Age‐related EBV‐associated B‐cell lymphoproliferative disorders and other EBV + lymphoproliferative diseases: New insights into immune escape and immunodeficiency through staining with anti‐PD‐L1 antibody clone SP142

Epstein–Barr virus (EBV) is prevalent among healthy individuals, and is implicated in numerous reactive and neoplastic processes in the immune system. The authors originally identified a series of senile or age‐related EBV‐associated B‐cell lymphoproliferative disorders (LPD) bearing a resemblance to immunodeficiency‐associated ones. These LPDs may be associated with immune senescence and are now incorporated into the revised 4th edition of 2017 WHO lymphoma classification as EBV‐positive (EBV+) diffuse large B‐cell lymphoma (DLBCL), not otherwise specified (NOS). These EBV+ B‐cells often have a Hodgkin/Reed‐Sternberg (HRS)‐like appearance and are shared beyond the diagnostic categories of mature B‐cell neoplasms, mature T‐cell neoplasms, classic Hodgkin lymphoma, and immunodeficiency‐associated LPD. In addition, peculiar new diseases, such as EBV+ mucocutaneous ulcer and EBV+ DLBCL affecting the young, were recognized. On the other hand, lymphoma classification is now evolving in accord with deeper understanding of the biology of programmed death ligand 1 (PD‐L1). Assessing PD‐L1 positivity by staining with the anti‐PD‐L1 monoclonal antibody SP142 provides new insight by discriminating between immune evasion and senescence or immunodeficiency. The aim of the present review is to briefly summarize the diagnostic use of immunostaining with SP142 in malignant lymphomas and/or LPDs that feature tumor and nonmalignant large B‐cells harboring EBV.