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 EBVencoded RNA 1 (EBER1) signals by RNA in 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‐GCB cells, and EBV+ DLBCL frequently have a non‐functional IgH gene owing to crippling mutation.