Brain metastasis from lung adenocarcinoma associated with Lemierre syndrome in a middle-aged man: a case report and review of the literature

Brain metastasis from lung adenocarcinoma associated with Lemierre syndrome in a middle-aged man: a case report and review of the literature | 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 Brain metastasis from lung adenocarcinoma associated with Lemierre syndrome in a middle-aged man: a case report and review of the literature XiaoXia Yang, Jin Gang Han, Zhi Yu, Jian Hua Nian, Jie Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7405277/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Jan, 2026 Read the published version in BMC Infectious Diseases → Version 1 posted 12 You are reading this latest preprint version Abstract Background Lemierre syndrome, typically caused by oropharyngeal infection with Fusobacterium necrophorum, represents a rare yet life-threatening condition, particularly when it coincides with brain metastases from lung adenocarcinoma. The occurrence of Lemierre syndrome complicated by brain metastasis from lung adenocarcinoma is exceedingly uncommon, with only a limited number of cases reported. Case presentation: A 42-year-old male presented with neck pain and infection, which led to the development of cervical venous thrombosis, cervical lymphadenopathy, and multiple pulmonary nodules, ultimately diagnosed as Lemierre syndrome. The patient was treated with anticoagulation, antibiotics, anti-inflammatory agents, and anaerobic coverage. Chest pain was also present, and CT imaging revealed lung inflammation and nodules. Further investigation confirmed a diagnosis of lung adenocarcinoma. Targeted therapy in combination with chemotherapy was initiated. During follow-up, the patient developed a headache, and subsequent CT imaging identified brain metastasis from the lung adenocarcinoma. Therapy was adjusted, with an increase in memetinib dosage. The patient’s condition improved, and he was discharged. Conclusions This case underscores the importance of clinicians’ heightened awareness of the complex interplay between lung adenocarcinoma brain metastases and Lemierre syndrome. Early recognition and intervention in such multifaceted cases are crucial for preventing mortality. Lemierre syndrome Lung adenocarcinoma Leptomeningeal metastasis. Fusobacterium necrophorum Tyrosine Kinase Inhibitors.Multidisciplinary management Figures Figure 1 Figure 2 Figure 3 Introduction Lemierre syndrome (LS), often referred to as the "forgotten disease," is a rare condition with an incidence of approximately 0.6–2.3 cases per million people[1]. It is defined by a recent oropharyngeal infection, clinical or radiological evidence of internal jugular vein thrombosis, and the isolation of anaerobic pathogens, primarily Fusobacterium necrophorum[2]. First described in The Lancet in 1936 by French microbiologist André Lemierre[3], LS can lead to severe systemic complications if not diagnosed and treated promptly[4]. Lung cancer (LC) is among the most aggressive malignancies, ranking within the top three cancers worldwide in terms of both incidence and mortality[5]. It also exhibits the highest rate of brain metastasis from primary tumors[6]. Brain metastasis poses a significant clinical challenge for patients with advanced LC, affecting approximately 20%-40% of cases. It often results in severe neurological symptoms, a poor prognosis, and significantly contributes to LC-related mortality[7]. The process of brain metastasis involves multiple complex steps, including local invasion, intravasation, tumor cell circulation through the bloodstream, disruption of the blood-brain barrier, extravasation into brain parenchyma, and interaction with the brain’s microenvironment[8]. The concurrent occurrence of brain metastases from LC and LS is exceedingly rare. This report presents a case of LS complicated by LC, further complicated by brain metastases. Given the extreme rarity of this combination, the case warrants special consideration. The goal of this report is to provide a comprehensive account of our clinical management approach, offering valuable insights into this uncommon and complex clinical entity. Case report A 42-year-old male with no significant medical history presented to our outpatient clinic in July 2020. Two days prior, he experienced sudden-onset right-sided chest pain at home, without any obvious triggers. The pain worsened when lying down or assuming certain positions but was relieved by changing posture. He denied fever, cough, sputum production, chest tightness, dyspnea, nausea, or vomiting. Chest computed tomography (CT) conducted on July 1 revealed bilateral pulmonary inflammation, with multiple scattered nodules and micronodules in both lungs, localized pleural thickening on both sides, and mild pleural reaction in the right lower lung. Enlarged mediastinal lymph nodes were also observed. Consequently, the patient was admitted for further evaluation and treatment. Upon admission, physical examination showed a red tongue with a thin yellow coating and a floating, rapid pulse. Auscultation revealed coarse breath sounds in both lungs. Other vital signs and systemic findings were stable, with no signs of critical illness. Laboratory tests performed the following day revealed normal platelet count (170 × 10 9 /L), white blood cell count (8.3 × 10 9 /L), and a mildly elevated neutrophil percentage (63.5%). C-reactive protein (CRP) was elevated at 54.3 mg/L. D-dimer was significantly elevated (4.83 mg/L), as was fibrinogen (5.62 g/L). Serum creatinine was normal (58.9 µmol/L), while blood glucose was mildly elevated (6.85 mmol/L). Procalcitonin remained within normal limits (0.05 ng/ml). Tumor markers showed alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) within normal limits (4.2 ng/ml and 1.4 ng/ml, respectively). During hospitalization, the patient developed swelling and pain in the right side of the neck, accompanied by cervical lymphadenopathy, difficulty swallowing, and localized tenderness in the right anterior cervical region. Routine magnetic resonance imaging (MRI) on July 13 (Fig. 1 A– 1 E) revealed thrombosis in the right internal and external jugular veins, as well as the right subclavian vein. Inflammatory changes were noted in the right parapharyngeal space and supraclavicular fossa, along with multiple enlarged lymph nodes. Follow-up CT and MRI scans demonstrated stable pulmonary nodules and persistent pleural effusion with minimal absorption. Hepatic dysfunction and fatty liver were also noted. (D)Abnormal signal intensity in the right cervical musculature became more pronounced, with persistent patchy hyperintense areas. (E) The hyperintense region on the right side appeared slightly expanded, extending toward the posterior neck A subsequent CTPA on July 17 (Fig. 2 A– 2 B) suggested pulmonary arterial thrombosis in the right lower lung, with absorption of inflammation in both lungs compared to the previous scan on July 1. Multiple scattered nodules and micronodules persisted, and pleural effusion remained on the left side. Multiple slightly enlarged mediastinal lymph nodes were also similar to those noted previously. A routine chest CT performed on July 21 revealed chronic inflammatory lesions in the left lower lobe and a small amount of left-sided pleural effusion.