95 - Pulmonary Langerhans Cell Histiocytosis and Other Rare Diffuse Infiltrative Lung Diseases

Abstract

Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon diffuse lung disease usually manifesting in young adult smokers. Up to one-half of all PLCH cases are associated with the BRAFV600E mutation that results in persistent activation of myeloid cell survival pathways, thereby enabling their activation and persistence. These myeloid cells infiltrate the lungs and secondarily cause inflammatory cell recruitment and diffuse lung disease. Imaging with high-resolution chest computed tomography may reveal nodular or cystic lesions, and sometimes a characteristic combination of both, predominantly in the middle and upper lung regions. Biopsy of the lung is required for definitive diagnosis. Imaging with positron emission tomography may help identify disease outside of the chest that is present in 10–15% of patients with PLCH. Management should be individualized and includes smoking cessation when applicable, screening for and management of complications such as secondary pulmonary hypertension and pneumothorax, and use of advanced therapies (cladribine or BRAF-inhibitor therapy in patients with BRAF mutations) for patients with progressive disease. Lung manifestations are seen in a variety of other rare infiltrative disorders, including neurofibromatosis, Niemann-Pick and Gaucher diseases (lysosomal storage disorders), dyskeratosis congenita, Hermansky-Pudlak syndrome, and pulmonary alveolar microlithiasis. Salient features of these rare diffuse lung disorders are included in this chapter.