• Gábor Méhes, Gábor Irsai, Judit Bedekovics, Lívia Beke, Ferenc Fazakas, Tímea Rózsa, and Csongor Kiss.
• *Department of Pathology †Department of Pediatric Hematology-Oncology, Institute of Pediatrics, University of Debrecen Clinical Centre, Debrecen, Hungary.
• Am. J. Surg. Pathol. 2014 Dec 1; 38 (12): 1644-8.

AbstractLangerhans cell histiocytosis (LCH) is a rare neoplastic disease originating from cells characterized by antigen-presenting Langerhans cell phenotype. The clinical spectrum of LCH is highly variable including localized and disseminated forms mostly occurring in children. Recently, about 60% of LCHs were reported to carry the activating BRAF mutation V600E. In our retrospective study, we evaluated the occurrence and prognostic impact of the V600E mutation in formaldehyde-fixed, paraffin-embedded samples from 15 pediatric LCH cases treated at our institution. Allele-specific polymerase chain reaction (PCR) and direct sequencing were used to demonstrate the presence of V600E mutation, and immunohistochemistry (IHC) using the mutant protein-specific VE1 antibody clone was performed to confirm mutant BRAF protein expression. Eight of 15 (53.3%) cases proved to be BRAF mutants by any of the methods applied, with a single case showing a discrepancy (PCR negative/IHC positive). Four of the BRAF-mutant cases (50.0%) showed refractory disease and progressed to death within 43 months, whereas the remaining mutant cases were stable and responded well to therapy. Wild-type BRAF cases (7/15, 46.6%) with generally comparable initial presentation were all treated successfully. In conclusion, activating V600E BRAF mutation can be frequently demonstrated in pediatric LCH by both allele-specific PCR and IHC. Unfavorable risk cases potentially also responding to BRAF-inhibitory therapy can be identified by mutation testing using archival formaldehyde-fixed, paraffin-embedded tumor samples.

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