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LCH was formerly known as “histiocytosis X”, a term that grouped three major syndromes, which are now considered as clinical variants of the same disease:

Eosinophilic granuloma: Unifocal LCH with a solitary bone lesion
Hand-Schüller-Christian disease: Multifocal LCH with the classic triad of skull lesions, exophtalmos, and diabetes insipidus
Letterer-Siwe disease: Fulminant LCH with multiple organ involvement </aside>

https://www.youtube.com/watch?v=peVcZVMQucM

https://www.youtube.com/watch?v=nLswIe6mRUo

Etiopathology

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LCH lesion composition:

![The composition of LCH lesions is very heterogenous with the presence of different components of the immune system. Crosstalk between the LCH cells and the infiltrating immune cells contributes to the formation of a highly inflammatory and dysfunctional microenvironment that inhibits the clearance of the LCH cells by the immune cells and favors their persistence and survival in the lesions. Created with Biorender.com.

Tommaso Sconocchia, Johannes Foßelteder, Sconocchia G, Reinisch A. Langerhans cell histiocytosis: current advances in molecular pathogenesis. Frontiers in Immunology. 2023;14. doi:https://doi.org/10.3389/fimmu.2023.1275085](attachment:30dd1b86-bd32-48b6-be78-92b2fadc7c09:fimmu-14-1275085-g004.jpg)

The composition of LCH lesions is very heterogenous with the presence of different components of the immune system. Crosstalk between the LCH cells and the infiltrating immune cells contributes to the formation of a highly inflammatory and dysfunctional microenvironment that inhibits the clearance of the LCH cells by the immune cells and favors their persistence and survival in the lesions. Created with Biorender.com.

Histopathology:

https://doi.org/10.1038/modpathol.2013.181

https://www.youtube.com/watch?v=doiUthlxlCw

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Histopathological examination shows tissue infiltration by abnormal Langerhans cells as well as normal inflammatory cells (T cells, eosinophils, macrophages and multinucleated giant cells).

Diagnosis is confirmed by the morphologic identification of the Langerhans cells and positive immunohistochemical staining with CD1a and/or CD207. The identification of Birbeck granules on electron microscopy, which are cytoplasmic tennis-racket-shaped organelles characteristic of Langerhans cells, is nowadays rarely performed.

https://doi.org/10.1136%2Fadc.2007.125872

http://scholar.google.com/scholar_lookup?&title=Langerhans cell histiocytosis%3A a review of the current recommendations of the Histiocyte Society&journal=Pediatr Dermatol&volume=25&issue=29&pages=1-295&publication_year=2008&author=Satter%2CEK&author=High%2CWA

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![Histologic Features of LCH. Panel A shows typical LCH lesions with large cells, pale cytoplasm, and reniform nuclei on hematoxylin and eosin staining (A1); CD207-positive immunostaining (A2); VE1-positive immunostaining for BRAF V600E protein (A3); and Birbeck granules visualized with electron microscopy (A4). Panel B shows liver involvement, which is frequently characterized by periportal infiltration by histiocytes (B1) and variable CD207-positive staining (B2). Panel C shows biopsy specimens from a patient with severe LCH-associated neurodegeneration (LCH-ND),19 characterized by peri- vascular VE1-positive staining (C1), CD163-positive staining (C2), and a P2RY12 infiltrate with occasional P2RY12- positive, tissue-resident microglia (C3). Panel D shows histiocytic lesions that are characteristic of both LCH and juvenile xanthogranuloma (JXG), with heterogeneous histologic features on hematoxylin and eosin staining (D1), including distinct cell populations that are CD207-positive (D2) and CD68-positive (D3).

Allen CE, Merad M, McClain KL. Langerhans-Cell Histiocytosis. New England Journal of Medicine. 2018;379(9):856-868. doi:https://doi.org/10.1056/nejmra1607548](attachment:7222d60b-b227-43d1-940a-826774ea9988:LCH.jpg)

Histologic Features of LCH. Panel A shows typical LCH lesions with large cells, pale cytoplasm, and reniform nuclei on hematoxylin and eosin staining (A1); CD207-positive immunostaining (A2); VE1-positive immunostaining for BRAF V600E protein (A3); and Birbeck granules visualized with electron microscopy (A4). Panel B shows liver involvement, which is frequently characterized by periportal infiltration by histiocytes (B1) and variable CD207-positive staining (B2). Panel C shows biopsy specimens from a patient with severe LCH-associated neurodegeneration (LCH-ND),19 characterized by peri- vascular VE1-positive staining (C1), CD163-positive staining (C2), and a P2RY12 infiltrate with occasional P2RY12- positive, tissue-resident microglia (C3). Panel D shows histiocytic lesions that are characteristic of both LCH and juvenile xanthogranuloma (JXG), with heterogeneous histologic features on hematoxylin and eosin staining (D1), including distinct cell populations that are CD207-positive (D2) and CD68-positive (D3).

Allen CE, Merad M, McClain KL. Langerhans-Cell Histiocytosis. New England Journal of Medicine. 2018;379(9):856-868. doi:https://doi.org/10.1056/nejmra1607548

Presentation

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LCH primarily affects children <10 years of age, with potential to develop lesions in virtually any organ system, most frequently bone and skin. Adults are also affected, typically in the third to fifth decades of life.

https://doi.org/10.1038/s41572-021-00307-9

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Clinical subtypes

Clinical presentations in children and adults are highly variable, with symptoms based on the sites of disease. Lesions in the spleen, liver and bone marrow are considered high risk owing to their association with an increased potential for death compared with lesions in other low-risk sites.