Pulmonary Langerhans cell histiocytosis incidentally detected during routine follow-up of nasopharyngeal carcinoma

Pulmonary Langerhans cell histiocytosis incidentally detected during routine follow-up of nasopharyngeal carcinoma | 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 Pulmonary Langerhans cell histiocytosis incidentally detected during routine follow-up of nasopharyngeal carcinoma Mehmet Akif Tükenmez, Elanur Karaman, Gizem Teoman, Hatice Tükenmez This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8449131/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 Aim Langerhans cell histiocytosis (LCH) is a rare disease originating from myeloid dendritic cells with an unknown etiology. As well as multiorgan involvement, it can also be seen symptomatically or incidentally in the lungs. In this study we aimed to present a case of pulmonary Langerhans cell histiocytosis (PLCH) incidentally detected during routine follow-up of a patient with nasopharyngeal carcinoma. Case A 66 year-old male who complained of hoarseness was diagnosed with locally advanced nasopharyngeal cancer and treated with chemoradiotherapy curatively. Then he involved follow up program and in post treatment eighteenth month newly developed metastasis suspicious pulmonary parenchymal lesions were detected. On chest computed tomography (CT) scan lesions were cystic in nature and were located in the apicoposterior segments. The patient was operated after discussed in the multidiscipliner thorax council. Post operative pathologic evaluation revealed cystic and noduler structures composed of langerhans cells. Immunohistochemical examination showed diffuse positivity in the langerhans cells with S-100 and CD1 antigen (CD1a). Thus case was diagnosed with (PLCH). Conclusion PLCH is an uncommon and smoking related intertisial lung disease. It usually has a good prognosis especially after smoking cessation. Langerhans cell histiocytosis nasopharyngeal carcinoma CD1 antigen Figures Figure 1 Figure 2 Introduction Nasopharyngeal carcinoma (NPC) is the most common type of nasopharynx rarely seen worldwide and displays various racial and geographic distribution reflecting its multifactorial etiology. Because of tumor radiosensitivity, anatomic challenging for surgery and survival advantage of chemotherapy addition; NPC is usually treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy in accordance to individual risk factors and clinical status. Langerhans cell histiocytosis (LCH) is a rare disease derived from myeloid dendritic cells and involves various organs commonly bone and soft tissue to a lesser extent bone marrow, liver, spleen, lungs, endocrine glands and central nervous system tissues, especially affecting children and young adults. Pulmonary Langerhans cell histiocytosis (PLCH) is a subgroup of LCH that particularly encountered in the lungs of adult cigarette smokers. In this study we present a rare case of Pulmonary Langerhans cell histiocytosis incidentally detected during routine follow-up of nasopharyngeal carcinoma that was initially considered as lung metastasis. Case A 66 year-old male applied to otorhinolaryngology clinics with the complaint of hoarseness 18 months ago. A mass in the nasopharynx and lymphadenopathies in the neck were detected and a biopsy was picked up from the nasopharynx. It was diagnosed with nonkeratinized nasopharyngeal carcinoma, undifferantiated type. Since he did not have distant metastasis and had bilateral metastatik lymph node involment none larger than 6 cm in greatest dimension, he was accepted as stage 4A and treated with curative concurrent chemoradiotherapy (6 weeks cisplatin 30mg/m 2 /week plus 33 fraction 212 cGy). 2 months after the completion of the treatment, 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) was carried out and residual lesions those did not retain 18F-FDG were detected. He was included in a 6-month follow-up program. He was referred by otorhinolaryngology department to medical oncology clinics as a result of development of new metastasis suspicous lung parenchymal lesions. On admission he had intermittent non productive cough for 3 months. He had no any other chronic diseases. He was active and heavy smoker but not alcohol consumer. He did not have drug abuse. In his family history, his father had died of intracranial tumor. On his physical examination, he looked well and ECOG performance status was 1. His blood pressure was 130/80mm Hg and pulse was 78 beats/min/rhytmic. His respiratory rate was 18/min and peripheric oxygen saturation was measured 95 with pulse oxymeter. On auscultation expiration time was slightly prolonged and respiratory sounds were diffusely diminished. Any other abnormality was not detected on his head-neck