Thrombus analysis revealing occult lung cancer: tumour embolism as a rare cause of ischaemic stroke. | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Thrombus analysis revealing occult lung cancer: tumour embolism as a rare cause of ischaemic stroke. Carlota Jauregui Larrañaga, Ines Albajar, María Aranzazu Juaristi-Abaunz, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9053404/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cancer-associated stroke represents an important diagnostic challenge, particularly when ischaemic stroke is the first manifestation of an occult malignancy. Although cancer-related hypercoagulability is the most common mechanism, tumour embolism is a rare and under-recognised cause. We report the case of a 76-year-old man presenting with acute left hemiplegia, hemianopsia and dysarthria (NIHSS 18). CT angiography demonstrated occlusion of the right middle cerebral artery and CT perfusion showed a favourable mismatch profile. Mechanical thrombectomy achieved partial recanalisation (TICI 2b). Histopathological examination of the retrieved thrombus revealed malignant cells. Subsequent chest CT identified a large necrotic mass in the left lung invading the pulmonary vein. Immunohistochemical analysis of the thrombus was consistent with non-small cell lung carcinoma with high PD-L1 expression. Echocardiography was normal, excluding non-bacterial thrombotic endocarditis. Despite initiation of immunotherapy, the patient developed brain metastases and died 51 days after the index stroke. This case highlights tumour embolism from lung cancer as a rare mechanism of cancer-associated stroke and underscores the diagnostic value of histopathological analysis of thrombi retrieved during mechanical thrombectomy, which may facilitate the early detection of occult malignancy. Stroke cancer-associated stroke tumour embolism mechanical thrombectomy lung cancer. Figures Figure 1 BACKGROUND Cancer-associated stroke (CAS) is increasingly recognised as a complex clinical entity resulting from multiple mechanisms including hypercoagulability, non-bacterial thrombotic endocarditis and treatment-related vascular toxicity. In some patients, ischaemic stroke may represent the first manifestation of an underlying malignancy 1 . Although cancer-related hypercoagulability is the most common mechanism, tumour embolism is a rare cause of stroke and may occur when malignant cells directly enter the systemic arterial circulation. Lung cancer, particularly when invading the pulmonary veins, has been described as a potential source of systemic tumour emboli 2 , 3 . We report a case in which histopathological examination of a thrombus retrieved during mechanical thrombectomy revealed malignant cells, leading to the diagnosis of previously unrecognised lung cancer. CASE PRESENTATION A 76-year-old man with a history of tobacco use presented with acute-onset left-sided hemiplegia, hemianopsia and dysarthria. Neurological examination revealed a National Institutes of Health Stroke Scale (NIHSS) score of 18. Non-contrast CT scan demonstrated early ischaemic changes, CT angiography confirmed occlusion of the right middle cerebral artery [ Figure 1 A ] and CT perfusion showed a substantial penumbral area with a favourable mismatch profile. Intravenous thrombolysis was contraindicated due to partially established infarction, so primary mechanical thrombectomy was performed, achieving partial recanalisation (TICI 2b). Chest CT subsequently identified a heterogeneous mass in the left lung (9 × 7 × 8 cm) with central necrosis, pulmonary vein invasion and mediastinal lymphadenopathy [ Figure 1 B ] . Histopathological analysis of the retrieved thrombus revealed nests of malignant cells [ Figure 1 C ] . Immunohistochemistry was consistent with non-small cell lung carcinoma, showing CK7 positivity, patchy weak TTF-1 expression and negativity for P40 and synaptophysin. Molecular profiling demonstrated high PD-L1 expression (90%) and TP53 mutation. Brain MRI confirmed extensive infarction in the right sylvian territory. Transthoracic echocardiography was normal, excluding cardiac sources of embolism. Laboratory testing was unremarkable except for D-dimer levels (1,476 ng/mL). Staging studies classified the tumour as poorly differentiated adenocarcinoma cT4N2M1c (stage IV). Immunotherapy with pembrolizumab was initiated. The patient experienced partial neurological recovery and was discharged with mild deficits (NIHSS 7, mRS 2). Thirty days later, he was readmitted with fever, behavioural changes, left-sided sensory impairment and hyperphagia due to newly