Immune Escape Mechanisms in Intravascular Large B-Cell Lymphoma: A Molecular Cytogenetic and Immunohistochemical Study

Objectives Intravascular large B-cell lymphomas (IVLBCLs) are rare extranodal LBCLs in which relapse is relatively frequent. We sought to further characterize potential immune escape mechanisms in IVLBCLs that newer therapies can exploit. Methods A series of 33 IVLBCLs were evaluated for programmed cell death ligand 1 (PD-L1) and PD-L2 expression by immunohistochemistry (IHC), chromosomal alterations (CAs) in the PDL1/PDL2 locus by fluorescence in situ hybridization, and loss of major histocompatibility complex (MHC) class I and II expression by IHC. Results Cases were subclassified as classical (n = 22) or hemophagocytic syndrome (HPS)-associated (n = 11) variants. A total of 12 cases (39%; n = 12/31) expressed PD-L1 and/or PD-L2. CAs were seen in 7 cases (7/29 [24%]) and included gains, amplifications, and rearrangements. CAs in classical variant cases (24%; n = 5/21) included gains (n =1), gains with concurrent rearrangements (n = 2), and amplifications (n = 2). The 2 HPS-associated variant cases with CAs (25%; n = 2/8) both showed amplification, including 1 case with a concurrent rearrangement. A majority of cases with CAs (71%; n = 5/7) were PD-L1/PD-L2 IHC positive. Among PD-L1/PD-L2 IHC-positive cases, 45% harbored a CA. Loss of MHC class I and/or class II was seen in 27% (n = 9/33) of cases. Conclusions Altogether, our data show that 65% (n = 20/31) of IVLBCLs may exploit immune evasion strategies through PD-L1/PD-L2 expression or downregulation of MHC proteins.