ADOPTING ORPHAN DISEASES RARE INTERSTITIAL LUNG DISEASES

adoptingorphandiseaseskapak

PULMONARY LANGERHANS CELL HISTIOCYTOSIS

Nilüfer Yiğit1 Erhan Uğurlu2

1Pamukkale University, Faculty of Medicine, Department of Chest Diseases, Denizli, Türkiye
2Pamukkale University, Faculty of Medicine, Department of Chest Diseases, Denizli, Türkiye

Yigit N, Ugurlu E. Pulmonary Langerhans Cell Histiocytosis. In: Altinisik G, McCormack FX, editors. Adopting Orphan Diseases: Rare Interstitial Lung Diseases. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.107-121.

ABSTRACT

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by the proliferation and infiltration of CD1a+ and Langerin+ dendritic cells, typically affecting young adult smokers. Although it can occur as part of a systemic Langerhans cell histiocytosis (LCH), PLCH most often presents as an isolated pulmonary manifestation. Pathogenesis is strongly associated with cigarette smoking, which induces cytokine release, dendritic cell activation, and abnormal accumulation in distal bronchioles, leading to bronchiolocentric granulomatous inflammation and subsequent cystic lung remodeling.

Clinically, patients may present with non-specific respiratory symptoms such as dry cough, dyspnea, and chest pain; however, many cases are incidentally detected on radiological imaging. Recurrent pneumothorax is a hallmark feature and may be the initial presentation in some patients. High-resolution computed tomography (HRCT) plays a crucial role in diagnosis. Radiological findings typically include bilateral, upper-lobe-predominant nodules and irregular cysts, frequently with relative sparing of costophrenic angles. Pulmonary function tests (PFTs) may show either obstructive, restrictive, or mixed patterns, and diffusing capacity for carbon monoxide (DLco) is often reduced.

Histopathological confirmation is required in uncertain cases, with transbronchial or surgical lung biopsies demonstrating characteristic Birbeck granule–containing Langerhans cells. Recent studies have identified somatic mutations, including BRAF V600E and MAP2K1, suggesting a neoplastic component and offering potential targets for therapy.

Smoking cessation is the cornerstone of management and may lead to disease stabilization or regression. In progressive or symptomatic disease, corticosteroids or chemotherapy may be considered, although evidence is limited. Targeted therapies against BRAF mutations have shown promise in refractory cases. Lung transplantation remains a consideration for end-stage disease.

In conclusion, PLCH is a unique smoking-related interstitial lung disease with heterogeneous clinical behavior. Early diagnosis, smoking cessation, and tailored management are essential to improve outcomes and reduce complications such as pulmonary hypertension and respiratory failure.

Keywords: Pulmonary Langerhans cell histiocytosis; Histiocytosis X; Recurrent pneumothorax; Smoking; Pulmonary cysts; BRAF mutation; Cystic lung diseases

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