Management Of Pulmonary Nodules Research Articles

RADAR: A Closed-Loop Quality Improvement Initiative Leveraging A Safety Net Model for Incidental Pulmonary Nodule Management

This study was conducted to assess whether patients with incidental pulmonary nodules (IPNs) received timely follow-up care after implementation of a quality improvement (QI) initiative between radiologists and primary care providers (PCPs). A QI study was conducted at an academic medical center for IPNs identified on chest imaging ordered by PCPs, performed between February 1, 2017, and March 31, 2019, and with at least one-year follow-up. A QI initiative, RADAR (Radiology Result Alert and Development of Automated Resolution), was implemented on March 1, 2018, consisting of (1) a novel, electronic communication tool enabling radiologist-generated alerts with time frame and modality for IPN follow-up recommendations, and (2) a safety net team for centralized care coordination to ensure that communication loops were closed. A preintervention IPN cohort was generated through a natural language processing (NLP) algorithm for radiology reports paired with manual chart review. A postintervention IPN cohort was identified using alerts captured in RADAR. The primary outcome was percentage of IPN follow-up alerts resolved on time (defined as receiving follow-up care within the recommended time frame), comparing pre- and postintervention IPN cohorts. Secondary outcomes included agreement between PCPs and radiologists on the recommended follow-up care plan. A total of 218 IPN alerts were assessed following exclusions: 110 preintervention and 108 postintervention. IPN timely follow-up improved from 64.5% (71/110) to 84.3% (91/108) (p = 0.001). Postintervention, there was 87.0% (94/108) agreement between PCPs and radiologists on the recommended follow-up plan. The RADAR QI initiative was associated with increased timely IPN follow-up. This safety net model may be scaled to other radiology findings and clinical care settings.

Management of Pulmonary Nodules in Oncologic Patients: AJR Expert Panel Narrative Review.

Cancer survivors are at higher risk than the general population for development of a new primary malignancy, most commonly lung cancer. Current lung cancer screening guidelines recommend low-dose chest CT for high-risk individuals, including patients with a history of cancer and a qualifying smoking history. However, major lung cancer screening trials have inconsistently included cancer survivors, and few studies have assessed management of lung nodules in this population. This narrative review highlights relevant literature and provides expert opinion for management of pulmonary nodules detected incidentally or by screening in oncologic patients. In patients with previously treated lung cancer, a new nodule most likely represents distant metastasis from the initial lung cancer or a second primary lung cancer; CT features such as nodule size and composition should guide decisions regarding biopsy, PET/CT, and CT surveillance. In patients with extrapulmonary cancers, nodule management requires individualized risk assessment; smoking is associated with increased odds of primary lung cancer, whereas specific primary cancer types are associated with increased odds of pulmonary metastasis. Nonneoplastic causes, such as infection, medication toxicity, and postradiation or postsurgical change, should also be considered. Future prospective studies are warranted to provide evidence-based data to assist clinical decision-making in this context.

MANEJO DE NÓDULOS PULMONARES INCIDENTAIS: UMA REVISÃO LITERÁRIA

Com a expansão do emprego da tomografia computadorizada, houve amplificação do número de achados incidentais em indivíduos assintomáticos, implicando na dificuldade de seguimento desses casos. Objetivou-se revisar e condensar as principais recomendações para manejo dos nódulos pulmonares encontrados incidentalmente, a partir de estudo qualitativo de nove artigos científicos da melhor qualidade. Verificou-se, na análise, que o follow-up dos nódulos pulmonares é determinado a partir da dimensão, atenuação, velocidade de crescimento e localização da lesão, além dos fatores de risco subjacentes, sendo imprescindível a elucidação desses aspectos e dos intervalos de acompanhamento do paciente.

Validation of the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a novel HRCT-based radiomic classifier for indeterminate pulmonary nodules.

