CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions.

McClain KL, Picarsic J, Chakraborty R, Zinn D, Lin H, Abhyankar H, Scull B, Shih A, Lim KPH, Eckstein O, Lubega J, Peters TL, Olea W, Burke T, Ahmed N, Hicks MJ, Tran B, Jones J, Dauser R, Jeng M, Baiocchi R, Schiff D, Goldman S, Heym KM, Wilson H, Carcamo B, Kumar A, Rodriguez-Galindo C, Whipple NS, Campbell P, Murdoch G, Kofler J, Heales S, Malone M, Woltjer R, Quinn JF, Orchard P, Kruer MC, Jaffe R, Manz MG, Lira SA, Parsons DW, Merad M, Man TK, Allen CE
Cancer 124 2607-2620 06/15/2018


BACKGROUND: Central nervous system Langerhans cell histiocytosis (CNS-LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH-ND) of unknown etiology. The goal of this study was to define the mechanisms of pathogenesis that drive CNS-LCH.

METHODS: Cerebrospinal fluid (CSF) biomarkers including CSF proteins and extracellular BRAFV600E DNA were analyzed in CSF from patients with CNS-LCH lesions compared with patients with brain tumors and other neurodegenerative conditions. Additionally, the presence of BRAFV600E was tested in peripheral mononuclear blood cells (PBMCs) as well as brain biopsies from LCH-ND patients, and the response to BRAF-V600E inhibitor was evaluated in 4 patients with progressive disease.

RESULTS: Osteopontin was the only consistently elevated CSF protein in patients with CNS-LCH compared with patients with other brain pathologies. BRAFV600E DNA was detected in CSF of only 2/20 (10%) cases, both with LCH-ND and active lesions outside the CNS. However, BRAFV600E


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