A Spindle Cell Variant Of Diffuse Large B-Cell Lymphoma Is Characterized By T-Cell/Myofibrohistio-Rich Stromal Alterations: Analysis Of 10 Cases And A Review Of The Literature

Spindle-shaped diffuse large B-cell lymphoma (Sp-DLBCL) has been recognized as a rare morphologic variant of DLBCL. However, the biological processes that contribute to the specific features of Sp-DLBCL remain poorly understood. In this study, a combined immunophenotypic and genetic analysis was performed in 10 Sp-DLBCL. First, we investigated several unique markers for anaplasia (CD30, ALK, CD68, and EBER-ISH), mesenchyma (SMA, desmin, and vimentin), and B-cell differentiation (CD10, BCL6, and MUM1). We also performed conventional cytogenetic and fluorescence in situ hybridization studies to look for common chromosomal break points (BCL2, BCL6, and MYC). We found that most Sp-DLBCLs were germinal center B cell-like and that none had any other specific phenotypes or any karyotypic abnormalities. Instead, T cells, CD68-positive macrophages and SMA-positive myofibroblasts were significantly increased in Sp-DLBCL when compared with conventional GCB origin DLBCL cases (n=10) (P=0.012, P<0.001, and P<0.0001, respectively). To further characterize Sp-DLBCL, we next compared the expression of fibroblast growth factor 2 (FGF2) and transforming growth factor-beta 1 (TGF beta 1) between the two types of DLBCL. Finally, we confirmed that the number of FGF2- and TGF beta 1-positive stromal cells was markedly increased in Sp-DLBCL and that the difference between these and conventional GCB origin DLBCLs was significant (P<0.0001 and P=0.0017, respectively). Thus, T-cell/myofibrohistio-rich stromal alterations in Sp-DLBCL, especially those mediated by TGF beta 1 and FGF2, may play a role in the transition of lymphoma cells into those with spindle-shaped features.