identified frontal metastases. Despite ongoing treatment, his condition deteriorated rapidly and he died 51 days after the initial stroke. DISCUSSION AND CONCLUSIONS This case illustrates CAS caused by tumour embolism secondary to lung adenocarcinoma invading the pulmonary vein. Direct tumour embolisation represents a rare but increasingly recognised mechanism of stroke. CAS poses a significant diagnostic challenge, particularly when ischaemic stroke precedes the diagnosis of malignancy 4 . Recent studies estimate that up to 5–10% of embolic strokes of undetermined source (ESUS) may be associated with previously undiagnosed cancer 5 , 6 . Adenocarcinomas, particularly those originating in the lung or pancreas, are the most frequently implicated 7 , 8 . Patients with CAS typically have a poor prognosis, with higher mortality, greater functional disability and increased risk of recurrent stroke compared with patients without malignancy. In many series, median survival is less than six months 9 . Mechanical thrombectomy has not only improved reperfusion outcomes in large vessel occlusion but also provides a unique diagnostic opportunity. Histopathological analysis of retrieved thrombi may reveal unusual stroke aetiologies, including tumour embolism, and may facilitate the early diagnosis of occult malignancy 10 . In the present case, thrombus analysis was crucial in establishing the underlying mechanism of stroke and in prompting oncological investigation. Although the overall prognosis remained poor, routine histological examination of thrombi retrieved during thrombectomy may therefore provide important diagnostic information and should be considered particularly in cases of cryptogenic stroke. Abbreviations CAS – Cancer-associated stroke ESUS – Embolic stroke of undetermined source NIHSS – National Institutes of Health Stroke Scale Declarations ETHICS APPROVAL The study was approved by the Research Ethics Committee of OSI Donostialdea (Donostia University Hospital, Spain). The study was conducted in accordance with the principles of the Declaration of Helsinki. CONSENT FOR PUBLICATION Written informed consent for publication of this case report and the accompanying images was obtained from the patient’s next of kin. A copy of the written consent is available for review by the Editor of this journal. AVAILABILITY OF DATA AND MATERIALS All relevant data are included in this article. COMPETING INTERESTS The authors declare that they have no competing interests. FUNDING The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. AUTHORS’ CONTRIBUTIONS CJ drafted the manuscript. IA and MJ contributed to data collection and clinical interpretation. JM supervised the study and critically revised the manuscript. All authors read and approved the final manuscript. ACKNOWLEDGEMENTS Not applicable. References Selvik HA, Bjerkreim AT, Thomassen L, et al. When to Screen Ischaemic Stroke Patients for Cancer. Cerebrovasc Dis. 2018;45(1–2):42–7. Heo JH, Yun J, Kim KH, et al. Cancer-Associated Stroke: Thrombosis Mechanism, Diagnosis, Outcome, and Therapeutic Strategies. J stroke. 2024;26(2):164–78. Carneado-Ruiz J. Cryptogenic embolic stroke and cancer. Front Neurol. 2025;16:1537779. Gon Y, Okazaki S, Terasaki Y, et al. Characteristics of cryptogenic stroke in cancer patients. Ann Clin Transl Neurol. 2016;3(4):280–7. Grazioli S, Paciaroni M, Agnelli G, et al. Cancer-associated ischemic stroke: A retrospective multicentre cohort study. Thromb Res. 2018;165:33–7. Ntaios G, Perlepe K, Lambrou D, et al. Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source. J Am Heart Assoc. 2019;8(15):1–9. Schwarzbach CJ, Schaefer A, Ebert A, et al. Stroke and cancer: The importance of cancer-associated hypercoagulation as a possible stroke etiology. Stroke. 2012;43(11):3029–34. Navi BB, Reiner AS, Kamel H, et al. Association between incident cancer and subsequent stroke. Ann Neurol. 2015;77(2):291–300. Cutting S, Wettengel M, Conners JJ et al. Three-Month Outcomes Are Poor in Stroke Patients with Cancer Despite Acute Stroke Treatment. J Stroke Cerebrovasc Dis [Internet]. 2017;26(4):809–15. Available from: https://www.sciencedirect.com/science/article/pii/S1052305716304232 Boeckh-Behrens T, Schubert M, Förschler A, et al. The Impact of Histological Clot Composition in Embolic Stroke. Clin Neuroradiol. 2016;26(2):189–97. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-9053404","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":606387532,"identity":"18945500-a55f-46bf-8c7f-50616c6a946a","order_by":0,"name":"Carlota Jauregui Larrañaga","email":"data:image/png;base64,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","orcid":"","institution":"Donostia Unibertsitate Ospitalea","correspondingAuthor":true,"prefix":"","firstName":"Carlota","middleName":"Jauregui","lastName":"Larrañaga","suffix":""},{"id":606387534,"identity":"80464dfa-bda6-4bbe-9920-8dc24267a762","order_by":1,"name":"Ines Albajar","email":"","orcid":"","institution":"Donostia Unibertsitate Ospitalea","correspondingAuthor":false,"prefix":"","firstName":"Ines","middleName":"","lastName":"Albajar","suffix":""},{"id":606387535,"identity":"f7d6cca2-e91b-409f-b21e-b678b0ef8112","order_by":2,"name":"María Aranzazu Juaristi-Abaunz","email":"","orcid":"","institution":"Donostia Unibertsitate Ospitalea","correspondingAuthor":false,"prefix":"","firstName":"María","middleName":"Aranzazu","lastName":"Juaristi-Abaunz","suffix":""},{"id":606387536,"identity":"775f1285-4561-4aab-9939-516f7f9982b3","order_by":3,"name":"Juan Marta Enguita","email":"","orcid":"","institution":"Marqués de Valdecilla University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"Marta","lastName":"Enguita","suffix":""}],"badges":[],"createdAt":"2026-03-06 19:08:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9053404/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9053404/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104867581,"identity":"c7b41c4d-9d56-476c-aca4-bddd3f67b48d","added_by":"auto","created_at":"2026-03-18 07:13:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":727865,"visible":true,"origin":"","legend":"\u003cp\u003e1A. CT angiography showing occlusion of the right middle cerebral artery.\u003c/p\u003e\n\u003cp\u003e1B. Chest CT demonstrating a heterogeneous mass in the left lower lobe (9 × 7 × 8 cm) with central necrosis and invasion of the pulmonary vein.\u003c/p\u003e\n\u003cp\u003e1C. Histopathological examination of the retrieved thrombus (H\u0026amp;E staining) showing nests of malignant cells.\u003c/p\u003e\n\u003cp\u003e1D. Immunohistochemistry consistent with non-small cell lung carcinoma: CK7 positive, patchy weak TTF-1 expression and negative P40 and synaptophysin.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9053404/v1/05aa52e6a00209c6050195a2.png"},{"id":105708458,"identity":"a899feee-331d-494d-872c-4aaa75c5e1b8","added_by":"auto","created_at":"2026-03-30 07:28:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1044696,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9053404/v1/e91e80b4-745c-4080-ad5e-144c40817763.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Thrombus analysis revealing occult lung cancer: tumour embolism as a rare cause of ischaemic stroke.","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eCancer-associated stroke (CAS) is increasingly recognised as a complex clinical entity resulting from multiple mechanisms including hypercoagulability, non-bacterial thrombotic endocarditis and treatment-related vascular toxicity. In some patients, ischaemic stroke may represent the first manifestation of an underlying malignancy\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough cancer-related hypercoagulability is the most common mechanism, tumour embolism is a rare cause of stroke and may occur when malignant cells directly enter the systemic arterial circulation. Lung cancer, particularly when invading the pulmonary veins, has been described as a potential source of systemic tumour emboli\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWe report a case in which histopathological examination of a thrombus retrieved during mechanical thrombectomy revealed malignant cells, leading to the diagnosis of previously unrecognised lung cancer.\u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003eA 76-year-old man with a history of tobacco use presented with acute-onset left-sided hemiplegia, hemianopsia and dysarthria. Neurological examination revealed a National Institutes of Health Stroke Scale (NIHSS) score of 18.\u003c/p\u003e \u003cp\u003eNon-contrast CT scan demonstrated early ischaemic changes, CT angiography confirmed occlusion of the right middle cerebral artery \u003cb\u003e[\u003c/b\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA\u003cb\u003e]\u003c/b\u003e and CT perfusion showed a substantial penumbral area with a favourable mismatch profile. Intravenous thrombolysis was contraindicated due to partially established infarction, so primary mechanical thrombectomy was performed, achieving partial recanalisation (TICI 2b).