Genomic Profile and Pathologic Features of Diffuse Large B-Cell Lymphoma Subtype of Methotrexate-associated Lymphoproliferative Disorder in Rheumatoid Arthritis Patients

Rheumatoid arthritis patients often develop the diffuse large B-cell lymphoma subtype of methotrexate-associated lymphoproliferative disorder (DLBCLMTX-LPD). We characterized the genomic profile and pathologic characteristics of 20 biopsies using an integrative approach. DLBCLMTX-LPD was associated with extranodal involvement, a high/high-intermediate international prognostic index in 53% of cases, and responded to MTX withdrawal. The phenotype was nongerminal center B-cell in 85% of samples and Epstein-Barr encoding region positive (EBER+) in 65%, with a high proliferation index and intermediate MYC expression levels. The immune microenvironment showed high numbers of CD8+ cytotoxic T lymphocytes and CD163+ M2 macrophages with an (CD163/CD68) M2 ratio of 3.6. Its genomic profile was characterized by 3p12.1-q25.31, 6p25.3, 8q23.1-q24.3, and 12p13.33-q24.33 gains, 6q22.31-q24.1 and 13q21.33-q34 losses, and 1p36.11-p35.3 copy neutral loss-of-heterozygosity. This profile was closer to nongerminal center B-cell DLBCL not-otherwise-specified, but with characteristic 3q, 12q, and 20p gains and lower 9p losses (P
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research