title: Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, Akademiska Hospital, Uppsala, Sweden. Eva.Baecklund@swipnet.se
authors.forename: Eva
authors.initials: E
authors.lastname: Baecklund
authors.forename: Carin
authors.initials: C
authors.lastname: Backlin
authors.forename: Anastasia
authors.initials: A
authors.lastname: Iliadou
authors.forename: Fredrik
authors.initials: F
authors.lastname: Granath
authors.forename: Anders
authors.initials: A
authors.lastname: Ekbom
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
authors.forename: Nils
authors.initials: N
authors.lastname: Feltelius
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000378:metabolism / Q000401:mortality; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D015897:Comorbidity; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000150:complications* / Q000378:metabolism / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology; D000099218:Interferon Regulatory Factor-4
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D015260:Neprilysin; D051560:Proto-Oncogene Proteins c-bcl-6; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human