Introduction
Langerhans cells are dendritic, bone marrow-derived cells that circulate between the epidermis and the local lymph nodes. They are known as antigen-presenting cells since their prime function effectively presents foreign antigens to the lymphocytes. They may also play a part in the presentation of tumor antigens. Other antigen-presenting dendritic cells, like melanocytes and Merkel cells, are also present in the dermis rather than the epidermis.
Langerhans cell histiocytosis can affect various organs such as skin, lungs, bone, lymph nodes, and the pituitary gland. Pulmonary Langerhans cell histiocytosis is a rare reversible pulmonary disorder. It is characterized by focal Langerhans cells granulomas infiltrating and destroying the bronchioles. The etiology of the disease is unknown. However, it is mostly associated with smoking. It is more commonly seen in Caucasians than Africans, Americans, or Asians. It is usually seen between 20-40 years of age, exclusively in young smokers.
What Is the Pathology of Pulmonary Langerhans Cells Histiocytosis?
The Langerhans cells are moderately sized with a convoluted nucleus and pale eosinophilic cytoplasm. The cell type can be confirmed with the help of immunohistochemical staining with monoclonal antibodies directed against the membrane antigen cluster of differentiation (CD1a). On electron microscopy, Langerhans cells in a Langerhans cell histiocytosis lesion contain numerous tennis racket-shaped Birbeck granules.
The nature of the Langerhans cells can also be confirmed with the help of an antibody against langerin, a lectin specifically expressed by Langerhans cells. Also, positive staining for the intracellular S100 protein low molecular weight protein is used to identify Langerhans cells. Accumulating these activated Langerhans cells into loose granulomas that develop in and destroy distal bronchioles is the hallmark of the disease.
Lymphocytes and inflammatory cells, including eosinophils and macrophages, are also found. The lesions are focal, poorly demarcated, and separated from the normal lung parenchyma. These lesions are centered on the terminal respiratory bronchioles, further destroying the airways.
What Are the Signs and Symptoms of Pulmonary Langerhans Cell Histiocytosis?
The signs and symptoms include
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Exertional dyspnea or difficulty in breathing.
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Non-productive cough.
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Fatigue.
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Weight loss.
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Pleuritic chest pain.
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Rarely can present with hemoptysis.
What Are the Diagnostic Tests to Be Carried Out?
The diagnostic tests that can be carried out are
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Chest X-Ray: Cysts are the main radiographic abnormality. They may be seen within the infiltrates and present symmetrically on both the lungs, predominantly in the upper and middle lung fields. The lung volumes may be normal or increased compared to other diffuse pulmonary infiltrating diseases. Pneumothorax may be visible on the chest X-ray.
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High-resolution Computed Tomography (HRCT): It is considered the gold standard in diagnosing Langerhans cells histiocytosis. It provides details about the cavitation of the nodules and the parenchymal abnormalities, typically not visible in a conventional radiograph. The typical characteristic features of an HRCT are small, poorly limited nodules, cavitated nodules, and thin-walled cysts. The lesions are focal, being separated from the lung parenchyma. They are usually present in the middle and upper portion of the lung, sparing the basal portion of the lung.
Cystic lesions are the most characteristic finding. They may vary in size, although mostly less than 1cm in diameter, and may be isolated or confluent, sometimes resembling centrilobular emphysema. The lesions may progress from nodules to cavitated nodules, then become thick-walled cysts, and finally become thin-walled cysts in the later stages. The cysts may mimic a honeycomb appearance due to a summation of air-filled spaces. The confluence of two or three cysts may result in a bizarre shape.
The nodules and the cavitated nodules are reversible and can resolve, but the cysts are irreversible and may persist and enlarge over time. It is also helpful for selecting surgical biopsy sites in patients who require further investigation. Ground glass attenuation and linear densities with emphysematous bullae secondary to cigarette smoke exposure.
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Pulmonary Function Tests: A characteristic feature is a reduction in the diffusing lung capacity for carbon monoxide (DLCO) in most cases. Common findings include low vital capacity, mild alteration in total lung capacity, and an increased residual volume to total lung capacity ratio. In the majority of cases, obstructive dysfunction can be observed. Very few cases with restrictive patterns are observed. An obstructive pattern with diffuse pulmonary infiltrates is highly suggestive of pulmonary Langerhans cells histiocytosis.
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Arterial Blood Gas (ABG) Analysis: The blood gas analysis is usually normal, although exertion may cause alveolar-arterial oxygen gradient elevation and hypoxemia.
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Bronchoalveolar Lavage (BAL): It is a common method useful to rule out infections and other infiltrating lung diseases that can usually be seen in young adults. It is of maximum use in the differential diagnosis of patients with atypical radiographic findings. The most common finding is a marked increase in the alveolar macrophages of more than 1x106 cells per ml. Increased macrophages can be strongly correlated with cigarette smoke exposure. Also, the presence of the Langerhans cells collected from the lavage sample using monoclonal antibodies directed against the cluster of differentiation (CD1a) is a useful diagnostic marker in pulmonary Langerhans cells' histiocytosis.
What Is the Management of Pulmonary Langerhans Cells Histiocytosis?
There is no specific treatment for the disease. Although smoking cessation has proven to be of utmost importance in reverting the condition to normal. In patients who continue to smoke, the condition may further aggravate with respiratory function deterioration and eventually result in pulmonary fibrosis. Corticosteroid therapy is most commonly used as symptomatic relief and has proven beneficial in the treatment. A lung transplant may be an ultimate resort in patients with rapidly progressive conditions, provided smoking has ceased.
What Are the Complications Associated With Pulmonary Langerhans Cells Histiocytosis?
The complications include the following:
Rupture of the cyst resulting in
Interstitial Fibrosis:
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Pulmonary artery hypertension.
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Cor pulmonale.
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Pulmonary fibrosis.
What Is the Differential Diagnosis of Pulmonary Langerhans Cell Histiocytosis?
Differential diagnoses include
Early nodular stage:
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Granulomatosis with polyangiitis.
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Miliary tuberculosis.
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Metastases.
Later cystic stage:
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Lymphangiomyomatosis.
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Centrilobular emphysema.
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Pneumocystis jiroveci pneumonia.
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Idiopathic pulmonary fibrosis.
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Lymphocytic interstitial pneumonitis.
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Cystic bronchiectasis from allergic bronchopulmonary aspergillosis (ABPA).
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Lymphocytic interstitial pneumonitis.
Conclusion
Pulmonary Langerhans cell histiocytosis is a relatively rare lung disease commonly associated with smoking. The pathologic hallmark is the presence of numerous Langerhans cells in small airways, resulting in the formation of nodular inflammatory lesions. The Langerhans cells' histiocytosis is a specific type of histiocytic syndrome characterized by the infiltration of tissues with a specific type of dendritic cell, the Langerhans cell. Formerly known as eosinophilic granuloma, the Langerhans cells are well differentiated from other dendritic cells by the presence of intracellular racket-shaped Birbeck granules and surface expression of CD1a receptor.
High-resolution CT is considered the gold standard diagnostic modality along with bronchoalveolar lavage. Further, a lung biopsy provides a definitive diagnosis of the disease. There is no specific treatment for the disease, and smoking cessation has caused a spontaneous reversal of the disease. The prognosis of the disease is relatively good. Proper counseling on the importance of smoking cessation plays an important role. Complications like pneumothorax and pulmonary artery hypertension may decrease life expectancy.