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eChest CT subsequently identified a heterogeneous mass in the left lung (9 \u0026times; 7 \u0026times; 8 cm) with central necrosis, pulmonary vein invasion and mediastinal lymphadenopathy \u003cb\u003e[\u003c/b\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB\u003cb\u003e]\u003c/b\u003e. Histopathological analysis of the retrieved thrombus revealed nests of malignant cells \u003cb\u003e[\u003c/b\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC\u003cb\u003e]\u003c/b\u003e. Immunohistochemistry was consistent with non-small cell lung carcinoma, showing CK7 positivity, patchy weak TTF-1 expression and negativity for P40 and synaptophysin. Molecular profiling demonstrated high PD-L1 expression (90%) and TP53 mutation.\u003c/p\u003e \u003cp\u003eBrain MRI confirmed extensive infarction in the right sylvian territory. Transthoracic echocardiography was normal, excluding cardiac sources of embolism. Laboratory testing was unremarkable except for D-dimer levels (1,476 ng/mL).\u003c/p\u003e \u003cp\u003eStaging studies classified the tumour as poorly differentiated adenocarcinoma cT4N2M1c (stage IV). Immunotherapy with pembrolizumab was initiated. The patient experienced partial neurological recovery and was discharged with mild deficits (NIHSS 7, mRS 2).\u003c/p\u003e \u003cp\u003eThirty days later, he was readmitted with fever, behavioural changes, left-sided sensory impairment and hyperphagia due to newly identified frontal metastases. Despite ongoing treatment, his condition deteriorated rapidly and he died 51 days after the initial stroke.\u003c/p\u003e "},{"header":"DISCUSSION AND CONCLUSIONS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cp\u003eThis case illustrates CAS caused by tumour embolism secondary to lung adenocarcinoma invading the pulmonary vein. Direct tumour embolisation represents a rare but increasingly recognised mechanism of stroke.\u003c/p\u003e \u003cp\u003eCAS poses a significant diagnostic challenge, particularly when ischaemic stroke precedes the diagnosis of malignancy\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Recent studies estimate that up to 5\u0026ndash;10% of embolic strokes of undetermined source (ESUS) may be associated with previously undiagnosed cancer\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Adenocarcinomas, particularly those originating in the lung or pancreas, are the most frequently implicated\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePatients with CAS typically have a poor prognosis, with higher mortality, greater functional disability and increased risk of recurrent stroke compared with patients without malignancy. In many series, median survival is less than six months\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMechanical thrombectomy has not only improved reperfusion outcomes in large vessel occlusion but also provides a unique diagnostic opportunity. Histopathological analysis of retrieved thrombi may reveal unusual stroke aetiologies, including tumour embolism, and may facilitate the early diagnosis of occult malignancy\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the present case, thrombus analysis was crucial in establishing the underlying mechanism of stroke and in prompting oncological investigation. Although the overall prognosis remained poor, routine histological examination of thrombi retrieved during thrombectomy may therefore provide important diagnostic information and should be considered particularly in cases of cryptogenic stroke.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCAS \u0026ndash; Cancer-associated stroke\u003c/p\u003e\n\u003cp\u003eESUS \u0026ndash; Embolic stroke of undetermined source\u003c/p\u003e\n\u003cp\u003eNIHSS \u0026ndash; National Institutes of Health Stroke Scale\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eETHICS APPROVAL\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Research Ethics Committee of OSI Donostialdea (Donostia University Hospital, Spain). The study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT FOR PUBLICATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of this case report and the accompanying images was obtained from the patient’s next of kin. A copy of the written consent is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAVAILABILITY OF DATA AND MATERIALS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll relevant data are included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS’ CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCJ drafted the manuscript. IA and MJ contributed to data collection and clinical interpretation. JM supervised the study and critically revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSelvik HA, Bjerkreim AT, Thomassen L, et al. When to Screen Ischaemic Stroke Patients for Cancer. Cerebrovasc Dis. 2018;45(1\u0026ndash;2):42\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeo JH, Yun J, Kim KH, et al. Cancer-Associated Stroke: Thrombosis Mechanism, Diagnosis, Outcome, and Therapeutic Strategies. J stroke. 