Pulmonary Langerhans Cell Histiocytosis Research Articles

Evaluation of the Interstitial Histological Lesions in Pulmonary Langerhans Cell Histiocytosis.

Pulmonary Langerhans cell histiocytosis is a cystic lung disease characterized by the proliferation of parenchymal dendritic cells. The disease can become chronic or even cause pulmonary fibrosis. Our aim in this study was to investigate the typical histological findings and interstitial fibrosis in pulmonary Langerhans cell histiocytosis cases. In the study, cases that had undergone diagnostic resection were screened. Smoking, histological stage (subacute, subacute-chronic), and cystic and eosinophilic granulomas were confirmed in the cases. In addition to emphysema, chronic nonspecific bronchiolitis, interstitial fibrosis (subpleural-paraseptal fibrosis, peribronchial fibrosis, fibrotic nonspecific interstitial pneumonia), honeycomb-type fibrocysts, and unexpected lesions were investigated. Descriptive and comparative (Fisher exact test) statistical analyses were used in the study (p < 0.05). A total of 27 cases were detected; age distribution was 17-68 (36.4). Smoking was present in 15 (55.5%) cases. Six (22.2%) cases were subacute, and 21 (7.7%) cases were subacute-chronic histological stage. A cystic lesion was present in 22 (81.4%) cases. All cases had emphysema accompanying the underlying lesions. Chronic nonspecific bronchiolitis was detected in 14 (51.8%) cases. Interstitial fibrosis was detected in 8 (29.6%) patients. Compared to interstitial fibrosis and nonfibrosis, there was no significant difference between being younger than 39 years, gender, smoking, and histological stage (p=0.41; 1; 0.69; 0.63, respectively). There is a risk of developing interstitial fibrosis patterns and honeycomb-type fibrocysts in the progression of pulmonary Langerhans cell histiocytosis. Histopathological evaluation can play an important role in the detection of risk groups.

Atypical case of pulmonary Langerhans cell histiocytosis presenting as miliary nodules

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare smoking-related interstitial lung disease affecting primarily young adult smokers. Diagnosis is made with typical radiographic findings of centrilobular nodules and cystic lesions on high resolution computed tomography (HRCT) confirmed with tissue biopsy. We describe a case of a 59-year-old man presenting with chronic tobacco use and cough who was found to have an atypical radiographic finding of miliary nodules on HRCT that was confirmed as PLCH on transbronchial lung biopsy.

Lymphangioleiomyomatosis and Langerhans cell histiocytosis - two case reports from our practice

Introduction. Lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis are the most common pulmonary cystic diseases. Although they differ in pathogenesis, they share several features. The aim of this paper is to present the similarities and differences between these diseases, as well as to describe two cases from our practice. Outlines of cases. The patient with lymphangioleiomyomatosis (43 years old) had pulmonary changes detected during a regular examination within the underlying disease ? tuberous sclerosis. Four years after starting therapy with everolimus, she was still respiratory asymptomatic, a slight radiological deterioration of cystic changes was registered, the diffusion capacity was declining (by 12%). The second patient (23 years old) was admitted due to bilateral radiological lung changes and symptoms in the form of dry cough, quick fatigue, and chest pain. Pathohistological examination of the transbronchial biopsy showed numerous large-core histiocytes, immunohistochemically positive for CD1a and S100, so it was concluded that it was Langerhans cell histiocytosis. Cessation of smoking was advised. The follow-up examinations showed withdrawal of symptoms and an orderly finding of lung function, chest high-resolution computed tomography indicated slight regression of changes. In the meantime, the patient gave birth to a healthy child, the pregnancy and prenatal period were uneventful. Conclusion. These diseases are extremely rare and in cooperation with other specialties should be distinguished from diseases that mimic lung cysts.

