig. 1 H). Tragically, by October 27, 2021, the conclusive hematoma pathology illustrated irregular vascular lumens accompanied by hemorrhage and necrosis within the blood clot and degenerative exudates in the right occipital region. Focal areas revealed small amounts of brain tissue and trophoblastic proliferative plate necrosis, hinting at trophoblastic disease (Fig. 4 ). On October 30, 2021, the full set of tumor markers: carbohydrate antigen 12549.40U/mL, β - human chorionic gonadotropin (HCG) 214498.20U/L. The final diagnosis was multiple metastasis of choriocarcinoma, post-operative cerebral hemorrhage, and CVST. The patient received the EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) chemotherapy regimen, and after 9 cycles of chemotherapy at follow-up, the patient went into remission, leaving sequelae related to cerebral hemorrhage and neurological deficits, and no signs of tumor recurrence were seen on review 6 months later. The patient has provided informed consent for publication of the case. Discussion Owing to the scarcity of experience, the manifestations and radiographic indicators of CVST coupled with hemorrhagic stroke and choriocarcinoma featuring cerebral metastases might intersect with each other in pregnant patients. The exceedingly low probability of the simultaneous occurrence of both conditions exacerbates the complexity of diagnosing them, thereby potentially delaying a conclusive diagnosis. The simultaneous occurrence of choriocarcinoma with a typical intrauterine pregnancy is a rarity, and pinpointing the primary site of choriocarcinoma during pregnancy is challenging without a histopathological evaluation of the placenta. Reviewing the relevant literature, there are few clinical records on maternal and infant survival in patients with GTN during pregnancy, and in some cases the primary tumor may remain small or even spontaneously regress after metastasis [5]. In this specific case, the placenta was not retained for histopathological analysis following the cesarean section, as the likelihood of GTN had not been anticipated prior to the surgery, and β-HCG monitoring was not conducted during the gestation period. The patient did not exhibit vaginal bleeding, which is usually the initial symptom of GTN, but rather presented a complicated and rapidly evolving clinical history, including pre-eclampsia, a significant predisposing factor for stroke during pregnancy, and she was noted for symptoms suggestive of cerebral hemorrhage. Radiological examinations revealed cerebral hematoma alterations and a solitary subpleural mass in the upper segment of the right lung. Consequently, the preliminary clinical diagnosis was solely centered around cerebral hemorrhage subsequent to CVST, accompanied by an infection in the upper right lung lobe, neglecting the potential existence of GTN lung-brain metastasis. The reported incidence of venous thrombosis during pregnancy and the postpartum period fluctuates between 0.018% and 0.2%, with CVST occurrences being substantially lower [4, 6]. The clinical manifestations of CVST can vary extensively, thereby complicating the diagnosis process, as its symptoms frequently mimic other common pregnancy-related discomforts such as headaches, lethargy, nausea, and vomiting. Furthermore, vascular rupture could potentially culminate in cerebral hemorrhage. Hemorrhagic events are noted in approximately 60% of choriocarcinoma cerebral metastases, yet the emergence of multiple cerebral hemorrhages in normal pregnancies accompanying choriocarcinoma cerebral metastases is exceedingly rare, having only been documented in a few cases. In our comprehensive search of the PubMed database for materials published between January 1, 1956, and July 31, 2023, utilizing the keywords "choriocarcinoma" or "gestational trophoblastic neoplasm" along with "embolism" or "thrombus", we discovered pertinent insights. We excluded cases of choriocarcinoma or GTN regarding pulmonary embolism because of the relatively large number of cases regarding pulmonary embolism, as well as the literature review conducted by some of the authors. This search ultimately yielded 12 articles in English (see Table 1 ), identifying merely two instances where choriocarcinoma was complicated by CVST, and both were identified post-chemotherapy [7, 8]. Table 1 Reported cases of choriocarcinoma with embolism Author, Year Age, gender Before or after treatment Site of embolization Serum or urine HCG Embolectomy Anticoagulation Chemotherapy Outcome Xiaodong Li, 2020 17 21, F Before PVT、systemic thrombosis 196783 IU/L No LMWH EP, EMA-CO CR In Young Kim, 2019 18 23, F Before OVT > 200,000 IU/L No Rivaroxaban MTX-FA CR Louise Bonnet, 2015 19 57, F Before Pulmonary vein 155.2 IU/L No Unfractionated heparin EMA-CO CR Jirí Spácil, 2015 20 77, F Before Left axillary artery 763 IU Yes Enoxaparin, warfarin Yes (no detail) PD Maria Okumura, 2012 21 43, F Before Postcava 53,414 mIU/mL Yes No EMAO CR Taymaa May, 2011 8 31, F After CVT 5875 mIU/mL No Heparin EMA-CO, EMA-EP CR Sanju Cyriac, 2009 7 30, F After CVT 90000 IU No Enoxaparin, warfarin EMA-CO CR Ilya Blokh, 2003 22 60, M Before Right lower extremity venous 8533 mIU/mL No No ICD PR Jovan D, 1990 23 26, F After Coronary N/A No No Methotrexate, actinomycin D PD Bergljot Holm Arstad, 1980 24 24, F Before Right subclavian vein, right atrium 94000 IU/24 hours No Enoxaparin, warfarin N/A CR Goroku OHTA, 1968 25 37, F Before Right external iliac, femoral veins N/A Yes N/A N/A N/A PVT: pulmonary vein thrombosis; LMWH: low molecular weight heparin; CR: complete recovery in outcome; OVT:Ovarian vein thrombosis; MTX-FA: methotrexate, folinic acid; EMA-CO: etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine; EMAO: etoposide, methotrexate, actinomycin D, and vincristine; CVT: Cerebral venous thrombosis; EMA-EP:Etoposide, methotrexate, actinomycin D, etoposide and cisplatin; ICD:Etoposide, Ifosfamide, Cisplatin; PR: partial response; N/A: not available; PD: progress development or death in outcome. At present, there are no published scholarly articles or case studies that extensively illustrate the link between choriocarcinoma and CVST. The etiology and pathophysiology underlying CVST during pregnancy are intricate and remain largely unexplored. They might be associated with blood stasis, heightened coagulative states, and elements or conditions inducing cerebral vascular endothelial rupture [9]. Choriocarcinoma, as a malignant tumor, is hypothesized to be involved in the genesis and progression of CVST, and the possible mechanisms are as follows: (1) Escalation in procoagulant active substances: Research by Estellés A et al. has highlighted considerable elevations in plasma PAI-1 antigen and placental PAI-1 antigen and mRNA levels in molar pregnancies in comparison to control groups. Tissue factor, a precursor to the extrinsic coagulation pathway, exhibits a positive correlation with venous thromboembolism in patients with tumors [10]. Several studies have demonstrated significant expression of tissue factors in individuals suffering from various cancers, such as glioma, pancreatic, breast, and ovarian cancers, potentially leading to increased risks of venous thromboembolism [11]. Moreover, tissue factor plays a crucial