Implementation of low-dose chest computed tomography (CT) lung cancer screening and the ever-increasing use of cross-sectional imaging are resulting in the identification of many screen- and incidentally detected indeterminate pulmonary nodules. While the management of nodules with low or high pre-test probability of malignancy is relatively straightforward, those with intermediate pre-test probability commonly require advanced imaging or biopsy. Noninvasive risk stratification tools are highly desirable. We previously developed the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a conventional predictive radiomic model based on eight imaging features capturing nodule location, shape, size, texture and surface characteristics. Herein we report its external validation using a dataset of incidentally identified lung nodules (Vanderbilt University Lung Nodule Registry) in comparison to the Brock model. Area under the curve (AUC), as well as sensitivity, specificity, negative and positive predictive values were calculated. For the entire Vanderbilt validation set (n=170, 54% malignant), the AUC was 0.87 (95% CI 0.81-0.92) for the Brock model and 0.90 (95% CI 0.85-0.94) for the BRODERS model. Using the optimal cut-off determined by Youden's index, the sensitivity was 92.3%, the specificity was 62.0%, the positive (PPV) and negative predictive values (NPV) were 73.7% and 87.5%, respectively. For nodules with intermediate pre-test probability of malignancy, Brock score of 5-65% (n=97), the sensitivity and specificity were 94% and 46%, respectively, the PPV was 78.4% and the NPV was 79.2%. The BRODERS radiomic predictive model performs well on an independent dataset and may facilitate the management of indeterminate pulmonary nodules.

Lung cancer screening implementation: Complexities and priorities.

Lung cancer is the number one cause of cancer death worldwide. The benefits of lung cancer screening to reduce mortality and detect early-stage disease are no longer in any doubt based on the results of two landmark trials using LDCT. Lung cancer screening has been implemented in the US and South Korea and is under consideration by other communities. Successful translation of demonstrated research outcomes into the routine clinical setting requires careful implementation and co-ordinated input from multiple stakeholders. Implementation aspects may be specific to different healthcare settings. Important knowledge gaps remain, which must be addressed in order to optimize screening benefits and minimize screening harms. Lung cancer screening differs from all other cancer screening programmes as lung cancer risk is driven by smoking, a highly stigmatized behaviour. Stigma, along with other factors, can impact smokers' engagement with screening, meaning that smokers are generally 'hard to reach'. This review considers critical points along the patient journey. The first steps include selecting a risk threshold at which to screen, successfully engaging the target population and maximizing screening uptake. We review barriers to smoker engagement in lung and other cancer screening programmes. Recruitment strategies used in trials and real-world (clinical) programmes and associated screening uptake are reviewed. To aid cross-study comparisons, we propose a standardized nomenclature for recording and calculating recruitment outcomes. Once participants have engaged with the screening programme, we discuss programme components that are critical to maximize net benefit. A whole-of-programme approach is required including a standardized and multidisciplinary approach to pulmonary nodule management, incorporating probabilistic nodule risk assessment and longitudinal volumetric analysis, to reduce unnecessary downstream investigations and surgery; the integration of smoking cessation; and identification and intervention for other tobacco related diseases, such as coronary artery calcification and chronic obstructive pulmonary disease. National support, integrated with tobacco control programmes, and with appropriate funding, accreditation, data collection, quality assurance and reporting mechanisms will enhance lung cancer screening programme success and reduce the risks associated with opportunistic, ad hoc screening. Finally, implementation research must play a greater role in informing policy change about targeted LDCT screening programmes.

Expanding Role of Stereotactic Body Radiation Therapy (SBRT) for Lung Nodules in a Prospective Screening Cohort following Multidisciplinary Evaluation

