What is Langerhans cell histiocytosis (LCH)?

Updated: Jun 12, 2020
  • Author: Christopher R Shea, MD; Chief Editor: William D James, MD  more...
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Answer

Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the presence of cells with characteristics similar to bone marrow–derived Langerhans cells juxtaposed against a backdrop of hematopoietic cells, including T-cells, macrophages, and eosinophils.

In 1868, Paul Langerhans discovered the epidermal dendritic cells that now bear his name. The ultrastructural hallmark of the Langerhans cell, the Birbeck granule, was described a century later. The term Langerhans cell histiocytosis is generally preferred to the older term, histiocytosis X. This newer name emphasizes the histogenesis of the condition by specifying the type of lesional cell and removes the connotation of the unknown ("X") because its cellular basis has now been clarified. [1]

Although the epidermal Langerhans cell has been presumed to be the cell of origin in LCH, recent studies have called this belief into question. Specifically, a variety of other cellular populations have been identified that possess phenotypic characteristics similar to Langerhans cells, including expression of CD207 and Birbeck granules. Therefore, in addition to epidermal Langerhans cells, other potential cellular origins for LCH include dermal langerin+ dendritic cells, lymphoid tissue-resident langerin+ dendritic cells, and monocytes that can be induced by local environmental stimuli to acquire a Langerhans cell phenotype. [2, 3]

Notably, LCH cells have been found to express markers of both resting epidermal Langerhans cells (CD1a, intracellular major histocompatibility complex II [MHCII], Birbeck granules) and activated Langerhans cells (including CD54 and CD58). As a result, the pathologic cells of LCH have been hypothesized to represent Langerhans cells in a state of arrested maturation. [3] Taken together, these findings have led some to speculate that LCH is not a specific disease of epidermal Langerhans cells, but rather one of mononuclear phagocyte dysregulation. [3]

The working group of the Histiocyte Society divided histocytic disorders into three groups: (1) dendritic cell histiocytosis, (2) macrophage-related disorders, and (3) malignant histiocytosis. [4] LCH belongs in group 1 and encompasses a number of diseases. On one end, the clinical spectrum includes an acute, fulminant, disseminated disease called Letterer-Siwe disease, and, on the other end, solitary or few, indolent and chronic lesions of bone or other organs called eosinophilic granulomas. The intermediate clinical form called Hand-Schüller-Christian disease is characterized by multifocal, chronic involvement and classically presents as the triad of diabetes insipidus, proptosis, and lytic bone lesions. A congenital, self-healing form called Hashimoto-Pritzker disease has also been described.

More recently, histiocytic diseases have been reclassified into five groups: (1) Langerhans-related, (2) cutaneous and mucocutaneous, (3) malignant histiocytosis, (4) Rosai-Dorfman disease, and (5) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. LCH belongs in the first category, along with Erdheim-Chester disease and juvenile xanthogranuloma. [5]


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