Systemic Histiocytosis (Langerhans Cell Histiocytosis, Erdheim-Chester Disease, Destombes-Rosai-Dorfman Disease): from Oncogenic Mutations to Inflammatory Disorders.

ABSTRACT

PURPOSE OF REVIEW Provide an overview of recent progress in decoding the pathogenesis and treatment of systemic histiocytoses. RECENT FINDINGS: Advances in molecular techniques over the last few years, enabling the identification of several MAPK mutations in lesion histiocytes, have revolutionized our understanding of histiocytosis that led to a revised classification and new treatments. Since the 2010 discovery of the BRAFV600E mutation in 57% of Langerhans cell histiocytosis (LCH) lesions, several other kinase mutations have been found, mostly in the MAPK pathway, and also in other key signaling pathways, in LCH, Erdheim-Chester Disease (ECD) and, less frequently, Destombes-Rosai-Dorfman disease (RDD). Those revolutionary breakthroughs enhanced our understanding of the pathogenesis of histiocytosis and led to trials with targeted therapies that demonstrated notable efficacy.