The number of pulmonary nodules identified incidentally or through lung cancer screening programs has dramatically increased. The role of radiation therapy (RT) in this patient population is not defined. Our institution established a multidisciplinary Pulmonary Nodule and Lung Cancer Screening Clinic (PNLCSC) to optimize the management of these patients. In this study, we describe the role of radiation oncologists in the multidisciplinary evaluation and management of incidental and screening-identified pulmonary nodules. This study included patients referred to the PNLCSC between 10/2012 and 9/2019. Indications for referral included a Lung-RADS 4 finding on screening CT or an incidental pulmonary nodule measuring ≥6 mm. At each clinic session, a multidisciplinary team including diagnostic/interventional radiologists, pulmonologists, medical oncologists, thoracic surgeons, and radiation oncologists made recommendations regarding the work-up, management, and follow-up of each patient. Demographic and clinical characteristics as well as data on follow-up and treatments were prospectively recorded. Collection and analysis of the data was approved by institutional IRB. Of 1,150 patients evaluated by the PNLCSC, 234 (20.3%) were screening patients, and 916 (79.7%) had incidental nodules. Among screening patients, 41 (17.5%) underwent therapeutic intervention, 31 (13.2%) with surgical resection and 10 (4.3%) with RT. RT represented 24.4% of all treatments received by screening patients. Among patients with incidental pulmonary nodules, 227 underwent therapeutic intervention, with 167 (18.2%) and 60 (6.6%) receiving surgery and RT, respectively. The overall rate of patients undergoing RT was stable over time, ranging from 6.0% in 2014-2016 to 6.7% in 2017-2019. However, the rate of screening patients receiving RT increased from 1.7% in 2014-2016 to 4.3% in 2017-2019. Among the 70 RT patients, 58 (82.9%) were treated for clinically diagnosed lung cancer, while 12 (17.1%) had biopsy-proven non-small cell lung cancer. Nearly all (95.7%) patients treated with RT, and 100% of those with screening detected nodules, had stage I disease and received SBRT to a median dose of 50 Gy (range 48–50 Gy) in 5 fractions (range 4–5 fractions). Compared to patients who underwent surgical intervention, those receiving RT were older (median age 67.6 vs. 73.8 years, p < 0.001) and more likely to be current/former smokers (76.8% vs. 95.7%, p = 0.001). In this large prospective cohort, 24.4% of all screening patients with lung nodules requiring intervention were treated with SBRT. The high percentage of patients receiving RT without biopsy may reflect careful multidisciplinary evaluation. Altogether, this unique data highlights the important role radiation oncologists can play in the diagnosis and treatment of patients with screening-detected and incidental lung nodules.

Progress of Lung Cancer Screening with Low Dose Helical Computed Tomography

肺癌严重危害人类健康，呈现疾病负担重、晚期肺癌占比大和5年生存率低的现状。因此，开展肺癌人群筛查以提高早诊早治至关重要。美国肺癌筛查试验（National Lung Screening Trial, NLST）公布的低剂量螺旋计算机断层扫描（low dose helical computed tomography, LDCT）筛查可以降低肺癌死亡率，给肺癌的早诊早治带来了希望。近年来，LDCT肺癌筛查研究不断取得新进展。然而，目前关于LDCT用于肺癌筛查是否可以大规模推广应用仍存在争议。本文将从LDCT肺癌筛查的发展史、高危人群选择、结节管理、筛查效果、筛查接受度和成本效益等方面进行综述。

Delivering low-dose CT screening for lung cancer: a pragmatic approach

Lung cancer kills an estimated 35 000 people in the UK every year. Despite the improvements in treating late-stage disease, lung cancer outcomes have changed little in the last 40...

Physician Agreement With Recommendations Contained in a National Guideline for the Management of Incidental Pulmonary Nodules: A Case Study

Since the 1980s, there has been a growing emphasis on the use of evidence-based practice guidelines in medicine [1]. However, national guidelines are based on evidence of variable quality, including non-evidence-based common medical practice. Although attempts are made to ensure impartial recommendations during guideline development, if there is lack of sufficient clinical evidence, some recommendations could be the result of inadvertent bias [2]. At times, guidelines from different organizations on the same clinical entity can also contradict each other [3].

Impact of the Percepta Genomic Classifier on Clinical Management Decisions in a Multicenter Prospective Study

The Percepta genomic classifier has been clinically validated as a complement to bronchoscopy for lung nodule evaluation. The goal of this study was to examine the impact on clinical management decisions of the Percepta result in patients with low- and intermediate-risk lung nodules. A prospective "real world" registry was instituted across 35 US centers to observe physician management of pulmonary nodules following a nondiagnostic bronchoscopy. To assess the impact on management decisions of the Percepta genomic classifier, a subset of patients was analyzed who had an inconclusive bronchoscopy for a pulmonary nodule, a Percepta result, and an adjudicated lung diagnosis with at least 1 year of follow-up. In this cohort, change in the decision to pursue additional invasive procedures following Percepta results was assessed. A total of 283 patients met the study eligibility criteria. In patients with a low/intermediate risk of malignancy for whom the clinician had designated a plan for a subsequent invasive procedure, a negative Percepta result down-classified the risk of malignancy in 34.3%of cases. Of these down-classified patients, 73.9%had a change in their management plan from an invasive procedure to surveillance, and the majority avoided a procedure up to 12months following the initial evaluation. In patients with confirmed lung cancers, the time to diagnosis was not significantly delayed when comparing Percepta down-classified patients vspatients who were not down-classified (P= .58). The down-classification of nodule malignancy risk with the Percepta test decreased additional invasive procedures without a delay in time to diagnosis among those with lung cancer.