(Fig. 3 A- 3 E). Multiple scattered nodules and micronodules were observed in both lungs, appearing largely unchanged compared to the July 1 scan. Localized pleural thickening was noted bilaterally, with mild pleural reaction in the right lower lung. Additionally, multiple slightly enlarged mediastinal lymph nodes were identified. Thrombosis of the superior vena cava and subclavian vein was also observed. The patient was diagnosed with right internal and external jugular vein thrombosis, right subclavian vein thrombosis, cervical cellulitis, right pulmonary artery embolism, pneumonia, left-sided pleural effusion, multiple pulmonary nodules (suggestive of pulmonary space-occupying lesions), fatty liver, hepatic dysfunction, and type 2 diabetes mellitus. Cervical swelling and pain, which progressed to thrombosis of the right jugular and subclavian veins, indicated local thrombus formation. Additionally, the detection of right pulmonary artery embolism suggested the development of distant septic emboli. Persistent systemic inflammation led to a multidisciplinary evaluation, after which the patient was diagnosed with LS. The patient received comprehensive treatment, including anticoagulation, antimicrobial therapy (with anaerobic coverage), and anti-inflammatory measures. During hospitalization, abnormalities in glucose metabolism were identified, and type 2 diabetes mellitus was confirmed by the endocrinology team, leading to the initiation of insulin therapy. After stabilization, the patient was discharged on July 22, 2020, with a prescription for oral rivaroxaban (20 mg daily) for ongoing anticoagulation, and scheduled for regular outpatient follow-up. At a follow-up outpatient visit two weeks after discharge, a PET-CT scan performed at another hospital on August 10, 2020, revealed normal brain parenchymal structures. Radiotracer distribution in the cerebral cortex, basal ganglia, and cerebellum was homogeneous, with no abnormal uptake, brain metastasis, or central nervous system (CNS) involvement. Mild inflammatory changes were noted in the head and neck region, consistent with non-neoplastic processes. However, significant abnormalities in the pulmonary and thoracic systems raised strong suspicion for primary LC with metastatic involvement. The presumed primary lesion was a nodule in the dorsal segment of the left lower lobe, accompanied by multiple metastatic lymph nodes. Left-sided pleural effusion persisted. Additionally, multiple bone metastases were identified. Based on these findings, the patient was diagnosed with metastatic adenocarcinoma, with both bone and lymphatic involvement.. Since August 2020, the patient was initiated on first-line targeted therapy with afatinib, alongside zoledronic acid for managing bone metastases. Chest CT showed a partial response (PR) to the treatment. In May 2021, molecular testing identified the T790M resistance mutation, leading to a switch to second-line targeted therapy with osimertinib (AZD9291) in June 2021. Imaging again showed a PR. In mid-2024, the patient developed new symptoms, including headache. Brain MRI revealed abnormal meningeal enhancement in the right frontal and occipital lobes. Cerebrospinal fluid (CSF) analysis detected EGFR 19del, TP53, and CTNNB1 mutations, indicating leptomeningeal metastasis. Consequently, treatment was escalated to third-generation EGFR-TKI furmonertinib, at an initial dose of 160 mg daily. At this point, the disease was classified as EGFR-mutant metastatic lung adenocarcinoma with CNS involvement. By late 2024, due to CNS progression and acquired resistance to targeted therapy, the treatment strategy was revised following multidisciplinary discussion and patient consent. The patient was started on combination therapy with chemotherapy, anti-angiogenic agents, and continued EGFR-TKI: Pemetrexed (0.9 g IV on day 1), Carboplatin (600 mg IV on day 1), and Bevacizumab (0.6 g IV on day 1), administered every 3 weeks (Q3W), while furmonertinib was continued orally once daily. Carboplatin was later discontinued, and the patient was maintained on pemetrexed, bevacizumab, and furmonertinib. In March 2025, brain contrast-enhanced MRI with T2 FLAIR revealed mild cortical swelling in the bilateral frontal lobes and parieto-occipital junction, along with abnormal signals in the left insular region, suggestive of chronic ischemic changes. Patchy linear enhancements were observed in the sulci of the bilateral occipital lobes and left frontal lobe, consistent with leptomeningeal metastasis. By mid-2025, the patient underwent a seventh cycle of combined chemotherapy and targeted therapy, which included pemetrexed (0.9 g IV) and bevacizumab (0.6 g IV) on day 1 every 3 weeks (Q3W), with an increased dose of furmonertinib (240 mg daily). Post-treatment, the patient reported occasional headaches but no significant respiratory or gastrointestinal symptoms. For further evaluation and management, the patient was readmitted with a diagnosis of malignant pulmonary neoplasm. Upon readmission on May 29, 2025, routine electrocardiography (ECG) showed a normal sinus rhythm with no abnormalities. Transthoracic echocardiography revealed mild mitral and tricuspid regurgitation. Cytopathological analysis of the CSF detected adenocarcinoma cells, confirming the presence of leptomeningeal metastasis from lung adenocarcinoma. Contrast-enhanced brain MRI with T2 FLAIR revealed disease progression compared to the March 2025 images, showing linear enhancements in the sulci of the bilateral cerebral hemispheres and cerebellum, along with an increase in both the number and size of subcortical patchy lesions—indicative of progressive leptomeningeal metastasis. High-resolution CT scans of the upper chest and full chest (both non-contrast and contrast-enhanced) indicated overall stable disease without significant progression. Neck and supraclavicular ultrasonography (US), including thyroid and cervical lymph nodes with elastography, demonstrated a reduction in the size of multiple right supraclavicular lymph nodes compared to prior imaging, along with chronic thrombosis in the right internal jugular vein. No other significant abnormalities were observed. Laboratory tests revealed a normal complete blood count. Liver function tests showed elevated ALT (60 U/L), and creatine kinase (CK) was markedly elevated at 1680 U/L. CRP remained within normal limits. On the day of admission (May 29, 2025), the patient received the 8th cycle of combined chemotherapy and targeted therapy, including Pemetrexed (0.9 g IV on day 1), Bevacizumab (0.6 g IV on day 1), and Furmonertinib (240 mg orally once daily), administered every 3 weeks (Q3W). Upon discharge, the patient was stable, with normal vital signs. Cardiac auscultation revealed no pathological murmurs, and no dry or moist rales were heard in either lung. The abdomen was soft, non-tender, with no palpable masses or shifting dullness. No adverse events were noted during this hospitalization. Discussion This case exemplifies the rare comorbidity of LS and advanced lung adenocarcinoma, complicated by leptomeningeal metastasis. Such a combination is extremely uncommon and contributes to the expanding understanding of managing complex, overlapping clinical conditions. This case highlights the importance of thorough evaluation in patients presenting with cervical swelling and pain, parapharyngeal space infection, venous thrombosis, multiple pulmonary nodules, pneumonia, and pulmonary artery embolism. Once LS is diagnosed, clinicians should be vigilant for the potential development of pneumonia and underlying malignancies, such