Pulmonary Langerhans cell histiocytosis (PLCH) is an interstitial lung disease characterized by an abnormal proliferation of Langerhans cells. While Langerhans cell histiocytosis (see Chapter 92) may involve the lung as part of a systemic hematopoietic neoplasm, PLCH is distinct in that it occurs mainly in smoking adults in whom pulmonary involvement is the sole or predominant manifestation of the disease.^1,2

PLCH is a rare disease; precise data regarding prevalence are not available, partly because it is not always biopsied or histologically documented. A large series of hundreds of patients undergoing surgical lung biopsies for diffuse lung disease reported PLCH in 4% to 5% of biopsies for interstitial lung disease.³ In a series of PLCH diagnosed on clinical and radiologic findings, the incidence was nearly 7%.⁴

PLCH, in contrast to systemic LCH, has been considered a nonneoplastic process.⁵ PLCH is thought to be a manifestation of an immune response to an unknown exogenous antigen related to cigarette smoke.^6,7 Since only a small percentage of cigarette smokers develop PLCH, underlying host factors must be a factor.⁸ Cigarette smoking is associated with an increase in dendritic cells and Langerhans cells in the alveolar epithelium^9,10 and induces the secretion of bombesin-like peptides by pulmonary neuroendocrine cells.¹¹ Oligoclonal expansion would contribute to the maintenance of Langerhans cells at the sites of disease.⁵ Recently, BRAF V600E mutation and BRAF expression have been reported in a subset (up to 28%) of PLCH suggesting that some cases do represent a true clonal process and might be true neoplasms.¹²

Although classified as an interstitial lung disease, PLCH affects small airways, explaining the exquisite bronchiolocentric distribution of the nodules. The cystic lesions are thought to arise from the destruction of the bronchioles.^13,14

PLCH affects young adults between the ages of 20 and 70 years, with a median age of 33 years.⁷ There is no gender predilection, but there may be a predominance in Caucasians.⁸ As nearly all patients are current or former smokers, PLCH is considered a form of smokingrelated interstitial lung disease. Most patients with PLCH are symptomatic. Spontaneous pneumothorax occurs in nearly 25% of patients. Extrapulmonary involvement is rare in PLCH.⁷ Pulmonary function tests are variable. The most common abnormality is reduced diffusion capacity. Restriction, obstruction, or mixed ventilatory defects are also seen.

The coexistence of upper lung nodules and cysts in a smoker is highly suggestive of PLCH (Fig. 24.1).¹⁵ Cystic lesions are the most common high-resolution CT feature and measure from <10 mm in diameter to 20 mm. Cysts are often seen in association with nodules, although reticulonodular densities are relatively uncommon. The cysts occur predominantly in upper lung zones.⁸ Rarely, PLCH can present as a solitary macronodule or an obstructing endobronchial tumor.^16,17