Development of Squamous Cell Carcinoma Following Complete Resolution of Mycobacterium xenopi Pulmonary Infection - Case Report

Development of Squamous Cell Carcinoma Following Complete Resolution of Mycobacterium xenopi Pulmonary Infection - Case Report | 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 Development of Squamous Cell Carcinoma Following Complete Resolution of Mycobacterium xenopi Pulmonary Infection - Case Report Christian Alvarez, Marc El Khoury This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8289988/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 Background: Mycobacterium xenopi is a slow-growing, nontuberculous mycobacterium (NTM) capable of causing pulmonary infections, often mimicking tuberculosis. Case Presentation: A 56-year-old man with a 30-pack-year smoking history and rheumatoid arthritis on methotrexate and infliximab presented with a persistent cough and fatigue. Imaging revealed a cavitary lesion in the right upper lobe. Transbronchial biopsy culture grew M. xenopi . He was treated with moxifloxacin, azithromycin, ethambutol, and rifampin with complete resolution after 18 months of therapy. Repeat CT scan of the chest showed a new small, spiculated mass (15.37 mm x 11.79 mm) at the same site. Transbronchial biopsy showed squamous cell carcinoma on pathology, followed by lobar resection with clean margins. Patient is doing well 6 years later. Conclusion: This case highlights a rare occurrence of carcinoma developing at a prior M. xenopi infection site. Although causality remains unproven, it underscores the importance of post-infection surveillance in high-risk patients. Mycobacterium xenopi squamous cell carcinoma lung cancer case report nontuberculous mycobacteria biologic therapy Figures Figure 1 Figure 2 Introduction Mycobacterium xenopi is a slow-growing nontuberculous mycobacterium (NTM) that can cause pulmonary infection. While cancers have been reported at prior infection sites, including those involving M. xenopi , no causal relationship has been established. This report adds to the limited literature describing malignant transformation following nontuberculous mycobacterial infection and emphasizes the need for continued radiologic monitoring even after microbiologic cure, particularly in immunosuppressed patients with long-term follow-up. Case Report A 56-year-old man with a 30-pack-year smoking history, previously diagnosed with rheumatoid arthritis seven years prior and well controlled on methotrexate and infliximab, was initially admitted to the hospital with reports of a consistent dry cough, night sweats, fatigue, and minor chills; he denied any fever or shortness of breath. Patient’s family and psychosocial history were non-contributory. On exam he was hemodynamically stable, oxygen saturation 98% on room air and a temperature of 37.7 degrees celsius. On exam, his lungs were clear bilaterally without crackles, wheezing or ronchi. The rest of the exam was unremarkable. His laboratory testing showed a White blood cell count of 10700 cells per mL, hemoglobin 12.9 g/dL, platelets of 328000 per mL and a normal complete metabolic panel. The chest x-ray showed a dense consolidation at the right pulmonary apex, atelectasis in the right lower lobe. A CT scan of the chest showed a large, irregular right upper lobe (RUL) cavitary mass with surrounding septal thickening and calcified granuloma in the posterior segment of the right lower lobe and platelike atelectasis or scarring at both bases (Fig. 1 A, 1 B). A bronchoscopy and a transbronchial lung biopsy were done. In pathology, Gomori GMS(Grococtt-Gomori Methanine Silver), PAS(Periodic Acid-Shiff), and AFB(Acid-fast bacilli) stains were negative. His quantiferon gold-TB testing prior to the start of infliximab was negative. His serum beta-D-glucan, aspergillus antigen and cryptococcus antigen screen were negative.AFB smears were negative on bronchioalveolar lavage and the sputum samples were submitted for mycobacterium cultures. The patient was started empirically on antituberculous therapy with daily rifampin 600 mg, isoniazid 300 mg, pyrazinamide 1750 mg, and ethambutol HCl 1600 mg (RIPE), as well as pyridoxine 50 mg pending final mycobacterial cultures. M. xenopi grew two months later, thus RIPE was switched to rifampin, ethambutol, azithromycin, and moxifloxacin. Follow up CT scans, at four, ten and