The characteristics of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma:: Comparison between EBV+ and EBV- cases in Japanese population

We have investigated 114 cases with diffuse large B-cell lymphoma (DLBCL) to clarify the characteristics of DLBCL with Epstein-Barr virus (EBV) infection. Thirteen cases (11.4%) showed EBV-encoded RNA 1 (EBER1) signals by RNA itt situ hybridization. EBV-encoded latent membrane protein 1 (LMP1) and EBV-encoded nuclear antigen 2 (EBNA2) were expressed in 11 and 4 cases, respectively. Expression of CD30, Bcl-6 and immunoglobulin (Ig) was found in 92%, 31% and 23% with EBV+ DLBCL, and in 15%, 79% and 82% with EBV- DLBCL, respectively. The sequence of rearranged Ig heavy chain (IgH) variable (V) region gene was analyzed in 5 cases with EBV+ DLBCL and 61 cases with EBV- DLBCL. Somatic mutation was found in all cases except one with EBV- DLBCL. Average mutation frequency was 9.6% in EBV+ DLBCL vs, 11.5% in EBV-DLBCL. The rates of replacement mutation vs. silent mutation (R/S values) in complementarity determining region II and framework region III were 2.7 and 1.5 in EBV+ DLBCL, 2.6 and 1.4 in EBV- DLBCL, Crippling mutation generating a stop codon was found in 2 of 5 cases (40%) with EBV+ DLBCL, but none of 61 cases (0%) with EBV- DLBCL. These findings suggest that EBV+ DLBCL and EBV- DLBCL were both derived from germinal center (GC) or post-GC B cells, and EBV+ DLBCL frequently have a non-functional IgH gene owing to crippling mutation.