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Treatment of Langerhans cell histiocytosis

Kenneth L McClain, MD, PhD
Section Editors
Laurence A Boxer, MD
Julie R Park, MD
Deputy Editor
Alan G Rosmarin, MD


Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder most commonly characterized by single or multiple osteolytic bone lesions demonstrating infiltration with histiocytes with "bean-shaped" nuclei on biopsy with or without histiocytic infiltration of extraskeletal lesions (most notably the skin, lungs, and central nervous system).

Histiocytic disorders are thought to be derived from mononuclear phagocytic cells (macrophages and dendritic cells) or histiocytes. This group has generally been divided into Langerhans cell histiocytosis and non-Langerhans histiocytosis. LCH is so named because the morphology and immunophenotype of the abnormal cells is similar to that of Langerhans cells, which are specialized dendritic cells found in the skin and mucosa. Gene expression array data on the dendritic cells from LCH have shown a unique profile distinct from the skin Langerhans cells [1]. Further evaluation of the pathologic dendritic cells in blood and bone marrow has proven that LCH is caused by myeloid dendritic cells with activation of the RAS pathway [2]. It is known that myeloid dendritic cells can express the same antigens (CD1a, CD207) as the skin Langerhans cell [3]. The non-Langerhans histiocytoses are thought to be derived from other dendritic cells that ultimately produce the monocyte-macrophage lineage.

For now, "Langerhans cell histiocytosis" remains the preferred nomenclature, although new terminology may evolve when the precise origin of the CD-207+ cells in LCH is fully understood. The historical terms histiocytosis-X, Letterer-Siwe disease, Hand-Schüller-Christian disease, and diffuse reticuloendotheliosis should be abandoned. The term "eosinophilic granuloma" is sometimes used to describe the pathology of an individual lesion, particularly isolated lytic processes in bone.

The management of LCH in children and adults will be presented here. The epidemiology, clinical manifestations, pathologic features, diagnosis, and differential diagnosis of LCH are presented separately, as is additional detail regarding solitary LCH involving either the lung or bone. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis" and "Pulmonary Langerhans cell histiocytosis" and "Langerhans cell histiocytosis (eosinophilic granuloma) of bone in children and adolescents".)


While all aspects of a complete history and physical examination are important, some elements of this evaluation are particularly relevant to complications that might arise due to the disease or its management. The evaluation should pay particular attention to signs or symptoms that may reflect involvement of the central nervous system (eg, excessive thirst and urination, abnormal growth velocity, abnormal findings on neurologic exam) or risk organs (eg, hepatosplenomegaly, symptoms due to cytopenias).


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Literature review current through: Dec 2016. | This topic last updated: Fri Oct 30 00:00:00 GMT+00:00 2015.
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