eighteen months later were done (Figs. 1 C, 1 D, 1 E, 1 F, 2 A, 2 B), showing the mass lesion and infiltration has improved significantly over time with residual cavity at the apex. However on the last CT scan a new spiculated nodule (11 x15 mm) appearing in the RUL suggestive of a malignant process (Fig. 2 A- 2 B). The patient underwent bronchoscopy and transbronchial biopsy. Pathology had negative fungal and AFB stains however it was positive for moderately differentiated squamous cell carcinoma. Mycobacterial cultures were negative, fungal cultures had candida species. A RUL lobectomy was performed a few weeks later. Pathology from the lung tissue confirmed the diagnosis and showed clear margins of resection with no spread to the lymph nodes. Fungal and mycobacterial cultures from the lung tissue obtained during surgery were negative as well. The patient had an uneventful post-surgical recovery. Follow-up CT scans every 6 months initially then yearly later, were done with no recurrence on the latest CT scan 6 years later ( Fig. 2 C- 2 D). Discussion This case highlights the development of a squamous cell carcinoma in the same pulmonary location previously affected by M. xenopi infection, approximately eighteen months after successful antimicrobial therapy and resolution of the infection. To our knowledge, this case report is one of few which document squamous cell carcinoma succeeding a M. xenopi infection, similar cases linking M. xenopi to subsequent pulmonary malignancy (Asenjo et. al, and Doshi et. al,) are exceedingly rare. While this temporal and anatomical association raises important clinical questions, no causal relationship between M. xenopi infection and lung cancer has been firmly established in the literature. M. xenopi is a slow-growing, nontuberculous mycobacterium (NTM) that primarily affects immunocompromised patients or those with structural lung disease [ 5 , 15 ] . It typically presents with nonspecific pulmonary symptoms such as chronic cough, fatigue, weight loss, and radiographic features mimicking tuberculosis, including cavitary lesions and nodules. This overlap often delays accurate diagnosis, as seen in this patient, where initial treatment was directed toward presumed tuberculosis [ 2 , 6 , 8 , 9 ] . A small number of case reports have documented the new onset of malignancies arising in regions previously affected by NTM infections, including M. xenopi [ 1 , 4 , 7 , 13 , 16 ] . However, these observations remain anecdotal, and no studies have demonstrated a definitive mechanistic or epidemiological link. Chronic inflammation caused by persistent infections has been proposed as a possible cofactor in carcinogenesis [ 3 ] . The hypothesis is that long-standing infection may induce repeated cycles of tissue injury and repair, leading to genetic instability and increased risk of malignant transformation the mechanism of which has been described elsewhere [ 10 , 17 ] . In this case, the patient’s significant 30-pack-year smoking history remains a strong independent risk factor for his squamous cell carcinoma in the lung [ 11 ] . It is unclear whether prior M. xenopi infection contributed to tumor development or if the location was coincidental. Thus, this case supports the need for ongoing surveillance in patients with NTM infections, especially those with known other cancer risk factors [ 11 , 12 , 14 ] . Moreover, this case underlines the diagnostic challenges presented by M. xenopi , particularly due to its prolonged culture time and nonspecific symptoms. The delay in definitive identification emphasizes the importance of considering NTM in differential diagnoses for cavitary lung lesions, particularly in high-risk populations [ 9 , 15 ] . Conclusion Though M. xenopi infections are uncommon, clinicians should still consider the potential of this mycobacterium mimicking, preceding, or coexisting with an underlying malignancy, even if the microbiological infection seems to have completely cleared. Follow-up imaging is recommended in patients with relevant underlying risk factors, as discussed. Declarations Funding No external funding was received for this work. Conflict of Interest The authors declare no conflict of interest. Ethics Approval Not Applicable. Consent of Participation Patient’s written informed consent was obtained and is available on demand for the participation of this case. Consent for Publication Written informed consent was obtained from the patient for publication of this case and associated images. Availability of Data and Material Not Applicable. Code Availability Not Applicable. Authors Contributions All Authors wrote the main manuscript text and C.A prepared all figures. All Authors reviewed the manuscript. References Andrejak, C., et al. (2008). Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France. Thorax , 64(4), 291–296. https://doi.org/10.1136/thx.2008.096842 Andrejak, C., et al. (2012). Improving existing tools for Mycobacterium xenopi treatment. Journal of Antimicrobial Chemotherapy , 68(3), 659–665. https://doi.org/10.1093/jac/dks421 Ardies, C. M. (2003). Inflammation as cause for scar cancers of the lung. Integrative Cancer Therapies , 2 (3), 238–246. https://doi.org/10.1177/1534735403256332 Asenjo, M. M., et al. (2017). Mycobacterium xenopi and Squamous Cell Carcinoma of the Lung. Archivos De Bronconeumología , 53(12), 698–700. https://doi.org/10.1016/j.arbr.2017.10.007 De Moura, V. C. N., Nguyen, M. H., Hunkins, J. J., Daley, C. L., & Khare, R. (2023). In vitro susceptibility patterns for slowly growing non-tuberculous mycobacteria in the USA from 2018 to 2022. Journal of Antimicrobial Chemotherapy , 78 (12), 2849–2858. https://doi.org/10.1093/jac/dkad317 Diagnosis and treatment of disease caused by nontuberculous mycobacteria. (1997). American Journal of Respiratory and Critical Care Medicine , 156 (2), S1–S25. https://doi.org/10.1164/ajrccm.156.2.atsstatement Doshi, V. K., et al. (2014). A Case of Lung Cancer Originating from Cavitary Mycobacterium xenopi Infection. Respiratory Care , 60(3), e56–e58. https://doi.org/10.4187/respcare.03549 Furlan, K., et al. (2019). Mycobacterium Spindle Cell Pseudotumor Caused by Mycobacterium xenopi . Int. J. Surg. Pathol. , 28(3), 316–320. https://doi.org/10.1177/1066896919879745 Habib, S., Rajdev, K., Pervaiz, S., Siddiqui, A. H., Azam, M., & Chalhoub, M. (2018). 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Inflammation as cause for scar cancers of the lung. Integr Cancer Ther. 2003;2(3):238–46. https://doi.org/10.1177/1534735403256332 . Asenjo MM, et al. Mycobacterium xenopi and Squamous Cell Carcinoma of the Lung. Arch Bronconeumol. 2017;53(12):698–700. https://doi.org/10.1016/j.arbr.2017.10.007 . De Moura VCN, Nguyen MH, Hunkins JJ, Daley CL, Khare R. In vitro susceptibility patterns for slowly growing non-tuberculous mycobacteria in the USA from 2018 to 2022. J Antimicrob Chemother. 2023;78(12):2849–58. https://doi.org/10.1093/jac/dkad317 . Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Respir Crit Care Med. 1997;156(2):S1–25. https://doi.org/10.1164/ajrccm.156.2.atsstatement . Doshi VK, et al. A Case of Lung Cancer Originating from Cavitary Mycobacterium xenopi Infection. Respir Care. 2014;60(3):e56–8. https://doi.org/10.4187/respcare.03549 . Furlan K, et al. Mycobacterium Spindle Cell Pseudotumor Caused by Mycobacterium xenopi . Int J Surg Pathol. 2019;28(3):316–20. https://doi.org/10.1177/1066896919879745 . Habib S, Rajdev K, Pervaiz S, Siddiqui AH, Azam M, Chalhoub M. Pulmonary Cavitary Disease Secondary to Mycobacterium xenopi Complicated by Respiratory Failure. Cureus. 2018;10(10):e3512. https://doi.org/10.7759/cureus.3512 . Kuraishy A, Karin M, Grivennikov SI. Tumor promotion via Injury- and Death-Induced inflammation. Immunity. 2011;35(4):467–77. https://doi.org/10.1016/j.immuni.2011.09.006 . Lung cancer risk factors | Smoking & lung cancer . (n.d.). American Cancer Society. https://www.cancer.org/cancer/types/lung-cancer/causes-risks-prevention/risk-factors.html Nalbandian A, Yan B, Pichugin A, Bronson RT, Kramnik I. Lung carcinogenesis induced by chronic tuberculosis infection: the experimental model and genetic control. Oncogene. 2009;28(17):1928–38. https://doi.org/10.1038/onc.2009.32 . Parrot RG, et al. Post-surgical outcome of 57 patients with Mycobacterium xenopi pulmonary infection. Tubercle. 1988;69:47–55. Risk factors: immunosuppression . (2015, April 29). Cancer.gov. https://www.cancer.gov/about-cancer/causes-prevention/risk/immunosuppression Sexton P, Harrison AC. Susceptibility to nontuberculous mycobacterial lung disease. Eur Respir J. 2008;31(6):1322–33. https://doi.org/10.1183/09031936.00140007 . Souilamas R, et al. Lung cancer occurring with Mycobacterium xenopi and Aspergillus . Eur J Cardiothorac Surg. 2001;20(1):211–3. https://doi.org/10.1016/s1010-7940(01)00720-5 . Yu Y, Liao C, Hsu W, Chen H, Liao W, Muo C, Sung F, Chen C. Increased Lung Cancer Risk among Patients with Pulmonary Tuberculosis: A Population Cohort Study. J Thorac Oncol. 