role in advancing tumor progression. (2) Vascular endothelial cell damage: The secretion of procoagulant substances and inflammatory cytokines by tumor cells can wreak havoc on vascular endothelial cells, initiating the exposure of extracellular matrices, and precipitating platelet activation and adhesion. Continuous platelet aggregation can consequently foster thrombosis formation, while collagen fibers activate coagulation factors, initiating intrinsic coagulation pathways. (3) Hemodynamic alterations: Tumor patients often exhibit elevated levels of fibrinogen and other protein components, fostering increased blood viscosity due to enhanced erythrocyte aggregation. The action of vascular endothelial growth factors amplifies the volume of tumor interstitial fluid and blood viscosity, thereby accentuating blood hypercoagulability [12]. (4) Finally, CVST considers the possibility of tumor thrombus formed by blood circulation or invasion of adjacent veins by tumor with hemorrhage. To summarize, the triggers for venous thrombosis may be ascribed to hypercoagulability, either connected to pregnancy or primary malignant disorders, and direct assault or external compression of adjacent venous channels by cerebral metastases, culminating in blood stagnation and embolisms in venous sinuses. Due to cerebral venous return obstruction, CVST can compensate for the opening of many collateral venous circulation pathways, dilatation of common cerebral surface veins and deep veins, stasis of venous blood, and formation of collateral circulation can be seen on DSA examination in this case. Given the patient's pregnant state, chest X-ray or CT scans were not conducted upon admission; instead, a chest CT was performed post-delivery. The images revealed a solitary mass in the pleura of the upper right lung lobe, accompanied by slight exudation around it. Due to a limited comprehension of the imaging characteristics associated with choriocarcinoma showing multiple metastases, timely identification of the metastasis was missed. Generally, in patients with choriocarcinoma, pulmonary metastases imaging predominantly showes a higher prevalence of lesions in the medial and lower fields of both lungs, predominantly found in the right lung and more frequently located in the lateral zone compared to the central and inner zones. Moreover, the lesion diameters tend to be under 3 cm, accompanied by a scarcity of cavities. The variations in manifestations are contingent upon the internal hemorrhage extent, edema, necrosis, and tissue clot occurrences. The clarity of the boundary delineation is dependent on the surrounding lung tissue alterations. Specifically, lesions with pronounced hemorrhage and edema present indistinct boundaries, while those encircled by fibrous tissues offer clear demarcations. A notable imaging characteristic is a ground-glass attenuation halo encircling a pulmonary nodule, commonly known as the halo sign, resulting from peritumoral hemorrhages [13]. A considerable influx of tissue fragments into the bloodstream may provoke acute pulmonary embolism [14]. Even though CT scans can pinpoint more metastases compared to plain films, their impact on the treatment approach remains undefined. Hence, the International Federation of Gynecology and Obstetrics (FIGO) advocates the utilization of chest X-ray films as opposed to chest CT for assessing metastases extent [15]. Choriocarcinoma complicated with cerebral metastases commonly occurs after pulmonary metastases. The latter can compromise pulmonary venules, entering the bloodstream, subsequently flowing back to the left heart, and potentially disseminating to various organs through systemic circulation. Tumor cells can generate emboli that infiltrate the cerebral circulation, fostering cerebral metastases which are primary contributors to mortality. Irrespective of the cerebral metastases dimensions, they can potentially incite fatal intracranial hemorrhages. Consequently, even minor cerebral metastases can provoke hematoma within brain parenchyma or subdural spaces, escalating intracranial pressure. These scenarios necessitate urgent interventions, including craniotomy to alleviate space-occupying impacts and curtail intracranial hypertension, followed swiftly by supportive chemotherapy. Alongside clinical and radiological signs, a paramount diagnostic indicator of GTN is heightened levels of serum β-HCG. A marked elevation in serum β-HCG amidst normal or aberrant pregnancies hints at a potential GTN occurrence. β-HCG serves not merely as a diagnostic and treatment monitoring tool but also assists in follow-ups and predicting recurrences. Distinguishing imaging features between brain metastases of choriocarcinoma with hemorrhage and hemorrhage caused by cerebrovascular disease remains challenging due to the diversity of clinical and radiological presentations. Consequently, lessons can be garnered, women in their reproductive years presenting with menopause, abdominal discomfort, and unaccountable bleeding should undergo β-HCG testing to rule out pregnancy-related ailments. When identification proves challenging, timely surgical exploration should be considered, meticulously checking for unexpected lesions during surgery. Cases arousing high suspicion warrant prompt pathological examinations. Particularly in reproductive-aged women manifesting recurrent intracranial hemorrhages coupled with intrapulmonary masses, GTN metastasis should be considered, necessitating immediate β-HCG evaluations and associated examinations, with a focus on CVST. The prognosis for choriocarcinoma patients has markedly improved courtesy of potent cytotoxic chemotherapy. The EMA-CO regimen stands as the foremost effective treatment for high-risk groups (FIGO stage IV and score > 7), boasting an impressive long-term survival rate of up to 95% [1,16]. Conclusions Through this case study, we aim to foster a more profound comprehension of CVST and choriocarcinoma during pregnancy. This can help facilitate earlier diagnoses and improve patient outcomes, encouraging clinicians to exercise more informed decisions, refine imaging and laboratory examinations, minimize instances of incorrect and overlooked diagnoses, and thereby better assist patients especially during the initial phases. Abbreviations GTN Gestational trophoblastic neoplasm CVST Cerebral venous sinus thrombosis ICH Intracerebral hemorrhage MRI Magnetic Resonance Imaging DSA Digital subtraction angiography CT Computed tomography β-hCG β-Human chorionic gonadotropin EMA-CO Etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine FIGO The International Federation of Gynecology and Obstetrics Declarations Acknowledgements Not applicable. Authors contributions S.W. drafted the manuscript. CR.W. reviewed the tissue pathology. F.Y. reviewed the literature. S.W. and F.Y. revised the manuscript. All authors have read and approved the manuscript. Funding The authors indicated that there was no external funding for this study. Availability of data and materials All data generated or analysed during this study are included in this published article. Declarations Ethics approval and consent to participate Written informed consent was obtained from the patient for her participation in this case report and accompanying images. Consent for publication Written informed consent was obtained from the patient. Competing interests The authors declare no competing interests. References Ngan HYS, Seckl MJ, Berkowitz RS, et al. Diagnosis and management of gestational trophoblastic disease: 2021 update. Int J Gynaecol Obstet. 