Effectiveness of high-flow nasal cannula during exercise training in a patient with pulmonary Langerhans cell histiocytosis

Effectiveness of high-flow nasal cannula during exercise training in a patient with pulmonary Langerhans cell histiocytosis

Diagnostic value and safety of medical thoracoscopy under local anesthesia for unexplained diffuse interstitial lung disease: A retrospective study.

ObjectiveWe aimed to explore the safety and diagnostic value of medical thoracoscopic lung biopsy in patients with unexplained diffuse interstitial lung disease (ILD) in a single center pilot study.MethodWe retrospectively analyzed clinical and pathological diagnostic data from 52 patients with diffuse ILD undergoing medical thoracoscopic lung biopsy.ResultsForty-four cases of diffuse ILD were confirmed pathologically, giving a diagnostic rate of 84.6%. Among these 44 patients, 11 patients were diagnosed with cancer, including eight patients with lung adenocarcinoma, three patients with metastases; two from a gastrointestinal malignancy, and one from a granulosa cell tumor of the ovary. There were 17 cases of idiopathic interstitial pneumonia, including nine cases of usual interstitial pneumonia (UIP), four cases of non-specific interstitial pneumonia (NSIP), three cases of cryptogenic organizing pneumonia (COP), and one case of acute interstitial pneumonia (AIP). There were 12 cases of rare interstitial pneumonias, which included six cases of pulmonary alveolar proteinosis, one case each of pulmonary Langerhans cell histiocytosis (LCH) and pulmonary lymphangiomyomatosis, two cases of nodular sarcoidosis, and two cases of chronic eosinophilic pneumonia. We recorded various complications, including bleeding, infection, and pneumothorax. A total of 28 patients (53.8%) experienced at least one of the above complications, but there were no deaths associated with biopsy.ConclusionsMedical thoracoscopic lung biopsy appears a safe and effective method for diagnosing diffuse ILD of unknown cause but further prospective studies, with larger numbers, including comparison with other established techniques are required.

Treatment outcomes and prognostic factors of patients with adult Langerhans cell histiocytosis.

Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had multiple lesions within a single system (SS-m), and 182 patients had multisystem disease (MS). The most common organ involved in MS patients was the bone (69.8%), followed by the pituitary (61.5%) and lung (61.0%). BRAFV600E , BRAF deletion, and MAP2K1 mutation were detected in 38.8%, 25.4%, and 19.4% patients, respectively. BRAF deletion was found more common in patients with MS LCH compared to single-system LCH (38.5% vs 7.1%, p=.004), also in patients with liver involvement (69.2% vs 14.3%, p < .001). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 94.4% and 54.7%, respectively, in SS-m and MS LCH. Multivariate Cox regression showed that involvement of the liver or spleen at baseline predicted poor EFS and receiving cytarabine-based therapy as a first-line treatment and age older than 30 years at diagnosis predicted favorable EFS. The involvement of risk organs and age older than 50 years predicted poor OS, and receiving cytarabine-based therapy predicted favorable OS. Therefore, BRAF deletion was correlated with MS LCH, particularly those with liver involvement. Liver or spleen involvement at baseline indicates a poor prognosis, and a cytarabine-based regimen could be considered as first-line treatment for adult LCH patients.

Promising Real World Survival Data in Adult-Onset Langerhans Cell Histiocytosis: An Australasian Lymphoma Alliance 20 Year Retrospective Study