and systemic examination. On laboratory tests, glomerular fitration rate was 97ml/min/1,73m 2 , transaminases and cholestatic enzymes were normal. No abnormality was detected on complete blood count and thyroid function tests. On radiologic examination of thoracal computed tomography (CT) multiple cystic and metastasis suspicious parenchymal nodules of both lungs, the largest of which is 8 mm in diameter in the apicoposterior of the upper lobe of the left lung were observed (Fig. 1). They appeared after the interval period and were distributed diffusely throughout the lung. There was not any other metastatic lesion on neck, brain and abdominal imagings. Accompanied by these findings case was presented in multidisciplinary thoracic oncology council in order to evaluate metastasis suspicious lesions. It was decided to surgically excise the largest cavitary lesion which is located in the left apical lobe. Then the patient was operated and microscopic examination of the wedge resection specimen showed alveoli infiltrated by noduler structures composed of langerhans cells with lobulated contours and slightly eosinophilic cytoplasm accompanied by eosinophils and sporadic alveolar macrophages containing anthracose pigment. Immunohistochemical examination showed diffuse positivity in the langerhans cells with S-100 and CD1a (Fig. 2). Therefore, the case was diagnosed as “Langerhans cell hystiocytosis”. He was strongly advised to quit smoking and to be evaluated and medically followed by pulmonogist and hematologist. Discussion PLCH is a rarely seen intertisial lung disease primarly affects young adults. Male to female ratio differs in different studies ranging from male predominance to equal distribution [ 1 , 2 ]. Pathologic histiocyte in the disease is a dendritic cell originated from monocyte-macrophage line like cutenous Langerhans cells. CD1a, S100 and CD207 are characteristic cell biomarkers of histiocytes of PLCH. PLCH is considered as a consequence of neoplastic myeloid process depending on the recently detected somatic oncogenic alterations in pulmonary CD1a dendritic cells [ 3 , 4 ]. Lesions frequently affect middle and upper zones of the lung. BRAF V600E and MAPK2K1 mutations are most commonly encountered somatic alterations that result in cell proliferation and survival via activating MAPK signaling [ 3 – 5 ]. PLCH is strongly associated with cigarette smoking attributing to various mechanisms [ 4 ]. PLCH has widely variable clinical presentation. Whereas disease can be detected incidentally on chest imaging as in our case, patients can also present with various symptoms such as cough, exertional dyspnea, hemoptysis, spontenous pneumothorax, polyuria, polydipsia associated with diabetes insipitus, rash, bone pain and lymhp node (LN) enlargement [ 6 ]. High resolution computed tomography (HRCT) of the chest is the essential part of diagnostic approach to PLCH. The most common findings in HRCT are cystic patterns (51.4%) followed by noduler patterns (45.9%), cord shadows (27.5%), multiple LN enlargement (26.6%), pulmonay bulla (19.3%), plevral incrassation (17.4%), emphsymea (10.1%), honeycomb and reticular patterns (7.3%), [ 6 ]. Pulmonary function tests should be performed to determine the severity of the disease and respiratory disturbance. Detection of CD-1a and CD207 expressing cells in tissue acquired by transbronchial lung biopsy and bronchoalveolar lavage (BAL) fluid increases the accuracy of diagnosis, in majority of patients [ 7 ]. Due to strong association of cigarette smoking and PLCH, both active and also passive smoking cessation should be essential approach to the management of PLCH. Identification of somatic alterations in the Mitogen-activated protein kinase (MAPK) pathway, such as BRAF V600E and MAPK2K1, in both LCH and PLCH has been brought up the targeted therapy with inhibitors of mutated BRAF. In a study evaluating 122 BRAF-mutated non-melanoma patients, 18 were LCH or Erdheim–Chester disease (ECD), [ 8 ]. Treatment with a BRAF inhibitor resulted in disease regression in the majority of patients and no patients had progressive disease while receiving treatment [ 8 ]. In advanced PLCH, lung transplantation is an alternative. In a multicenter analysis of 39 lung transplant patients, overall survival was 77 percent at one year and 54 percent at 10 years [ 9 ]. The natural course of PLCH is variable. Athough prognosis is generally good, a small number of patients may lead to end stage lung disease and respiratory failure. In a prospective study involving 206 patients with pulmonary LCH, the 5- and 10-year survival were 94 and 93 percent, respectively, at the end of median 5.1 years of follow-up [ 10 ]. Declarations Consent for participation and ethics approval