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Langerhans Cell Histiocytosis Treatment (PDQ®): Treatment - Health Professional Information [NCI]
General Information About Langerhans Cell Histiocytosis (LCH)
Histiocytic diseases in children and adults are caused by an abnormal accumulation of cells of the mononuclear phagocytic system. This summary discusses only Langerhans cell histiocytosis (LCH), a myeloid-derived dendritic cell disorder.
Histiocytic diseases have been reclassified into five categories, with LCH in the L group (see Table 1).[1,2] LCH results from the clonal proliferation of immunophenotypically and functionally immature, morphologically rounded LCH cells found in relevant lesions, along with eosinophils, macrophages, lymphocytes, and, occasionally, multinucleated giant cells.[3,4] The pathological histiocytes and normal Langerhans cells of the epidermis (LCs) have identical immunophenotypic characteristics, including the presence of Birbeck granules identified by electron microscopy. There are clear morphological, phenotypic, and gene expression differences between the pathological variant of the LCH lesions (LCH cells) and the normal LCs, hence the term LCH cells.
| Histiocytosis Group | Diseases | |
|---|---|---|
| AXG = adult xanthogranuloma; BCH = benign cephalic histiocytosis; GEH = generalized eruptive histiocytosis; HLH = hemophagocytic lymphohistiocytosis; JXG = juvenile xanthogranuloma; LCH = Langerhans cell histiocytosis; MRH = multicentric reticulohistiocytosis; NXG = necrobiotic xanthogranuloma; PNH = progressive nodular histiocytosis; RDD = Rosai-Dorfman disease; SRH = solitary reticulohistiocytoma; XD = xanthoma disseminatum. | ||
| a Adapted from Emile et al.[2] | ||
| b Reprinted fromBlood, Volume 135, Issue 16, Carlos Rodriguez-Galindo, Carl E. Allen, Langerhans cell histiocytosis, Pages 1319–1331, Copyright 2020, with permission from Elsevier.[1] | ||
| L Group | LCH | |
| Indeterminate-cell histiocytosis (ICH) | ||
| Erdheim-Chester disease (ECD) | ||
| Mixed LCH/ECD | ||
| C Group | Cutaneous non-LCH | |
| Xanthomatous granuloma (XG) family: JXG, AXG, SRH, BCH, GEH, PNH | ||
| Non-XG family: Cutaneous RDD, NXG, other | ||
| Cutaneous non-LCH with a major systemic component | ||
| XG family: XD | ||
| Non-XG family: MRH | ||
| R Group | Familial RDD | |
| Sporadic RDD | ||
| Classical RDD | ||
| Extranodal RDD | ||
| RDD with neoplasia or immune disease | ||
| Unclassified | ||
| M Group | Primary malignant histiocytoses | |
| Secondary malignant histiocytoses | ||
| H Group | Primary HLH: Monogenic inherited conditions leading to HLH | |
| Secondary HLH (non-Mendelian HLH) | ||
| HLH of unknown/uncertain origin | ||
LCH cells, known for many years to be a clonal proliferation, have now been shown to likely derive from a myeloid precursor whose proliferation is uniformly associated with activation of the MAPK/ERK signaling pathway.[5,6]
Clinically, LCH is a heterogenous disease that may involve a single organ (single-system LCH), which may be a single site (unifocal) or involve multiple sites (multifocal). It may also involve multiple organs (multisystem LCH). Multisystem LCH may involve a limited number of organs or be disseminated. Involvement of specific organs such as the liver, spleen, and hematopoietic system separates multisystem LCH into high-risk (multisystem risk-organ positive) and low-risk (multisystem risk-organ negative) groups, where risk indicates the risk of death from the disease.
References:
- Rodriguez-Galindo C, Allen CE: Langerhans cell histiocytosis. Blood 135 (16): 1319-1331, 2020.
- Emile JF, Abla O, Fraitag S, et al.: Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 127 (22): 2672-81, 2016.
- Berres ML, Lim KP, Peters T, et al.: BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med 211 (4): 669-83, 2014.
- Allen CE, Merad M, McClain KL: Langerhans-Cell Histiocytosis. N Engl J Med 379 (9): 856-868, 2018.
- 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.
- Yu RC, Chu C, Buluwela L, et al.: Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet 343 (8900): 767-8, 1994.