▪Background: Langerhans Cell Histiocytosis (LCH) is a rare inflammatory neoplasm originating from bone marrow-derived CD207+/CD1+ clonal dendritic cells, with cells expressing BRAF V600E in around 50% of cases. Although more common in the paediatric setting, LCH is rare in adults, with an incidence of 1 to 2 cases per million. This combination of disease heterogeneity and infrequency means that data on treatment strategies and outcomes is limited, and a consensus on management is lacking. Data has historically been extrapolated from the larger paediatric cohort, with emerging phase II data on the efficacy and safety of upfront methotrexate and cytosine arabinoside (AraC) in adult LCH. Other agents used include cladribine (CdA), hydroxyurea, vinblastine, and prednisolone-based regimens, and more recently MEK/BRAF inhibitors, but none of these have been trialled prospectively. LCH can be an aggressive disease with a poor prognosis.Methods : We included patients aged ≥18 years diagnosed with LCH on histopathology between January 1, 2000 and August 1, 2021 from ten sites across Australia and New Zealand. Variables included demographic data, system and organ involvement, central nervous system (CNS) involvement, bone marrow involvement and BRAF V600E mutation status. Outcomes measured included overall survival (OS), progression-free survival (PFS) and total lines of therapy. Response to therapy was modified from the Scoring System of the HS LCH III trial: Complete response (CR) was defined by resolution of all signs of disease activity, including neuroendocrine dysfunction, skin and radiological lesions; and a partial response (PR) was defined as patients with “active disease better” and those with “mixed response”. Stable or worsening symptoms/radiology were classified as progressive disease (PD). Patients who were alive or lost to follow-up were censored on the date of last follow-up.Results : We identified 46 patients with a median age at diagnosis of 39 years (range 18-81) (Table 1). The sex ratio was 1. 41% of patients had MS-LCH at diagnosis, of which 24% had high risk organ (liver, bone marrow, or spleen) involvement. 37% had multifocal bone disease. 28% of patients had CNS involvement at diagnosis. BRAF V600E mutation status was assessed in only 43% of cases, with a mutation frequency of 40%. The median number of lines of therapy was 1.7 (range 0-9). Three patients (7%) underwent lung transplantation for isolated pulmonary LCH. 31% percent of patients were treated with chemotherapy upfront, with the majority receiving AraC (43%,) and the remainder receiving vinblastine, prednisolone and 6-mercaptopurine (6-MP) (21%), vinblastine/prednisolone (21%), CdA (14%) or methotrexate and 6-MP (2%). Of note, 67% (n=4) of patients who were treated with upfront AraC and 100% (n=2) of patients treated with upfront CdA had a CR, while those patients treated with upfront vincristine-based regimes had, at best, a PR (50%, n=3) or PD (50%).Of the 46 patients, with a median follow up of 34.6 months (range 0.63-250.2), there were 7 deaths (15%) with 6/7 due to progressive disease, and the remaining death due to complications of lung transplantation. Median OS was not reached (Figure 1), while OS at 5 years was 85%. Median PFS was 9 years (range 0.05-21) (Figure 2), with a non-significant trend towards reduced PFS in patients with MS-LCH (5 years) compared to SS-LCH (9 years) (Figure 3). There was also a trend towards reduced OS in patients who received AraC as systemic therapy versus other forms of systemic therapy.Conclusion: We report the largest multicentre Australasian cohort of patients diagnosed with adult-onset LCH. OS and PFS were longer than previously reported in the literature. There remains significant heterogeneity in diagnostic and treatment strategies. There was a trend towards improved response rate to upfront AraC or CdA when compared to the vinblastine-based regimens, and further prospective research with these agents is required in this setting. Progress in this disease is challenging due its rarity, highlighting the need for standardisation of diagnostic and treatment strategies as well as a national and/or international registry. [Display omitted] DisclosuresFong: Amgen: Research Funding; AbbVie, Amgen, Novartis, Pfizer, Astellas: Honoraria; Amgen, BMS: Speakers Bureau. Ku: Antegene: Consultancy; Roche: Consultancy; Genor Biopharma: Consultancy. Cunningham: Principia Biopharma: Research Funding; Rigel: Research Funding; Janssen: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Amgen: Research Funding; Astex: Research Funding; Celgene: Research Funding. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

P16‐112: A case of pulmonary langerhans cell histiocytosis (PLCH) presenting as massive hemoptysis

P16‐112: A case of pulmonary langerhans cell histiocytosis (PLCH) presenting as massive hemoptysis

