Complete resolution of non-tuberculous mycobacterial pulmonary nodule following cryobiopsy: he first case report

Complete resolution of non-tuberculous mycobacterial pulmonary nodule following cryobiopsy: he first 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 Complete resolution of non-tuberculous mycobacterial pulmonary nodule following cryobiopsy: he first case report Sung Joon Han, Dongil Park This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4573825/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 Non-tuberculous mycobacterial (NTM) lung disease encompasses a diverse group of pulmonary conditions, present significant diagnostic challenges, especially in radiological interpretation. The disease can mimic lung cancer, tuberculosis, and other bronchopulmonary disorders, complicating accurate diagnosis. Case Presentation: A 46-year-old healthy woman was incidentally found to have a 1.3-cm pulmonary nodule in the left anterior basal segment during a routine health examination, with no symptoms or significant medical history. Initial CT imaging raised suspicions of T1a lung cancer. Subsequent endobronchial ultrasound transbronchial lung biopsy (EBUS-TBLB) and transbronchial lung cryobiopsy (TBLC) revealed granulomatous inflammation. Tests for tuberculosis and NTM were negative. Following the biopsies, chest X-rays showed an enlarged shadow at the lesion, suggesting necrosis after cryobiopsy. The patient was treated with moxifloxacin, leading to symptom improvement. A final diagnosis of NTM infection, specifically Mycobacterium avium , was confirmed from bronchoalveolar lavage (BAL) fluid. At four months post-biopsy, a chest CT scan showed complete resolution of the nodule. Conclusion: NTM nodules may undergo necrosis and resolution due to the ablation effect of cryobiopsy, suggesting cryoablation as a potential option for inoperable localized NTM disease. Cryobiopsy mycobacterial nodule lung cancer Figures Figure 1 Figure 2 Figure 3 Introduction Non-tuberculous mycobacterial (NTM) lung disease encompasses a complex group of pulmonary conditions caused by non-tuberculous mycobacteria. These diseases present a wide range of clinical manifestations, posing significant challenges in diagnosis, especially regarding radiological interpretation. The radiographic features of NTM lung disease can mimic those of lung cancer, tuberculosis, and other bronchopulmonary disorders, thereby complicating accurate diagnosis( 1 ). Recent studies have highlighted the diverse radiological presentations of NTM lung disease, particularly the emergence of cases presenting with a solitary pulmonary nodule( 2 ). These findings suggest that the radiographic appearance of NTM lung disease is not limited to typical presentations such as multifocal pneumonia or bronchiectasis; it can occasionally manifest as a solitary nodule. This is particularly important for the differential diagnosis of lung cancer( 3 ). The primary diagnosis of NTM lung disease is predominantly obtained by conducting microbiological examination via bronchoscopy. However, in some cases, tissue biopsies are also employed for diagnosis( 4 ). Conventionally, radial endobronchial ultrasound (EBUS)-guided forceps biopsy is commonly employed for the bronchoscopic tissue examination of peripheral lesions( 5 ). Cryobiopsy is increasingly recognized for its role in enhancing the accuracy of lung cancer tissue analyses. This method also improves the diagnostic yield for benign lesions, often necessitating the identification of specific diagnostic findings( 6 ). Identifying distinct tissue characteristics indicative of conditions such as tuberculosis, NTM lung disease, or parasitic infections presents a substantial challenge, particularly in small biopsy samples( 7 ). We report a case in which a lesion was diagnosed as an NTM infection through cryobiopsy and was concurrently treated with cryoablation. Case Report/Case Presentation A 46-year-old healthy woman was incidentally found to have a 1.3-cm-sized pulmonary nodule in the left anterior basal segment during a routine health examination(Fig. 1 ). She reported no symptoms and had no significant medical history, including no history