as lung adenocarcinoma, which may coexist with the syndrome. The patient initially presented with stabbing chest pain, leading to the discovery of pulmonary inflammation and infection. During hospitalization, further investigations revealed cervical swelling and pain, parapharyngeal space infection, jugular vein thrombosis, pulmonary artery embolism, and enlarged lymph nodes in the pharyngeal region. Following a multidisciplinary team (MDT) consultation, the diagnosis of LS was confirmed. Subsequent follow-up visits led to a diagnosis of metastatic lung adenocarcinoma, though no leptomeningeal involvement was evident at that time. The patient continued regular surveillance, and by mid-2025, brain metastases secondary to lung adenocarcinoma were identified. LS is a rare condition typically caused by bacterial infections originating in the oropharyngeal region. It is commonly characterized by septic thrombophlebitis of the internal jugular vein and septic pulmonary emboli, the latter being the most frequent manifestation of disseminated infection [9,10]. Previous studies have reported pulmonary involvement in up to 92% of cases [11], suggesting that septic thrombosis of the internal jugular vein can lead to complications in distant organs via hematogenous spread. In this case, chest CT at admission revealed multiple nodular lesions in both lungs, consistent with pulmonary involvement secondary to septic embolization. In this case, the patient had no prior history of respiratory tract infection, with the initial presentation being chest pain and pneumonia. The clinical course eventually progressed to include pulmonary infection complicated by cervical vein thrombosis and pulmonary artery embolism. Type 2 diabetes was diagnosed during hospitalization, which may have compromised immune function and predisposed the patient to more severe infection due to underlying immune suppression. Previous studies have examined the potential synergistic role of Fusobacterium species in colorectal cancer, suggesting mechanisms such as the activation of oncogenic signaling pathways and suppression of host immune responses, which promote tumorigenesis and progression [12]. In our case, although it remains unclear whether lung adenocarcinoma contributed to the development of LS, their coexistence raises the possibility of a more complex interplay between infection and malignancy. Following hospital admission, the patient was treated with anticoagulation, antimicrobial therapy, anti-inflammatory measures, and additional agents targeting anaerobic bacteria to manage disease progression. The use of anticoagulation therapy in LS remains controversial. Some studies recommend anticoagulation in cases of antibiotic failure or progressive thrombus extension [13]. However, in this case, given the severity of infection and significant swelling, early initiation of anticoagulation was deemed appropriate. This decision highlights the importance of multidisciplinary consultation to assess the need for anticoagulation on a case-by-case basis. Ultimately, this case emphasizes the critical role of a multidisciplinary approach in managing complex clinical conditions, integrating medical, surgical, and supportive therapies to ensure comprehensive, proactive patient care. Subsequent imaging revealed pulmonary nodules, confirming the diagnosis of metastatic lung adenocarcinoma. The patient was treated with multiple tyrosine kinase inhibitors (TKIs), including afatinib, osimertinib, and furmonertinib, in combination with chemotherapy and anti-angiogenic therapy. The therapeutic response in each phase was classified as PR. TKIs are used in targeted therapy to disrupt signaling pathways that regulate malignant cell proliferation and survival [14]. Combination TKI-based strategies can delay the onset of drug resistance, prolong survival, and improve control of CNS metastases. Following the diagnosis of leptomeningeal metastasis, the treatment regimen was adjusted by increasing the dose of furmonertinib and administering combined chemotherapy and targeted therapy, leading to successful disease stabilization and the patient’s subsequent discharge. Clinically, it is crucial to recognize the potential coexistence of LS with malignancy and distant metastases. Comprehensive systemic evaluation and timely radiological imaging are essential. Specifically, when characteristic features of LS are accompanied by CT findings such as pulmonary nodules or primary lung lesions, clinicians should consider the possibility of concurrent lung adenocarcinoma. Given the high metastatic potential of lung adenocarcinoma, regular follow-up is necessary. If the patient develops symptoms in other anatomical regions, distant metastases should be suspected, and appropriate diagnostic work-up and interventions should be pursued accordingly. Conclusion In conclusion, this case presents a documented instance of LS complicated by brain metastases from lung adenocarcinoma. A comprehensive overview of the diagnostic and therapeutic process in this patient may enhance clinical awareness and understanding of this rare comorbidity. This case emphasizes the urgent need for clinicians to recognize the potential interplay between distant metastases of lung adenocarcinoma and LS, as their coexistence can exacerbate each condition. Increased awareness is critical to minimizing misdiagnosis and treatment delays. Furthermore, the successful management and recovery of this patient underline the importance of early detection, proactive intervention, and routine surveillance to monitor disease progression and inform timely therapeutic decisions. Abbreviations LS Lemierre syndrome LC Lung cancer CT Chest computed tomography CRP C-reactive protein AFP alpha-fetoprotein CEA carcinoembryonic antigen CSPINE cervical spine CNS central nervous system PR partial response CSF Cerebrospinal fluid ECG electrocardiography US ultrasonography CK creatine kinase MDT multidisciplinary team TKIs tyrosine kinase inhibitors . Declarations Ethics Approval and Consent to Participate All research conformed to the Helsinki Declaration and this study has obtained ethical approval from the Ethics Committee of the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine and the patient agreed in writing to publish his medical history and photographs Clinical trial number not applicable. Consent for Publication Written and informed consent was obtained from the patient for publication of this Case Report and any accompanying images. Data availability statement No additional data Conflicts of interest The authors declare no conflicts of interest. Funding Statement This study was supported by Zhejiang Research Fund of Traditional Chinese Medicine (2025ZL327) Authors' contributions XXY conceived the study and contributed to the data. JGH , ZYpeoformed the software. JHN analyzed the data. J C drafted the original paper revised and edited the paper. reviewed the papaer. All authors have read the final paper and approved it for publication. Acknowledgements The authors thank all of the participants who recruited patients in this study. We gratefully acknowledge. References Mohammed, A. and Tims-Cook, Z., 2019. Pulmonary Infiltrates Clues to the Forgotten Disease. In B59. BACTERIAL INFECTION CASE REPORTS (pp. A3715-A3715). American Thoracic Society. Karkos, P.D., Asrani, S., Karkos, C.D., Leong, S.C., Theochari, E.G., Alexopoulou, T.D. and Assimakopoulos, A.D., 2009. Lemierre's syndrome: a systematic review. The Laryngoscope, 119(8), pp.1552–1559. Lemierre A. On certain septicaemias due to anaerobic organisms. The Lancet. 