Langerhans Cell Histiocytosis In Bone: A Case Report

Langerhans cell histiocytosis (LCH) is a rare disease in which histiocytic infiltrations can be seen in bone, skin, lymph nodes, lungs, liver, spleen, bone marrow, central nervous system and endocrine glands. Pulmonary LCH has been closely associated with smoking while there is no data on genetic, viral or neoplastic etiology. In LCH with multiple system involvement, unifocal/multifocal infiltrations occur in two or more organs together with systemic symptoms such as weight loss and fever. In histology, Langerhans cells that do not contain phagocytic material in their cytoplasm, have a folded "coffee bean" appearance in their nucleus, express histiocyte markers CD1a, S100 and C207 and contain Birbeck granules under electron microscope. In treatment, if there is a risk of collapse in spinal or femoral bone lesions, surgery and radiotherapy can be applied for stabilization; if necessary, chemotherapy can be applied in multisystem disease. Here, we reported a LCH patient with a malignant shaped lytic lesion in the thoracic spine and adjacent bone.

Long-term outcomes of adult pulmonary Langerhans cell histiocytosis: a prospective cohort

The long-term outcomes of adult pulmonary Langerhans cell histiocytosis (PLCH), particularly survival, are largely unknown. Two earlier retrospective studies reported a high rate of mortality, which contrasts with our clinical experience. To address this issue, all patients with newly diagnosed PLCH referred to the French national reference centre for histiocytoses between 2004 and 2018 were eligible for inclusion. The primary outcome was survival, which was defined as the time from inclusion to lung transplantation or death from any cause. Secondary outcomes included the cumulative incidences of chronic respiratory failure (CRF), pulmonary hypertension (PH), malignant diseases and extrapulmonary involvement in initially isolated PLCH. Survival was estimated using the Kaplan-Meier method. 206 patients (mean age 39±13 years, 60% female, 95% current smokers) were prospectively followed for a median duration of 5.1 years (IQR 3.2-7.6 years). Of these, 12 patients (6%) died. The estimated rate of survival at 10 years was 93% (95% CI 89-97%). The cumulative incidences of CRF and/or PH were <5% at both 5 and 10 years, and 58% of these patients died. 27 malignancies were observed in 23 patients. The estimated standardised incidence ratio of lung carcinoma was 17.0 (95% CI 7.45-38.7) compared to an age- and sex-matched French population. Eight (5.1%) of the 157 patients with isolated PLCH developed extrapulmonary involvement. The long-term prognosis of PLCH is significantly more favourable than has previously been reported. Patients must be closely monitored after diagnosis to detect severe complications early.