of tuberculosis or lung infections. To investigate the possibility of lung cancer, the patient underwent endobronchial ultrasound transbronchial lung biopsy (EBUS-TBLB) using a guide sheath, followed by transbronchial lung cryobiopsy (TBLC) employing a cryoprobe with a 1-mm diameter, performed four times through the same guide sheath. The procedure was successfully completed with only minor bleeding and no serious adverse events such as severe bleeding or pneumothorax requiring chest tube drainage. Biopsy revealed granulomatous inflammation in both the forceps and cryobiopsy specimens. The results of the tests conducted on the tissue samples yielded negative findings for tuberculosis as well as for NTM. One week post-biopsy, a follow-up outpatient chest radiograph revealed an enlarged shadow at the location of the original lesion, suggesting that the lesion was caused by necrosis following repeated cryobiopsies(Fig. 1 ). The patient reported discharge of a purulent and intermittent blood-tinged sputum and was administered a daily dose of 400 mg of moxifloxacin. Two weeks later, chest radiograph indicated a slight increase in the size of the lesion, but there was an improvement in her symptoms, with no other abnormal findings such as fever. Therefore, antibiotic therapy was continued with regular outpatient follow-ups. Three weeks after tissue biopsy, the lesion demonstrated improvement on chest radiograph. Additionally, the growth of acid-fast bacilli (AFB) was reported in the bronchoalveolar lavage (BAL) fluid obtained during examination. The final diagnosis was confirmed as NTM infection, specifically Mycobacterium avium (Fig. 2 .). Four months after tissue biopsy, a follow-up chest CT scan revealed that the previously observed pulmonary nodule in the left lower lobe had disappeared(Fig. 3 .). Moreover, there were no signs suggestive of NTM recurrence at any other location. Discussion This case involved the incidental discovery of a pulmonary nodule, and it represents a typical example of the diagnostic challenges posed by NTM lung disease. The initial CT imaging raised suspicions of T1a lung cancer, underscoring the radiological challenges in differentiating NTM infections from malignancies. Such differentiation is crucial, considering the distinct treatment approaches and prognoses for cancer and NTM infections. In this case, the tissue biopsy result revealed granulomatous inflammation. In lung tissue biopsies, granulomatous inflammation is frequently associated with specific infectious diseases, with tuberculosis being one of the most common causes, alongside others such as NTM, sarcoidosis, and certain fungal infections such as histoplasmosis( 8 , 9 ). In lung cancer, granulomatous inflammation usually does not manifest directly; however, such inflammatory responses may occasionally be observed in the tissues surrounding the cancer. This could result from the impact of cancer cells on adjacent tissues, necessitating further observation and possibly re-biopsy if no specific infectious disease is diagnosed( 10 , 11 ). In this case, the results of both tuberculosis and NTM polymerase chain reaction (PCR) conducted on the tissue were negative, and a diagnosis of mycobacterium avium infection was made based on the BAL fluid specimen obtained at the time of examination. Given that the sensitivity of PCR on paraffin-embedded lung tissues is 35.3–52.9%, BAL should be considered in cases where NTM infection cannot be ruled out in lung nodules suspected of cancer( 12 ). Recently, local ablation therapies such as radiofrequency ablation and cryoablation have been attempted in patients with lung cancer who are unfit for surgery because of systemic conditions or advanced age( 13 – 17 ). Cryoablation utilizes the Joule-Thomson effect, wherein a rapid temperature drop occurs as the gas expands from high to low pressure. This results in rapid freezing of the target tissue, with ice crystals destroying the cellular structure and causing necrosis in abnormal tissues( 18 ). Cryobiopsy is widely used in the diagnosis of peripheral pulmonary lesions and is known to significantly increase diagnostic yield by removing normal anatomical barriers