eMedicine Specialties > Radiology > Chest

Eosinophilic Granuloma, Thoracic

Author: Scott C Williams, MD, Section Chief, Nuclear Medicine Associate Attending Radiologist, Advanced Radiology Consultants, Bridgeport Hospital
Coauthor(s): Matthew D Gilman, MD, Thoracic Radiologist, Department of Radiology, Massachusetts General Hospital
Contributor Information and Disclosures

Updated: May 5, 2009

Introduction

Background

Langerhans cell histiocytosis (LCH) describes a group of syndromes that share the common pathologic feature of infiltration of involved tissues by Langerhans cells. Typically, the skeletal system is involved, with a characteristic lytic bone lesion form that occurs in young children or a more acute disseminated form that occurs in infants (see Eosinophilic Granuloma, Skeletal). Pulmonary involvement is not unusual in systemic forms of LCH, but symptoms are rarely a prominent feature.

Frequency

United States

Langerhans cell histiocytosis (LCH; eosinophilic granuloma) is rare; it constitutes only 3.4-5% of chronic diffuse interstitial lung disease.

International

The international prevalence is generally considered equal to that in the US.

In a study of Langerhans cell histiocytosis (LCH) in patients aged 0-16 years in the United Kingdom and Ireland over a 2-year period, 94 cases were identified. The incidence of LCH in children aged 0-14 years was 4.1 per million per year. Single-system disease (primarily bony involvement) accounted for 73% of cases; and 27% had multisystem disease, of whom 7% had involvement of the liver, lung, spleen, or bone marrow. Three of the patients died.¹

Mortality/Morbidity

The course of pulmonary disease varies. Remission occurs in approximately 25-30% of patients, stabilization in 30-50%, and progression of the disease in 25-30%. Death from respiratory failure or cor pulmonale occurs in 5%.

Asymptomatic or minimally symptomatic patients tend to have the best outcomes. Decreased survival is associated with the following:

• Diagnosis made at very young or very old age
• Persistence of systemic symptoms
• Recurrent pneumothoraces
• Extrathoracic disease (except bone lesions)
• Diffuse cystic lesions on chest radiograph
• Lower forced expiratory volume in 1 second/forced vital capacity ratio at diagnosis
• Higher respiratory volume/total lung volume ratio at diagnosis
• Need for steroid therapy

Race

Langerhans cell histiocytosis (LCH; eosinophilic granuloma) usually affects whites. The disorder is rare in blacks.

Sex

Male-to-female ratio is equal, although young men appear to have the worst prognosis.

Age

Most patients with isolated pulmonary LCH (eosinophilic granuloma, thoracic) are young adults aged 20-40 years.

Presentation

Pathophysiology

Pulmonary involvement in Langerhans cell histiocytosis (LCH) is characterized by a granulomatous infiltration of the alveolar septa and bronchial walls by Langerhans cells that produces small, 1-5 mm nodules. The infiltrate can result in progressive lung destruction and widespread cystic change.

Langerhans cells are one part of the widespread system of "dendritic cells" that arise from bone marrow stem cells and normally are present in the lung. Cytoplasmic immunostaining with S100 antigen distinguishes them from histiocytes.

Other unique features of Langerhans cells are (1) the presence of Birbeck granules (rod-shaped intracellular structures identified by electron microscopy) and (2) the presence of CD1a antigen on the cell surface. As a result of these features, some authors prefer to term the disorder Langerhans cell "granulomatosis," since the Langerhans cell is not a member of the mononuclear phagocytic system (ie, not a macrophage or "histiocyte"). Since Langerhans cells may be identified in several pathologic pulmonary processes, the presence of pulmonary Langerhans cells is not diagnostic of pulmonary LCH (eosinophilic granuloma, thoracic).

A strong association exists between pulmonary LCH and smoking (90-95% of patients are smokers, and many are heavy smokers). Cessation of smoking often brings symptomatic improvement and radiologic resolution.²

Pulmonary LCH has also been reported in patients who received radiation therapy and/or chemotherapy for Hodgkin’s disease or other lymphomas.³ No known genetic factors predispose patients to pulmonary LCH.