2010;6(1):32–7. https://doi.org/10.1097/jto.0b013e3181fb4fcc . Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":252139,"visible":true,"origin":"","legend":"\u003cp\u003e: CT scans at initial diagnosis and subsequent follow up\u003c/p\u003e\n\u003cp\u003e(A,B): Transverse and coronal views at diagnosis showing irregular cavitary mass in the apical segment of RUL with surrounding septal thickening and groundglass opacities, mild predominantly paraseptal emphysema, calcified granuloma in the posterior segment of the RLL, and platelike atelectasis or scarring of both bases.(C,D): Transverse and coronal view at four months of treatment showing reduction of cavitary lesion with thin residual walls. (E,F): Transverse and coronal cuts at ten months of treatment showing near complete resolution of the cavitary lesion.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8289988/v1/6ce1eb9d56e70483428b92b1.png"},{"id":99495534,"identity":"36b1941b-a599-4d5e-96c4-f48a2d1b4027","added_by":"auto","created_at":"2026-01-05 06:17:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":714279,"visible":true,"origin":"","legend":"\u003cp\u003eCT scans at initial diagnosis of lung cancer and post lobectomy\u003c/p\u003e\n\u003cp\u003e(A,B): Transverse and coronal view at 18 months of therapy, shows a new onset of a spiculated nodule in the posterior segment of the RUL (15.3 × 11.8 mm) (C,D): Transverse and coronal view, at 6 year follow up post lobectomy showing clear lung fields and minimal postoperative fibrosis.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8289988/v1/20bd9c2b17693fbb1fe40c6d.png"},{"id":99791418,"identity":"a0670c47-1b59-4ff4-9c7e-c5465e99be0c","added_by":"auto","created_at":"2026-01-08 12:59:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1517021,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8289988/v1/e2c57453-771a-4f6f-b70a-1982defa235e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Development of Squamous Cell Carcinoma Following Complete Resolution of Mycobacterium xenopi Pulmonary Infection - Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eMycobacterium xenopi\u003c/em\u003e is a slow-growing nontuberculous mycobacterium (NTM) that can cause pulmonary infection. While cancers have been reported at prior infection sites, including those involving \u003cem\u003eM. xenopi\u003c/em\u003e, no causal relationship has been established. This report adds to the limited literature describing malignant transformation following nontuberculous mycobacterial infection and emphasizes the need for continued radiologic monitoring even after microbiologic cure, particularly in immunosuppressed patients with long-term follow-up.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 56-year-old man with a 30-pack-year smoking history, previously diagnosed with rheumatoid arthritis seven years prior and well controlled on methotrexate and infliximab, was initially admitted to the hospital with reports of a consistent dry cough, night sweats, fatigue, and minor chills; he denied any fever or shortness of breath. Patient\u0026rsquo;s family and psychosocial history were non-contributory. On exam he was hemodynamically stable, oxygen saturation 98% on room air and a temperature of 37.7 degrees celsius. On exam, his lungs were clear bilaterally without crackles, wheezing or ronchi. The rest of the exam was unremarkable. His laboratory testing showed a White blood cell count of 10700 cells per mL, hemoglobin 12.9 g/dL, platelets of 328000 per mL and a normal complete metabolic panel.\u003c/p\u003e \u003cp\u003eThe chest x-ray showed a dense consolidation at the right pulmonary apex, atelectasis in the right lower lobe. A CT scan of the chest showed a large, irregular right upper lobe (RUL) cavitary mass with surrounding septal thickening and calcified granuloma in the posterior segment of the right lower lobe and platelike atelectasis or scarring at both bases (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). A bronchoscopy and a transbronchial lung biopsy were done. In pathology, Gomori GMS(Grococtt-Gomori Methanine Silver), PAS(Periodic Acid-Shiff), and AFB(Acid-fast bacilli) stains were negative. His quantiferon gold-TB testing prior to the start of infliximab was negative. His serum beta-D-glucan, aspergillus antigen and cryptococcus antigen screen were negative.AFB smears were negative on bronchioalveolar lavage and the sputum samples were submitted for mycobacterium cultures.