A written informed consent form was obtained from the patient who participated in the study and the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 Funding None. Author Contribution M.A.T. , E.K. and H.T. wrote the main manuscript text and G.T. prepared figure 1. All authors reviewed the manuscript. Acknowledgement The authors are thankful to doctors of thoracic surgery, radiology, otorhinolaryngology, radiation oncology departments of Karadeniz Technical University Faculty of Medicine and to the patient for their contribitons and cooperations. Data Availability The data supporting the findings of this case report are available from the corresponding author upon reasonable request. The data are not publicly available due to ethical restrictions and patient confidentiality. References Schönfeld N, Frank W, Wenig S, Uhrmeister P, Allica E, Preussler H et al (1993) Clinical and radiologic features, lung function and therapeutic results in pulmonary histiocytosis X. Respiration 60(1):38–44 Delobbe A, Durieu J, Duhamel A, Wallaert B (1996) Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord. Eur Respir J 9(10):2002–2006 Roden AC, Hu X, Kip S, Parrilla Castellar ER, Rumilla KM, Vrana JA et al (2014) BRAF V600E expression in Langerhans cell histiocytosis: clinical and immunohistochemical study on 25 pulmonary and 54 extrapulmonary cases. Am J Surg Pathol 38(4):548–551 Brown NA, Elenitoba-Johnson KSJ (2018) Clinical implications of oncogenic mutations in pulmonary Langerhans cell histiocytosis. Curr Opin Pulm Med 24(3):281–286 Yousem SA, Dacic S, Nikiforov YE, Nikiforova M (2013) Pulmonary Langerhans cell histiocytosis: profiling of multifocal tumors using next-generation sequencing identifies concordant occurrence of BRAF V600E mutations. Chest 143(6):1679–1684 Miao HL, Zhao AL, Duan MH, Zhou DB, Cao XX, Li J (2020) Clinical presentation and prognostic analysis of adult patients with Langerhans cell histiocytosis with pulmonary involvement. BMC Cancer 20(1):911 King TE Jr (1995) Bronchoscopy in interstitial lung disease. In: Fein SH AM (ed) Textbook of Bronchoscopy, Feinsilver. Williams & Wilkins, Baltimore, p 185 Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY et al (2015) Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med 373(8):726–736 Dauriat G, Mal H, Thabut G, Mornex JF, Bertocchi M, Tronc F et al (2006) Lung transplantation for pulmonary langerhans' cell histiocytosis: a multicenter analysis. Transplantation 81(5):746–750 Amira Benattia E, Bugnet et al (2022) Anouk Walter-Petrich, Constance de Margerie-Mellon, Véronique Meignin, Agathe Seguin-Givelet, Long-term outcomes of adult pulmonary Langerhans cell histiocytosis: a prospective cohort. European Respiratory Journal 59.5 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-8449131","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":573524696,"identity":"903fc941-3fd2-49f5-bfc3-3ea9faa61db4","order_by":0,"name":"Mehmet Akif 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1","display":"","copyAsset":false,"role":"figure","size":570920,"visible":true,"origin":"","legend":"\u003cp\u003eCT findings and Pathologic findings of pulmonary wedge resection of the case. The typical cystic nodules located in superior lobes bilaterally. A: Transverse section, B: Coronal section ; C: Nodular lesions infiltrating the lung alveoli. D: Irregularly boundaried langerhans cells stained slightly eosinophilic and occasionally observed eosinophils. E: Langerhans cells staining positive for CD1a.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8449131/v1/6fe0a19bcf321e2d90dca423.png"},{"id":100407244,"identity":"c8975996-f73b-44c9-a4b5-807df466fa6b","added_by":"auto","created_at":"2026-01-16 13:04:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":832705,"visible":true,"origin":"","legend":"\u003cp\u003ePathologic findings of pulmonary wedge resection of the case. C: Nodular lesions infiltrating the lung alveoli; D: Irregularly boundaried langerhans cells stained slightly eosinophilic and occasionally observed eosinophils; E: Langerhans cells staining positive for CD1a.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8449131/v1/574abdadaec7686ef60ca0f7.png"},{"id":104403839,"identity":"a02ffa44-8990-4620-bff5-d7138dfc23a2","added_by":"auto","created_at":"2026-03-11 12:19:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1821340,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8449131/v1/6dd3ad8c-1c73-41e1-858f-7f213cae8184.