Langerhans cell histiocytosis: pragmatic empirism on the road to rational cure

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the accumulation of clonal dendritic cells in different organs. Most recent findings (e.g., activating BRAF mutations) favor the hypothesis that LCH may represent a neoplasm with varying behavior, but the ultimate pathogenesis remains to be uncovered. In view of the gaps in the basic understanding of the disease, its clinical management foots on empirical knowledge and is pragmatically oriented. Some of the current guidelines for clinical and radiological evaluation are based on outdated knowledge and therefore appropriately designed prospective studies are urgently needed. Furthermore, there is a need for biological markers, for disease activity and treatment-response assessment. The upcoming prospective clinical trial of the Histiocyte Society, LCH-IV, is expected to address the most burning issues concerning optimal patient management.