\u003c/p\u003e \u003cp\u003eThe patient was started empirically on antituberculous therapy with daily rifampin 600 mg, isoniazid 300 mg, pyrazinamide 1750 mg, and ethambutol HCl 1600 mg (RIPE), as well as pyridoxine 50 mg pending final mycobacterial cultures. \u003cem\u003eM. xenopi\u003c/em\u003e grew two months later, thus RIPE was switched to rifampin, ethambutol, azithromycin, and moxifloxacin. Follow up CT scans, at four, ten and eighteen months later were done (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB), showing the mass lesion and infiltration has improved significantly over time with residual cavity at the apex. However on the last CT scan a new spiculated nodule (11 x15 mm) appearing in the RUL suggestive of a malignant process (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003eThe patient underwent bronchoscopy and transbronchial biopsy. Pathology had negative fungal and AFB stains however it was positive for moderately differentiated squamous cell carcinoma. Mycobacterial cultures were negative, fungal cultures had candida species. A RUL lobectomy was performed a few weeks later. Pathology from the lung tissue confirmed the diagnosis and showed clear margins of resection with no spread to the lymph nodes. Fungal and mycobacterial cultures from the lung tissue obtained during surgery were negative as well. The patient had an uneventful post-surgical recovery. Follow-up CT scans every 6 months initially then yearly later, were done with no recurrence on the latest CT scan 6 years later ( Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC-\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case highlights the development of a squamous cell carcinoma in the same pulmonary location previously affected by \u003cem\u003eM. xenopi\u003c/em\u003e infection, approximately eighteen months after successful antimicrobial therapy and resolution of the infection. To our knowledge, this case report is one of few which document squamous cell carcinoma succeeding a M. \u003cem\u003exenopi\u003c/em\u003e infection, similar cases linking M. \u003cem\u003exenopi\u003c/em\u003e to subsequent pulmonary malignancy (Asenjo et. al, and Doshi et. al,) are exceedingly rare. While this temporal and anatomical association raises important clinical questions, no causal relationship between \u003cem\u003eM. xenopi\u003c/em\u003e infection and lung cancer has been firmly established in the literature.\u003c/p\u003e \u003cp\u003e \u003cem\u003eM. xenopi\u003c/em\u003e is a slow-growing, nontuberculous mycobacterium (NTM) that primarily affects immunocompromised patients or those with structural lung disease\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. It typically presents with nonspecific pulmonary symptoms such as chronic cough, fatigue, weight loss, and radiographic features mimicking tuberculosis, including cavitary lesions and nodules. This overlap often delays accurate diagnosis, as seen in this patient, where initial treatment was directed toward presumed tuberculosis\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA small number of case reports have documented the new onset of malignancies arising in regions previously affected by NTM infections, including \u003cem\u003eM. xenopi\u003c/em\u003e \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. However, these observations remain anecdotal, and no studies have demonstrated a definitive mechanistic or epidemiological link. Chronic inflammation caused by persistent infections has been proposed as a possible cofactor in carcinogenesis \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. The hypothesis is that long-standing infection may induce repeated cycles of tissue injury and repair, leading to genetic instability and increased risk of malignant transformation the mechanism of which has been described elsewhere\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this case, the patient\u0026rsquo;s significant 30-pack-year smoking history remains a strong