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pulmonary Langerhans cell histiocytosis incidentally detected during routine follow-up of nasopharyngeal carcinoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNasopharyngeal carcinoma (NPC) is the most common type of nasopharynx rarely seen worldwide and displays various racial and geographic distribution reflecting its multifactorial etiology. Because of tumor radiosensitivity, anatomic challenging for surgery and survival advantage of chemotherapy addition; NPC is usually treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy in accordance to individual risk factors and clinical status.\u003c/p\u003e \u003cp\u003eLangerhans cell histiocytosis (LCH) is a rare disease derived from myeloid dendritic cells and involves various organs commonly bone and soft tissue to a lesser extent bone marrow, liver, spleen, lungs, endocrine glands and central nervous system tissues, especially affecting children and young adults. Pulmonary Langerhans cell histiocytosis (PLCH) is a subgroup of LCH that particularly encountered in the lungs of adult cigarette smokers.\u003c/p\u003e \u003cp\u003eIn this study we present a rare case of Pulmonary Langerhans cell histiocytosis incidentally detected during routine follow-up of nasopharyngeal carcinoma that was initially considered as lung metastasis.\u003c/p\u003e"},{"header":"Case","content":"\u003cp\u003eA 66 year-old male applied to otorhinolaryngology clinics with the complaint of hoarseness 18 months ago. A mass in the nasopharynx and lymphadenopathies in the neck were detected and a biopsy was picked up from the nasopharynx. It was diagnosed with nonkeratinized nasopharyngeal carcinoma, undifferantiated type. Since he did not have distant metastasis and had bilateral metastatik lymph node involment none larger than 6 cm in greatest dimension, he was accepted as stage 4A and treated with curative concurrent chemoradiotherapy (6 weeks cisplatin 30mg/m\u003csup\u003e2\u003c/sup\u003e/week plus 33 fraction 212 cGy). 2 months after the completion of the treatment, 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) was carried out and residual lesions those did not retain 18F-FDG were detected. He was included in a 6-month follow-up program. He was referred by otorhinolaryngology department to medical oncology clinics as a result of development of new metastasis suspicous lung parenchymal lesions.\u003c/p\u003e \u003cp\u003eOn admission he had intermittent non productive cough for 3 months. He had no any other chronic diseases. He was active and heavy smoker but not alcohol consumer. He did not have drug abuse. In his family history, his father had died of intracranial tumor. On his physical examination, he looked well and ECOG performance status was 1. His blood pressure was 130/80mm Hg and pulse was 78 beats/min/rhytmic. His respiratory rate was 18/min and peripheric oxygen saturation was measured 95 with pulse oxymeter. On auscultation expiration time was slightly prolonged and respiratory sounds were diffusely diminished. Any other abnormality was not detected on his head-neck and systemic examination.\u003c/p\u003e \u003cp\u003eOn laboratory tests, glomerular fitration rate was 97ml/min/1,73m\u003csup\u003e2\u003c/sup\u003e, transaminases and cholestatic enzymes were normal. No abnormality was detected on complete blood count and thyroid function tests.\u003c/p\u003e \u003cp\u003eOn radiologic examination of thoracal computed tomography (CT) multiple cystic and metastasis suspicious parenchymal nodules of both lungs, the largest of which is 8 mm in diameter in the apicoposterior of the upper lobe of the left lung were observed (Fig.\u0026nbsp;1). They appeared after the interval period and were distributed diffusely throughout the lung. There was not any other metastatic lesion on neck, brain and abdominal imagings.\u003c/p\u003e \u003cp\u003eAccompanied by these findings case was presented in multidisciplinary thoracic oncology council in order to evaluate metastasis suspicious lesions. It was decided to surgically excise the largest cavitary lesion which is located in the left apical lobe. Then the patient was operated and microscopic examination of the wedge resection specimen showed alveoli infiltrated by noduler structures composed of langerhans cells with lobulated contours and slightly eosinophilic cytoplasm accompanied by eosinophils and sporadic alveolar macrophages containing anthracose pigment. Immunohistochemical examination showed diffuse positivity in the langerhans cells with S-100 and CD1a (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eTherefore, the case was diagnosed as \u0026ldquo;Langerhans cell hystiocytosis\u0026rdquo;. He was strongly advised to quit smoking and to be evaluated and medically followed by pulmonogist and hematologist.