Ibrutinib, a BTK inhibitor, inhibits NF-κB signaling pathway and has been used for treatments of systemic non-GCB DLBCLs14 and PCNSLs.16,38 An 83% partial response rate was reported in a recent clinical trial of ibrutinib in PCNSL.16 Our findings suggest that identification of the MYD88 L265P mutation in PCNSLs may help evaluate the benefits associated with the use of targeted therapy in these patients. This evidence concerns the gene NFKB1 and primary central nervous system lymphoma.