DIFFUSE CYSTIC LUNG DISEASE SECONDARY TO METASTATIC COLON CANCER

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Diffuse cystic lung diseases (DCLD) encompass a group of lung disorders characterized by multiple spherical densities with a thin well-defined wall adjacent to normal lung tissue1. Causes of DCLD include lymphoproliferative disorders, interstitial lung diseases, infections, developmental defects, and smoking. Rarely, DCLD can be the result of a malignant process. We report a case of DCLD resulting from metastatic colorectal adenocarcinoma. CASE PRESENTATION: A 49-year-old male former smoker with past medical history significant for advanced colon cancer on palliative chemotherapy with FOLFOX and bevacizumab presented to our facility with several week history of progressively worsening generalized weakness, fatigue, weight loss, cough and shortness of breath. On presentation, the patient was tachycardic and tachypneic with oxygen saturation of 92% on 3 liters nasal cannula O2. Initial laboratory studies noted white blood cell count 12.0, procalcitonin 2.37, c-reactive protein 2.99, and sedimentation rate 50. CTA pulmonary showed extensive, bilateral cystic changes and bilateral interstitial opacities which were significantly worse when compared to chest imaging done three months prior. DISCUSSION: Given the patient's smoking history, known history of colon cancer, and radiologic picture, pulmonary Langerhans cell histiocytosis (PLCH) and metastatic lung disease were considered likely etiologies. The patient was initially started on empiric antibiotics and subsequently underwent bronchoscopy with bronchoalveolar lavage (BAL). Initial BAL fluid studies noted 256 leukocytes with lymphocytic predominance. Gram stain and respiratory cultures were negative. Cytology then resulted with malignant cells consistent with metastatic adenocarcinoma. At this point, the patient's oncologist and palliative care were consulted. Given the patient's overall poor prognosis, the decision was made to pursue home hospice and the patient was discharged home. CONCLUSIONS: Review of the medical literature notates only one previous case of DCLD from metastatic colorectal adenocarcinoma making this a rare pathophysiologic phenomenon2. Neoplastic causes of DCLD include lymphangioleiomyomatosis, PLCH, and other primary and metastatic cancers1. A multi-disciplinary team effort including both pulmonology and oncology should be sought in order to formulate an appropriate treatment plan. Treatment options are based on the underlying etiology of the DCLD. Unfortunately, in this case, patient's disease process was already advanced and palliative care was pursued. REFERENCE #1: 1. Gupta, N., Vassallo, R., Wikenheiser-Brokamp, K. A., & McCormack, F. X. (2015). Diffuse Cystic Lung Disease. Part I. American journal of respiratory and critical care medicine, 191(12), 1354–1366. https://doi.org/10.1164/rccm.201411-2094CI REFERENCE #2: 2. Fielli, M., Avila, F., Saino, A., Seimah, D., & Fernández Casares, M. (2016). Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma. Respiratory medicine case reports, 17, 83–85. https://doi.org/10.1016/j.rmcr.2015.12.006 DISCLOSURES: No relevant relationships by Comfort Adewunmi, source=Web Response no disclosure on file for Yalew Debella; No relevant relationships by Henry Ogbuagu, source=Web Response No relevant relationships by Sameena Salcin, source=Web Response no disclosure on file for Molla Teshome

Drug Repurposing Patent Applications April–June 2021

Drug Repurposing Patent Applications April–June 2021

Association between pulmonary artery to aorta diameter ratio with pulmonary hypertension and outcomes in diffuse cystic lung diseases.

To investigate the importance of pulmonary vascular measurements on computed tomography (CT) in predicting pulmonary hypertension (PH) and worse outcomes in diffuse cystic lung diseases (DCLDs).We conducted a cross-sectional study of patients with DCLDs. Patients underwent pulmonary function tests, a six-minute walk test (6MWT), chest CT, transthoracic echocardiography, and right heart catheterization. Pulmonary artery (PA) diameter and PA-ascending aorta ratio (PA-Ao ratio) were obtained from CT. Mean pulmonary artery pressure (mPAP) from right heart catheterization was correlated with tomographic, functional, and echocardiographic variables. The association between the PA-Ao ratio with outcomes was determined by Kaplan–Meier curves.Thirty-four patients were included (18 with pulmonary Langerhans cell histiocytosis and 16 with lymphangioleiomyomatosis, mean age 46 ± 9 years). Forced expiratory volume in the first second and lung diffusing capacity for carbon monoxide were 47 ± 20% and 38 ± 21% predicted, respectively. PA diameter and PA-Ao ratio were 29 ± 6 mm and 0.95 ± 0.24, respectively. PA-Ao ratio > 1 occurred in 38.2% of patients. PA-Ao ratio was a good predictor of PH. mPAP correlated best with PA-Ao ratio, PA diameter, oxygen desaturation during six-minute walk test, and echocardiographic variables. Patients with PA-Ao ratio > 1 had greater mPAP, and a higher risk of death or lung transplantation (log-rank, P < .001) than those with PA-Ao ratio ≤ 1.The PA-Ao ratio measured on CT scan has a potential role as a non-invasive tool to predict the presence of PH and as a prognostic parameter in patients with DCLDs.

