Lymphoma subtypes in patients with rheumatoid arthritis: increased proportion of diffuse large B cell lymphoma

Arthritis Rheum. 2003 Jun;48(6):1543-50. doi: 10.1002/art.11144.


Objective: Patients with rheumatoid arthritis (RA) have an increased risk of developing malignant lymphoma. It is not clear whether the increase is confined to certain subtypes of lymphomas. Immunosuppressive therapy and Epstein-Barr virus (EBV) have been linked to the development of these lymphomas. To gain information about the baseline pattern of lymphoma subtypes in RA before the current widespread use of immunosuppressive drugs, we examined the distribution of lymphoma subtypes and the presence of EBV in a cohort of RA patients with a low frequency and duration of treatment with immunosuppressive drugs.

Methods: By linking data from the Swedish Hospital Discharge Register and the Swedish Cancer Register, 42 cases of lymphoma were identified among 11683 patients with RA in the Uppsala Health Care Region between 1964 and 1984. The medical records and paraffin-embedded lymphoma tissues were collected, and the lymphomas were reclassified using the World Health Organization classification. In situ hybridization was used to detect EBV.

Results: Tissues from 35 patients were reviewed. Non-Hodgkin's lymphoma (NHL) was found in 33 patients and Hodgkin's lymphoma in 2 patients. There was an increased frequency of diffuse large B cell lymphoma (DLBCL) (22 of 33 NHL patients, 67%) compared with that in the general population (30-40%). EBV was detected in 5 of 30 examined lymphomas from patients (17%). Twenty of the 22 DLBCL patients had RA with medium or high inflammatory activity, and 6 had been treated with a disease-modifying antirheumatic drug for >or=1 year.

Conclusion: The findings of this study suggest an increased incidence of one specific lymphoma subtype, DLBCL, in RA patients, as well as a possible association with RA disease activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / epidemiology
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / epidemiology
  • Female
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • In Situ Hybridization
  • Lymphoma, B-Cell / epidemiology
  • Lymphoma, B-Cell / etiology*
  • Lymphoma, Large B-Cell, Diffuse / epidemiology
  • Lymphoma, Large B-Cell, Diffuse / etiology*
  • Male
  • Middle Aged
  • RNA, Viral / analysis
  • Registries*
  • Retrospective Studies
  • Sweden / epidemiology


  • RNA, Viral