Chest
ReviewsPulmonary Langerhans Cell Histiocytosis: Emerging Concepts in Pathobiology, Radiology, and Clinical Evolution of Disease
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.
References (70)
- et al.
Langerhans cell histiocytosis research: past, present, and future
Hematol Oncol Clin North Am
(1998) - et al.
Origin and differentiation of dendritic cells
Trends Immunol
(2001) - et al.
Dendritic cells as recipients of cytokine signals
- et al.
The widespread distribution of Langerhans cells in pathologic tissues: an ultrastructural and immunohistochemical study
Hum Pathol
(1986) - et al.
An update on clonality, cytokines, and viral etiology in Langerhans cell histiocytosis
Hematol Oncol Clin North Am
(1998) - et al.
Tobacco smoke induced lung granulomas and tumors: association with pulmonary Langerhans cells
Pathology
(1995) - et al.
Transgenic expression of granulocyte-macrophage colony-stimulating factor induces the differentiation and activation of a novel dendritic cell population in the lung
Blood
(2000) - et al.
Histiocytosis X in the lung
Hum Pathol
(1983) - et al.
Complete resolution of roentgenographic changes in a patient with pulmonary histiocytosis X
Chest
(1990) - et al.
Pleural effusion as a complication of solitary eosinophilic granuloma of the rib
Hum Pathol
(1980)
Bronchogenic carcinoma in patients with pulmonary histiocytosis X
Chest
Historical review: the Langerhans cell histiocytosis X files revealed
Br J Haematol
Histiocytosis X: histogenetic arguments for a Langerhans cell origin
Biomedicine
Histiocytosis: integration of eosinophilic granuloma of the bone, Letterer-Siwe disease and Hand-Schuller-Christian disease as related manifestations of a single nosologic entity
Arch Pathol
Contemporary classification of histiocytic disorders
Med Pediatr Oncol
Taking the X out of histiocytosis X
Radiology
Dendritic cell system and its role in immunogenicity
Annu Rev Immunol
Dendritic cells: immunologic regulators in health and disease
Physiol Rev
Dendritic cells: a complex simplicity
Transplantation
Phenotypic characterization of dendritic cells
Cells of the dendritic cell lineage in human lung carcinomas and pulmonary histiocytosis X
Cigarette smoking-induced changes in the number and differentiated state of pulmonary dendritic cells/Langerhans cells
Am Rev Respir Dis
The coexistence of Langerhans’ cell granulomatosis and malignant lymphoma may take different forms: report of seven cases with a review of the literature
Hum Pathol
Langerhans’ cell histiocytosis (histiocytosis X): a clonal proliferative disease
N Engl J Med
Pulmonary histiocytosis X in the adult
UpToDate
Langerhans cell histiocytosis
Langerhans cells in Langerhans cell granulomatosis are not actively proliferating cells
Am J Pathol
Evidence that Langerhans cells in adult pulmonary Langerhans cell histiocytosis are mature dendritic cells: importance of the cytokine microenvironment
J Immunol
Accumulation of Langerhans’ cells on the epithelial surface of lower respiratory tract in normal subjects in association with cigarette smoking
Am Rev Respir Dis
Decreased tobacco-glycoprotein-induced lymphocyte proliferationin vitroin pulmonary eosinophilic granuloma
Am J Respir Crit Care Med
Pulmonary Langerhans cell granulomatosis (histiocytosis X)
Annu Rev Med
Pulmonary Langerhans’ cell histiocytosis
N Engl J Med
Pulmonary Langerhans’-cell histiocytosis [letter]
N Engl J Med
Development of pulmonary histiocytosis X after chemotherapy for Hodgkin’s disease
AJR Am J Roentgenol
Evidence that granulocyte macrophage-colony-stimulating-factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers
J Clin Invest
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