One significant factor limiting enthusiasm about this analyte is that cDNAV600E can be found only in the fraction of patients with LCH harboring DNAV600E in the tumor, predominantly younger children with multisystem LCH and the risk organ (liver, spleen, and hematological system) involvement, thereby restricting its practical applicability in LCH patients who have other than BRAF-V600E mutation genetic alterations within MAPK pathway [46–51]. This evidence concerns the gene BRAF and Langerhans cell histiocytosis.