such as the bronchial mucosa, allowing for the obtaining of larger samples( 6 , 19 ). In this case, although cryoablation was not performed for therapeutic purposes, tissue samples larger than 5 mm in size in the maximum dimension were obtained four times, effectively achieving the effects of cryoablation. In the treatment of NTM lung disease, surgery is generally considered for localized diseases, such as bronchiectasis or solitary nodules that do not respond to medical therapy( 20 ). In conclusion, this case demonstrates that NTM nodules may undergo necrosis and resolution owing to the ablation effect of cryobiopsy, suggesting that cryoablation might be a viable option for inoperable localized NTM disease. Declarations Patient was required to provide written informed consent before participate in this study. Written informed consent was obtained from the patient for publication of this case report and any accompanying images Data Availability Statement All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author. Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding Sources The funder had no role in the design, data collection, data analysis, and reporting of this study. Author Contributions Contributions (I) Conception and design: Dongil Park; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: Sung Joon Han; (V) Data analysis and interpretation: Dongil Park; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Acknowledgement This is a short text to acknowledge the contributions of specific colleagues, institutions, or agencies that aided the efforts of the authors Statement of Ethics Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Patient was required to provide written informed consent before participating in this study. References Martinez S, McAdams HP, Batchu CS. The many faces of pulmonary nontuberculous mycobacterial infection. AJR Am J Roentgenol. 2007;189(1):177-86. Yan Q, Wang W, Zhao W, Zuo L, Wang D, Chai X, et al. Differentiating nontuberculous mycobacterium pulmonary disease from pulmonary tuberculosis through the analysis of the cavity features in CT images using radiomics. BMC Pulm Med. 2022;22(1):4. Hong SJ, Kim TJ, Lee JH, Park JS. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer: Clinicoradiologic features and diagnostic implications. Medicine (Baltimore). 2016;95(26):e3978. Lee C, Park J, Lim JK, Park J, Park B. Nontuberculous Mycobacterial Infection mimicking lung cancer in a patient with usual interstitial pneumonia pattern interstitial lung disease: A Case Report. Curr Med Imaging. 2023. Ma L, Fang Y, Zhang T, Xue P, Bo L, Liu W, at al. Comparison in efficacy and safety of forceps biopsy for peripheral lung lesions guided by endobronchial ultrasound-guided sheath (EBUS-GS) and electromagnetic navigation bronchoscopy combined with EBUS (ENB-EBUS). Am J Transl Res. 2020;12(8):4604-11. Chung C, Kim Y, Lee JE, Kang DH, Park D. Diagnostic Value of Transbronchial Lung cryobiopsy using an ultrathin cryoprobe and guide sheath for peripheral pulmonary lesions. J Bronchology Interv Pulmonol. 2024;31(1):13-22. Kim KE, Jung SS, Park HS, Lee JE, Chung C, Kang DH, et al. The first case report of Paragonimus westermani infection diagnosed by transbronchial lung cryobiopsy. Int J Infect Dis. 2023;128:184-6. Somboonviboon D, Wattanathum A, Keorochana N, Wongchansom K. Sarcoidosis developing after COVID-19: A case report. Respirol Case Rep. 2022;10(9):e01016. Mukhopadhyay S, Katzenstein AL. Biopsy findings in acute pulmonary histoplasmosis: unusual histologic features in 4 cases mimicking lymphomatoid granulomatosis. Am J Surg Pathol. 2010;34(4):541-6. Kennedy MP, Jimenez CA, Mhatre AD, Morice RC, Eapen GA. Clinical implications of granulomatous inflammation detected by endobronchial ultrasound transbronchial needle aspiration in patients with suspected cancer recurrence in the mediastinum. J Cardiothorac Surg. 2008;3:8. Dagaonkar RS, Choong CV, Asmat AB, Ahmed DB, Chopra A, Lim AY, et al. Significance of coexistent granulomatous inflammation and lung cancer. J Clin Pathol. 2017;70(4):337-41. Kim YN, Kim KM, Choi HN, Lee JH, Park HS, Jang KY, et al. Clinical Usefulness of PCR for Differential diagnosis of tuberculosis and nontuberculous mycobacterial infection in paraffin-embedded lung tissues. J Mol Diagn. 