Etiology

Etiology of the disorder is not known. The bronchocentricity and the tendency of the disease to regress following the cessation of smoking suggest a reactive immune response in the bronchioles to an inhaled antigen in cigarette smoke that is mediated by the Langerhans cell system. The recurrence of LCH in patients who have undergone lung transplantation for the disease suggests that extrapulmonary factors also are involved in its pathogenesis or that the condition may represent a neoplastic disorder.

An association between eosinophilic granuloma (EG) and lymphoma has been described.⁴ Bronchogenic carcinoma has been identified with increased frequency in patients with pulmonary LCH. Lung scarring and smoking may contribute to the development of lung cancer in these patients. Although intriguing, evidence likely is insufficient to either prove or refute the association between pulmonary LCH and malignant neoplasms.

Clinical manifestations

Of LCH patients, 25-33% are asymptomatic at presentation. Symptomatic patients may present with the following:

• Cough (66%), which is nonproductive
• Progressive dyspnea
• Weight loss
• Fever
• Diabetes insipidus (25%)
• Pneumothorax (10-25%), which may be bilateral or recurrent
• Hemoptysis ( <5%)

Pulmonary function tests do not provide consistent findings, but mild airway obstruction is common. A reduction in carbon monoxide diffusion capacity is present in 60-90% of patients. On bronchoalveolar lavage (BAL), an increased number of cells are seen, particularly macrophages; however, this may be a manifestation of the patient's smoking history. Langerhans cells also can be found on BAL. A diagnosis of pulmonary LCH (eosinophilic granuloma, thoracic) is likely when the proportion of Langerhans cells in the BAL fluid is greater than 5%, although this finding is not specific for the disorder.

A confident diagnosis of pulmonary LCH often can be made based on the patient's age, smoking history, and characteristic high-resolution CT findings, especially if patients are followed without treatment.

Definitive diagnosis, if necessary, can be made by identification of Langerhans cell granulomas in lung biopsy samples acquired by video-assisted thoracoscopy. Biopsy sites are selected on the basis of high-resolution CT findings.³ Transbronchial biopsy has a low diagnostic yield (10-40%) because of the patchy nature of the disease and the small amounts of tissue obtained.

Treatment

Treatment consists of smoking cessation, which stabilizes symptoms in most patients. Corticosteroids are used in progressive or systemic disease. Cytotoxic agents (eg, cyclophosphamide) can be employed for patients who do not respond to smoking cessation and steroids. No treatment has been confirmed to be useful, and no double-blind therapeutic trials have been reported.

Lung transplantation also has been performed for treatment of LCH. No specific criteria exist for determining which pulmonary LCH patients are candidates for lung transplantation. Patients with rapidly declining lung function, severe pulmonary symptoms, and a lack of response to other treatments are the best candidates for transplant consideration; however, the disorder may recur in the transplanted lung.

Preferred Examination

In patients with suggested eosinophilic granuloma (EG), obtain a chest radiograph and high-resolution chest CT.^3,5

Differential Diagnoses

Other Problems to Be Considered

The differential diagnosis depends on the stage of the disorder.

When only small nodules are identified, consider the following:
Granulomatous infections (eg, tuberculosis, fungi)
Other infections (eg, varicella; however, nodules usually are poorly defined)
Other granulomatous disorders (eg, sarcoid)
Pneumoconiosis (eg, silicosis, coal worker's pneumoconiosis)
Neoplasm (eg, metastatic disease)

When both nodules and small cysts are present, consider the following:
Lymphocytic interstitial pneumonitis
Neoplasm (eg, cavitary metastases)
Any nodular disease with coexistent emphysema

When only cysts are present, consider the following:
Lymphangioleiomyomatosis
Chronic Pneumocystis jiroveci pneumonia with cyst formation
Central acinar emphysema
Cystic lung light chain deposition disease⁶

Increased lung volumes with interstitial disease, consider the following:
Pulmonary LCH
Emphysema with concomitant interstitial disease
Lymphangioleiomyomatosis
Cystic fibrosis (produces "interstitial" appearance)
Acute interstitial infiltrate

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