Findings in a 66-year-old man with ECD. (A) Contrast-enhanced sagittal magnetic resonance imaging scan demonstrates lobulated enhancing masses arising from the cerebral meninges. (B) Fluorodeoxyglucose-avid lesions in the abdomen, pelvis, and long bones are shown, and (C) the classic scintigraphic uptake in the long bones is demonstrated. NRAS_182A>G (Q61R) mutation detection assay by MassARRAY (Sequenom) genotyping is demonstrated in (D). This method is designed to generate a small amplicon at a known mutation site from small amounts of tumor FFPE DNA. Mutation calls are based on the mass differences between the wild-type extension product and the mutant extension products as resolved by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The single nucleotide change in the extension product is detected by mass spectroscopy. The allele from the tumor (top panel) contains a mutated G allele at position 182. A control wild-type allele is shown (bottom panel). (E) Sanger sequencing of tumor tissue demonstrates the NRAS Q61R mutation in the tumor (left), NRAS wild type in the peripheral blood lymphocytes (middle), and NRAS Q61 mutant melanoma cell line (right) as a positive control. (F) Biopsy result of the presacral mass demonstrates a xanthomatous histiocytic infiltrate, consistent with ECD. (G) Immunohistochemistry result for phosphoextracellular signal-regulated kinase (pERK1/2) is positive in the nuclei of tumor histiocytes (blue arrow) and in the surrounding vasculature but is negative in the nontumor stromal cells (red arrow).