Langerhans cell histiocytosis: Current concepts and treatments.

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of cells with the phenotype of activated Langerhans cells. The diagnosis of LCH is often delayed or missed. Many questions about LCH remain to be answered, including whether it is caused by a malignancy or by immune dysregulation. Data from the early 1990s showed that LCH consisted of an accumulation of monoclonal LCH cells, suggesting a neoplastic disorder. However, further investigations with current sophisticated techniques have not shown consistent genomic aberrations. Recent data which suggests a role for an IL-17A dependant pathway of dendritic cell fusion in LCH remains to be proven. The most recent data taken together swing the pendulum towards an immunologic aberration. The clinical course of LCH is highly variable, ranging from a self-healing solitary bone lesion to widely disseminated life-threatening disease. Patients with multisystem (MS) disease with organ dysfunction, particularly those refractory to front line therapy, and those with multiple reactivations of disease associated with significant permanent sequelae represent the greatest challenge. Early switch of refractory patients to salvage therapies has contributed to the improvement in survival of MS-LCH patients. Due to the rarity of LCH in children and adults, patients must be enrolled on multi-national clinical trials, whenever possible, to advance our knowledge of the optimal therapeutic strategies and long-term outcomes.