2015;17(5):597-604. Koizumi T, Tsushima K, Tanabe T, Agatsuma T, Yokoyama T, Ito M, et al. Bronchoscopy-Guided Cooled Radiofrequency ablation as a novel intervention therapy for peripheral lung cancer. Respiration. 2015;90(1):47-55. Xie F, Zheng X, Xiao B, Han B, Herth FJF, Sun J. Navigation Bronchoscopy-Guided Radiofrequency ablation for nonsurgical peripheral pulmonary tumors. Respiration. 2017;94(3):293-8. Vergnon JM, Schmitt T, Alamartine E, Barthelemy JC, Fournel P, Emonot A. Initial combined cryotherapy and irradiation for unresectable non-small cell lung cancer. Preliminary results. Chest. 1992;102(5):1436-40. Tian Y, Qi X, Jiang X, Shang L, Xu K, Shao H. Cryoablation and immune synergistic effect for lung cancer: A review. Frontiers in Immunology. 2022;13. Inoue M, Nakatsuka S, Jinzaki M. Cryoablation of early-stage primary lung cancer. Biomed Res Int. 2014;2014:521691. Sprenkle PC, Mirabile G, Durak E, Edelstein A, Gupta M, Hruby GW, et al. The effect of argon gas pressure on ice ball size and rate of formation. J Endourol. 2010;24(9):1503-7. Kim SH, Mok J, Jo E-J, Kim M-H, Lee K, Kim KU, et al. The Additive Impact of transbronchial cryobiopsy using a 1.1-mm diameter cryoprobe on conventional biopsy for peripheral lung nodules. Cancer Res Treat. 2023;55(2):506-12. Lu M, Fitzgerald D, Karpelowsky J, Selvadurai H, Pandit C, Robinson P, et al. Surgery in nontuberculous mycobacteria pulmonary disease. Breathe (Sheff). 2018;14(4):288-301. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies 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-4573825","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":323096878,"identity":"54a32ad6-3d9f-42e7-a797-3a49de13ce63","order_by":0,"name":"Sung Joon Han","email":"","orcid":"","institution":"Chungnam National University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sung","middleName":"Joon","lastName":"Han","suffix":""},{"id":323096879,"identity":"484518fe-f35d-4b53-8e4f-6053070bfffa","order_by":1,"name":"Dongil Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYFACHgbGDww2QAZj4wGitTBLMKSBtDQQrwWIDoOZxGkxbz97dIPEn/N2a9sPA22psYkmqEXmTF7ajcK228nbziQCtRxLy20gpEWCIcfshmTD7WSzA0AtjA2HidDC/8bsBs+fc8lm5x8Sq0UCaAsP2wE7sxtE2yLxxuy2ZFtygtkNoC0JRPmFP8fs5oc/dvZm59MfPvhQY0NYCwwkglUmEKscBOxJUTwKRsEoGAUjDAAAdjFHVfQ19q8AAAAASUVORK5CYII=","orcid":"","institution":"Chungnam National University","correspondingAuthor":true,"prefix":"","firstName":"Dongil","middleName":"","lastName":"Park","suffix":""}],"badges":[],"createdAt":"2024-06-13 06:06:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4573825/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4573825/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60605195,"identity":"9f9ea096-9591-4862-9fb7-61bceda3729e","added_by":"auto","created_at":"2024-07-18 16:41:56","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57378,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Chest x-ray radiograph of solitary pulmonary nodule in left lower lobe field. (b) Peripheral pulmonary nodule is shown by the red arrow. (c) Increase in density consistent at the left lung’s lower zone, as shown by chest x-ray radiograph.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4573825/v1/db7d63362398b6b32645da42.jpg"},{"id":60605196,"identity":"d688fc00-e7d3-43f0-ad21-9892436d3d89","added_by":"auto","created_at":"2024-07-18 16:41:56","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":84366,"visible":true,"origin":"","legend":"\u003cp\u003ePathologic findings of transbronchial lung biopsy revealed focal granulomas (red arrows) with infiltration of inflammatory cells (H\u0026amp;E stain, x40).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4573825/v1/e44718fcbcc2288c701a3454.jpg"},{"id":60605197,"identity":"38076097-3c47-4a2f-83e0-59096328a57f","added_by":"auto","created_at":"2024-07-18 16:41:56","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":68271,"visible":true,"origin":"","legend":"\u003cp\u003e(a),(b),(c) Chest x-ray photograph and chest CT showing the absence of the peripheral pulmonary nodule.