Pulmonary Langerhans Cell Histiocytosis: Emerging Concepts in Pathobiology, Radiology, and Clinical Evolution of Disease

doi:10.1378/chest.123.5.1673

Chest

Volume 123, Issue 5, May 2003, Pages 1673-1683

https://doi.org/10.1378/chest.123.5.1673 Get rights and content

Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon disorder of adult smokers associated with a significant morbidity. Arising from the aberrant accumulation of Langerhans and other immune cells, PLCH tends to cause a relatively isolated pulmonary involvement as compared to other forms of Langerhans cell (LC) and histiocytic disorders. Increased knowledge of cytokine triggers, dendritic cell trafficking, and clonality of LC populations in PLCH have resulted in an improved understanding of the pathobiology of PLCH. High-resolution CT (HRCT) of the chest has led to better appreciation of nodular and cystic radiographic abnormalities characteristic of the disease. Correlation of HRCT abnormalities with lung pathologic changes has led to an improved comprehension of clinical evolution of PLCH. Current clinical predictors for PLCH outcomes remain poor, although long-term follow-up and radiologic monitoring may help to define disease progression. This review discusses advances in PLCH emphasizing the etiopathologic bases of the disease and currently available radiologic modalities for monitoring disease progression.

Section snippets

Nomenclature and Historical Perspective

Attributing LC as causal to the lesions of PLCH took over a century since the original description of dendritic cells by Paul Langerhans in 1868.¹ In 1973, Nezelof and colleagues² reported in a classic article that histiocytes in PLCH share a common cytoplasmic organelle by electron microscopy (the Birbeck granule) with the LCs of the skin. Litchenstein³ had previously suggested that a common histiocytic cell pool populated the pathologic lesions of three disparate clinical conditions:

Etiologic Considerations

The LC is a specialized immune cell belonging to the family of dendritic cells that form a network of antigen-presenting and migratory cells in lymphoid and nonlymphoid organs such as the skin, heart, and lung.⁶ Closely related to the monocyte-macrophage system, the dendritic cell system originates from a common bone marrow progenitor and undergoes differentiation under the influence of specific growth factors.⁵⁷ The origins of tissue dendritic cells are controversial. Three developmental

Pulmonary LC histiocytosis vs Disseminated LC histiocytosis

LC accumulation in tissues can occur as a result of a local reaction to inflammatory/neoplastic stimuli as is seen in lungs of smokers, or with certain lymphomas and solid tumors.¹³¹⁴¹⁵¹⁶ LC histiocytoses (LCHs), however, are comprised of disorders characterized by disease manifestations that are explained by excess activated LCs in various tissues.⁴ Depending on the extent of organ involvement, LCHs are classified as LCH with single-organ involvement (eg, PLCH), LCH with multiorgan involvement

Clinical Picture

The majority of patients with LCH are smokers who commonly acquire disease in the third or fourth decade of life.²⁵³⁶³⁷³⁸³⁹⁴⁰ Although there does not appear to be a gender preponderance, female patients with PLCH tend to present later in life.³⁹ Estimates of the incidence of PLCH may be biased, as most studies are based on histopathology results from open-lung biopsies.³⁹ The clinical presentation of PLCH varies; dyspnea, cough, and chest pain are predominant symptoms.¹⁹³⁷ Constitutional

Pathology of PLCH and Disease Course

Histologically, early PLCH lesions are characterized by cellular interstitial infiltrates composed of LCs, lymphocytes, macrophages, eosinophils, plasma cells, and fibroblasts.⁴⁰ These infiltrates enlarge to form nodules centered on small airways.²⁵⁴⁰ Cavitation within nodules represents either an airway remnant or de novo cavitation due to an enlarging inflammatory infiltrate.²⁵⁴⁰ Centripetal replacement of granulomatous nodular infiltrates by fibroblasts results in symmetric stellate lesions

Radiologic Spectrum of PLCH

An abnormal chest radiographic finding may be the only clue to the disease in the 25% of asymptomatic patients with PLCH.³⁷⁴⁹ Pneumothorax with chest pain is the initial clinical manifestation in 15% of patients with PLCH (Fig 2).⁵⁰ Pneumothoraces may be recurrent, requiring thorocotomy and chest tube placement for relief of symptoms (Fig 3).

A spectrum of chest radiographic abnormalities is seen in patients with PLCH with ill-defined nodules and curvilinear/reticular opacities predominating in

Therapeutic Considerations

Smoking cessation is recommended because of a potential pathogenetic association,²³²⁴ the rarely documented resolution of disease following cessation of smoking⁵² and the increased risk of bronchogenic cancer in PLCH.⁶⁵ The nature of cancer in patients with PLCH does not appear to be that of a scar cancer.⁶⁶ Bronchogenic cancers have been reported most commonly in those who continue to smoke heavily.⁶⁶ Corticosteroids and other immunosuppressive therapies²⁶ have not been evaluated in

Conclusion

Current understanding of PLCH has evolved in terms of the basic processes contributing to the natural history of the disease. The LC, a cell belonging to the dendritic cell system, accumulates in the lungs along with macrophages, lymphocytes, and eosinophils, and gives rise to typical granulomas centered on small airways. These cells differ from the quiescent LCs of the skin. They have larger and more pleomorphic Birbeck granules and express markers of activation. LCs in PLCH lesions are

ACKNOWLEDGMENT

The authors thank Dr. John Hoidal for his suggestions.

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