Assessing the Accuracy of a Deep Learning Method to Risk Stratify Indeterminate Pulmonary Nodules.

Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.Objectives: To develop and validate a deep learning method to improve the management of IPNs.Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions.Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4–90.7%) and 91.9% (95% CI, 88.7–94.7%), compared with 78.1% (95% CI, 68.7–86.4%) and 81.9 (95% CI, 76.1–87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts.Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.

Approaches to lung nodule risk assessment: clinician intuition versus prediction models.

Pulmonary nodules are increasingly identified on imaging exams performed for a number of clinical presentations and can pose a diagnostic problem for clinicians. Guideline-directed management algorithms are structured on nodule pre-test probability of malignancy. The risk of malignancy can be clinician-assigned or calculated utilizing validated risk prediction calculators. Once pre-test probability of cancer is estimated, nodule management options range from a conservative approach with serial imaging to more invasive measures including biopsy procedures or surgical resection. Here we review pulmonary nodule management with a focus on methods for assigning malignancy risk and highlight novel ways currently under active research to improve nodule risk assessment and management.

Advances in Diagnosis and Management of Subcentimeter Pulmonary Nodules

随着高分辨多层螺旋计算机断层扫描(computed tomography, CT)的广泛应用和定期体检的普及，临床诊断的肺部亚厘米结节的数量日益增多。肺部亚厘米结节的恶性概率和恶性程度较低，诊治难度较高，易误诊、漏诊，因此肺部亚厘米结节的定性和诊疗策略一直为临床工作的重点难点和研究热点。本文对肺部亚厘米结节病变的性质评估、处理治疗及预后等方面的进展进行了综述，并对肺部亚厘米结节的临床诊疗进行了总结及分析。

Genomic characterization of sub-centimeter pulmonary nodules.

e13530 Background: There has been a dramatic increase in the detection of indeterminate pulmonary nodules (IPNs), many of which are 10 mm or less in diameter. The management of subcentimeter pulmonary nodules remains controversial. Deciphering the genomic landscape of subcentimeter pulmonary nodules will provide critical insights to the mechanisms of carcinogenesis and pave the way for the early prevention and interception of lung cancer. Methods: We subjected 439 IPN samples including 249 subcentimeter pulmonary nodules (≤10 mm in diameter) and 190 larger pulmonary nodules (&gt;10 and ≤30mm in diameter) to deep next generation sequencing by using customized panels of 1021 genes. Clinical parameters of these IPNs were collected. The genomic landscape of subcentimeter pulmonary nodules and differences from that of larger pulmonary nodules were defined. Results: The proportions of atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (ADC) in the subcentimeter group and the larger nodule group were 2.81% vs 0.00%, 13.25% vs 0.80%, 28.92% vs 4.82% and 55.02% vs 70.68%, respectively. The most commonly mutated genes in subcentimeter group were in EGFR, ERBB2, BRAF, MED12 and MAP2K1. Compared with the larger nodule group, the subcentimeter nodule group had lower TMB ( p&lt; 0.0001), lower mutation frequencies in EGFR, TP53, RBM10, and SMARCA4 ( p&lt; 0.05), but higher mutation frequencies in ERBB2, BRAF, MAP2K1, and TSC1 ( p&lt; 0.05). In the subset of ADC, the subcentimeter nodule group had lower TMB ( p&lt; 0.0001), lower mutation frequencies in EGFR, TP53, RBM10, and PIK3CA ( p&lt; 0.05), but higher mutation frequencies in ERBB2, BRAF ( p&lt; 0.05). Clonal index analysis of driver genes in lung adenocarcinoma showed that the larger nodule group had more driver mutations, but the clonality index of BRAF was higher in the subcentimeter group ( p= 0.0014). Furthermore, in the subcentimeter nodule group, the mutation frequency of BRAF was significantly higher in pre-invasive group (AAH/AIS) than that in the invasive group (IAC). And BRAF and EGFR were significantly mutually exclusive ( q&lt; 0.001) in subcentimeter nodules, which showed the subgroup with BRAF mutations was a special subtype. Conclusions: Our results provided the distinct mutation pattern of subcentimeter nodules and showed that BRAF could play different roles in early phase of lung carcinogenesis. It would be helpful for understanding the genomic evolution mechanisms underlying the progression and invasiveness of early lung adenocarcinoma.