1936 Mar 28;227(5874):701-3. Nygren D, Holm K. Invasive infections with Fusobacterium necrophorum including Lemierre's syndrome: an 8-year Swedish nationwide retrospective study. Clinical Microbiology and Infection. 2020 Aug 1;26(8):1089-e7. Zhu Y, Cui Y, Zheng X, Zhao Y, Sun G. Small-cell lung cancer brain metastasis: From molecular mechanisms to diagnosis and treatment. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2022 Dec 1;1868(12):166557. Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. Journal of neuro-oncology. 2005 Oct;75(1):5–14. Martínez-Espinosa I, Serrato JA, Ortiz-Quintero B. MicroRNAs in Lung Cancer Brain Metastasis. International Journal of Molecular Sciences. 2024 Sep 25;25(19):10325. Rios-Hoyo A, Arriola E. Immunotherapy and brain metastasis in lung cancer: connecting bench side science to the clinic. Frontiers in Immunology. 2023 Oct 9;14:1221097. Johannesen KM, Bodtger U. Lemierre’s syndrome: current perspectives on diagnosis and management. Infection and drug resistance. 2016 Sep 14:221-7. Qureshi A, Bailey T, Atkinson M, Tayabali K. Atypical Lemierre’s syndrome. A case report and review of Literature. Journal of Community Hospital Internal Medicine Perspectives. 2022 Jan 31;12(1):36. Riordan T. Human infection with Fusobacterium necrophorum (Necrobacillosis), with a focus on Lemierre's syndrome. Clinical microbiology reviews. 2007 Oct;20(4):622 − 59. King M, Hurley H, Davidson KR, Dempsey EC, Barron MA, Chan ED, Frey A. The link between Fusobacteria and colon cancer: a fulminant example and review of the evidence. Immune network. 2020 Aug 4;20(4):e30. Riordan T, Wilson M. Lemierre’s syndrome: more than a historical curiosa. Postgraduate Medical Journal. 2004 Jun;80(944):328 − 34. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New England journal of medicine. 2004 Jun 3;350(23):2335-42. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 14 Jan, 2026 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 11 Sep, 2025 Reviews received at journal 10 Sep, 2025 Reviews received at journal 08 Sep, 2025 Reviewers agreed at journal 08 Sep, 2025 Reviews received at journal 06 Sep, 2025 Reviewers agreed at journal 06 Sep, 2025 Reviewers agreed at journal 05 Sep, 2025 Reviewers invited by journal 05 Sep, 2025 Editor invited by journal 04 Sep, 2025 Editor assigned by journal 26 Aug, 2025 Submission checks completed at journal 26 Aug, 2025 First submitted to journal 19 Aug, 2025 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-7405277","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":513448247,"identity":"68cea186-c0f2-4ab2-a5a4-217ac9291fc1","order_by":0,"name":"XiaoXia Yang","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"XiaoXia","middleName":"","lastName":"Yang","suffix":""},{"id":513448250,"identity":"5b9508e0-a8da-4cc2-99af-535f6c3c2b67","order_by":1,"name":"Jin Gang Han","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYBACAxBOADMZGx//qbBhYJAgXgtzswHPmTTitEABe5sEb8thwlrM2c8eKHi4o1benH9hm4Rkw3l7fukeA4YfFdtwarHsyUswSDxz3HDnjIfNFoY7bifOnHPGgLHnzG3cDjuQY2CQ2HaMccONg403Es/cTjC4kWPAzNiGR8v5N2At9kAtDRIH287ZE9ZyA2xLTeKG841Nko1tB4DWEdQCtuVA8oYbjM3GDGeSE2fOSCs4iNcv53PMDH+21dluOH/84WOGCjt7fonkjQ9+VODWAgRswLgBRUcCQugAPvVAwPyAgaGOgYGfkLpRMApGwSgYsQAAv05kctTMvm0AAAAASUVORK5CYII=","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang Chinese Medical University","correspondingAuthor":true,"prefix":"","firstName":"Jin","middleName":"Gang","lastName":"Han","suffix":""},{"id":513448251,"identity":"f99101da-903b-4593-a1af-a9556854f1f8","order_by":2,"name":"Zhi Yu","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhi","middleName":"","lastName":"Yu","suffix":""},{"id":513448252,"identity":"9b1895af-fb2e-4da9-83d5-5947222d5eb8","order_by":3,"name":"Jian Hua Nian","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"Hua","lastName":"Nian","suffix":""},{"id":513448253,"identity":"85ad0e89-594e-4fb1-bf60-7568fbcff644","order_by":4,"name":"Jie Chen","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-08-19 06:53:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7405277/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7405277/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-025-12359-3","type":"published","date":"2026-01-14T16:28:27+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":91486470,"identity":"74fa5155-d6bc-46c8-b4d1-bb9a19afe32e","added_by":"auto","created_at":"2025-09-17 04:57:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1132163,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative routine MRI scans of the cervical spine performed on July 13. The imaging region covered the cervical spine (CSPINE), using conventional T2-weighted and fat-suppressed T2-weighted sequences (T2 TSE and T2 TSE FS). (A) No abnormal findings were observed. (B) No abnormal findings were observed. (C) Mild patchy hyperintensities were noted in the region of the right trapezius and levator scapulae muscles, indicating subtle abnormalities.\u003c/p\u003e\n\u003cp\u003e(D)Abnormal signal intensity in the right cervical musculature became more pronounced, with persistent patchy hyperintense areas. (E) The hyperintense region on the right side appeared slightly expanded, extending toward the posterior neck\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7405277/v1/b2b49ac46abf00245555d669.jpg"},{"id":91486477,"identity":"4d663667-5ea2-4549-b4ee-fbbdc101a65b","added_by":"auto","created_at":"2025-09-17 04:57:20","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2626798,"visible":true,"origin":"","legend":"\u003cp\u003eRoutine chest CT images obtained on July 17. (A) The distal course of the right lower pulmonary artery appears slightly interrupted or narrowed. (B) Most of the previously observed ground-glass opacities and linear shadows in the bilateral lower lobes had resolved, with only a few residual linear opacities remaining. A crescent-shaped fluid level was noted in the subpleural region of the left lower lobe, exerting pressure on the lung parenchyma—findings similar to those observed on July 1. Scattered micronodules remained unchanged, and no significant change was observed in the size of the mediastinal lymph nodes.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7405277/v1/99579ae485281fe54b035bd1.jpg"},{"id":91486480,"identity":"d9829295-77d6-4f8f-b1d1-a770d29f36c7","added_by":"auto","created_at":"2025-09-17 04:57:20","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3507026,"visible":true,"origin":"","legend":"\u003cp\u003eNon-contrast chest CT images obtained on July 21. (A) Scattered ground-glass opacities and small nodules were observed in the left lower lobe, with mild pleural thickening suggestive of inflammatory irritation. (B) Thickened pulmonary markings were noted, along with scattered micronodules and patchy opacities in both lungs. A prominent ground-glass opacity was seen in the posterior basal segment of the left lower lobe. Left-sided pleural effusion was causing compressive atelectasis of adjacent lung tissue. Peribronchiolar haziness in both lungs indicated chronic inflammatory changes. (C) Pleural thickening was observed at the same level, including notable thickening on the right side. (D) The superior vena cava appeared narrowed in its course, with abnormal enhancement also noted in the regions of the ribs and subclavian vein, suggestive of possible thrombosis. (E) Multiple enlarged mediastinal lymph nodes were clearly visible, along with calcified lymph nodes in the axillary and hilar regions.