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4573825/v1/cf92a80d585392f639f227bf.jpg"},{"id":64611850,"identity":"2ad542df-2fcc-4a5c-a22d-7b5efe898f17","added_by":"auto","created_at":"2024-09-16 14:16:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":446146,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4573825/v1/bc3a39bc-d590-4d45-be02-5c6cf46635e8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Complete resolution of non-tuberculous mycobacterial pulmonary nodule following cryobiopsy: he first case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNon-tuberculous mycobacterial (NTM) lung disease encompasses a complex group of pulmonary conditions caused by non-tuberculous mycobacteria. These diseases present a wide range of clinical manifestations, posing significant challenges in diagnosis, especially regarding radiological interpretation. The radiographic features of NTM lung disease can mimic those of lung cancer, tuberculosis, and other bronchopulmonary disorders, thereby complicating accurate diagnosis(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecent studies have highlighted the diverse radiological presentations of NTM lung disease, particularly the emergence of cases presenting with a solitary pulmonary nodule(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). These findings suggest that the radiographic appearance of NTM lung disease is not limited to typical presentations such as multifocal pneumonia or bronchiectasis; it can occasionally manifest as a solitary nodule. This is particularly important for the differential diagnosis of lung cancer(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe primary diagnosis of NTM lung disease is predominantly obtained by conducting microbiological examination via bronchoscopy. However, in some cases, tissue biopsies are also employed for diagnosis(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Conventionally, radial endobronchial ultrasound (EBUS)-guided forceps biopsy is commonly employed for the bronchoscopic tissue examination of peripheral lesions(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCryobiopsy is increasingly recognized for its role in enhancing the accuracy of lung cancer tissue analyses. This method also improves the diagnostic yield for benign lesions, often necessitating the identification of specific diagnostic findings(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Identifying distinct tissue characteristics indicative of conditions such as tuberculosis, NTM lung disease, or parasitic infections presents a substantial challenge, particularly in small biopsy samples(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe report a case in which a lesion was diagnosed as an NTM infection through cryobiopsy and was concurrently treated with cryoablation.\u003c/p\u003e"},{"header":"Case Report/Case Presentation","content":"\u003cp\u003eA 46-year-old healthy woman was incidentally found to have a 1.3-cm-sized pulmonary nodule in the left anterior basal segment during a routine health examination(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e). She reported no symptoms and had no significant medical history, including no history of tuberculosis or lung infections.\u003c/p\u003e \u003cp\u003eTo investigate the possibility of lung cancer, the patient underwent endobronchial ultrasound transbronchial lung biopsy (EBUS-TBLB) using a guide sheath, followed by transbronchial lung cryobiopsy (TBLC) employing a cryoprobe with a 1-mm diameter, performed four times through the same guide sheath. The procedure was successfully completed with only minor bleeding and no serious adverse events such as severe bleeding or pneumothorax requiring chest tube drainage.\u003c/p\u003e \u003cp\u003eBiopsy revealed granulomatous inflammation in both the forceps and cryobiopsy specimens. The results of the tests conducted on the tissue samples yielded negative findings for tuberculosis as well as for NTM. One week post-biopsy, a follow-up outpatient chest radiograph revealed an enlarged shadow at the location of the original lesion, suggesting that the lesion was caused by necrosis following repeated cryobiopsies(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The patient reported discharge of a purulent and intermittent blood-tinged sputum and was administered a daily dose of 400 mg of moxifloxacin. Two weeks later, chest radiograph indicated a slight increase in the size of the lesion, but there was an improvement in her symptoms, with no other abnormal findings such as fever. Therefore, antibiotic therapy was continued with regular outpatient follow-ups.