Scientific Comments have known that although many organs can harbor proliferating LCs, only if organ function were disrupted was such involvement of prognostic significance. Patients could then be stratified into different risk categories based on the extent of their disease and the degree of organ dysfunction. This is the basis of the treatment of LCH, and the report by Terra Bebeto et al.(1) exemplifies how these treatment paradigms can be used to effectively treat those unfortunate children. Treatment for patients with LCH is currently risk- adapted; patients with single-system disease confined to a single site usually require only local therapy or observation and patients with more extensive disease require systemic therapy. The best therapeutic option in these cases has not been defined and responses have been observed with short courses of steroids with or without the addition of chemotherapeutic agents. The treatment recommended by the Histiocyte Society for this group of patients includes a 6- week induction with prednisone and vinblastine, followed by continuation treatment with pulses of the same agents every 3 weeks for approximately 12 months. The prognosis for this group of patients is usually excellent although approximately 30% of the patients will experience disease reactivation that continue to respond to treatment. As noted earlier and in the report by Terra Babeto et al.,(1) involvement of the risk organs carries the worst prognosis. This high-risk group of patients is characterized by early age at presentation (usually < 2 years) and different degrees of liver, spleen or hematopoietic system involvement. Patients respond poorly to treatment, and the mortality rate is as high as 40%. The advances in our understanding of the disease and the risk-stratification therapeutic approaches have slowly increased the cure rates; survival for children with LCH xxx exceeds 80%. However, patients with reactivation or chronic disease may experience severe permanent consequences that reduce their quality of life; these sequelae are characterized by fibrosis and degeneration that may affect the brain, lungs or liver. Thus, cure should not be our only goal; we must continue to unravel the intricacies underlying the pathogenesis of this disease and develop better treatments for those affected. What was once known as Histiocytosis X continues to offer challenges to resolve, starting with its own identity. Decades of research have placed the disease in a context that floats between the paradigms of the reactive and the neoplastic disorders and somewhat limited our ability to approach the diagnosis and treatment of LCH in a more rational and effective manner. Recent advances have opened the field to a new and very provocative view of the disease. Molecular analyses of mouse models and human LCH samples suggest that the cell of origin in LCH lesions may not be the epidermal LC itself but a myeloid-derived precursor. Furthermore, advanced genomic technologies have revealed the presence of activating, somatic BRAF mutations in the majority of patient specimens. Together, these observations have produced a new picture of LCH as a myeloid neoplasm. These advances are likely to have profound implications for the use of targeted therapeutics in LCH. We may be back to the drawing board and back to Histiocytosis X? Reference 1. Babeto LT, de Oliveira BM, de Castro LP, Campos MK, Valadares MT, Viana MB. Langerhans cell histiocytosis: 37 cases in a single Brazilian institution. Rev Bras Hematol Hemoter.2011;33(5): 353-7. 336 Rev Bras Hematol Hemoter. 2011;33(5):328-36