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

AbstractLangerhans cell histiocytosis (LCH) is a clonal histiocytic disorder with recurrent mutations ofBRAF andMAP2K1, 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 inBRAFV600 andMAP2K1 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 showedBRAFV600E, one case aBRAFV600D and eleven (30%) aMAP2K1 mutation. Nine cases were unmutated for both genes. All cases with risk organ involvement showed eitherBRAFV600 orMAP2K1 mutation. Patients withBRAFV600 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-BRAFV600/MAP2K1 mutated  = 2/7, 29%). In addition, 8/9 cases with skin involvement including all Hashimoto-Pritzker cases (n = 3) were positive forBRAFV600E. Infants below 2  years more frequently hadBRAFV600 mutations (p = 0.013). Despite favorable prognosis, pediatric LCH shows a high frequency of relapses and long-term medical sequelae.
Source: Annals of Hematology - Category: Hematology Source Type: research