Primary diffuse large B-cell lymphomas of central nervous system exhibit remarkably high prevalence of oncogenic MYD88 and CD79B mutations.

MYD88 and CD79B mutations that activate nuclear factor (NF)-κB signaling are prevalent in subsets of diffuse large B-cell lymphoma (DLBCL). We examined the prevalence of somatic mutations in the Toll/interleukin-1 receptor (TIR) domain of MYD88 and the tyrosine-based activation motif (ITAM) domain of CD79A/B in 18 primary central nervous system (CNS) DLBCLs, and their immunoprofile. MYD88 mutation was found in 17 cases (94.4%), all of which were L265P substitutions. CD79B mutation was found in 11 cases (61.1%), 10 (55.6%) of which were Y196C/D/H substitutions. Mutation of CD79A was completely absent. Immunohistochemically, all the tumors were CD3-/CD5-/CD20+/CD79a+/ GCET1-/BCL6+/MUM1+. Three (16.7%) cases were CD10+, but the majority (15 cases, 83.3%) were CD10-. Overall, all cases harbored either MYD88(L265P) or CD79B(Y196C/D/H), or both, irrespective of their immunoprofile. Our results suggest that CNS DLBCL is a group of tumors harboring a characteristic mutation profile which triggers NF-κB signaling in the immune-privileged site.