Integrated Biomarker for the Management of Indeterminate Pulmonary Nodules

Integrated Biomarker for the Management of Indeterminate Pulmonary Nodules

6 - SUMMIT study: protocolised management of pulmonary nodules in a lung cancer screening cohort

6 - SUMMIT study: protocolised management of pulmonary nodules in a lung cancer screening cohort

Integrated, Multidisciplinary Management of Pulmonary Nodules Can Streamline Care and Improve Adherence to Recommendations.

Every year millions of pulmonary nodules are discovered incidentally and through lung cancer screening programs. Management of these nodules is often suboptimal, with low follow-up rates and poor provider understanding of management approaches. There is an emerging body of literature about how to optimize management of pulmonary nodules. The Pulmonary Nodule and Lung Cancer Screening Clinic (PNLCSC) at Massachusetts General Hospital was founded in 2012 to manage pulmonary nodules via a multidisciplinary approach with optimized support staff. Recommendations from clinic providers and treatment details were recorded for all patients seen at the PNLCSC. Adherence to recommendations and outcomes were also tracked and reviewed. From October 2012 to September 2019, 1,136 patients were seen at the PNLCSC, each for a mean of 1.8 appointments (range, 1-10). A total of 356 procedures were recommended by the clinic and 271 patients were referred for surgery and/or radiation. The majority of interventions (74%) were recommended at the initial PNLCSC appointment. In total, 211 patients (19%) evaluated at the PNLCSC had pathologically confirmed pulmonary malignancies or were treated empirically with radiation. Among patients followed by the clinic, the adherence rate to clinic recommendations was 95%. This study shows how a multidisciplinary approach to pulmonary nodule management can streamline care and optimize follow-up. The PNLCSC provides a template that can be replicated in other health systems. It also provides an example of how multidisciplinary approaches can be applied to other complex conditions. IMPLICATIONS FOR PRACTICE: This work demonstrates how an integrated, multidisciplinary approach to management of pulmonary nodules can streamline patient care and improve adherence to provider recommendations. This approach has the potential to improve patient outcomes and reduce health care costs.

Pre-surgical lung biopsy in management of solitary pulmonary nodules: a cost effectiveness analysis

Objectives: Tissue diagnosis prior to thoracic surgery with curative intent is vital in thoracic lesions concerning for lung cancer. Methods of obtaining tissue diagnosis are variable within the United Kingdom.Methods: We performed a model-based analysis to identify the most efficient method of diagnosis using both a health care perspective. Our analysis concerns adults in the UK presenting with a solitary pulmonary nodule suspicious for a primary lung malignancy, patients with more advanced disease (for example lymph node spread) were not considered. Model assumptions were derived from published sources and expert reviews, cost data were obtained from healthcare research group cost estimates (2016–17). Outcomes were measured in terms of costs experienced to healthcare trusts.Results: Our results show that CT guided percutaneous lung biopsy using an ambulatory approach, is the most cost-effective method of diagnosis. Indeed, using this approach, trust experience approximately half of the cost of an approach of surgical lung biopsy performed at the time of potential resection (‘frozen section’).Limitations and conclusions: Whilst this analysis is limited to the specific scenario of a solitary pulmonary nodule, these findings have implications for the implementation of lung cancer screening in the UK, which is likely to result in increased numbers of patients with such early disease.

P1.01-131 The Comparison Between Non-Intubated and Intubated Anesthesia Video-Assisted Thoracoscopic Surgery: A Meta-Analysis

