Clinical impact of BRAFV600E mutation in adult pulmonary Langerhans cell histiocytosis

Background: The clinical significance of the BRAFV600E mutation in tissue lesions from patients with pulmonary Langerhans cell histiocytosis (PLCH) has not been evaluated. Objective: To search for an association between BRAFV600E mutation and PLCH presentation and outcome. Methods:BRAFV600E genotyping was performed in biopsies from 83 patients with PLCH (43 males, median age 36 years, 65 current smokers). The outcome was based on variations of lung function tests and the occurrence of a new pneumothorax during the study [1]. Cox models were used to estimate the strength of association of baseline characteristics on the hazard of PLCH progression. P-values ≤0.05 denoted statistical significance. Results: A BRAFV600E mutation was detected in 31(37%) cases. No difference was identified in PLCH presentation, including smoking status (p=0.42), pneumothorax (p=0.29), or lung function (p>0.05), according to BRAF status. Patients were followed for a median time of 5 years. Thirty-eight (46%) patients experienced lung progression. BRAF status was not associated with PLCH outcome (Figure). In multivariable analysis, airflow obstruction at diagnosis was associated with increased risk of lung progression (p=0.028). Conclusions:BRAFV600E mutation was not associated with clinical features or outcome in adult PLCH patients. Airflow obstruction at diagnosis was the main factor associated with the risk of lung progression overtime.