Chapter 61: Pulmonary Langerhans’ Cell Histiocytosis

Introduction

Pulmonary Langerhans’ cell histiocytosis is part of a large spectrum of disorders characterized by abnormal organ infiltration by Langerhans’ cells, which are highly differentiated cells in the monocyte-macrophage line that are also found in the dermis of the skin, reticuloendothelial system, pleura, and lung. Clinically, these disorders vary greatly, ranging from mild, single-organ disease to acute, disseminated life-threatening presentations. Depending on the sites involved and severity, the entity now referred to as Langerhans’ cell histiocytosis has been previously defined as eosinophilic granuloma, Hand–Schüller–Christian disease, and Letterer–Siwe disease. A more recent and simplified system of classification includes Langerhans’ cell histiocytosis with single-organ involvement or with multisystem involvement.¹

Pulmonary Langerhans’ cell histiocytosis is an uncommon, smoking-related, interstitial lung disease that primarily affects young adults. Usually, lung involvement occurs in isolation; less frequently, involvement of other systems, for example, bone, skin, pituitary gland, is seen. Although there is some similarity to other diffuse interstitial lung diseases, pulmonary Langerhans’ cell histiocytosis, as a specific disease entity, is distinct in its clinical, radiologic, and pathologic manifestations.

Epidemiology

The true incidence and prevalence of pulmonary Langerhans’ cell histiocytosis are unknown. Studies in which diagnoses were confirmed by lung biopsy showed that pulmonary Langerhans’ cell histiocytosis is an uncommon, if not rare, disease.^2,3 A Japanese study of discharge diagnoses in hospitals with 200 beds estimated the disease prevalence at 0.27 and 0.07 per 100,000 population in males and females, respectively.⁴ These reports may underestimate the true incidence of the disease, as lung biopsy is not performed in all cases of pulmonary Langerhans’ cell histiocytosis, and some patients exhibit no symptoms or experience spontaneous remission. Occupational or geographical predisposition has not been reported. Of note, nearly all affected persons report a current or prior smoking history. Thus, tobacco smoke is thought to play a key role in the pathogenesis of pulmonary Langerhans’ cell histiocytosis of adulthood. Other diffuse parenchymal lung diseases associated with cigarette smoking are respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonitis.⁵

Most patients with pulmonary Langerhans’ cell histiocytosis present to medical attention in young adulthood (20–40 years of age). Pulmonary Langerhans’ cell histiocytosis, however, may present in any age group. Older literature suggested a male preponderance; however, recent literature suggests an equal sex distribution, with increasing presentations in middle age. In general, women tend to present at an older age than men. These differences in prevalence may reflect the changing smoking habits of women in our society. For unknown reasons, whites are affected much more commonly than blacks or Asians, in whom this disease is very rare.

Pulmonary Langerhans’ cell histiocytosis has reportedly been associated with a number of malignancies and may be a premalignant condition. Lymphoma, both Hodgkin’s and non-Hodgkin’s, and other hematologic and solid cancers have been reported in association with pulmonary Langerhans’ cell histiocytosis.⁶ However, the evidence regarding ...