2021;155 Suppl 1:86-93. Lukinovic N, Malovrh EP, Takac I, Sobocan M, Knez J. Advances in diagnostics and management of gestational trophoblastic disease. Radiol Oncol. 2022;56(4):430-439. Roth J, Deck G. Neurovascular disorders in pregnancy: A review. Obstet Med. 2019;12(4):164-167. Bousser MG, Crassard I. Cerebral venous thrombosis, pregnancy and oral contraceptives. Thromb Res. 2012;130 Suppl 1:S19-22. Yu P, Diao W, Jiang X. A Successfully Treated Metastatic Choriocarcinoma Coexistent With Pregnancy: A Case Report of a 4-Year Follow-Up. Medicine (Baltimore). 2016;95(21):e3505. James AH, Bushnell CD, Jamison MG, Myers ER. Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol. 2005;106(3):509-516. Cyriac S, Sagar TG, Mahajan V. Choriocarcinoma with arterial and venous thrombosis. Neurol India. 2009;57(4):505-507. May T, Rabinowe SN, Berkowitz RS, Goldstein DP. Cerebral venous sinus thrombosis presenting as cerebral metastasis in a patient with choriocarcinoma following a non-molar gestation. Gynecol Oncol. 2011;122(1):199-200. Bousser MG, Crassard I. Cerebral venous thrombosis, pregnancy and oral contraceptives. Thromb Res. 2012;130 Suppl 1:S19-22. Li H, Yu Y, Gao L, et al. Tissue factor: a neglected role in cancer biology. J Thromb Thrombolysis. 2022;54(1):97-108. Kobayashi S, Koizume S, Takahashi T, et al. Tissue factor and its procoagulant activity on cancer-associated thromboembolism in pancreatic cancer. Cancer Sci. 2021;112(11):4679-4691. Baronzio G, Freitas I, Kwaan HC. Tumor microenvironment and hemorheological abnormalities. Semin Thromb Hemost. 2003;29(5):489-497. Shaaban AM, Rezvani M, Haroun RR, et al. Gestational Trophoblastic Disease: Clinical and Imaging Features. Radiographics. 2017;37(2):681-700. Soper JT. Gestational Trophoblastic Disease: Current Evaluation and Management. Obstet Gynecol. 2021;137(2):355-370. FIGO Oncology Committee. FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee. Int J Gynaecol Obstet. 2002;77(3):285-287. Braga A, Elias KM, Horowitz NS, Berkowitz RS. Treatment of high-risk gestational trophoblastic neoplasia and chemoresistance/relapsed disease. Best Pract Res Clin Obstet Gynaecol. 2021;74:81-96. Li X, Peng H. Complete remission of choriocarcinoma with pulmonary vein thrombosis in the third trimester of pregnancy treated with systemic chemotherapy and anticoagulation: A case report. Medicine. 2021;100(21):e26145. Kim IY, Kim SH, Hwang IT, Ha JG, Cha JH. A rare case of ovarian vein thrombosis in a gestational trophoblastic neoplasia patient. Obstet Gynecol Sci. 2019;62(3):190-193. Bonnet L, Raposo N, Blot-Souletie N, et al. Stroke Caused by a Pulmonary Vein Thrombosis Revealing a Metastatic Choriocarcinoma. Circulation. 2015;131(23):2093-4. Spácil J, Hradec J, Král J. Opakované embolizace do periferních tepen z plicní metastázy choriokarcinomu [Recurrent peripheral arterial embolism from metastatic lung choriocarcinoma]. Cas Lek Cesk. 2006;145(2):160-1. Czech. Okumura M, Fushida K, Pulcineli Vieira Francisco R, Schultz R, Zugaib M. Sonographic appearance of an advanced invasive mole and associated metastatic thrombus in the inferior vena cava. J Clin Ultrasound. 2013 Feb;41(2):113-5. Blokh I, Oiseth SJ, Fuks J, Jain D, Eapen S, Koulova L, Alexandrescu D, Li YY, Dutcher J, Wiernik PH. Metastatic choriocarcinoma in a middle-aged man presenting as a right thigh mass with venous thrombosis: a case report. Med Oncol. 2003;20(2):189-94. Vasiljevic JD, Abdulla AK. Coronary embolism by metastatic choriocarcinoma of the uterus: an unusual cause of ischemic heart disease. Gynecol Oncol. 1990 Aug;38(2):289-92. Arstad BH, Bergsjø P, Eie H. Hydatidiform mole with large ovarian cysts and venous thrombosis: a case report. Int J Gynaecol Obstet. 1980 Jan-Feb;17(4):323-7. Ohta G, Nishino H. Pulmonary endoarterial choriocarcinoma and thrombosis in the right iliac vein system. Report of an autopsy case. Acta Pathol Jpn. 1968 Feb;18(1):17-21. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 30 May, 2024 Submission checks completed at journal 26 May, 2024 First submitted to journal 24 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4472426","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":308508719,"identity":"b87685e3-1cbb-4d6d-afc8-8b3a23a19dff","order_by":0,"name":"Sheng Wang","email":"","orcid":"","institution":"Wuhu Hospital, East China Normal University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sheng","middleName":"","lastName":"Wang","suffix":""},{"id":308508720,"identity":"4d4232fd-9ffe-4438-9371-70ff3074cf7f","order_by":1,"name":"Changrong Wang","email":"","orcid":"","institution":"Hangzhou First People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Changrong","middleName":"","lastName":"Wang","suffix":""},{"id":308508721,"identity":"811ab1a2-9c9e-492c-9c80-63ebe39490fd","order_by":2,"name":"Feng You","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIie2SsQrCMBCGEwKZol0TKtpHCBQy9U1c6hIn9w4FC0JdhL6K4AsUDjIVfATr4qwg0tE4OPdGwXzDDwf3HdxxhAQCvwhrfRRyHjEGPU7huY8uS9WeW41XaG1Xx7NIJMrQjrnrswN6AkE0KbMlQuHrdFYAMzBpe+LsphpVLgcTyw64gWmuaQUIxUWvWNUg0p3QEqkIrh61lZphFeW4if2RtQR/5Byzy9SxmxoKuW0agP5eZuNK0voHEN8qH2v/sPBD6YDpDAQCgf/lDYv8QD/Ug5FwAAAAAElFTkSuQmCC","orcid":"","institution":"Hangzhou First People's Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"You","suffix":""}],"badges":[],"createdAt":"2024-05-24 12:21:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4472426/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4472426/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58145591,"identity":"9ba1a56b-5969-4c32-b839-fe1814602b03","added_by":"auto","created_at":"2024-06-11 18:33:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1334505,"visible":true,"origin":"","legend":"\u003cp\u003e(A, B) Head MRI of the patient on day 2 after admission shows acute cerebral hemorrhage in the right occipital lobe with displacement of midline structures. (C) Head CT shows a hematoma in the right occipital lobe with a little surrounding edema. (D) Head CT on day 4 shows a new hemorrhage in the left frontal lobe. (E) Nightly follow-up CT shows an increase in hemorrhage in the left frontal lobe compared with D. (F) Postoperative CT shows postoperative changes in the hematoma and a little bleeding in the left frontal lobe. (G) Repeat CT on postoperative day 2 shows increased density of hematoma in the left frontal lobe. (H) Head CT on postoperative day 5 shows a new issue of hemorrhage visible in the left occipital lobe.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4472426/v1/09a00730ab4aebd59a01de19.png"},{"id":58145592,"identity":"1153e6d6-17b1-4d36-98ca-d8afc2380aa3","added_by":"auto","created_at":"2024-06-11 18:33:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":713354,"visible":true,"origin":"","legend":"\u003cp\u003e(A) The right internal carotid artery system shows no significant abnormality. (B) The arrow shows the manifestation of a filling defect in the superior sagittal sinus near the sinus confluence.