Pulmonary Langerhans Cell Histiocytosis

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare clonal myeloid neoplasm, not simply an inflammatory reaction to cigarette smoke. Abnormal myeloid-derived Langerhans cells acquire constitutive activation of the MAPK-ERK pathway; BRAF V600E is found in approximately half of pulmonary lesions, MAP2K1 mutations in another roughly 20%, and ERK activation is demonstrable in more than 90% of cases. The 2022 WHO classification therefore places Langerhans cell histiocytosis with the myeloid and histiocytic/dendritic cell neoplasms. The clinical association is striking: approximately 90–95% of adults are current or former tobacco smokers, and concurrent cannabis smoking is reported in a substantial minority. Most patients present in the third or fourth decade, although age alone does not establish or exclude the diagnosis. Tobacco smoke, vaping or e-cigarette exposure, cannabis, and other inhaled substances should all be assessed because continued inhalational exposure can sustain disease activity. The abnormal cells accumulate around small airways. Early bronchiolocentric lesions form nodules, some of which cavitate; later lesions remodel into thick-walled and then thin-walled cysts. This sequence explains the characteristic imaging pattern and the major complications: - airway and interstitial...