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7405277/v1/9b6fdec9edc7606d27318ad5.jpg"},{"id":100614598,"identity":"5ca86dce-4598-4368-bbc3-954097cb9a44","added_by":"auto","created_at":"2026-01-19 17:22:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7692183,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7405277/v1/14684fd7-5244-4ad2-926d-39a0b8693d00.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Brain metastasis from lung adenocarcinoma associated with Lemierre syndrome in a middle-aged man: a case report and review of the literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLemierre syndrome (LS), often referred to as the \"forgotten disease,\" is a rare condition with an incidence of approximately 0.6\u0026ndash;2.3 cases per million people[1]. It is defined by a recent oropharyngeal infection, clinical or radiological evidence of internal jugular vein thrombosis, and the isolation of anaerobic pathogens, primarily Fusobacterium necrophorum[2]. First described in The Lancet in 1936 by French microbiologist Andr\u0026eacute; Lemierre[3], LS can lead to severe systemic complications if not diagnosed and treated promptly[4].\u003c/p\u003e\u003cp\u003eLung cancer (LC) is among the most aggressive malignancies, ranking within the top three cancers worldwide in terms of both incidence and mortality[5]. It also exhibits the highest rate of brain metastasis from primary tumors[6]. Brain metastasis poses a significant clinical challenge for patients with advanced LC, affecting approximately 20%-40% of cases. It often results in severe neurological symptoms, a poor prognosis, and significantly contributes to LC-related mortality[7]. The process of brain metastasis involves multiple complex steps, including local invasion, intravasation, tumor cell circulation through the bloodstream, disruption of the blood-brain barrier, extravasation into brain parenchyma, and interaction with the brain\u0026rsquo;s microenvironment[8].\u003c/p\u003e\u003cp\u003eThe concurrent occurrence of brain metastases from LC and LS is exceedingly rare. This report presents a case of LS complicated by LC, further complicated by brain metastases. Given the extreme rarity of this combination, the case warrants special consideration. The goal of this report is to provide a comprehensive account of our clinical management approach, offering valuable insights into this uncommon and complex clinical entity.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 42-year-old male with no significant medical history presented to our outpatient clinic in July 2020. Two days prior, he experienced sudden-onset right-sided chest pain at home, without any obvious triggers. The pain worsened when lying down or assuming certain positions but was relieved by changing posture. He denied fever, cough, sputum production, chest tightness, dyspnea, nausea, or vomiting.\u003c/p\u003e\u003cp\u003eChest computed tomography (CT) conducted on July 1 revealed bilateral pulmonary inflammation, with multiple scattered nodules and micronodules in both lungs, localized pleural thickening on both sides, and mild pleural reaction in the right lower lung. Enlarged mediastinal lymph nodes were also observed. Consequently, the patient was admitted for further evaluation and treatment.\u003c/p\u003e\u003cp\u003eUpon admission, physical examination showed a red tongue with a thin yellow coating and a floating, rapid pulse. Auscultation revealed coarse breath sounds in both lungs. Other vital signs and systemic findings were stable, with no signs of critical illness.\u003c/p\u003e\u003cp\u003eLaboratory tests performed the following day revealed normal platelet count (170 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L), white blood cell count (8.3 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L), and a mildly elevated neutrophil percentage (63.5%). C-reactive protein (CRP) was elevated at 54.3 mg/L. D-dimer was significantly elevated (4.83 mg/L), as was fibrinogen (5.62 g/L). Serum creatinine was normal (58.9 \u0026micro;mol/L), while blood glucose was mildly elevated (6.85 mmol/L). Procalcitonin remained within normal limits (0.05 ng/ml). Tumor markers showed alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) within normal limits (4.2 ng/ml and 1.4 ng/ml, respectively).\u003c/p\u003e\u003cp\u003eDuring hospitalization, the patient developed swelling and pain in the right side of the neck, accompanied by cervical lymphadenopathy, difficulty swallowing, and localized tenderness in the right anterior cervical region. Routine magnetic resonance imaging (MRI) on July 13 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA\u0026ndash;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE) revealed thrombosis in the right internal and external jugular veins, as well as the right subclavian vein. Inflammatory changes were noted in the right parapharyngeal space and supraclavicular fossa, along with multiple enlarged lymph nodes.\u003c/p\u003e\u003cp\u003eFollow-up CT and MRI scans demonstrated stable pulmonary nodules and persistent pleural effusion with minimal absorption. Hepatic dysfunction and fatty liver were also noted.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e(D)Abnormal signal intensity in the right cervical musculature became more pronounced, with persistent patchy hyperintense areas. (E) The hyperintense region on the right side appeared slightly expanded, extending toward the posterior neck\u003c/p\u003e\u003cp\u003eA subsequent CTPA on July 17 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA\u0026ndash;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) suggested pulmonary arterial thrombosis in the right lower lung, with absorption of inflammation in both lungs compared to the previous scan on July 1. Multiple scattered nodules and micronodules persisted, and pleural effusion remained on the left side. Multiple slightly enlarged mediastinal lymph nodes were also similar to those noted previously.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA routine chest CT performed on July 21 revealed chronic inflammatory lesions in the left lower lobe and a small amount of left-sided pleural effusion.(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA-\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE). Multiple scattered nodules and micronodules were observed in both lungs, appearing largely unchanged compared to the July 1 scan. Localized pleural thickening was noted bilaterally, with mild pleural reaction in the right lower lung. Additionally, multiple slightly enlarged mediastinal lymph nodes were identified. Thrombosis of the superior vena cava and subclavian vein was also observed.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe patient was diagnosed with right internal and external jugular vein thrombosis, right subclavian vein thrombosis, cervical cellulitis, right pulmonary artery embolism, pneumonia, left-sided pleural effusion, multiple pulmonary nodules (suggestive of pulmonary space-occupying lesions), fatty liver, hepatic dysfunction, and type 2 diabetes mellitus.\u003c/p\u003e\u003cp\u003eCervical swelling and pain, which progressed to thrombosis of the right jugular and subclavian veins, indicated local thrombus formation. Additionally, the detection of right pulmonary artery embolism suggested the development of distant septic emboli. Persistent systemic inflammation led to a multidisciplinary evaluation, after which the patient was diagnosed with LS.