Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis.
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.
Baecklund
Eva
E
Department of Rheumatology, Akademiska Hospital, Uppsala, Sweden. Eva.Baecklund@swipnet.se
Backlin
Carin
C
Iliadou
Anastasia
A
Granath
Fredrik
F
Ekbom
Anders
A
Amini
Rose-Marie
RM
Feltelius
Nils
N
Enblad
Gunilla
G
Sundström
Christer
C
Klareskog
Lars
L
Askling
Johan
J
Rosenquist
Richard
R
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
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