Severe RA Ups Risk for One Subtype Of Diffuse Large B-Cell Lymphoma

The increased lymphoma risk seen in patients with severe rheumatoid arthritis appears to involve a specific subtype of diffuse large B-cell lymphoma that arises from activated peripheral blood B cells.

Dr. Eva Baecklund of Akademiska Hospital in Uppsala, Sweden, and her associates identified 139 RA patients with diffuse large B-cell lymphoma from within a population-based case-control study of 378 RA patients with lymphoma. The RA patients with lymphoma were originally identified from linkage of the nationwide Swedish Inpatient Register with the Swedish Cancer Register.

Diffuse large B-cell lymphoma (DLBCL) can be classified into two major subtypes based on gene expression profiles. One tumor subtype expresses genes characteristic of germinal center (GC) B cells. The other tumor subtype (non-GC) expresses genes seen in activated peripheral blood B cells.

In this study, the cases of DLBCL were classified as GC or non-GC based on immunohistochemistry using a three-marker system. CD10, Bcl-6, and interferon regulatory factor 4 (IRF-4, also known as multiple myeloma oncogene 1) were tested. Staining of 30% or more of tumor cells was defined as positive.

Investigators reviewed the original slides and paraffin-embedded lymphoma tissues from pathology laboratories and reclassified the tumors according to the World Health Organization classification system. Immunohistochemical staining for CD10, Bcl-6, and IRF-4 antibodies was performed on paraffin-imbedded tissue. Gene expression profiling could not be performed because of the lack of frozen tissue.

All tumors that stained positive for CD10, whether positive or negative for Bcl-6, were classified as GC-like. Tumors that stained negative for both CD10 and Bcl-6 were classified as non-GC-like. Tumors that showed negative staining for CD10 but positive staining for Bcl-6 were tested for IRF-4. CD10-negative/Bcl-6-positive tumor cells that showed positive staining for IRF-4 were classified as non-GC subtype, and those that showed negative IRF-4 staining were classified as GC subtype.

DLBCL tumors from 42 patients (30%) were identified as GC subtype, and DLBCL tumors from 97 patients (70%) were identified as non-GC subtype. Women were the majority in both the GC and non-GC groups (57% and 60%, respectively). The mean age of RA onset was around 50 years in each group. The mean age at lymphoma diagnosis was 70 years (range: 32–84 years) for patients with GC subtype DLBCL, compared with 71 years (range: 48–89) for patients with non-GC subtype DLBCL.

There were no significant differences between the two groups in RA functional class, disease activity, or RA treatment. Compared with patients with GC subtype DLBCL tumors, a higher proportion of patients with non-GC subtype DLBCL tumors had RA disease activity in functional classes III and IV, but the trend did not reach statistical significance (P = .07).

Tumor stage differed significantly in patients with non-GC subtype tumors, compared with those with GC subtype tumors (P = .005). A higher proportion of patients with non-GC subtype DLBCL tumors (60 patients; 64%) had disseminated lymphoma (Ann Arbor stage IV), compared with patients with GC DLBCL tumors (15 patients; 38%). Among patients in whom extranodal involvement could be assessed, significantly more patients with non-GC DLCBL tumors (72/93; 77%) had extranodal involvement, compared with patients with GC DLCBL tumors (25/39; 64%; P = .03).

In RA patients with advanced lymphoma, the prognosis was worse if the tumor subtype was non-GC.

The 5-year overall survival was 33% for patients with GC-subtype DLCBL tumors, compared with 16% for patients with non-GC subtype DLCBL tumors, the investigators wrote (Arthritis Rheum. 2006;12:3774–81).

The increased lymphoma risk seen in patients with severe rheumatoid arthritis appears to involve a specific subtype of diffuse large B-cell lymphoma that arises from activated peripheral blood B cells.

Dr. Eva Baecklund of Akademiska Hospital in Uppsala, Sweden, and her associates identified 139 RA patients with diffuse large B-cell lymphoma from within a population-based case-control study of 378 RA patients with lymphoma. The RA patients with lymphoma were originally identified from linkage of the nationwide Swedish Inpatient Register with the Swedish Cancer Register.

Diffuse large B-cell lymphoma (DLBCL) can be classified into two major subtypes based on gene expression profiles. One tumor subtype expresses genes characteristic of germinal center (GC) B cells. The other tumor subtype (non-GC) expresses genes seen in activated peripheral blood B cells.

In this study, the cases of DLBCL were classified as GC or non-GC based on immunohistochemistry using a three-marker system. CD10, Bcl-6, and interferon regulatory factor 4 (IRF-4, also known as multiple myeloma oncogene 1) were tested. Staining of 30% or more of tumor cells was defined as positive.

Investigators reviewed the original slides and paraffin-embedded lymphoma tissues from pathology laboratories and reclassified the tumors according to the World Health Organization classification system. Immunohistochemical staining for CD10, Bcl-6, and IRF-4 antibodies was performed on paraffin-imbedded tissue. Gene expression profiling could not be performed because of the lack of frozen tissue.

All tumors that stained positive for CD10, whether positive or negative for Bcl-6, were classified as GC-like. Tumors that stained negative for both CD10 and Bcl-6 were classified as non-GC-like. Tumors that showed negative staining for CD10 but positive staining for Bcl-6 were tested for IRF-4. CD10-negative/Bcl-6-positive tumor cells that showed positive staining for IRF-4 were classified as non-GC subtype, and those that showed negative IRF-4 staining were classified as GC subtype.