\u003c/p\u003e\u003cp\u003eThe patient received comprehensive treatment, including anticoagulation, antimicrobial therapy (with anaerobic coverage), and anti-inflammatory measures. During hospitalization, abnormalities in glucose metabolism were identified, and type 2 diabetes mellitus was confirmed by the endocrinology team, leading to the initiation of insulin therapy. After stabilization, the patient was discharged on July 22, 2020, with a prescription for oral rivaroxaban (20 mg daily) for ongoing anticoagulation, and scheduled for regular outpatient follow-up.\u003c/p\u003e\u003cp\u003eAt a follow-up outpatient visit two weeks after discharge, a PET-CT scan performed at another hospital on August 10, 2020, revealed normal brain parenchymal structures. Radiotracer distribution in the cerebral cortex, basal ganglia, and cerebellum was homogeneous, with no abnormal uptake, brain metastasis, or central nervous system (CNS) involvement.\u003c/p\u003e\u003cp\u003eMild inflammatory changes were noted in the head and neck region, consistent with non-neoplastic processes. However, significant abnormalities in the pulmonary and thoracic systems raised strong suspicion for primary LC with metastatic involvement.\u003c/p\u003e\u003cp\u003eThe presumed primary lesion was a nodule in the dorsal segment of the left lower lobe, accompanied by multiple metastatic lymph nodes. Left-sided pleural effusion persisted. Additionally, multiple bone metastases were identified. Based on these findings, the patient was diagnosed with metastatic adenocarcinoma, with both bone and lymphatic involvement..\u003c/p\u003e\u003cp\u003eSince August 2020, the patient was initiated on first-line targeted therapy with afatinib, alongside zoledronic acid for managing bone metastases. Chest CT showed a partial response (PR) to the treatment. In May 2021, molecular testing identified the T790M resistance mutation, leading to a switch to second-line targeted therapy with osimertinib (AZD9291) in June 2021. Imaging again showed a PR.\u003c/p\u003e\u003cp\u003eIn mid-2024, the patient developed new symptoms, including headache. Brain MRI revealed abnormal meningeal enhancement in the right frontal and occipital lobes. Cerebrospinal fluid (CSF) analysis detected EGFR 19del, TP53, and CTNNB1 mutations, indicating leptomeningeal metastasis. Consequently, treatment was escalated to third-generation EGFR-TKI furmonertinib, at an initial dose of 160 mg daily. At this point, the disease was classified as EGFR-mutant metastatic lung adenocarcinoma with CNS involvement.\u003c/p\u003e\u003cp\u003eBy late 2024, due to CNS progression and acquired resistance to targeted therapy, the treatment strategy was revised following multidisciplinary discussion and patient consent. The patient was started on combination therapy with chemotherapy, anti-angiogenic agents, and continued EGFR-TKI: Pemetrexed (0.9 g IV on day 1), Carboplatin (600 mg IV on day 1), and Bevacizumab (0.6 g IV on day 1), administered every 3 weeks (Q3W), while furmonertinib was continued orally once daily. Carboplatin was later discontinued, and the patient was maintained on pemetrexed, bevacizumab, and furmonertinib.\u003c/p\u003e\u003cp\u003eIn March 2025, brain contrast-enhanced MRI with T2 FLAIR revealed mild cortical swelling in the bilateral frontal lobes and parieto-occipital junction, along with abnormal signals in the left insular region, suggestive of chronic ischemic changes. Patchy linear enhancements were observed in the sulci of the bilateral occipital lobes and left frontal lobe, consistent with leptomeningeal metastasis.\u003c/p\u003e\u003cp\u003eBy mid-2025, the patient underwent a seventh cycle of combined chemotherapy and targeted therapy, which included pemetrexed (0.9 g IV) and bevacizumab (0.6 g IV) on day 1 every 3 weeks (Q3W), with an increased dose of furmonertinib (240 mg daily). Post-treatment, the patient reported occasional headaches but no significant respiratory or gastrointestinal symptoms. For further evaluation and management, the patient was readmitted with a diagnosis of malignant pulmonary neoplasm.\u003c/p\u003e\u003cp\u003eUpon readmission on May 29, 2025, routine electrocardiography (ECG) showed a normal sinus rhythm with no abnormalities. Transthoracic echocardiography revealed mild mitral and tricuspid regurgitation. Cytopathological analysis of the CSF detected adenocarcinoma cells, confirming the presence of leptomeningeal metastasis from lung adenocarcinoma.\u003c/p\u003e\u003cp\u003eContrast-enhanced brain MRI with T2 FLAIR revealed disease progression compared to the March 2025 images, showing linear enhancements in the sulci of the bilateral cerebral hemispheres and cerebellum, along with an increase in both the number and size of subcortical patchy lesions\u0026mdash;indicative of progressive leptomeningeal metastasis.\u003c/p\u003e\u003cp\u003eHigh-resolution CT scans of the upper chest and full chest (both non-contrast and contrast-enhanced) indicated overall stable disease without significant progression.\u003c/p\u003e\u003cp\u003eNeck and supraclavicular ultrasonography (US), including thyroid and cervical lymph nodes with elastography, demonstrated a reduction in the size of multiple right supraclavicular lymph nodes compared to prior imaging, along with chronic thrombosis in the right internal jugular vein. No other significant abnormalities were observed. Laboratory tests revealed a normal complete blood count. Liver function tests showed elevated ALT (60 U/L), and creatine kinase (CK) was markedly elevated at 1680 U/L. CRP remained within normal limits.\u003c/p\u003e\u003cp\u003eOn the day of admission (May 29, 2025), the patient received the 8th cycle of combined chemotherapy and targeted therapy, including Pemetrexed (0.9 g IV on day 1), Bevacizumab (0.6 g IV on day 1), and Furmonertinib (240 mg orally once daily), administered every 3 weeks (Q3W). Upon discharge, the patient was stable, with normal vital signs. Cardiac auscultation revealed no pathological murmurs, and no dry or moist rales were heard in either lung. The abdomen was soft, non-tender, with no palpable masses or shifting dullness. No adverse events were noted during this hospitalization.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case exemplifies the rare comorbidity of LS and advanced lung adenocarcinoma, complicated by leptomeningeal metastasis. Such a combination is extremely uncommon and contributes to the expanding understanding of managing complex, overlapping clinical conditions. This case highlights the importance of thorough evaluation in patients presenting with cervical swelling and pain, parapharyngeal space infection, venous thrombosis, multiple pulmonary nodules, pneumonia, and pulmonary artery embolism. Once LS is diagnosed, clinicians should be vigilant for the potential development of pneumonia and underlying malignancies, such as lung adenocarcinoma, which may coexist with the syndrome.\u003c/p\u003e\u003cp\u003eThe patient initially presented with stabbing chest pain, leading to the discovery of pulmonary inflammation and infection. During hospitalization, further investigations revealed cervical swelling and pain, parapharyngeal space infection, jugular vein thrombosis, pulmonary artery embolism, and enlarged lymph nodes in the pharyngeal region. Following a multidisciplinary team (MDT) consultation, the diagnosis of LS was confirmed.