The etiology of diffuse cystic lung diseases: an analysis of 1010 consecutive cases in a LAM clinic

BackgroundThe differential diagnosis of diffuse cystic lung disease (DCLD) is a clinical challenge. We wish to analyze the distribution of the etiology of DCLD based on data from a single lymphangioleiomyomatosis (LAM) clinic.MethodsAll DCLD patients at the LAM Clinic of Peking Union Medical College Hospital between January 2006 and December 2019 were analyzed. Information on the demographic, clinical, radiological, and pathological features was collected.ResultsA total of 1010 patients with DCLD on CT scan were evaluated. A sum of 711(70.4%) patients were diagnosed with definite or probable LAM. Other diagnoses included Birt–Hogg–Dubé syndrome (46), Sjogren's syndrome (38), pulmonary Langerhans cell histiocytosis (14), lung tumors (3), Castleman disease (2), antineutrophil cytoplasmic antibody-associated vasculitis (2), systemic lupus erythematosus (1), Marfan syndrome (1), amyloidosis (1), congenital cystic adenomatoid malformation of the lung (1), and pleuroparenchymal fibroelastosis (1). In the 38 patients diagnosed with Sjogren's syndrome, 2 were diagnosed with light-chain deposition disease, 2 were diagnosed with amyloidosis and 1 was diagnosed with lymphocytic interstitial pneumonia. One hundred and eighty-nine patients (18.7%) were undiagnosed. Lung biopsy results were available in 27 patients in the undiagnosed DCLD group but did not provide a diagnosis.ConclusionApproximately 70% of DCLD patients in our LAM clinic had LAM. The common differential diagnoses included Birt–Hogg–Dubé syndrome, Sjogren’s syndrome, and pulmonary Langerhans cell histiocytosis. Detailed clinical information and laboratory, genetic, and pathological investigations provide correct diagnoses in most patients with DCLD.

Phenotypes and prognostic factors in adults with Langerhans cell histiocytosis.

7049 Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognostic factors including risk organ (RO) involvement (liver, spleen, and bone marrow) in adult LCH, which we sought to address in this study. Methods: Single-center retrospective study of patients ≥18y diagnosed with LCH from 1998 to 2020. Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were conducted using age, sex, organ involvement, LCH subtype, year of diagnosis, BRAF V600E status, and treatments. Results: We included 219 patients with LCH; median age 43y (range 19-88), females 51%, SS unifocal (23%), SS multifocal (6%), pulmonary (31%) and MS (40%). Commonly involved organs included lung (53%), bone (42%), skin (24%), pituitary (16%), and CNS (12%). BRAF V600E was positive in 40/88 (46%). Median follow-up duration was 6.1y (95% CI, 5.1- 7.1). On univariate analysis, factors associated with worse PFS were bone LCH, RO involvement, multifocal/MS LCH, and radiation therapy alone; those with worse OS included RO involvement, MS disease, BRAF V600E+, and age ≥45y at diagnosis. In multivariate analysis, BRAF V600E and age ≥45y at diagnosis were associated with worse mortality (Table). Median PFS was not reached (NR-NR) for SS unifocal LCH, 5mo (0-12.7) for SS multifocal LCH, 110mo (84.7-135.3) for pulmonary LCH, and 27mo (17.2-36.8) for MS LCH. 5-year OS was 97.4% for SS unifocal LCH, 100% for SS multifocal LCH, 96.1% for pulmonary LCH, and 79.9% for MS LCH. 41 (18.7%) developed a second primary malignancy (SPM), of which 11 were hematologic neoplasms. There was a trend towards a higher prevalence of SPMs in patients with BRAF V600E (28% vs. 17%; p = 0.22). Conclusions: In our large single-center study, PFS for multifocal and MS LCH was worse than SS unifocal or pulmonary LCH. RO involvement was not associated with outcomes in multivariate analysis. Overall prognosis was excellent for all subtypes except MS LCH. BRAF V600E and older age were associated with worse OS. The prevalence of SPMs was very high and needs to be explored further.[Table: see text]

BRAFV600E frequency and impact on outcomes in adults with langerhans cell histiocytosis.