\u003c/p\u003e \u003cp\u003eThree weeks after tissue biopsy, the lesion demonstrated improvement on chest radiograph. Additionally, the growth of acid-fast bacilli (AFB) was reported in the bronchoalveolar lavage (BAL) fluid obtained during examination. The final diagnosis was confirmed as NTM infection, specifically \u003cem\u003eMycobacterium avium\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e.).\u003c/p\u003e \u003cp\u003eFour months after tissue biopsy, a follow-up chest CT scan revealed that the previously observed pulmonary nodule in the left lower lobe had disappeared(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e.). Moreover, there were no signs suggestive of NTM recurrence at any other location.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case involved the incidental discovery of a pulmonary nodule, and it represents a typical example of the diagnostic challenges posed by NTM lung disease. The initial CT imaging raised suspicions of T1a lung cancer, underscoring the radiological challenges in differentiating NTM infections from malignancies. Such differentiation is crucial, considering the distinct treatment approaches and prognoses for cancer and NTM infections.\u003c/p\u003e \u003cp\u003eIn this case, the tissue biopsy result revealed granulomatous inflammation. In lung tissue biopsies, granulomatous inflammation is frequently associated with specific infectious diseases, with tuberculosis being one of the most common causes, alongside others such as NTM, sarcoidosis, and certain fungal infections such as histoplasmosis(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn lung cancer, granulomatous inflammation usually does not manifest directly; however, such inflammatory responses may occasionally be observed in the tissues surrounding the cancer. This could result from the impact of cancer cells on adjacent tissues, necessitating further observation and possibly re-biopsy if no specific infectious disease is diagnosed(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this case, the results of both tuberculosis and NTM polymerase chain reaction (PCR) conducted on the tissue were negative, and a diagnosis of mycobacterium avium infection was made based on the BAL fluid specimen obtained at the time of examination. Given that the sensitivity of PCR on paraffin-embedded lung tissues is 35.3\u0026ndash;52.9%, BAL should be considered in cases where NTM infection cannot be ruled out in lung nodules suspected of cancer(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecently, local ablation therapies such as radiofrequency ablation and cryoablation have been attempted in patients with lung cancer who are unfit for surgery because of systemic conditions or advanced age(\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCryoablation utilizes the Joule-Thomson effect, wherein a rapid temperature drop occurs as the gas expands from high to low pressure. This results in rapid freezing of the target tissue, with ice crystals destroying the cellular structure and causing necrosis in abnormal tissues(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCryobiopsy is widely used in the diagnosis of peripheral pulmonary lesions and is known to significantly increase diagnostic yield by removing normal anatomical barriers such as the bronchial mucosa, allowing for the obtaining of larger samples(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this case, although cryoablation was not performed for therapeutic purposes, tissue samples larger than 5 mm in size in the maximum dimension were obtained four times, effectively achieving the effects of cryoablation. In the treatment of NTM lung disease, surgery is generally considered for localized diseases, such as bronchiectasis or solitary nodules that do not respond to medical therapy(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn conclusion, this case demonstrates that NTM nodules may undergo necrosis and resolution owing to the ablation effect of cryobiopsy, suggesting that cryoablation might be a viable option for inoperable localized NTM disease.