\u003c/p\u003e\u003cp\u003eSubsequent follow-up visits led to a diagnosis of metastatic lung adenocarcinoma, though no leptomeningeal involvement was evident at that time. The patient continued regular surveillance, and by mid-2025, brain metastases secondary to lung adenocarcinoma were identified.\u003c/p\u003e\u003cp\u003eLS is a rare condition typically caused by bacterial infections originating in the oropharyngeal region. It is commonly characterized by septic thrombophlebitis of the internal jugular vein and septic pulmonary emboli, the latter being the most frequent manifestation of disseminated infection [9,10]. Previous studies have reported pulmonary involvement in up to 92% of cases [11], suggesting that septic thrombosis of the internal jugular vein can lead to complications in distant organs \u003cem\u003evia\u003c/em\u003e hematogenous spread. In this case, chest CT at admission revealed multiple nodular lesions in both lungs, consistent with pulmonary involvement secondary to septic embolization.\u003c/p\u003e\u003cp\u003eIn this case, the patient had no prior history of respiratory tract infection, with the initial presentation being chest pain and pneumonia. The clinical course eventually progressed to include pulmonary infection complicated by cervical vein thrombosis and pulmonary artery embolism. Type 2 diabetes was diagnosed during hospitalization, which may have compromised immune function and predisposed the patient to more severe infection due to underlying immune suppression. Previous studies have examined the potential synergistic role of Fusobacterium species in colorectal cancer, suggesting mechanisms such as the activation of oncogenic signaling pathways and suppression of host immune responses, which promote tumorigenesis and progression [12]. In our case, although it remains unclear whether lung adenocarcinoma contributed to the development of LS, their coexistence raises the possibility of a more complex interplay between infection and malignancy.\u003c/p\u003e\u003cp\u003eFollowing hospital admission, the patient was treated with anticoagulation, antimicrobial therapy, anti-inflammatory measures, and additional agents targeting anaerobic bacteria to manage disease progression. The use of anticoagulation therapy in LS remains controversial. Some studies recommend anticoagulation in cases of antibiotic failure or progressive thrombus extension [13]. However, in this case, given the severity of infection and significant swelling, early initiation of anticoagulation was deemed appropriate. This decision highlights the importance of multidisciplinary consultation to assess the need for anticoagulation on a case-by-case basis. Ultimately, this case emphasizes the critical role of a multidisciplinary approach in managing complex clinical conditions, integrating medical, surgical, and supportive therapies to ensure comprehensive, proactive patient care.\u003c/p\u003e\u003cp\u003eSubsequent imaging revealed pulmonary nodules, confirming the diagnosis of metastatic lung adenocarcinoma. The patient was treated with multiple tyrosine kinase inhibitors (TKIs), including afatinib, osimertinib, and furmonertinib, in combination with chemotherapy and anti-angiogenic therapy. The therapeutic response in each phase was classified as PR.\u003c/p\u003e\u003cp\u003eTKIs are used in targeted therapy to disrupt signaling pathways that regulate malignant cell proliferation and survival [14]. Combination TKI-based strategies can delay the onset of drug resistance, prolong survival, and improve control of CNS metastases.\u003c/p\u003e\u003cp\u003eFollowing the diagnosis of leptomeningeal metastasis, the treatment regimen was adjusted by increasing the dose of furmonertinib and administering combined chemotherapy and targeted therapy, leading to successful disease stabilization and the patient\u0026rsquo;s subsequent discharge. Clinically, it is crucial to recognize the potential coexistence of LS with malignancy and distant metastases. Comprehensive systemic evaluation and timely radiological imaging are essential. Specifically, when characteristic features of LS are accompanied by CT findings such as pulmonary nodules or primary lung lesions, clinicians should consider the possibility of concurrent lung adenocarcinoma.\u003c/p\u003e\u003cp\u003eGiven the high metastatic potential of lung adenocarcinoma, regular follow-up is necessary. If the patient develops symptoms in other anatomical regions, distant metastases should be suspected, and appropriate diagnostic work-up and interventions should be pursued accordingly.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this case presents a documented instance of LS complicated by brain metastases from lung adenocarcinoma. A comprehensive overview of the diagnostic and therapeutic process in this patient may enhance clinical awareness and understanding of this rare comorbidity.\u003c/p\u003e\u003cp\u003eThis case emphasizes the urgent need for clinicians to recognize the potential interplay between distant metastases of lung adenocarcinoma and LS, as their coexistence can exacerbate each condition. Increased awareness is critical to minimizing misdiagnosis and treatment delays.\u003c/p\u003e\u003cp\u003eFurthermore, the successful management and recovery of this patient underline the importance of early detection, proactive intervention, and routine surveillance to monitor disease progression and inform timely therapeutic decisions.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eLemierre syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eLung cancer\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eChest computed tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCRP C-reactive protein\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAFP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ealpha-fetoprotein\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCEA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecarcinoembryonic antigen\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCSPINE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecervical spine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecentral nervous system\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003epartial response\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCerebrospinal fluid\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eECG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eelectrocardiography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eUS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eultrasonography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCK\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecreatine kinase\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMDT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emultidisciplinary team\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTKIs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003etyrosine kinase inhibitors .