PULMONARY LANGERHANS CELL HISTIOCYTOSIS
Pulmonary Langerhans cell histiocytosis (PLCH) of the lung primarily affects young adults between the ages of 20 to 40 years. Whites are affected more commonly than individuals of African or Asian descent. The pathogenesis of PLCH is unknown. The near universal association of PLCH with cigarette smoking strongly implies a causative role.
The clinical presentation is variable, from an asymptomatic state (16%) to a rapidly progressive condition. The duration of illness is usually less than 1 year before diagnosis. The most common clinical manifestations at presentation are cough (56%-70%), dyspnea (40%- 87%), chest pain that is frequently pleuritic (10%-21%), fatigue (30%), weight loss (20%-30%), and fever (15%). Pneumothorax occurs in about 25% of patients and is occasionally the ﬁrst manifestation of the illness. Pulmonary hypertension is common. Hemoptysis occurs in approximately 13% of cases and should prompt consideration of superimposed infection or malignancy. In addition, diabetes insipidus, secondary to hypothalamic involvement, may be present in approximately 15% of patients and is believed to portend a worse prognosis. Cystic bone lesions are present in 4% to 20% of patients and may produce localized pain or a pathologic bone fracture. The physical examination ﬁndings are usually normal. Routine laboratory studies are nonspeciﬁc.
The radiographic features vary depending on the stage of the disease. The combination of ill-deﬁned or stellate nodules (2-10 mm in size), reticular or nodular opacities, upper zone cysts or honeycombing, preservation of lung volume, and costophrenic angle sparing are highly speciﬁc for PLCH. High-resolution computed tomography (HRCT) lung scanning that reveals the combination of nodules and thin-walled cysts with a mid to upper zone predominance and interstitial thickening in a young smoker is so characteristic that it can be diagnostic of PLCH. Serial chest CT scanning suggests a sequence of progression from nodules to cavitating nodules to cystic lesions.
Physiologically, the most prominent and frequent pulmonary function abnormality is a markedly reduced DLCO (diffusing capacity for carbon monoxide), but varying degrees of restrictive disease, airﬂow limitation, and diminished exercise capacity are described. Whereas predominantly nodular disease is usually associated with normal or restrictive pulmonary function tests, cystic disease is more likely to be associated with airﬂow limitation and hyperinﬂation. Limitations in activity and exercise intolerance out of proportion to pulmonary function abnormalities are commonly present. Gas exchange abnormalities, reﬂected by a worsening alveolar–arterial oxygen difference with increasing exercise, are seen in the majority of patients.
The ﬁnding of more than 5% Langerhans cells on bronchoalveolar lavage strongly suggests the diagnosis of PLCH. Transbronchial biopsy can be sufﬁcient to make the diagnosis; however, a substantial number of false-negative or nondiagnostic biopsies may result from sampling error and insufﬁcient tissue. Video thoracoscopic lung biopsy is generally deﬁnitive. Langerhans cells can be recognized by their characteristic staining for S-100 protein. Tissue immunostaining with the monoclonal antibody OKT-6 (CD1a) distinguishes Langerhans cells from other histiocytes and can be a useful adjunct in difﬁcult cases. These cells also demonstrate staining with the monoclonal antibody MT-1.
Smoking cessation is the key treatment, resulting in clinical improvement in many subjects. Immunosuppressive therapies (i.e., glucocorticoids and cytotoxic agents) are of limited value. Lung transplantation should be considered in patients with advanced disease. Recurrence of the condition in the transplanted lung may occur. Estimated 5- and 10-year survival rates are 74% and 64%, respectively. Respiratory failure is the most common cause of death. The other major cause of death is malignancy, primarily of hematologic or epithelial origin.