The diagnosis was made by performing next-generation molecular testing on ctDNA in the CSF with MSK-IMPACT, a FDA-authorized DNA sequencing panel targeting over 400 oncogenes and tumor suppressor genes identifying mutations, copy number alterations, and gene fusions.8 The presence of MYD88, CD58, HIST1H1C, KMT2D, and LCK in the patient’s CSF made the molecular diagnosis of PCNSL and guided treatment. This evidence concerns the gene KMT2D and primary central nervous system lymphoma.