\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll research conformed to the Helsinki Declaration and this study has obtained ethical approval from the Ethics Committee of the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine and the patient agreed in writing to publish his medical history and photographs\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten and informed consent was obtained from the patient for publication of this Case Report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo additional data\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by \u0026nbsp;Zhejiang Research Fund of Traditional Chinese Medicine (2025ZL327)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXXY\u0026nbsp;conceived the study and contributed to the data.\u0026nbsp;JGH\u0026nbsp;,\u0026nbsp;ZYpeoformed the software.\u0026nbsp;JHN\u0026nbsp;analyzed the data. J\u0026nbsp;C\u0026nbsp;drafted the original paper revised and edited the paper. \u0026nbsp;reviewed the papaer. All authors have read the final paper and approved it for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all of the participants who recruited patients in this study. We gratefully acknowledge.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMohammed, A. and Tims-Cook, Z., 2019. Pulmonary Infiltrates Clues to the Forgotten Disease. In B59. BACTERIAL INFECTION CASE REPORTS (pp. A3715-A3715). American Thoracic Society.\u003c/li\u003e\n\u003cli\u003eKarkos, P.D., Asrani, S., Karkos, C.D., Leong, S.C., Theochari, E.G., Alexopoulou, T.D. and Assimakopoulos, A.D., 2009. Lemierre's syndrome: a systematic review. The Laryngoscope, 119(8), pp.1552–1559.\u003c/li\u003e\n\u003cli\u003eLemierre A. On certain septicaemias due to anaerobic organisms. The Lancet. 1936 Mar 28;227(5874):701-3.\u003c/li\u003e\n\u003cli\u003eNygren D, Holm K. Invasive infections with Fusobacterium necrophorum including Lemierre's syndrome: an 8-year Swedish nationwide retrospective study. Clinical Microbiology and Infection. 2020 Aug 1;26(8):1089-e7.\u003c/li\u003e\n\u003cli\u003eZhu Y, Cui Y, Zheng X, Zhao Y, Sun G. Small-cell lung cancer brain metastasis: From molecular mechanisms to diagnosis and treatment. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2022 Dec 1;1868(12):166557.\u003c/li\u003e\n\u003cli\u003eGavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. Journal of neuro-oncology. 2005 Oct;75(1):5–14.\u003c/li\u003e\n\u003cli\u003eMartínez-Espinosa I, Serrato JA, Ortiz-Quintero B. MicroRNAs in Lung Cancer Brain Metastasis. International Journal of Molecular Sciences. 2024 Sep 25;25(19):10325.\u003c/li\u003e\n\u003cli\u003eRios-Hoyo A, Arriola E. Immunotherapy and brain metastasis in lung cancer: connecting bench side science to the clinic. Frontiers in Immunology. 2023 Oct 9;14:1221097.\u003c/li\u003e\n\u003cli\u003eJohannesen KM, Bodtger U. Lemierre’s syndrome: current perspectives on diagnosis and management. Infection and drug resistance. 2016 Sep 14:221-7.\u003c/li\u003e\n\u003cli\u003eQureshi A, Bailey T, Atkinson M, Tayabali K. Atypical Lemierre’s syndrome. A case report and review of Literature. Journal of Community Hospital Internal Medicine Perspectives. 2022 Jan 31;12(1):36.\u003c/li\u003e\n\u003cli\u003eRiordan T. Human infection with Fusobacterium necrophorum (Necrobacillosis), with a focus on Lemierre's syndrome. Clinical microbiology reviews. 2007 Oct;20(4):622 − 59.\u003c/li\u003e\n\u003cli\u003eKing M, Hurley H, Davidson KR, Dempsey EC, Barron MA, Chan ED, Frey A. The link between Fusobacteria and colon cancer: a fulminant example and review of the evidence. Immune network. 2020 Aug 4;20(4):e30.\u003c/li\u003e\n\u003cli\u003eRiordan T, Wilson M. Lemierre’s syndrome: more than a historical curiosa. Postgraduate Medical Journal. 2004 Jun;80(944):328 − 34.\u003c/li\u003e\n\u003cli\u003eHurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New England journal of medicine. 2004 Jun 3;350(23):2335-42.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Lemierre syndrome, Lung adenocarcinoma, Leptomeningeal metastasis. Fusobacterium necrophorum, Tyrosine Kinase Inhibitors.Multidisciplinary management","lastPublishedDoi":"10.21203/rs.3.rs-7405277/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7405277/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eLemierre syndrome, typically caused by oropharyngeal infection with Fusobacterium necrophorum, represents a rare yet life-threatening condition, particularly when it coincides with brain metastases from lung adenocarcinoma. The occurrence of Lemierre syndrome complicated by brain metastasis from lung adenocarcinoma is exceedingly uncommon, with only a limited number of cases reported.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e\u003cp\u003eA 42-year-old male presented with neck pain and infection, which led to the development of cervical venous thrombosis, cervical lymphadenopathy, and multiple pulmonary nodules, ultimately diagnosed as Lemierre syndrome. The patient was treated with anticoagulation, antibiotics, anti-inflammatory agents, and anaerobic coverage. Chest pain was also present, and CT imaging revealed lung inflammation and nodules. Further investigation confirmed a diagnosis of lung adenocarcinoma. Targeted therapy in combination with chemotherapy was initiated. During follow-up, the patient developed a headache, and subsequent CT imaging identified brain metastasis from the lung adenocarcinoma. Therapy was adjusted, with an increase in memetinib dosage. The patient\u0026rsquo;s condition improved, and he was discharged.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis case underscores the importance of clinicians\u0026rsquo; heightened awareness of the complex interplay between lung adenocarcinoma brain metastases and Lemierre syndrome. Early recognition and intervention in such multifaceted cases are crucial for preventing mortality.\u003c/p\u003e","manuscriptTitle":"Brain metastasis from lung adenocarcinoma associated with Lemierre syndrome in a middle-aged man: a case report and review of the literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-17 04:57:15","doi":"10.21203/rs.3.rs-7405277/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-11T06:07:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-10T13:40:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-08T09:26:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99706547144492448686739951382581230540","date":"2025-09-08T08:59:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-06T08:22:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"105834629682239277721157049491810485250","date":"2025-09-06T04:54:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325134096757674086002452806910116963338","date":"2025-09-06T03:52:38+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-06T03:45:33+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-04T05:17:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-27T00:14:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-27T00:13:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-08-19T06:43:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fb273c81-c4e1-4704-9a7f-a78938e35803","owner":[],"postedDate":"September 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-19T16:45:45+00:00","versionOfRecord":{"articleIdentity":"rs-7405277","link":"https://doi.org/10.1186/s12879-025-12359-3","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2026-01-14 16:28:27","publishedOnDateReadable":"January 14th, 2026"},"versionCreatedAt":"2025-09-17 04:57:15","video":"","vorDoi":"10.1186/s12879-025-12359-3","vorDoiUrl":"https://doi.org/10.1186/s12879-025-12359-3","workflowStages":[]},"version":"v1","identity":"rs-7405277","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7405277","identity":"rs-7405277","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}