The discovery of the B-Rapidly Accelerated Fibrosarcoma gene (BRAF) mutation in 2010 [20] gave new insights into LCH pathogenesis (Figures 3, 4, 5, 6, 7, and 8) and led to the hypothesis that the lesional IL-1 autocrine/paracrine loop [58,59] plays a major role in LCH pathogenesis as shown in Figures 3, 4, and 5 (IL-1 loop model). The gene discussed is IL1B; the disease is Langerhans cell histiocytosis.