Cigarette smoke is associated with the development of severe, diffuse interstitial inflammation, resulting in interstitial lung disease (ILD).1 A distinct entity termed smoking-related ILD, occurring exclusively in smokers, includes: Pulmonary Langerhans cell histiocytosis (PLCH), respiratory bronchiolitis (RB)-associated interstitial lung disease (RB-ILD), and desquamative interstitial pneumonia (DIP). These three diseases have overlapping diagnostic features, suggesting that they may represent a spectrum of lung disease from cigarette smoke.2 We report a case of histologically-proven PLCH and RB-ILD in an active smoker.
A 63-year-old male, active smoker, was seen with increasing dyspnea. He required home oxygen and his medications included albuterol, ipratropium, and mometasone inhalers with variable compliance. He molded polyurethane foam for 24 years and had worked with organic solvents in the past. He denied any exposure to dust, animals, pets, or mold. On examination, he had an oxygen saturation of 84%. Chest examination revealed bilateral inspiratory crackles. Pertinent laboratory testing revealed a hemoglobin of 18.6 g/dL. Chest radiograph showed bilateral diffuse reticular markings. High-resolution computed tomography (HRCT) showed severe paraseptal and centrilobular emphysema, with diffuse cysts and scattered subcentimeter nodules (Fig 1). Pulmonary function tests revealed normal static and dynamic lung functions with severely reduced diffusing capacity of the lung for carbon monoxide (DLco) of 21%. Open lung biopsy showed scattered alveolar macrophages containing intracytoplasmic brown pigment in a peribronchial distribution, with chronic inflammation of the terminal bronchioles and alveolar ducts, consistent with histologic manifestations of RBILD. Additionally, there were bilateral nodular aggregates of cells with grooved nuclei and abundant eosinophilic cytoplasm, associated with alveolar cell hyperplasia and focal interstitial fibrosis. These cells were positive for CD1a and S100, characteristic of Langerhans cell histiocytosis (Fig. 2).
RBILD and PLCH are rare ILDs associated with cigarette smoke, with distinct radiographic features and histopathologic findings. Chest radiographs in patients with RBILD demonstrate diffuse reticulonodular interstitial infiltrates. HRCT reveals patchy ground glass opacities, fine nodules, intralobular and interstitial thickening, or emphysema. The classic histologic findings in RBILD are the accumulation of pigmented alveolar macrophages in a bronchiolocentric distribution with mild bronchiolar fibrosis. PLCH, on the other hand, is characterized by multiple cysts and nodules predominantly in the middle to upper lung zones, with interstitial thickening. Langerhans cells are unique in their histopathology with their characteristic staining for S-100 protein, CD1a, and monoclonal antibody MT-1. The diagnosis of PLCH can be confirmed by the presence of Birbeck granules under electron microscopy. However, despite the identifying characteristics of these two separate entities, there are increasing reports of patients with diagnosis of these occurring concurrently. In a retrospective study of smokers with biopsy proven PLCH, coexistant RBILD/DIP-like changes were ubiquitous.2 This finding raises the consideration that all smoking-related ILDs are ultimately the same disease with variable phenotypic expressions, and there may be a subgroup of patients with RBILD and/or DIP that is more susceptible in developing PLCH. The treatment for all smoking-related ILDs is smoking cessation, while the role of corticosteroid therapy and immunosuppressive agents has not been defined.
The mechanism of this tobacco-related injury in the development of ILD is not well understood. This case of an active smoker with histologically-proven PLCH and RBILD is further evidence of the overlapping characteristics of smoking-related ILDs.
Lillian Tseng, No Financial Disclosure Information; No Product/Research Disclosure Information