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePLCH is a rarely seen intertisial lung disease primarly affects young adults. Male to female ratio differs in different studies ranging from male predominance to equal distribution [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePathologic histiocyte in the disease is a dendritic cell originated from monocyte-macrophage line like cutenous Langerhans cells. CD1a, S100 and CD207 are characteristic cell biomarkers of histiocytes of PLCH. PLCH is considered as a consequence of neoplastic myeloid process depending on the recently detected somatic oncogenic alterations in pulmonary CD1a dendritic cells [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Lesions frequently affect middle and upper zones of the lung.\u003c/p\u003e \u003cp\u003eBRAF V600E and MAPK2K1 mutations are most commonly encountered somatic alterations that result in cell proliferation and survival via activating MAPK signaling [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. PLCH is strongly associated with cigarette smoking attributing to various mechanisms [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePLCH has widely variable clinical presentation. Whereas disease can be detected incidentally on chest imaging as in our case, patients can also present with various symptoms such as cough, exertional dyspnea, hemoptysis, spontenous pneumothorax, polyuria, polydipsia associated with diabetes insipitus, rash, bone pain and lymhp node (LN) enlargement [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHigh resolution computed tomography (HRCT) of the chest is the essential part of diagnostic approach to PLCH. The most common findings in HRCT are cystic patterns (51.4%) followed by noduler patterns (45.9%), cord shadows (27.5%), multiple LN enlargement (26.6%), pulmonay bulla (19.3%), plevral incrassation (17.4%), emphsymea (10.1%), honeycomb and reticular patterns (7.3%), [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePulmonary function tests should be performed to determine the severity of the disease and respiratory disturbance. Detection of CD-1a and CD207 expressing cells in tissue acquired by transbronchial lung biopsy and bronchoalveolar lavage (BAL) fluid increases the accuracy of diagnosis, in majority of patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDue to strong association of cigarette smoking and PLCH, both active and also passive smoking cessation should be essential approach to the management of PLCH.\u003c/p\u003e \u003cp\u003eIdentification of somatic alterations in the Mitogen-activated protein kinase (MAPK) pathway, such as \u003cem\u003eBRAF\u003c/em\u003e V600E and MAPK2K1, in both LCH and PLCH has been brought up the targeted therapy with inhibitors of mutated BRAF. In a study evaluating 122 BRAF-mutated non-melanoma patients, 18 were LCH or Erdheim\u0026ndash;Chester disease (ECD), [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Treatment with a BRAF inhibitor resulted in disease regression in the majority of patients and no patients had progressive disease while receiving treatment [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In advanced PLCH, lung transplantation is an alternative. In a multicenter analysis of 39 lung transplant patients, overall survival was 77 percent at one year and 54 percent at 10 years [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe natural course of PLCH is variable. Athough prognosis is generally good, a small number of patients may lead to end stage lung disease and respiratory failure. In a prospective study involving 206 patients with pulmonary LCH, the 5- and 10-year survival were 94 and 93 percent, respectively, at the end of median 5.1 years of follow-up [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConsent for participation and ethics approval\u003c/h2\u003e \u003cp\u003eA written informed consent form was obtained from the patient who participated in the study and the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNone.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.A.T. , E.K. and H.T. wrote the main manuscript text and G.T. prepared figure 1. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors are thankful to doctors of thoracic surgery, radiology, otorhinolaryngology, radiation oncology departments of Karadeniz Technical University Faculty of Medicine and to the patient for their contribitons and cooperations.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this case report are available from the corresponding author upon reasonable request. The data are not publicly available due to ethical restrictions and patient confidentiality.