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4472426/v1/41bce7738a0a85d3d3d19378.png"},{"id":58145593,"identity":"08a3dcc1-c9b3-4d9f-8b48-aafc760a7764","added_by":"auto","created_at":"2024-06-11 18:33:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1249193,"visible":true,"origin":"","legend":"\u003cp\u003e(A, B) Single subpleural mass in the upper lobe of the right lung. (C) Follow-up head and neck MRV (arrow) shows stenosis in the sigmoid sinus near the transverse sinus on both sides.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4472426/v1/82709fce90b59c2269fab989.png"},{"id":58145594,"identity":"76f6a4ae-7142-4cb9-be22-6062fc0a8e5e","added_by":"auto","created_at":"2024-06-11 18:33:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":4599516,"visible":true,"origin":"","legend":"\u003cp\u003eHematoxylin and eosin stain of the hematoma tissue. Small nested trophoblast cells seen within the clot. Immunohistochemical stain: trophoblast-like cells showing positive staining for HCG (C) and HPL (D). (A) Low-power view ×100. (B) High-power view ×400. (C, D) Low-power view ×100.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4472426/v1/e298464c45ce37432a519f94.png"},{"id":58145658,"identity":"e0a2197d-c250-4d3e-a9bf-ae3ef64ad500","added_by":"auto","created_at":"2024-06-11 18:33:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":10126380,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4472426/v1/8a808d16-c806-4c22-adf7-134ff064cecc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Choriocarcinoma metastases complicated with cerebral venous sinus thrombosis in the third trimester of pregnancy: a case report and literature review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGestational trophoblastic neoplasm (GTN) is a type of malignant tumor that arises in connection with pregnancy [1]. The primary manifestations of GTN include irregular vaginal bleeding and symptoms emanating from metastatic sites. Around 10\u0026ndash;19% of individuals with GTN already exhibit distant metastases at the initial diagnosis, pulmonary metastases form the most prevalent pattern (76\u0026ndash;87%), succeeded by vaginal (30%), liver (10%), and cerebral occurrences (10%) [2]. The onset of the disease marked by brain hemorrhage is an uncommon phenomenon. Notably, choriocarcinoma, a specific subtype of GTN, exhibits a high sensitivity to radiotherapy, making early diagnosis and intervention pivotal in enhancing patient survival rates. Concurrently, pregnancy-induced hypercoagulability alongside hemodynamic shifts imposes substantial thrombosis risks on women during the third trimester and in the early puerperium [3]. Cerebral venous sinus thrombosis (CVST), a distinct category of cerebrovascular disease, is characterized by escalated intracranial pressure, resulting from hindered cerebral venous reflux and disrupted cerebrospinal fluid absorption due to various etiological factors. It accounts for a small fraction, about 0.5%-1.0%, of all cerebrovascular diseases, with 27%-57% of strokes during pregnancy related to CVST primarily occurring in puerperal women [4]. The relationship between choriocarcinoma and CVST is unclear. To date, there are no published case reports of choriocarcinoma with pulmonary and cerebral metastases occurring during pregnancy associated with maternal CVST. In this report, we review the uncommon instance of a 33-year-old woman who, during her third trimester of pregnancy, experienced CVST and repeated intracerebral hemorrhage (ICH) and was subsequently diagnosed with choriocarcinoma, accompanied by pulmonary and cerebral metastases, following a cesarean section.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 33-year-old female patient, at 32\u003csup\u003e+\u0026thinsp;4\u003c/sup\u003e weeks of gestation (G4P1), expected to deliver by December 2, 2021, was hospitalized on October 6, 2021, due to experiencing blurred vision persisting for over half a month. Initially, she was diagnosed with severe preeclampsia, gestational diabetes mellitus, a left ovarian teratoma, and a scarred uterus. She reported that regular blood glucose monitoring was manageable, and OGTT results illustrated a blood glucose profile of 5.14-8.98-9.8 mmol/L. Approximately two weeks prior, she noticed blurred vision, yet didn't experience headaches, dizziness, anxiety, or chest tightness. She consulted the local hospital's ophthalmology department, which didn't find any significant abnormalities, thus no specialized treatment was administered. However, four days ago, she revisited the hospital after experiencing a headache accompanied by vomiting. Examination by the Otorhinolaryngological department revealed papilloedema in the fundus associated with bleeding. At this time, her blood pressure had surged to 147/73 mmHg and she had proteinuria (++). Therapeutic interventions included oral administration of Amlodipine besylate tablets, intravenous magnesium sulfate for symptomatic relief, and intramuscular dexamethasone injections to promote fetal lung maturity. She exhibited fluctuating postprandial blood glucose levels between 7.4\u0026ndash;9.4 mmol/L and fasting levels between 4.9\u0026ndash;6.2 mmol/L. Currently, she still experiences blurred vision but no other discomforts, such as vaginal bleeding. Considering her relatively early stage of pregnancy, we advised further treatment and facilitated her transfer to our facility for comprehensive care. Upon admission, her vital signs were noted as follows: temperature 36.9℃, pulse 78 beats/min, respiration rate 20 breaths/min, and blood pressure 140/80 mmHg. Obstetric examination revealed a uterine fundal height of 31 cm, an abdominal circumference of 97 cm, and an estimated fetal weight of 2.0 kg. Auxiliary examination on 2021.10.05 obstetric ultrasound (local hospital) showed intrauterine pregnancy, single live fetus.\u003c/p\u003e \u003cp\u003eThe next day post-admission, the patient encountered a severe headache. An urgent head magnetic resonance imaging (MRI) displayed an ICH in the right occipital lobe and a subarachnoid hemorrhage (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA-B). After the consultation with the neurosurgery department, this patient was advised to transfer to the neurosurgery department for further treatment after the termination of pregnancy. Consequently, she underwent a cesarean section and left ovarian cyst removal on October 8, 2021. During this procedure, the peritoneum was notably adherent to the anterior uterine wall, necessitating adhesion separation and an 8-month-sized uterus with an undeveloped lower segment was noted. A female infant, weighing 2123 g, was delivered with Apgar scores of 8, 9, and 9 at 1, 5, and 10 minutes post-delivery, respectively. The placenta was situated on the posterior wall of the uterus, showing complete and autonomous delivery with unbroken fetal membranes. There was a cyst on the left ovary, which was removed and pathological evaluation identified the cyst as a mature teratoma. Considering that the patient was a pregnant woman with hypercoagulable blood, it was necessary to exclude post-thrombotic hemorrhage of venous sinus, and there was an indication for cerebral digital subtraction angiography (DSA). Subsequently, on the afternoon of October 10, 2021, she exhibited symptoms of disoriented speech and numbness in her right upper limb. Emergency computed tomography (CT) scan (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD) revealed a new hemorrhagic area in the left frontal lobe, and a repeated CT scan (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE) later that night indicated an escalating hemorrhage in the left frontal-parietal region. Emergency cranial DSA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) at night showed bilateral internal carotid arterial system shows no significant abnormality, slow intracranial venous drainage, poor visualization of the superior sagittal sinus, part of the draining vein was seen in the right cortex, and the draining vein disappeared from the left central sulcus area, and the current diagnosis was intracranial venous sinus with cortical venous thrombosis, and intracranial venous sinus cannulae thrombolytic surgery was performed after the family's consent was solicited. The patient's consciousness deteriorated, and craniotomy was performed immediately after DSA to remove the hematoma. During this operation, the left cortical vein appeared darkened and purple, displaying poor reflux and a ruptured cortical hematoma. Following bilateral hematoma removal, she was transferred to the ICU.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOn October 11, 2021, a follow-up head CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF) exhibited alterations post-hematoma evacuation, indicating a reduced size of the left frontal hematoma. Chest CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA-B) revealed sporadic lesions in the right lower lobe of the lung, considering the possibility of inflammatory lesions, along with exudative alterations in the dorsal portions of both lower lungs. Ultrasound evaluations did not detect any notable irregularities in the liver, gallbladder, pancreas, spleen, uterus, or bilateral ovaries. Regrettably, on October 12, 2021, a subsequent head CT revealed an elevated hematoma density within the left frontal lobe (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eG). Laboratory assessments showed a D-dimer level of 1890 ug/L and a C-reactive protein level of 163 mg/L. On October 15, 2021, cranial MRV examination (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC) showed stenosis at the junction of bilateral transverse sinus and sigmoid sinus. On October 16, 2021, the patient experienced a worsening headache, and a CT reevaluation highlighted a fresh hematoma in the right occipital lobe (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eH). Tragically, by October 27, 2021, the conclusive hematoma pathology illustrated irregular vascular lumens accompanied by hemorrhage and necrosis within the blood clot and degenerative exudates in the right occipital region. Focal areas revealed small amounts of brain tissue and trophoblastic proliferative plate necrosis, hinting at trophoblastic disease (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). On October 30, 2021, the full set of tumor markers: carbohydrate antigen 12549.40U/mL, β - human chorionic gonadotropin (HCG) 214498.20U/L. The final diagnosis was multiple metastasis of choriocarcinoma, post-operative cerebral hemorrhage, and CVST. The patient received the EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) chemotherapy regimen, and after 9 cycles of chemotherapy at follow-up, the patient went into remission, leaving sequelae related to cerebral hemorrhage and neurological deficits, and no signs of tumor recurrence were seen on review 6 months later. The patient has provided informed consent for publication of the case.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOwing to the scarcity of experience, the manifestations and radiographic indicators of CVST coupled with hemorrhagic stroke and choriocarcinoma featuring cerebral metastases might intersect with each other in pregnant patients. The exceedingly low probability of the simultaneous occurrence of both conditions exacerbates the complexity of diagnosing them, thereby potentially delaying a conclusive diagnosis. The simultaneous occurrence of choriocarcinoma with a typical intrauterine pregnancy is a rarity, and pinpointing the primary site of choriocarcinoma during pregnancy is challenging without a histopathological evaluation of the placenta. Reviewing the relevant literature, there are few clinical records on maternal and infant survival in patients with GTN during pregnancy, and in some cases the primary tumor may remain small or even spontaneously regress after metastasis [5]. In this specific case, the placenta was not retained for histopathological analysis following the cesarean section, as the likelihood of GTN had not been anticipated prior to the surgery, and β-HCG monitoring was not conducted during the gestation period. The patient did not exhibit vaginal bleeding, which is usually the initial symptom of GTN, but rather presented a complicated and rapidly evolving clinical history, including pre-eclampsia, a significant predisposing factor for stroke during pregnancy, and she was noted for symptoms suggestive of cerebral hemorrhage. Radiological examinations revealed cerebral hematoma alterations and a solitary subpleural mass in the upper segment of the right lung. Consequently, the preliminary clinical diagnosis was solely centered around cerebral hemorrhage subsequent to CVST, accompanied by an infection in the upper right lung lobe, neglecting the potential existence of GTN lung-brain metastasis.\u003c/p\u003e \u003cp\u003eThe reported incidence of venous thrombosis during pregnancy and the postpartum period fluctuates between 0.018% and 0.2%, with CVST occurrences being substantially lower [4, 6]. The clinical manifestations of CVST can vary extensively, thereby complicating the diagnosis process, as its symptoms frequently mimic other common pregnancy-related discomforts such as headaches, lethargy, nausea, and vomiting. Furthermore, vascular rupture could potentially culminate in cerebral hemorrhage. Hemorrhagic events are noted in approximately 60% of choriocarcinoma cerebral metastases, yet the emergence of multiple cerebral hemorrhages in normal pregnancies accompanying choriocarcinoma cerebral metastases is exceedingly rare, having only been documented in a few cases. In our comprehensive search of the PubMed database for materials published between January 1, 1956, and July 31, 2023, utilizing the keywords \"choriocarcinoma\" or \"gestational trophoblastic neoplasm\" along with \"embolism\" or \"thrombus\", we discovered pertinent insights. We excluded cases of choriocarcinoma or GTN regarding pulmonary embolism because of the relatively large number of cases regarding pulmonary embolism, as well as the literature review conducted by some of the authors. This search ultimately yielded 12 articles in English (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), identifying merely two instances where choriocarcinoma was complicated by CVST, and both were identified post-chemotherapy [7, 8].