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003ePatient was required to provide written informed consent before participate in this study.\u003c/p\u003e\n\u003cp\u003eWritten 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\u003eAll data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe funder had no role in the design, data collection, data analysis, and reporting of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eContributions\u003c/em\u003e (I) Conception and design:\u0026nbsp;Dongil Park; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: Sung Joon Han; (V) Data analysis and interpretation: Dongil Park; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a short text to acknowledge the contributions of specific colleagues, institutions, or agencies that aided the efforts of the authors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;of Ethics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. Patient was required to provide written informed consent before participating in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMartinez S, McAdams HP, Batchu CS. The many faces of pulmonary nontuberculous mycobacterial infection. AJR Am J Roentgenol. 2007;189(1):177-86.\u003c/li\u003e\n\u003cli\u003eYan Q, Wang W, Zhao W, Zuo L, Wang D, Chai X, et al. Differentiating nontuberculous mycobacterium pulmonary disease from pulmonary tuberculosis through the analysis of the cavity features in CT images using radiomics. BMC Pulm Med. 2022;22(1):4.\u003c/li\u003e\n\u003cli\u003eHong SJ, Kim TJ, Lee JH, Park JS. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer: Clinicoradiologic features and diagnostic implications. Medicine (Baltimore). 2016;95(26):e3978.\u003c/li\u003e\n\u003cli\u003eLee C, Park J, Lim JK, Park J, Park B. Nontuberculous Mycobacterial Infection mimicking lung cancer in a patient with usual interstitial pneumonia pattern interstitial lung disease: A Case Report. Curr Med Imaging. 2023.\u003c/li\u003e\n\u003cli\u003eMa L, Fang Y, Zhang T, Xue P, Bo L, Liu W, at al. Comparison in efficacy and safety of forceps biopsy for peripheral lung lesions guided by endobronchial ultrasound-guided sheath (EBUS-GS) and electromagnetic navigation bronchoscopy combined with EBUS (ENB-EBUS). Am J Transl Res. 2020;12(8):4604-11.\u003c/li\u003e\n\u003cli\u003eChung C, Kim Y, Lee JE, Kang DH, Park D. Diagnostic Value of Transbronchial Lung cryobiopsy using an ultrathin cryoprobe and guide sheath for peripheral pulmonary lesions. J Bronchology Interv Pulmonol. 2024;31(1):13-22.\u003c/li\u003e\n\u003cli\u003eKim KE, Jung SS, Park HS, Lee JE, Chung C, Kang DH, et al. The first case report of Paragonimus westermani infection diagnosed by transbronchial lung cryobiopsy. Int J Infect Dis. 2023;128:184-6.\u003c/li\u003e\n\u003cli\u003eSomboonviboon D, Wattanathum A, Keorochana N, Wongchansom K. Sarcoidosis developing after COVID-19: A case report. Respirol Case Rep. 2022;10(9):e01016.\u003c/li\u003e\n\u003cli\u003eMukhopadhyay S, Katzenstein AL. Biopsy findings in acute pulmonary histoplasmosis: unusual histologic features in 4 cases mimicking lymphomatoid granulomatosis. Am J Surg Pathol. 2010;34(4):541-6.\u003c/li\u003e\n\u003cli\u003eKennedy MP, Jimenez CA, Mhatre AD, Morice RC, Eapen GA. Clinical implications of granulomatous inflammation detected by endobronchial ultrasound transbronchial needle aspiration in patients with suspected cancer recurrence in the mediastinum. J Cardiothorac Surg. 2008;3:8.\u003c/li\u003e\n\u003cli\u003eDagaonkar RS, Choong CV, Asmat AB, Ahmed DB, Chopra A, Lim AY, et al. Significance of coexistent granulomatous inflammation and lung cancer. J Clin Pathol. 2017;70(4):337-41.\u003c/li\u003e\n\u003cli\u003eKim YN, Kim KM, Choi HN, Lee JH, Park HS, Jang KY, et al. Clinical Usefulness of PCR for Differential diagnosis of tuberculosis and nontuberculous mycobacterial infection in paraffin-embedded lung tissues. J Mol Diagn. 