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSch\u0026ouml;nfeld N, Frank W, Wenig S, Uhrmeister P, Allica E, Preussler H et al (1993) Clinical and radiologic features, lung function and therapeutic results in pulmonary histiocytosis X. Respiration 60(1):38\u0026ndash;44\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDelobbe A, Durieu J, Duhamel A, Wallaert B (1996) Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Groupe d'Etude en Pathologie Interstitielle de la Soci\u0026eacute;t\u0026eacute; de Pathologie Thoracique du Nord. Eur Respir J 9(10):2002\u0026ndash;2006\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoden AC, Hu X, Kip S, Parrilla Castellar ER, Rumilla KM, Vrana JA et al (2014) BRAF V600E expression in Langerhans cell histiocytosis: clinical and immunohistochemical study on 25 pulmonary and 54 extrapulmonary cases. Am J Surg Pathol 38(4):548\u0026ndash;551\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown NA, Elenitoba-Johnson KSJ (2018) Clinical implications of oncogenic mutations in pulmonary Langerhans cell histiocytosis. Curr Opin Pulm Med 24(3):281\u0026ndash;286\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYousem SA, Dacic S, Nikiforov YE, Nikiforova M (2013) Pulmonary Langerhans cell histiocytosis: profiling of multifocal tumors using next-generation sequencing identifies concordant occurrence of BRAF V600E mutations. Chest 143(6):1679\u0026ndash;1684\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiao HL, Zhao AL, Duan MH, Zhou DB, Cao XX, Li J (2020) Clinical presentation and prognostic analysis of adult patients with Langerhans cell histiocytosis with pulmonary involvement. BMC Cancer 20(1):911\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKing TE Jr (1995) Bronchoscopy in interstitial lung disease. In: Fein SH AM (ed) Textbook of Bronchoscopy, Feinsilver. Williams \u0026amp; Wilkins, Baltimore, p 185\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY et al (2015) Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med 373(8):726\u0026ndash;736\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDauriat G, Mal H, Thabut G, Mornex JF, Bertocchi M, Tronc F et al (2006) Lung transplantation for pulmonary langerhans' cell histiocytosis: a multicenter analysis. Transplantation 81(5):746\u0026ndash;750\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmira Benattia E, Bugnet et al (2022) Anouk Walter-Petrich, Constance de Margerie-Mellon, V\u0026eacute;ronique Meignin, Agathe Seguin-Givelet, Long-term outcomes of adult pulmonary Langerhans cell histiocytosis: a prospective cohort. European Respiratory Journal 59.5\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":"Langerhans cell histiocytosis, nasopharyngeal carcinoma, CD1 antigen","lastPublishedDoi":"10.21203/rs.3.rs-8449131/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8449131/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eAim\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLangerhans cell histiocytosis (LCH) is a rare disease originating from myeloid dendritic cells with an unknown etiology. As well as multiorgan involvement, it can also be seen symptomatically or incidentally in the lungs. In this study we aimed to present a case of pulmonary Langerhans cell histiocytosis (PLCH) incidentally detected during routine follow-up of a patient with nasopharyngeal carcinoma.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 66 year-old male who complained of hoarseness was diagnosed with locally advanced nasopharyngeal cancer and treated with chemoradiotherapy curatively. Then he involved follow up program and in post treatment eighteenth month newly developed metastasis suspicious pulmonary parenchymal lesions were detected. On chest computed tomography (CT) scan lesions were cystic in nature and were located in the apicoposterior segments. The patient was operated after discussed in the multidiscipliner thorax council. Post operative pathologic evaluation revealed cystic and noduler structures composed of langerhans cells. Immunohistochemical examination showed diffuse positivity in the langerhans cells with S-100 and CD1 antigen (CD1a). Thus case was diagnosed with (PLCH).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePLCH is an uncommon and smoking related intertisial lung disease. It usually has a good prognosis especially after smoking cessation.\u003c/p\u003e","manuscriptTitle":"Pulmonary Langerhans cell histiocytosis incidentally detected during routine follow-up of nasopharyngeal carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 10:48:12","doi":"10.21203/rs.3.rs-8449131/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":"64b89ef1-8a18-4fdc-86b8-168896544f69","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-08T01:08:44+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-16 10:48:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8449131","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8449131","identity":"rs-8449131","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}