Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis

Arthritis Rheum. 2006 Dec;54(12):3774-81. doi: 10.1002/art.22277.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / mortality
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Comorbidity
  • DNA-Binding Proteins / metabolism
  • Female
  • Germinal Center / pathology
  • Humans
  • Interferon Regulatory Factors / metabolism
  • Lymphoma, B-Cell / complications*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / mortality
  • Lymphoma, Large B-Cell, Diffuse / complications*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Neprilysin / metabolism
  • Proto-Oncogene Proteins c-bcl-6
  • Survival Rate
  • Sweden / epidemiology

Substances

  • Antigens, Neoplasm
  • BCL6 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Interferon Regulatory Factors
  • Proto-Oncogene Proteins c-bcl-6
  • interferon regulatory factor-4
  • Neprilysin