7050 Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm manifesting as unifocal, multifocal, multisystem (MS) or pulmonary LCH (smoking-related). In pediatric LCH, somatic BRAFV600E prevalence is reported at 55-70%, and associated with increased risk of multisystem disease and early treatment failure. Our aim was to describe the prevalence of BRAFV600E mutation and evaluate its association with clinical manifestations and outcomes in adults with LCH. Methods: A retrospective review of adult patients diagnosed with LCH consecutively seen at Mayo Clinic from 2011 to 2020 was performed.Evaluation of association of BRAFV600E mutational status and clinical factors was conducted by the Chi-square test for independence. Progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan Meier method and compared with the log-rank test to assess the effect of BRAFV600E. Results: Of the total LCH cohort ( n= 128), 88 patients with available BRAFV600E results were included in the study. Median age at diagnosis was 41y (range 19 - 88); 52.3% were male. 40 (45.5%) patients had a BRAFV600E mutation. Increasing age was associated with BRAFV600E (10-year increase OR 1.42, 95%CI 1.07-1.89; p= 0.017). No correlation was observed between BRAFV600E status and site of disease, risk organ (RO: liver, spleen, marrow) involvement, or MS disease. Patients with BRAFV600E were 4 times more likely to receive targeted therapy ( BRAF inhibitor) than non- BRAFV600E patients ( p= 0.018). After a median follow up of 46 mo (95% CI 30.8-61.2), PFS was similar between BRAFV600E and non- BRAFV600E patients ( p= 0.167). However, patients with BRAFV600E had a worse 3-year OS compared with non- BRAFV600E patients (84% vs. 97.1%, p= 0.027). Patients who died had a significantly higher age at LCH diagnosis (median 62 vs. 38 years; p= 0.0002). Conclusions: In our cohort of adults with LCH, BRAFV600E was less frequent than reported in pediatric literature and was associated with worse OS. The frequency of BRAFV600E was positively correlated with increasing age. Contrary to reports in pediatric LCH, there were no significant associations between BRAFV600E and high-risk or multisystem disease.[Table: see text]

English

The differential diagnosis of the cystic lung disease is extensive, ranging from an isolated incidental lung cyst to multiple diffuse lung cysts with other varied associated lung abnormalities. High resolution computed tomography (HRCT) thorax is the imaging modality of choice in the evaluation of these diseases, by improving the characterisation of the lung cysts (number, size, shape, distribution, wall thickness and regularity), and associated pulmonary and extrapulmonary abnormalities (like ground glass densities, nodules, interstitial fibrosis, mediastinal lymphadenopathy). After differentiating from the common cyst mimickers (cavity, centrilobular emphysema and cystic bronchiectasis), they should be grouped by location into subpleural cysts (paraseptal emphysema, bulla and honeycombing) and intraparenchymal cysts. Intraparenchymal cysts are in turn categorised into solitary / localised cysts (incidental cyst, congenital pulmonary airway malformations, intrapulmonary bronchogenic cyst and hydatid cyst) and multiple diffuse cysts. The next step will be the categorisation of these multiple diffuse cysts into those without other lung abnormalities (lymphangioleiomyomatosis and Birt-Hogg-Dube syndrome) and those with other lung abnormalities such as predominant ground glass densities (Pneumocystis jirovecii pneumonia, desquamative interstitial pneumonia, lymphoid interstitial pneumonia, subacute hypersensitivity pneumonitis and pneumatoceles) or predominant nodules (pulmonary Langerhans cell histiocytosis, amyloidosis, light chain deposition disease, follicular bronchiolitis, recurrent respiratory papillomatosis, cystic tuberculosis, cystic lung metastasis, sarcoidosis, and pulmonary mesenchymal cystic hamartomas). We conclude that this orderly radiologic approach in a given HRCT chest study of a cystic lung disease (in addition to correlation with clinical and laboratory findings), can lead us to a specific diagnosis in majority of instances, thereby optimising their treatment management, without the need of an invasive biopsy. KEY WORDS HRCT Thorax, Lung Cysts, Ground Glass Densities, Lung Nodules

