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Langerhans Cell Histiocytosis Treatment (PDQ®)

Health Professional Version
Last Modified: 02/03/2014

General Information About Langerhans Cell Histiocytosis (LCH)

The histiocytic diseases in children and adults include three major classes of disorders of which only one, Langerhans cell histiocytosis (LCH), a dendritic cell disorder, will be discussed. Erdheim-Chester disease (primarily found in adults) and juvenile xanthogranuloma (diagnosed in children and adults) are macrophage disorders. Other disorders of the macrophage/monocytoid lineages include Rosai-Dorfman disease and hemophagocytic lymphohistiocytosis. Malignant disorders include malignant histiocytosis of various histiocyte lineages (formerly called histiocytic sarcoma) and the monocytic or myelomonocytic leukemias.

LCH results from the clonal proliferation of immunophenotypically and functionally immature, morphologically rounded LCH cells along with eosinophils, macrophages, lymphocytes, and occasionally, multinucleated giant cells.[1] The term LCH cells is used because there are clear morphologic, phenotypic, and gene expression differences between Langerhans cells of the epidermis (LC cells) and those in LCH lesions (LCH cells). Controversy exists regarding whether the clonal proliferation of LCH cells results from a malignant transformation or is the result of an immunologic stimulus.[2,3]

Whether the clonal proliferation of LCH cells is a result of neoplastic changes or immunologic abnormalities, the primary treatment is with chemotherapeutic agents. Some of the chemotherapy drugs used have immunomodulatory activity as well.

Langerhans cell histiocytosis is the terminology currently preferred over histiocytosis X, eosinophilic granuloma, Abt-Letterer-Siwe disease, Hand-Schuller-Christian disease, or diffuse reticuloendotheliosis. This is because the pathologic histiocyte common to all of these diagnoses was identified by electron microscopy to have characteristic Birbeck granules identical to those of the LC cell found scattered in the dermal-epidermal junction of the skin.[4,5] More recent work has shown that the pathologic histiocyte (LCH cell) has a gene expression profile of a myeloid dendritic cell and not the skin LC.[6]

The nomenclature used for LCH indicates the disease extent. LCH may involve a single organ (single-system LCH), which may be a single site (unifocal) or involve multiple sites (multifocal); or LCH may involve multiple organs (multisystem LCH), which may involve a limited number of organs or it may be disseminated.

References
  1. Laman JD, Leenen PJ, Annels NE, et al.: Langerhans-cell histiocytosis 'insight into DC biology'. Trends Immunol 24 (4): 190-6, 2003.  [PUBMED Abstract]

  2. Willman CL, Busque L, Griffith BB, et al.: Langerhans'-cell histiocytosis (histiocytosis X)--a clonal proliferative disease. N Engl J Med 331 (3): 154-60, 1994.  [PUBMED Abstract]

  3. Yu RC, Chu C, Buluwela L, et al.: Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet 343 (8900): 767-8, 1994.  [PUBMED Abstract]

  4. Coppes-Zantinga A, Egeler RM: The Langerhans cell histiocytosis X files revealed. Br J Haematol 116 (1): 3-9, 2002.  [PUBMED Abstract]

  5. Arceci RJ, Longley BJ, Emanuel PD: Atypical cellular disorders. Hematology Am Soc Hematol Educ Program : 297-314, 2002.  [PUBMED Abstract]

  6. Allen CE, Li L, Peters TL, et al.: Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol 184 (8): 4557-67, 2010.  [PUBMED Abstract]