Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
SLE has been consistently associated with an increased incidence of malignant lymphoma, especially the DLBCL subtype. Since the last WHO classification of 2008 DLBCL are now further divided, based on the cell-of-origin (COO) subtypes. The two major subtypes were defined by gene expression profiling of fresh frozen (FF) samples as germinal centre B-cell-like (GCB) and activated B-cell-like (ABC). Using tissue microarray (TMA) and immunohistochemistry (IHC) in diagnostic formalin fixed paraffin embedded (FFPE) in biopsies, COO is routinely defined as GCB or non-GCB. The ABC/non-GCB subtype presents the worse prognosis and has previously been associated with rheumatoid arthritis. Our objective was to compare the frequency of non-GCB and GCB subtypes in DLBCL within a cohort of patients diagnosed with lupus.
From a multi-centre cohort, 13 cases of DLBCL in lupus patient were identified, for which tissue and pathologic diagnosis were available. Tissue microarrays (TMA) were then built and submitted to Vancouver where IHC and scoring was performed. Immunostains were performed including lineage markers (CD20, CD3) and COO markers CD10, BCL6, MUM1, GCET1 and FOXP1. The COO was determined using both the Hans and Choi algorithms.
Eleven cases of DLBCL in patients with established SLE could be included for analysis. The diagnosis of DLBCL was confirmed by a reference hematopathologist. In the SLE DLBCL cases, BCL6 was positive in 5/11 (45%), CD10 in 2/11 (18%), FOXP1 7/11 (64%), in GCET1 0/11 (0%) and MUM1 4/11 (36%). Of the SLE DLBCL cases, 7/11 (64%) were classified as non-GCB and 4/11 (36%) were classified as GCB. This contrasts with a recent analysis of COO based on a population-based registry study of DLBCL in British Columbia (n = 348) using the Hans algorithm, with 59% GCB and 41% non-GCB.
In conclusion, DLBCL arising in patients with a prior history of SLE show an enrichment of non-GCB cell-of-origin subtype, mimicking data seen in rheumatoid arthritis. Although a small sample size, these findings suggest that like lymphoma development in the face of chronic inflammation, DLBCL arising in SLE patients and related autoimmune disorders tends to be enriched in the ABC/non-GCB subtype. These findings have implications as we enter an era of COO-specific treatments based on improved biological understanding. Further studies are planned to increase the size of the cohort.
To cite this abstract in AMA style:Tessier Cloutier B, Farinha P, Bernatsky S, Baecklund E, Clarke AE, Ramsey-Goldman R, Gascoyne R. Cell of Origin of Diffuse Large B-Cell Lymphoma (DLBCL) in Patients with Systemic Lupus Erythematosus (SLE) [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/cell-of-origin-of-diffuse-large-b-cell-lymphoma-dlbcl-in-patients-with-systemic-lupus-erythematosus-sle/. Accessed February 27, 2020.
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