Langerhans cell histiocytosis. Advances in pathogenesis and clinical practice.

Langerhans cell histiocytosis (LCH) is a type of myeloid neoplasia that can affect different organs or tissues and exhibits substantial variability in its clinical presentation and biological behaviour, so it may mimic different diseases. Performance of different clinical assessments and laboratory and imaging tests is recommended to determine the extent of involvement, which may be of a single location or multisystemic, and the presence or absence of dysfunction in risk organs, such as the haematopoietic system, liver and spleen. The diagnosis must be confirmed by histological examination of a biopsy sample. Molecular tests have identified mutations in the mitogen-activated protein kinase (MAPK) pathway, which has expanded treatment options. The diagnosis is complex and there is controversy regarding the management of certain cases. Treatment recommendations depend on the location of the lesions and the extent of involvement. International collaborative studies have demonstrated the effectiveness of prolonged combination therapies such as vinblastine and prednisone in severe or multisystemic forms, and anti-inflammatory drugs such as indomethacin and other cytostatic combinations have proven beneficial. Langerhans cell histiocytosis is a good example of the importance of precision medicine and the benefit of identifying molecular targets, common to different neoplasms, to develop new therapies. MAPK pathway inhibitors offer an alternative treatment option in refractory cases and neurodegenerative forms of LCH. Molecular testing can contribute to the prognosis, treatment and follow-up of LCH, especially in severe forms of disease.