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReported cases of choriocarcinoma with embolism\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthor, Year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge, gender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore or after treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSite of embolization\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSerum or urine HCG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEmbolectomy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAnticoagulation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eXiaodong Li, 2020\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePVT、systemic\u003c/p\u003e \u003cp\u003ethrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e196783 IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLMWH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eEP, EMA-CO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIn Young Kim, 2019\u003csup\u003e18\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOVT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;200,000 IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRivaroxaban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMTX-FA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLouise Bonnet, 2015\u003csup\u003e19\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePulmonary vein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e155.2 IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnfractionated heparin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eEMA-CO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJir\u0026iacute; Sp\u0026aacute;cil, 2015\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft axillary artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e763 IU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEnoxaparin, warfarin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes (no detail)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaria Okumura, 2012\u003csup\u003e21\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePostcava\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53,414 mIU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eEMAO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTaymaa May, 2011\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAfter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5875 mIU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHeparin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eEMA-CO, EMA-EP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSanju Cyriac, 2009\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAfter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90000 IU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEnoxaparin, warfarin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eEMA-CO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIlya Blokh, 2003\u003csup\u003e22\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60, M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRight lower extremity venous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8533 mIU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eICD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJovan D, 1990\u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAfter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCoronary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMethotrexate, actinomycin D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBergljot Holm Arstad, 1980\u003csup\u003e24\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRight subclavian vein, right atrium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94000 IU/24\u003c/p\u003e \u003cp\u003ehours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEnoxaparin, warfarin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGoroku OHTA, 1968\u003csup\u003e25\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37, F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRight external iliac, femoral veins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003ePVT: pulmonary vein thrombosis; LMWH: low molecular weight heparin; CR: complete recovery in outcome; OVT:Ovarian vein thrombosis; MTX-FA: methotrexate, folinic acid; EMA-CO: etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine; EMAO: etoposide, methotrexate, actinomycin D, and vincristine; CVT: Cerebral venous thrombosis; EMA-EP:Etoposide, methotrexate, actinomycin D, etoposide and cisplatin; ICD:Etoposide, Ifosfamide, Cisplatin; PR: partial response; N/A: not available; PD: progress development or death in outcome.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAt present, there are no published scholarly articles or case studies that extensively illustrate the link between choriocarcinoma and CVST. The etiology and pathophysiology underlying CVST during pregnancy are intricate and remain largely unexplored. They might be associated with blood stasis, heightened coagulative states, and elements or conditions inducing cerebral vascular endothelial rupture [9]. Choriocarcinoma, as a malignant tumor, is hypothesized to be involved in the genesis and progression of CVST, and the possible mechanisms are as follows: (1) Escalation in procoagulant active substances: Research by Estell\u0026eacute;s A et al. has highlighted considerable elevations in plasma PAI-1 antigen and placental PAI-1 antigen and mRNA levels in molar pregnancies in comparison to control groups. Tissue factor, a precursor to the extrinsic coagulation pathway, exhibits a positive correlation with venous thromboembolism in patients with tumors [10]. Several studies have demonstrated significant expression of tissue factors in individuals suffering from various cancers, such as glioma, pancreatic, breast, and ovarian cancers, potentially leading to increased risks of venous thromboembolism [11]. Moreover, tissue factor plays a crucial role in advancing tumor progression. (2) Vascular endothelial cell damage: The secretion of procoagulant substances and inflammatory cytokines by tumor cells can wreak havoc on vascular endothelial cells, initiating the exposure of extracellular matrices, and precipitating platelet activation and adhesion. Continuous platelet aggregation can consequently foster thrombosis formation, while collagen fibers activate coagulation factors, initiating intrinsic coagulation pathways. (3) Hemodynamic alterations: Tumor patients often exhibit elevated levels of fibrinogen and other protein components, fostering increased blood viscosity due to enhanced erythrocyte aggregation. The action of vascular endothelial growth factors amplifies the volume of tumor interstitial fluid and blood viscosity, thereby accentuating blood hypercoagulability [12]. (4) Finally, CVST considers the possibility of tumor thrombus formed by blood circulation or invasion of adjacent veins by tumor with hemorrhage. To summarize, the triggers for venous thrombosis may be ascribed to hypercoagulability, either connected to pregnancy or primary malignant disorders, and direct assault or external compression of adjacent venous channels by cerebral metastases, culminating in blood stagnation and embolisms in venous sinuses. Due to cerebral venous return obstruction, CVST can compensate for the opening of many collateral venous circulation pathways, dilatation of common cerebral surface veins and deep veins, stasis of venous blood, and formation of collateral circulation can be seen on DSA examination in this case.