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Clinical manifestations, pathologic features, and diagnosis 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 having bean-shaped nuclei on biopsy. These histiocytes, along with lymphocytes, macrophages, and eosinophils may infiltrate nearly every organ (most notably the skin, lymph nodes, lungs, thymus, liver, spleen, bone marrow, or central nervous system with the exception of the heart and kidneys).

Histiocytic disorders are derived from mononuclear phagocytic cells (macrophages) and dendritic cells, which have several different origins and locations. 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 and other molecular investigations on LCH have shown that the skin Langerhans cell is not the cell of origin for LCH. Rather, it is a myeloid dendritic cell that expresses the same antigens (CD1a, CD207) as the skin Langerhans cell. In contrast, 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 epidemiology, clinical manifestations, pathologic features, diagnosis, and differential diagnosis of LCH will be presented here. The management of LCH is presented separately, as are specific discussions of solitary LCH involving lung or bone. (See "Treatment of Langerhans cell histiocytosis" and "Pulmonary Langerhans cell histiocytosis" and "Langerhans cell histiocytosis (eosinophilic granuloma) of bone in children and adolescents".)


The archaic term "histiocyte" refers to large white blood cells resident in tissues, including Langerhans cells, monocytes/macrophages, and dermal/interstitial dendritic cells [1].


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