It remains unclear whether the feasibility and safety of non-intubated VATS under LA is comparable or advantageous compared with conventionally intubated VATS under GA in different thoracic diseases. Consequently, a meta-analysis was conducted with the aim of assessing whether non-intubated VATS offered better perioperative outcomes over intubated VATS in terms of diverse thoracic diseases, including pulmonary nodules, spontaneous pneumothorax, and malignant pleural effusion. A comprehensive search of online databases was performed. Intraoperative and postoperative variables were compared between the subgroups. The odds ratio (OR) or SMD and its 95% CI was calculated using a random effects model. Heterogeneity across studies was examined by the Cochran Q chi-square test and the I2 statistic. A total of 15 eligible studies including 1964 patients were recruited. Each included study had comparable baseline characteristics and the same surgical procedures except for the regimens of anesthesia and ventilation. Non-intubated anesthesia VATS was performed on 959 patients, whereas the other 1005 patients underwent intubated VATS. In the overall analysis, patients who underwent non-intubated surgery associated with significant shorter postoperative hospital stays (SMD=-0.36, p<0.001), postoperative fasting time (SMD=-2.80, p<0.001) and anesthesia time as well as lower rates of mortality, postoperative overall, respiratory, and cardiovascular complications. Patients underwent non-intubated surgery also manifested a trend toward shorter operative time and less blood loss with no significant significance. Non-intubated VATS was confirmed as a safe and feasible alternative to intubated VATS and potentially provided a more rapid postoperative rehabilitation than intubated VATS overall and specifically in the management of pulmonary nodules, spontaneous pneumothorax, and malignant pleural effusion. Future large-scale multicenter studies are supposed to focus on prospective validation of feasibility and safety and immunological changes for non-intubated thoracoscopic approach

WHERE THERE IS NOT SMOKE THERE IS STILL FIRE: A CASE OF PULMONARY LANGERHANS CELL HISTOICYTOSIS IN A FORMER SMOKER WITH A HISTORY OF MULTIPLE MALIGNANCIES

SESSION TITLE: Diffuse Lung Diseases SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Pulmonary langerhans cell histiocytosis (PLCH) is a cystic interstitial lung disease (ILD) that occurs almost exclusively in smokers. We present a case of PLCH in a former smoker with a history of multiple previous non-pulmonary malignancies. CASE PRESENTATION: A 71 year old African American female presented to us for management of multiple pulmonary nodules discovered on a PET/CT scan done for malignancy monitoring. CT chest showed multiple areas of reticulo-nodular densities with few cysts in bilateral upper lobe. She noted only cough and dyspnea on moderate exertion. No other organs were noted to be PET-avid. She has a history of stage I breast cancer status post bilateral mastectomy, stage II adenocarcinoma of the colon status post right hemicolectomy, and was a previous 1 pack per day smoker quiting in 1998. This was confirmed on urine and saliva testing for nicotine and cotinine. CT-guided transthoracic fine needle aspiration was suggestive of PLCH but subsequent trans-bronchial biopsy was non diagnostic. The time since she quit smoking cast doubt on her diagnosis, so a video assisted thoracoscopic lung biopsy was performed to evaluate for malignancies. Pathology revealed langerhans cells that stained positive for S-100 and CD1a. Given her history of previous malignancies and lack of current smoking, genetic analysis was done revealing a B-RAFV600E mutation. Her symptoms and pulmonary function tests declined, and she was started on supplemental oxygen. She did not respond to oral corticosteroids. She was referred to hematology and started on Dabrafenib, a B-RAF inhibitor. At her three month follow up visit, the patient noted improvement of her dyspnea, cough, and a decrease in her supplemental oxygen requirement. DISCUSSION: PLCH occurs almost exclusively in current and former smokers and the mainstay of treatment is smoking cessation, though immunosuppression is sometimes used. The lag time between cessation and development of disease has not been quantified. Recently, B-RAFV600E mutations have been identified in LCH and in several cases of PLCH. LCH, though more common in children, can occur in adults before, during, or after other malignancies, but is rarely limited to the lungs. In patients with progressive disease despite removal of smoke exposure, cladiribine, a purine analogue cytotoxic to lymphocytes, has been used to some success. The discovery of the B-RAFV600E mutation has also opened the door to treatment with BRAF inhibitors, such as in our patient. CONCLUSIONS: This case highlights the development of PLCH in a patient who has not smoked in 10 years, but has had multiple prior malignancies putting her at risk for the development of LCH. The presence of the B-RAFV600E mutation should be evaluated in patients with PLCH and LCH, as it represents a possible treatment for those who are not smoking and those whose disease progresses despite standard therapy. Reference #1: Roden, A., Yi, E.S. Pulmonary Langerhans Cell Histiocytosis: An update from the pathologist’s perspective. Arch Pathol Lab Med. 2016 Mar;140(3):230-40. DISCLOSURES: No relevant relationships by Scott Blumhof, source=Web Response No relevant relationships by Kevin Dsouza, source=Web Response No relevant relationships by Tejaswini Kulkarni, source=Web Response No relevant relationships by Amitkumar Mehta, source=Web Response