Abstract
Langerhans cell histiocytosis (LCH) is a disorder of myeloid neoplasia of dendritic cells that affects 1 in 200,000 children <15 years of age and even fewer adults. lch presents with a spectrum of clinical manifestations. high-risk stratification is reserved for infiltration of blood, spleen, liver, and lungs. after decades of debate on the disease pathogenesis, a neoplastic mechanism is now favored on the basis of lch cell clonality, rare cases of familial clustering, and recent evidence of mutations involving the ras raf mek (mitogen-activated protein kinase kinase) erk (extracellular signal-regulated kinase) pathway in lesional biopsy specimens. somatic mutations are most often found in braf (brafv600e in 47.1% of reported patients) and map2k1 (21.7%) and uncommonly found in map3k1 or araf. increased levels of phospho-erk in lesional tissue, activation of ras raf mek erk signaling with these mutations in vitro, and the mutual exclusivity of these mutations in a given patient suggest a central role for activation of the ras raf mek erk oncogenic pathway in lch. immunohistochemical assessment of lesional tissue using the ve1 brafv600e mutation-specific antibody can serve as a screening tool for brafv600e-positive lch. case reports suggest that brafv600e-positive lch unresponsive to standard therapy might respond to b-raf-mek pathway inhibition, but rigorous randomized clinical trials have yet to be performed.>