\u003c/p\u003e \u003cp\u003eGiven the patient's pregnant state, chest X-ray or CT scans were not conducted upon admission; instead, a chest CT was performed post-delivery. The images revealed a solitary mass in the pleura of the upper right lung lobe, accompanied by slight exudation around it. Due to a limited comprehension of the imaging characteristics associated with choriocarcinoma showing multiple metastases, timely identification of the metastasis was missed. Generally, in patients with choriocarcinoma, pulmonary metastases imaging predominantly showes a higher prevalence of lesions in the medial and lower fields of both lungs, predominantly found in the right lung and more frequently located in the lateral zone compared to the central and inner zones. Moreover, the lesion diameters tend to be under 3 cm, accompanied by a scarcity of cavities. The variations in manifestations are contingent upon the internal hemorrhage extent, edema, necrosis, and tissue clot occurrences. The clarity of the boundary delineation is dependent on the surrounding lung tissue alterations. Specifically, lesions with pronounced hemorrhage and edema present indistinct boundaries, while those encircled by fibrous tissues offer clear demarcations. A notable imaging characteristic is a ground-glass attenuation halo encircling a pulmonary nodule, commonly known as the halo sign, resulting from peritumoral hemorrhages [13]. A considerable influx of tissue fragments into the bloodstream may provoke acute pulmonary embolism [14]. Even though CT scans can pinpoint more metastases compared to plain films, their impact on the treatment approach remains undefined. Hence, the International Federation of Gynecology and Obstetrics (FIGO) advocates the utilization of chest X-ray films as opposed to chest CT for assessing metastases extent [15].\u003c/p\u003e \u003cp\u003eChoriocarcinoma complicated with cerebral metastases commonly occurs after pulmonary metastases. The latter can compromise pulmonary venules, entering the bloodstream, subsequently flowing back to the left heart, and potentially disseminating to various organs through systemic circulation. Tumor cells can generate emboli that infiltrate the cerebral circulation, fostering cerebral metastases which are primary contributors to mortality. Irrespective of the cerebral metastases dimensions, they can potentially incite fatal intracranial hemorrhages. Consequently, even minor cerebral metastases can provoke hematoma within brain parenchyma or subdural spaces, escalating intracranial pressure. These scenarios necessitate urgent interventions, including craniotomy to alleviate space-occupying impacts and curtail intracranial hypertension, followed swiftly by supportive chemotherapy.\u003c/p\u003e \u003cp\u003eAlongside clinical and radiological signs, a paramount diagnostic indicator of GTN is heightened levels of serum β-HCG. A marked elevation in serum β-HCG amidst normal or aberrant pregnancies hints at a potential GTN occurrence. β-HCG serves not merely as a diagnostic and treatment monitoring tool but also assists in follow-ups and predicting recurrences. Distinguishing imaging features between brain metastases of choriocarcinoma with hemorrhage and hemorrhage caused by cerebrovascular disease remains challenging due to the diversity of clinical and radiological presentations. Consequently, lessons can be garnered, women in their reproductive years presenting with menopause, abdominal discomfort, and unaccountable bleeding should undergo β-HCG testing to rule out pregnancy-related ailments. When identification proves challenging, timely surgical exploration should be considered, meticulously checking for unexpected lesions during surgery. Cases arousing high suspicion warrant prompt pathological examinations. Particularly in reproductive-aged women manifesting recurrent intracranial hemorrhages coupled with intrapulmonary masses, GTN metastasis should be considered, necessitating immediate β-HCG evaluations and associated examinations, with a focus on CVST. The prognosis for choriocarcinoma patients has markedly improved courtesy of potent cytotoxic chemotherapy. The EMA-CO regimen stands as the foremost effective treatment for high-risk groups (FIGO stage IV and score\u0026thinsp;\u0026gt;\u0026thinsp;7), boasting an impressive long-term survival rate of up to 95% [1,16].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThrough this case study, we aim to foster a more profound comprehension of CVST and choriocarcinoma during pregnancy. This can help facilitate earlier diagnoses and improve patient outcomes, encouraging clinicians to exercise more informed decisions, refine imaging and laboratory examinations, minimize instances of incorrect and overlooked diagnoses, and thereby better assist patients especially during the initial phases.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGTN \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Gestational trophoblastic neoplasm\u003c/p\u003e\n\u003cp\u003eCVST \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cerebral venous sinus thrombosis\u003c/p\u003e\n\u003cp\u003eICH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Intracerebral hemorrhage\u003c/p\u003e\n\u003cp\u003eMRI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003eDSA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Digital subtraction angiography\u003c/p\u003e\n\u003cp\u003eCT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Computed tomography\u003c/p\u003e\n\u003cp\u003eβ-hCG \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; β-Human chorionic gonadotropin\u003c/p\u003e\n\u003cp\u003eEMA-CO \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine\u003c/p\u003e\n\u003cp\u003eFIGO \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;The International Federation of Gynecology and Obstetrics\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.W. drafted the manuscript. CR.W. reviewed the tissue pathology. F.Y. reviewed the literature. S.W. and F.Y. revised the manuscript. All authors have read and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors indicated that there was no external funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for her participation in this case report and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eNgan HYS, Seckl MJ, Berkowitz RS, et al. Diagnosis and management of gestational trophoblastic disease: 2021 update. Int J Gynaecol Obstet. 2021;155 Suppl 1:86-93.\u003c/li\u003e\n \u003cli\u003eLukinovic N, Malovrh EP, Takac I, Sobocan M, Knez J. Advances in diagnostics and management of gestational trophoblastic disease. Radiol Oncol. 2022;56(4):430-439.\u003c/li\u003e\n \u003cli\u003eRoth J, Deck G. Neurovascular disorders in pregnancy: A review. Obstet Med. 2019;12(4):164-167.\u003c/li\u003e\n \u003cli\u003eBousser MG, Crassard I. Cerebral venous thrombosis, pregnancy and oral contraceptives. Thromb Res. 2012;130 Suppl 1:S19-22.\u003c/li\u003e\n \u003cli\u003eYu P, Diao W, Jiang X. A Successfully Treated Metastatic Choriocarcinoma Coexistent With Pregnancy: A Case Report of a 4-Year Follow-Up. Medicine (Baltimore). 