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01-07-2019 | Langerhans Cell Histiocytosis | Original Article

Pediatric Langerhans cell histiocytosis: the impact of mutational profile on clinical progression and late sequelae

Authors: D. Nann, P. Schneckenburger, J. Steinhilber, G. Metzler, R. Beschorner, C. P. Schwarze, P. Lang, R. Handgretinger, Falko Fend, M. Ebinger, I. Bonzheim

Published in: Annals of Hematology | Issue 7/2019

Abstract

Langerhans cell histiocytosis (LCH) is a clonal histiocytic disorder with recurrent mutations of BRAF and MAP2K1, but data on the impact of genetic features on progression and long-term sequelae are sparse. Cases of pediatric LCH with long-term follow-up from our institution were analyzed for mutations in BRAF^V600 and MAP2K1 exons 2 and 3 by immunostaining with mutation-specific VE1 antibody, as well as allele-specific PCR and sequencing, respectively. Clinical and follow-up data were obtained from our files and a questionnaire sent to all former patients. Sixteen of 37 (43%) evaluable cases showed BRAF^V600E, one case a BRAF^V600D and eleven (30%) a MAP2K1 mutation. Nine cases were unmutated for both genes. All cases with risk organ involvement showed either BRAF^V600 or MAP2K1 mutation. Patients with BRAF^V600 mutation excluding Hashimoto-Pritzker cases had a significantly higher risk for relapses (p = 0.02). Long-term sequelae were present in 19/46 (41%) patients (median follow-up 12.5 years, range 1.0 to 30.8) with a trend for higher rates in mutated cases (mutated = 9/17, 53% versus non-BRAF^V600/MAP2K1 mutated = 2/7, 29%). In addition, 8/9 cases with skin involvement including all Hashimoto-Pritzker cases (n = 3) were positive for BRAF^V600E. Infants below 2 years more frequently had BRAF^V600 mutations (p = 0.013). Despite favorable prognosis, pediatric LCH shows a high frequency of relapses and long-term medical sequelae.

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Title: Pediatric Langerhans cell histiocytosis: the impact of mutational profile on clinical progression and late sequelae
Authors: D. Nann
P. Schneckenburger
J. Steinhilber
G. Metzler
R. Beschorner
C. P. Schwarze
P. Lang
R. Handgretinger
Falko Fend
M. Ebinger
I. Bonzheim
Publication date: 01-07-2019
Publisher: Springer Berlin Heidelberg
Keyword: Langerhans Cell Histiocytosis
Published in: Annals of Hematology / Issue 7/2019
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-019-03678-y

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