Abstract: Background and purpose: MYD88 gene has a certain mutation rate in diffuse large B-cell lymphoma (DLBCL), whereas its clinicopathological relevance is largely unknown. This study aimed to investigate the MYD88 gene mutation in DLBCL and its clinicopathological relevance. Methods: A total of 121 cases of DLBCL were collected. The immunophenotype was detected using immunohistochemistry. MYD88 gene mutation status was analyzed using a PCR assay and direct sequencing. Correlation analysis was performed using statistical methods. Results: Thirty-eight out of 121 DLBCL patients carried MYD88 L265P mutation, among whom 50 were males and 71 were females. There was no correlation between MYD88 mutation and gender. MYD88 mutation frequency in ≥60 years age group (25/62, 40.3%) was significantly higher than that in <60 years group (13/59, 22.0%) (P=0.030). This gene mutation occurred predominantly in extranodal sites, most commonly in breast (12/13, 92.3%), male reproductive system (10/11, 90.9%), female reproductive system (5/6, 83.3%) and central nervous system (4/6, 66.7%). The mutation frequency was much higher in extranodal DLBCL patients (35/98, 35.7%) than in nodal ones (2/20, 10.0%) (P=0.024). In non-GCB group, MYD88 mutation was found in 39.7% (25/63) cases, which was significantly higher than that in GCB group (10/55, 18.2%) (P=0.010). Among extranodal cases, MYD88 mutation was more significantly associated with the immunophenotype of DLBCL (P=0.003), while there was no correlation between these two parameters in nodal group (P=0.776). MYD88 mutation was more frequently seen in Bcl-2 positive group (30/77, 39.0%) than in Bcl-2 negative group (5/40, 12.5%) (P=0.003). In MYC/Bcl-2 double expression group, MYD88 mutation was significantly more common than in others (16/70, 22.9%) (P=0.034). DLBCL patients with high Ki-67 proliferation index (33/85, 38.8%) also had remarkably higher frequency of MYD88 mutation than those with low Ki-67 proliferation index (2/32, 6.3%) (P<0.001). Nevertheless neither MYC protein nor CD5 had correlation with MYD88 mutation (P=0.581 and 0.759). Conclusion: MYD88 L265P mutation in DLBCL is related with older age (≥60 years), non-GCB origin and special anatomic sites, including breast, reproductive system and central nervous system, which might also demonstrate a high proliferation index and MYC/Bcl-2 double expression rate. The survival relevance of MYD88 mutation needs to be further illustrated with larger cohort studies, and this gene mutation might provide new insights into the pathogenesis and targeted therapy for DLBCL.

Key words: Diffuse large B-cell lymphoma, MYD88 gene mutation, Immunophenotype, MYC, Bcl-2