2016;95(21):e3505.\u003c/li\u003e\n \u003cli\u003eJames AH, Bushnell CD, Jamison MG, Myers ER. Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol. 2005;106(3):509-516.\u003c/li\u003e\n \u003cli\u003eCyriac S, Sagar TG, Mahajan V. Choriocarcinoma with arterial and venous thrombosis. Neurol India. 2009;57(4):505-507.\u003c/li\u003e\n \u003cli\u003eMay T, Rabinowe SN, Berkowitz RS, Goldstein DP. Cerebral venous sinus thrombosis presenting as cerebral metastasis in a patient with choriocarcinoma following a non-molar gestation. Gynecol Oncol. 2011;122(1):199-200.\u003c/li\u003e\n \u003cli\u003eBousser MG, Crassard I. Cerebral venous thrombosis, pregnancy and oral contraceptives. Thromb Res. 2012;130 Suppl 1:S19-22.\u003c/li\u003e\n \u003cli\u003eLi H, Yu Y, Gao L, et al. Tissue factor: a neglected role in cancer biology. J Thromb Thrombolysis. 2022;54(1):97-108.\u003c/li\u003e\n \u003cli\u003eKobayashi S, Koizume S, Takahashi T, et al. Tissue factor and its procoagulant activity on cancer-associated thromboembolism in pancreatic cancer. Cancer Sci. 2021;112(11):4679-4691.\u003c/li\u003e\n \u003cli\u003eBaronzio G, Freitas I, Kwaan HC. Tumor microenvironment and hemorheological abnormalities. Semin Thromb Hemost. 2003;29(5):489-497.\u003c/li\u003e\n \u003cli\u003eShaaban AM, Rezvani M, Haroun RR, et al. Gestational Trophoblastic Disease: Clinical and Imaging Features. Radiographics. 2017;37(2):681-700.\u003c/li\u003e\n \u003cli\u003eSoper JT. Gestational Trophoblastic Disease: Current Evaluation and Management. Obstet Gynecol. 2021;137(2):355-370.\u003c/li\u003e\n \u003cli\u003eFIGO Oncology Committee. FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee. Int J Gynaecol Obstet. 2002;77(3):285-287.\u003c/li\u003e\n \u003cli\u003eBraga A, Elias KM, Horowitz NS, Berkowitz RS. Treatment of high-risk gestational trophoblastic neoplasia and chemoresistance/relapsed disease. Best Pract Res Clin Obstet Gynaecol. 2021;74:81-96.\u003c/li\u003e\n \u003cli\u003eLi X, Peng H. Complete remission of choriocarcinoma with pulmonary vein thrombosis in the third trimester of pregnancy treated with systemic chemotherapy and anticoagulation: A case report. Medicine. 2021;100(21):e26145.\u003c/li\u003e\n \u003cli\u003eKim IY, Kim SH, Hwang IT, Ha JG, Cha JH. A rare case of ovarian vein thrombosis in a gestational trophoblastic neoplasia patient. Obstet Gynecol Sci. 2019;62(3):190-193.\u003c/li\u003e\n \u003cli\u003eBonnet L, Raposo N, Blot-Souletie N, et al. Stroke Caused by a Pulmonary Vein Thrombosis Revealing a Metastatic Choriocarcinoma. Circulation. 2015;131(23):2093-4.\u003c/li\u003e\n \u003cli\u003eSp\u0026aacute;cil J, Hradec J, Kr\u0026aacute;l J. Opakovan\u0026eacute; embolizace do perifern\u0026iacute;ch tepen z plicn\u0026iacute; metast\u0026aacute;zy choriokarcinomu [Recurrent peripheral arterial embolism from metastatic lung choriocarcinoma]. Cas Lek Cesk. 2006;145(2):160-1. Czech.\u003c/li\u003e\n \u003cli\u003eOkumura M, Fushida K, Pulcineli Vieira Francisco R, Schultz R, Zugaib M. Sonographic appearance of an advanced invasive mole and associated metastatic thrombus in the inferior vena cava. J Clin Ultrasound. 2013 Feb;41(2):113-5.\u003c/li\u003e\n \u003cli\u003eBlokh I, Oiseth SJ, Fuks J, Jain D, Eapen S, Koulova L, Alexandrescu D, Li YY, Dutcher J, Wiernik PH. Metastatic choriocarcinoma in a middle-aged man presenting as a right thigh mass with venous thrombosis: a case report. Med Oncol. 2003;20(2):189-94.\u003c/li\u003e\n \u003cli\u003eVasiljevic JD, Abdulla AK. Coronary embolism by metastatic choriocarcinoma of the uterus: an unusual cause of ischemic heart disease. Gynecol Oncol. 1990 Aug;38(2):289-92.\u003c/li\u003e\n \u003cli\u003eArstad BH, Bergsj\u0026oslash; P, Eie H. Hydatidiform mole with large ovarian cysts and venous thrombosis: a case report. Int J Gynaecol Obstet. 1980 Jan-Feb;17(4):323-7.\u003c/li\u003e\n \u003cli\u003eOhta G, Nishino H. Pulmonary endoarterial choriocarcinoma and thrombosis in the right iliac vein system. Report of an autopsy case. Acta Pathol Jpn. 1968 Feb;18(1):17-21.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Gestational trophoblastic neoplasia, Choriocarcinoma, Cerebral venous sinus thrombosis, Brain metastasis, Intracerebral hemorrhages","lastPublishedDoi":"10.21203/rs.3.rs-4472426/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4472426/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e Intracerebral hemorrhage (ICH) in younger females is usually attributed to ruptured aneurysms or cerebrovascular malformations. By contrast, metastatic brain tumors and complications stemming from intracranial venous sinus thrombosis (CVST)-associated hemorrhagic strokes are rare instigators of ICH in women of childbearing age. We report a case of choriocarcinoma metastasis with rapid progression of cerebral venous sinus thrombosis in a patient in the third trimester. Additionally, the literature review revealed only two cases where choriocarcinoma was complicated by CVST, and both were identified post-chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation \u003c/strong\u003eA case of a 33-year-old expectant woman, in her 32\u003csup\u003e+\u003c/sup\u003e weeks of pregnancy, sought hospital admission owing to persistent blurred vision that had prevailed for over half a month. After her admission, she endured three instances of ICH within only one week, during which period digital subtraction angiography unveiled the presence of thrombosis within the superior sagittal sinus. Choriocarcinoma in the third trimester with lung and brain metastases, ICH, and CVST. The patient underwent an emergency caesarean section and delivered a premature baby girl. Catheter directed thrombolysis in the intracranial venous sinus and evacuation of the hematoma by craniotomy were subsequently performed. Eventually, this patient was diagnosed with choriocarcinoma with multiple metastases and received drug chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003eThe symptoms and imaging findings of brain metastases with hemorrhage and CVST overlap with each other, resulting in delaying and confusing the diagnosis. Furthermore, early diagnostic interventions for choriocarcinoma coupled with intensive treatment strategies can potentially improve patient prognosis and help avoid life-threatening consequences.\u003c/p\u003e","manuscriptTitle":"Choriocarcinoma metastases complicated with cerebral venous sinus thrombosis in the third trimester of pregnancy: a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-11 18:33:13","doi":"10.21203/rs.3.rs-4472426/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2024-05-30T06:35:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-26T23:29:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2024-05-24T12:19:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bc7baafb-b3e3-45b0-bfac-b4a735d00bfa","owner":[],"postedDate":"June 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-06-11T18:33:13+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-11 18:33:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4472426","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4472426","identity":"rs-4472426","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}