independent risk factor for his squamous cell carcinoma in the lung\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. It is unclear whether prior \u003cem\u003eM. xenopi\u003c/em\u003e infection contributed to tumor development or if the location was coincidental. Thus, this case supports the need for ongoing surveillance in patients with NTM infections, especially those with known other cancer risk factors\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Moreover, this case underlines the diagnostic challenges presented by \u003cem\u003eM. xenopi\u003c/em\u003e, particularly due to its prolonged culture time and nonspecific symptoms. The delay in definitive identification emphasizes the importance of considering NTM in differential diagnoses for cavitary lung lesions, particularly in high-risk populations\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThough M. \u003cem\u003exenopi\u003c/em\u003e infections are uncommon, clinicians should still consider the potential of this mycobacterium mimicking, preceding, or coexisting with an underlying malignancy, even if the microbiological infection seems to have completely cleared. Follow-up imaging is recommended in patients with relevant underlying risk factors, as discussed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;No external funding was received for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent of Participation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient\u0026rsquo;s written informed consent was obtained and is available on demand for the participation of this case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case and\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eassociated images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll Authors wrote the main manuscript text and C.A prepared all figures. 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J Thorac Oncol. 2010;6(1):32\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/jto.0b013e3181fb4fcc\u003c/span\u003e\u003cspan address=\"10.1097/jto.0b013e3181fb4fcc\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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":"Mycobacterium xenopi, squamous cell carcinoma, lung cancer, case report, nontuberculous mycobacteria, biologic therapy","lastPublishedDoi":"10.21203/rs.3.rs-8289988/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8289988/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e \u003cem\u003eMycobacterium xenopi\u003c/em\u003e is a slow-growing, nontuberculous mycobacterium (NTM) capable of causing pulmonary infections, often mimicking tuberculosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation:\u003c/strong\u003eA 56-year-old man with a 30-pack-year smoking history and rheumatoid arthritis on methotrexate and infliximab presented with a persistent cough and fatigue. Imaging revealed a cavitary lesion in the right upper lobe. Transbronchial biopsy culture grew \u003cem\u003eM. xenopi\u003c/em\u003e. He was treated with moxifloxacin, azithromycin, ethambutol, and rifampin with complete resolution after 18 months of therapy. Repeat CT scan of the chest showed a new small, spiculated mass (15.37 mm x 11.79 mm) at the same site. Transbronchial biopsy showed squamous cell carcinoma on pathology, followed by lobar resection with clean margins. Patient is doing well 6 years later.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This case highlights a rare occurrence of carcinoma developing at a prior \u003cem\u003eM. xenopi\u003c/em\u003e infection site. Although causality remains unproven, it underscores the importance of post-infection surveillance in high-risk patients.\u003c/p\u003e","manuscriptTitle":"Development of Squamous Cell Carcinoma Following Complete Resolution of Mycobacterium xenopi Pulmonary Infection - Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-05 06:17:08","doi":"10.21203/rs.3.rs-8289988/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":"21825559-fdc4-48e1-9b94-de043878243e","owner":[],"postedDate":"January 5th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-05T11:24:37+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-05 06:17:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8289988","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8289988","identity":"rs-8289988","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}