EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity

M. K. Gandhi, T. Hoang, S. C. Law, S. Brosda, K. O'Rourke, J. W.D. Tobin, F. Vari, V. Murigneux, L. Fink, J. