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Pulmonary Langerhans Cell Histiocytosis

(Eosinophilic Granuloma; Pulmonary Granulomatosis X; Pulmonary Langerhans' Cell Granulomatosis; Histiocytosis X)

By

Joyce Lee

, MD, MAS, University of Colorado Denver

Last full review/revision Jun 2021| Content last modified Jun 2021
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Pulmonary Langerhans cell histiocytosis (PLCH) is proliferation of monoclonal Langerhans cells in lung interstitium and airspaces. Etiology is unknown, but cigarette smoking plays a primary role. Symptoms are dyspnea, cough, fatigue, and pleuritic chest pain. Diagnosis is based on history and imaging tests and sometimes on bronchoalveolar lavage and biopsy findings. Treatment is smoking cessation. Corticosteroids are given in many cases, but efficacy is unknown. Lung transplantation is usually curative when combined with smoking cessation. Five-year survival is about 74%. Patients are at increased risk of cancer.

Pulmonary Langerhans cell histiocytosis is a disease in which monoclonal CD1a-positive Langerhans cells (a type of histiocyte) infiltrate the bronchioles and alveolar interstitium, accompanied by lymphocytes, plasma cells, neutrophils, and eosinophils. PLCH is one manifestation of Langerhans cell histiocytosis Langerhans Cell Histiocytosis Langerhans cell histiocytosis (LCH) is a proliferation of dendritic mononuclear cells with infiltration into organs locally or diffusely. Most cases occur in children. Manifestations may include... read more Langerhans Cell Histiocytosis , which can affect many organs (most notably the lungs, skin, bones, pituitary, and lymph nodes) in isolation or simultaneously. PLCH occurs in isolation 85% of the time.

The etiology of PLCH is unknown, but the disease occurs almost exclusively in whites 20 to 40 years of age who smoke. Men and women are affected equally. Women develop disease later, but differences in age at onset by sex may represent differences in smoking behavior. Pathophysiology may involve recruitment and proliferation of Langerhans cells in response to cytokines and growth factors secreted by alveolar macrophages in response to cigarette smoke.

Symptoms and Signs

Typical symptoms and signs of pulmonary Langerhans cell histiocytosis are dyspnea, nonproductive cough, fatigue, fever, weight loss, and pleuritic chest pain. Ten percent to 25% of patients have sudden, spontaneous pneumothorax Pneumothorax Pneumothorax is air in the pleural space causing partial or complete lung collapse. Pneumothorax can occur spontaneously or result from trauma or medical procedures. Diagnosis is based on clinical... read more Pneumothorax .

About 15% of patients are asymptomatic, with disease noted incidentally on a chest x-ray taken for another reason.

Bone pain due to bone cysts (18%), rash (13%), and polyuria due to central diabetes insipidus Central Diabetes Insipidus Diabetes insipidus results from a deficiency of vasopressin (antidiuretic hormone [ADH]) due to a hypothalamic-pituitary disorder (central diabetes insipidus) or from resistance of the kidneys... read more (5%) are the most common manifestations of extrapulmonary involvement and occur in up to 15% of patients, rarely being the presenting symptoms of PLCH. There are few signs of PLCH; the physical examination results are usually normal.

Diagnosis

  • High-resolution CT (HRCT)

  • Pulmonary function tests

  • Sometimes bronchoscopy and biopsy

Pulmonary Langerhans cell histiocytosis is suspected based on history and chest x-ray and is confirmed by HRCT and bronchoscopy with biopsy and bronchoalveolar lavage.

Confirmation on HRCT of middle and upper lobe cysts (often with bizarre shapes) and/or nodules with interstitial thickening is considered diagnostic of PLCH.

Pulmonary function test Overview of Tests of Pulmonary Function Pulmonary function tests provide measures of airflow, lung volumes, gas exchange, response to bronchodilators, and respiratory muscle function. Basic pulmonary function tests available in the... read more findings are normal, restrictive, obstructive, or mixed depending on when the test is done during the course of the disease. Most commonly, the diffusing capacity for carbon monoxide (DLCO) is reduced and exercise is impaired.

Bronchoscopy and biopsy are indicated when imaging and pulmonary function tests are inconclusive. Finding > 5% of CD1a cells in bronchoalveolar lavage fluid is highly suggestive of the disease. Biopsy shows proliferation of Langerhans cells with occasional clustering of eosinophils (the origin of the outdated term eosinophilic granuloma) in the midst of cellular and fibrotic nodules that may take on a stellate configuration. Immunohistochemical staining is positive for CD1a, S-100 protein, and HLA-DR antigens.

Prognosis

Spontaneous resolution of symptoms occurs in some patients with minimally symptomatic pulmonary Langerhans cell histiocytosis; 5-year survival is about 75%, and median survival is 12 years. However, some patients develop slowly progressive disease, for which the clinical markers include

  • Continued smoking

  • Age extremes

  • Multiorgan involvement

  • Persistent constitutional symptoms

  • Numerous cysts on chest x-ray

  • Reduced DLCO

  • Low forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) ratio (< 66%)

  • High residual volume (RV)/total lung capacity (TLC) ratio (> 33%)

  • Need for prolonged corticosteroid use

Treatment

  • Smoking cessation

  • Possibly corticosteroids and cytotoxic drugs or lung transplantation

Empiric use of corticosteroids and cytotoxic drugs is common practice even though their effectiveness is unproved.

Lung transplantation Lung and Heart-Lung Transplantation Lung or heart-lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. The most common... read more is an option for otherwise healthy patients with accelerating respiratory insufficiency, but the disorder may recur in the transplanted lung if the patient continues or resumes smoking.

Key Points

  • In pulmonary Langerhans cell histiocytosis (PLCH), monoclonal Langerhans cells proliferate in alveolar interstitium and bronchioles.

  • Consider PLCH in patients age 20 to 40 who smoke and in whom chest x-ray shows bilaterally symmetric nodular opacities in the middle and upper lung fields with cystic changes.

  • Confirm the diagnosis with high-resolution CT or, if results are inconclusive, lung biopsy.

  • Recommend smoking cessation.

  • Consider corticosteroids and cytotoxic drugs and, if smoking has ceased, lung transplantation.

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