BRAFV600E mutation in cutaneous lesions of patients with adult Langerhans cell histiocytosis

Abstract

Background Langerhans cell histiocytosis (LCH) is characterized by the proliferation of pathologic Langerhans cells. The disease can develop in any age and can affect almost any organ. Cutaneous involvement is frequent in LCH. The recent demonstration of the activating, oncogenic BRAFV600E gene mutation in LCH samples strongly supports the neoplastic origin of the disease. Objectives Our aim was to analyse the clinical data of the patients and whether BRAFV600E mutation is present in skin lesions of patients with adult onset LCH, and to investigate whether the BRAFV600E mutation status has any effect on the clinical presentation and the outcome of the disease. Methods We diagnosed and treated 15 adult LCH patients in the period of 1987–2012 and collected their clinical data. Three of our patients suffered from skin involvement and 12 patients had multiorgan disease (five patients out of the multisystem group died). Eleven formalin‐fixed paraffin‐embedded skin samples from 10 patients were available for BRAFV600E mutation analysis. Results Among the 11 examined samples, 6 contained the BRAFV600E mutation (54.5%). Our results indicate that in the adult group of LCH patients the presence of BRAFV600E mutation is similar to what was previously suggested in case of the childhood forms, at least as far as skin lesions are concerned. The BRAF mutation status of our patients does not seem to correlate with the extent and/or the outcome of the disease. Conclusion Our results support the neoplastic origin of LCH and suggest that skin lesions of LCH are sufficient for the diagnosis of the disease and for assessing its BRAF status. In addition, analysis of BRAF status of patients with LCH can lead to the administration of new targeted therapies which may provide better disease control and prognosis.