Effect of targeted therapies on non-LCH and concomitant myeloid neoplasm. (A-E) Effect of vemurafenib on a 75-year-old patient with BRAFV600E-mutant ECD and concomitant JAK2V617F/IDH2R140Q-mutant MDS/MPN. (A) Absolute monocytes (orange line; left y-axis) and urinary BRAFV600E cell-free DNA quantitation (red line; right y-axis) pre- and postvemurafenib therapy (shaded area represents period of vemurafenib treatment). (B) ¹⁸F-FDG PET scan pre- (left) and postvemurafenib (right) with corresponding fused computed tomography/¹⁸F-FDG PET below. (C) Hematoxylin and eosin–stained biopsies of femoral bone revealing characteristic xanthogranulomatous lesion of ECD within a fibrotic background (histiocytes were CD68⁺ by immunohistochemistry [not shown]). Original magnification ×400. (D) Evidence of myeloid neoplasm because of the presence of dysplastic myeloid cells (hypogranulation and pseudo–Pelger-Huet cell) in BM aspirate (left; original magnification ×400), increased number of CD34⁺ cells (middle; original magnification ×100), and hematoxylin and eosin stain revealing hypercellular marrow with dysplastic megakaryocytes (right; original magnification ×200). (E-G) Effect of MEK inhibitor therapy on monocytosis and PB counts on the 66-year-old patient with NRASQ61R-mutant ECD and CMML described in Figure 1. ¹⁸F-FDG PET (F) and fused computed tomography/¹⁸F-FDG PET (G) pre- and 2 months posttrametinib treatment in this same patient.