2024;26(2):164\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarneado-Ruiz J. Cryptogenic embolic stroke and cancer. Front Neurol. 2025;16:1537779.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGon Y, Okazaki S, Terasaki Y, et al. Characteristics of cryptogenic stroke in cancer patients. Ann Clin Transl Neurol. 2016;3(4):280\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrazioli S, Paciaroni M, Agnelli G, et al. Cancer-associated ischemic stroke: A retrospective multicentre cohort study. Thromb Res. 2018;165:33\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNtaios G, Perlepe K, Lambrou D, et al. Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source. J Am Heart Assoc. 2019;8(15):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwarzbach CJ, Schaefer A, Ebert A, et al. Stroke and cancer: The importance of cancer-associated hypercoagulation as a possible stroke etiology. Stroke. 2012;43(11):3029\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNavi BB, Reiner AS, Kamel H, et al. Association between incident cancer and subsequent stroke. Ann Neurol. 2015;77(2):291\u0026ndash;300.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCutting S, Wettengel M, Conners JJ et al. Three-Month Outcomes Are Poor in Stroke Patients with Cancer Despite Acute Stroke Treatment. J Stroke Cerebrovasc Dis [Internet]. 2017;26(4):809\u0026ndash;15. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.sciencedirect.com/science/article/pii/S1052305716304232\u003c/span\u003e\u003cspan address=\"https://www.sciencedirect.com/science/article/pii/S1052305716304232\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoeckh-Behrens T, Schubert M, F\u0026ouml;rschler A, et al. The Impact of Histological Clot Composition in Embolic Stroke. Clin Neuroradiol. 2016;26(2):189\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Stroke, cancer-associated stroke, tumour embolism, mechanical thrombectomy, lung cancer.","lastPublishedDoi":"10.21203/rs.3.rs-9053404/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9053404/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCancer-associated stroke represents an important diagnostic challenge, particularly when ischaemic stroke is the first manifestation of an occult malignancy. Although cancer-related hypercoagulability is the most common mechanism, tumour embolism is a rare and under-recognised cause.\u003c/p\u003e \u003cp\u003eWe report the case of a 76-year-old man presenting with acute left hemiplegia, hemianopsia and dysarthria (NIHSS 18). CT angiography demonstrated occlusion of the right middle cerebral artery and CT perfusion showed a favourable mismatch profile. Mechanical thrombectomy achieved partial recanalisation (TICI 2b). Histopathological examination of the retrieved thrombus revealed malignant cells. Subsequent chest CT identified a large necrotic mass in the left lung invading the pulmonary vein. Immunohistochemical analysis of the thrombus was consistent with non-small cell lung carcinoma with high PD-L1 expression. Echocardiography was normal, excluding non-bacterial thrombotic endocarditis. Despite initiation of immunotherapy, the patient developed brain metastases and died 51 days after the index stroke.\u003c/p\u003e \u003cp\u003eThis case highlights tumour embolism from lung cancer as a rare mechanism of cancer-associated stroke and underscores the diagnostic value of histopathological analysis of thrombi retrieved during mechanical thrombectomy, which may facilitate the early detection of occult malignancy.\u003c/p\u003e","manuscriptTitle":"Thrombus analysis revealing occult lung cancer: tumour embolism as a rare cause of ischaemic stroke.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-18 07:12:15","doi":"10.21203/rs.3.rs-9053404/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"37cabf50-82cd-4e93-89f9-dba0dcd7c9b8","owner":[],"postedDate":"March 18th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T07:27:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-18 07:12:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9053404","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9053404","identity":"rs-9053404","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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