LAUSR

The pathogenesis and cellular origin of Langerhans cell histiocytosis (LCH) are debated. Recently, mutations on MAPK and PI3K pathways have been linked to disrupted cell proliferation in LCH. Janus Kinase 2 (JAK2) mutations play the same role in Philadelphia-negative chronic myeloproliferative neoplasms. We describe the case of a patient affected by JAK2-positive primary myelofibrosis (PMF) who developed a clonally related LCH while in treatment with ruxolitinib. JAK inhibitors are well known to affect function and differentiation of different hematological lineages, including mononuclear phagocytes precursors. Nevertheless, the literature describes cases of LCH clonally associated with non-LCH hematological neoplasm, suggesting how multilinear myeloid neoplasms may arise from bone marrow. Hence, we briefly discuss the possible pathogenic roles of genetic mutations and JAK inhibition therapy in the pathogenesis of LCH and associated neoplasms.