2015;17(5):597-604.\u003c/li\u003e\n\u003cli\u003eKoizumi T, Tsushima K, Tanabe T, Agatsuma T, Yokoyama T, Ito M, et al. Bronchoscopy-Guided Cooled Radiofrequency ablation as a novel intervention therapy for peripheral lung cancer. Respiration. 2015;90(1):47-55.\u003c/li\u003e\n\u003cli\u003eXie F, Zheng X, Xiao B, Han B, Herth FJF, Sun J. Navigation Bronchoscopy-Guided Radiofrequency ablation for nonsurgical peripheral pulmonary tumors. Respiration. 2017;94(3):293-8.\u003c/li\u003e\n\u003cli\u003eVergnon JM, Schmitt T, Alamartine E, Barthelemy JC, Fournel P, Emonot A. Initial combined cryotherapy and irradiation for unresectable non-small cell lung cancer. Preliminary results. Chest. 1992;102(5):1436-40.\u003c/li\u003e\n\u003cli\u003eTian Y, Qi X, Jiang X, Shang L, Xu K, Shao H. Cryoablation and immune synergistic effect for lung cancer: A review. Frontiers in Immunology. 2022;13.\u003c/li\u003e\n\u003cli\u003eInoue M, Nakatsuka S, Jinzaki M. Cryoablation of early-stage primary lung cancer. Biomed Res Int. 2014;2014:521691.\u003c/li\u003e\n\u003cli\u003eSprenkle PC, Mirabile G, Durak E, Edelstein A, Gupta M, Hruby GW, et al. The effect of argon gas pressure on ice ball size and rate of formation. J Endourol. 2010;24(9):1503-7.\u003c/li\u003e\n\u003cli\u003eKim SH, Mok J, Jo E-J, Kim M-H, Lee K, Kim KU, et al. The Additive Impact of transbronchial cryobiopsy using a 1.1-mm diameter cryoprobe on conventional biopsy for peripheral lung nodules. Cancer Res Treat. 2023;55(2):506-12.\u003c/li\u003e\n\u003cli\u003eLu M, Fitzgerald D, Karpelowsky J, Selvadurai H, Pandit C, Robinson P, et al. Surgery in nontuberculous mycobacteria pulmonary disease. Breathe (Sheff). 2018;14(4):288-301.\u003c/li\u003e\n\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":"Cryobiopsy, mycobacterial nodule, lung cancer","lastPublishedDoi":"10.21203/rs.3.rs-4573825/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4573825/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNon-tuberculous mycobacterial (NTM) lung disease encompasses a diverse group of pulmonary conditions, present significant diagnostic challenges, especially in radiological interpretation. The disease can mimic lung cancer, tuberculosis, and other bronchopulmonary disorders, complicating accurate diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation:\u003c/strong\u003e A 46-year-old healthy woman was incidentally found to have a 1.3-cm pulmonary nodule in the left anterior basal segment during a routine health examination, with no symptoms or significant medical history. Initial CT imaging raised suspicions of T1a lung cancer. Subsequent endobronchial ultrasound transbronchial lung biopsy (EBUS-TBLB) and transbronchial lung cryobiopsy (TBLC) revealed granulomatous inflammation. Tests for tuberculosis and NTM were negative. Following the biopsies, chest X-rays showed an enlarged shadow at the lesion, suggesting necrosis after cryobiopsy. The patient was treated with moxifloxacin, leading to symptom improvement. A final diagnosis of NTM infection, specifically \u003cem\u003eMycobacterium avium\u003c/em\u003e, was confirmed from bronchoalveolar lavage (BAL) fluid. At four months post-biopsy, a chest CT scan showed complete resolution of the nodule.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eNTM nodules may undergo necrosis and resolution due to the ablation effect of cryobiopsy, suggesting cryoablation as a potential option for inoperable localized NTM disease.\u003c/p\u003e","manuscriptTitle":"Complete resolution of non-tuberculous mycobacterial pulmonary nodule following cryobiopsy: he first case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 16:41:51","doi":"10.21203/rs.3.rs-4573825/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":"b1c27365-2dd2-4c45-af24-41533d59b7f9","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-16T14:08:05+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-18 16:41:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4573825","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4573825","identity":"rs-4573825","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}