Pulmonary Langerhans Cell Histiocytosis: Insights into Pathogenesis, Diagnostic Challenges, and Management Strategies

Peter Krisdiyanto (Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.)
Iin Noor Chozin (Dr. Saiful Anwar General Hospital, Malang, Indonesia.)
Sastia Rakhma (Institute of Clinical Medicine, Faculty of Medicine, National Cheng Kung University, Tainan, Taiwan.)

Jurnal Respirasi (JR)
Vol. 12 No. 3 (2026): September 2026

Introduction: Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung disease strongly linked to cigarette smoking, characterized by nodular and cystic lesions predominantly in the upper and middle lung zones. The disease course is heterogeneous, ranging from spontaneous remission to progressive respiratory failure, with diagnostic and therapeutic challenges requiring a multidisciplinary approach. Methods: This narrative review synthesized evidence from peer-reviewed journals and updated guidelines published in the last decade, emphasizing studies within the past five years. Relevant articles were identified through electronic databases focusing on epidemiology, pathogenesis, diagnostic modalities, and management strategies of PLCH. Results: Cigarette smoke is the main environmental trigger, sustaining Langerhans cell proliferation and chronic inflammation. Molecular studies demonstrate recurrent somatic mutations, particularly BRAF V600E and MAP2K1, confirming PLCH as an inflammatory myeloid neoplasm and supporting targeted therapy. High-resolution computed tomography (HRCT) remains the imaging cornerstone, showing nodular and cystic changes, while histopathology with immunohistochemistry (CD1a, langerin, S100) is the diagnostic gold standard. Pulmonary function testing, bronchoalveolar lavage, and molecular assays add diagnostic precision. Management emphasizes smoking cessation as the primary intervention, with variable outcomes from glucocorticoids and chemotherapy. Targeted therapy with BRAF and MEK inhibitors shows promise in mutation-positive patients, though long-term safety is still under study. For advanced disease, pulmonary hypertension management and lung transplantation are considered. Conclusion: PLCH illustrates the interaction between environmental exposure and molecular oncogenesis. Early diagnosis via HRCT and molecular confirmation is essential, smoking cessation remains central, and ongoing research into biomarkers and targeted interventions may improve personalized outcomes.