DLBCL tumors from 42 patients (30%) were identified as GC subtype, and DLBCL tumors from 97 patients (70%) were identified as non-GC subtype. Women were the majority in both the GC and non-GC groups (57% and 60%, respectively). The mean age of RA onset was around 50 years in each group. The mean age at lymphoma diagnosis was 70 years (range: 32–84 years) for patients with GC subtype DLBCL, compared with 71 years (range: 48–89) for patients with non-GC subtype DLBCL.

There were no significant differences between the two groups in RA functional class, disease activity, or RA treatment. Compared with patients with GC subtype DLBCL tumors, a higher proportion of patients with non-GC subtype DLBCL tumors had RA disease activity in functional classes III and IV, but the trend did not reach statistical significance (P = .07).

Tumor stage differed significantly in patients with non-GC subtype tumors, compared with those with GC subtype tumors (P = .005). A higher proportion of patients with non-GC subtype DLBCL tumors (60 patients; 64%) had disseminated lymphoma (Ann Arbor stage IV), compared with patients with GC DLBCL tumors (15 patients; 38%). Among patients in whom extranodal involvement could be assessed, significantly more patients with non-GC DLCBL tumors (72/93; 77%) had extranodal involvement, compared with patients with GC DLCBL tumors (25/39; 64%; P = .03).

In RA patients with advanced lymphoma, the prognosis was worse if the tumor subtype was non-GC.

The 5-year overall survival was 33% for patients with GC-subtype DLCBL tumors, compared with 16% for patients with non-GC subtype DLCBL tumors, the investigators wrote (Arthritis Rheum. 2006;12:3774–81).

The increased lymphoma risk seen in patients with severe rheumatoid arthritis appears to involve a specific subtype of diffuse large B-cell lymphoma that arises from activated peripheral blood B cells.

Dr. Eva Baecklund of Akademiska Hospital in Uppsala, Sweden, and her associates identified 139 RA patients with diffuse large B-cell lymphoma from within a population-based case-control study of 378 RA patients with lymphoma. The RA patients with lymphoma were originally identified from linkage of the nationwide Swedish Inpatient Register with the Swedish Cancer Register.

Diffuse large B-cell lymphoma (DLBCL) can be classified into two major subtypes based on gene expression profiles. One tumor subtype expresses genes characteristic of germinal center (GC) B cells. The other tumor subtype (non-GC) expresses genes seen in activated peripheral blood B cells.

In this study, the cases of DLBCL were classified as GC or non-GC based on immunohistochemistry using a three-marker system. CD10, Bcl-6, and interferon regulatory factor 4 (IRF-4, also known as multiple myeloma oncogene 1) were tested. Staining of 30% or more of tumor cells was defined as positive.

Investigators reviewed the original slides and paraffin-embedded lymphoma tissues from pathology laboratories and reclassified the tumors according to the World Health Organization classification system. Immunohistochemical staining for CD10, Bcl-6, and IRF-4 antibodies was performed on paraffin-imbedded tissue. Gene expression profiling could not be performed because of the lack of frozen tissue.

All tumors that stained positive for CD10, whether positive or negative for Bcl-6, were classified as GC-like. Tumors that stained negative for both CD10 and Bcl-6 were classified as non-GC-like. Tumors that showed negative staining for CD10 but positive staining for Bcl-6 were tested for IRF-4. CD10-negative/Bcl-6-positive tumor cells that showed positive staining for IRF-4 were classified as non-GC subtype, and those that showed negative IRF-4 staining were classified as GC subtype.

DLBCL tumors from 42 patients (30%) were identified as GC subtype, and DLBCL tumors from 97 patients (70%) were identified as non-GC subtype. Women were the majority in both the GC and non-GC groups (57% and 60%, respectively). The mean age of RA onset was around 50 years in each group. The mean age at lymphoma diagnosis was 70 years (range: 32–84 years) for patients with GC subtype DLBCL, compared with 71 years (range: 48–89) for patients with non-GC subtype DLBCL.

There were no significant differences between the two groups in RA functional class, disease activity, or RA treatment. Compared with patients with GC subtype DLBCL tumors, a higher proportion of patients with non-GC subtype DLBCL tumors had RA disease activity in functional classes III and IV, but the trend did not reach statistical significance (P = .07).

Tumor stage differed significantly in patients with non-GC subtype tumors, compared with those with GC subtype tumors (P = .005). A higher proportion of patients with non-GC subtype DLBCL tumors (60 patients; 64%) had disseminated lymphoma (Ann Arbor stage IV), compared with patients with GC DLBCL tumors (15 patients; 38%). Among patients in whom extranodal involvement could be assessed, significantly more patients with non-GC DLCBL tumors (72/93; 77%) had extranodal involvement, compared with patients with GC DLCBL tumors (25/39; 64%; P = .03).

In RA patients with advanced lymphoma, the prognosis was worse if the tumor subtype was non-GC.

The 5-year overall survival was 33% for patients with GC-subtype DLCBL tumors, compared with 16% for patients with non-GC subtype DLCBL tumors, the investigators wrote (Arthritis Rheum. 2006;12:3774–81).