VATS biopsy of an adult with pulmonary langerhans cell histiocytosis: case report

VATS biopsy of an adult with pulmonary langerhans cell histiocytosis: case report

RESPIRATORY SYSTEM AND PULMONARY INTERSTITIAL DISEASE DUE TO CIGARETTE SMOKE IN RADIOLOGICAL ASPECTS

Smoking is a risk factor for disease that contributes the most to lung and respiratory diseases. Lung disease related with cigarette smoke can be classified as COPD (Chronic Obstructive Pulmonary Disease) and several types of interstitial lung disease such as pulmonary langerhans cell histiocytosis, bronchiolitis, desquamative interstitial pneumonitis and interstitial fibrosing lung disease. This literature review aims to shed a light that cigarette smoke not only causes inflammation and damages the epithelium of the large respiratory tract but also the small airways and lung parenchyma. COPD (including chronic bronchitis and emphysema) is one of the most common lung diseases and causes death due to smoking. Lung disease related with smoking in addition to providing a mass image can also provide an interstitial picture such as Langerhans cell histiocytosis, bronchiolitis, desquamative interstitial pneumonitis and interstitial fibrosing lung disease. Radiological overview in lung disease caused by cigarette smoke can also occur in combination. Although the radiological overview / image of computerized tomography can provide adequate information, a comprehensive diagnostic by combining clinical symptoms and histopathological features will be quite meaningful, especially for overlapping cases.

Erdheim-Chester Disease in a Patient after Double Lung Transplantation for Pulmonary Langerhans Cell Histiocytosis

Introduction Both, Langerhans cell histiocytosis (LCH) and Erdheim-Chester Disease (ECD) belong to the heterogeneous group of histiocytoses. Their association is exceptional and thought to be linked to the BRAF mutation. Both diseases express with different radiographic and histopathologic phenotypes. Radiological features of pulmonary LCH include cystic and fibrotic changes sparing the costophrenic angles. On histology, positive staining with CD1a and Langerin is characteristic. Lung transplantation is the only therapeutical option in end-stage LCH. Radiologic manifestations of ECD include sclerotic bone lesions, retroperitoneal fibrosis, and cardiovascular involvement with infiltration of tissues by foamy histiocytes negative for CD1a. Case Report With an end-stage pulmonary LCH, a 38 years old man received a double lung transplantation (DLuTX). The explanted lungs revealed on histology clusters of Langerhans cells histiocytes positive for CD1a. Nine years after DLuTX and continuous immunosuppression, a PET-CT presented sclerotic changes in the scapula and 3rd thoracic vertebra, soft-tissue infiltration of the right atrium and circumferentially surrounding aorta and right coronary artery (“coated” aspect) and edematous thickening of the renal capsule (”hairy kidney“). The imaging findings were thus compatible with ECD. Bone biopsy showed fibrosis of the bone marrow. Biopsy of the retroperitoneum revealed fibrosis, cells inconsistent with Langerhans cells, immune-histochemically lacking CD1a expression. The mediastinal changes slowly progressed over years, requiring biopsy, which also yielded fibrotic tissue. Additionally, the patient developed a massive jaundice and anorexia. The abdominal CT showed intra- and extrahepatic cholangiectasis with circumferential soft tissue sheathing of the common bile duct (CBD). An ERCP with biopsy of the CBD revealed cells positive for langerin and CD1a. Further cranial CT showed symmetric sclerotic bone lesions. Patient died 12 years after DLuTx due to cardiovascular complications. He had never developed any dysfunction of his lung allografts. Summary Distinctive histopathologic results of various tissues at different time points and the extensive radiologic features in the same patient indicate the concomitant occurrence of two distinct histiocytoses, LCH and ECD after DLuTX.