Abstract
Objective
Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA‐associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)–like and non–GC‐like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes.
Methods
We identified 139 patients with DLBCLs within a population‐based case–control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl‐6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non‐GC subtypes, and then correlated with clinical parameters.
Results
We found a statistically significant predominance of the non‐GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5‐year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non‐GC cases occurring in RA patients with the highest overall disease activity scores.
Conclusion
These findings suggest that severe RA is particularly associated with the non‐GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.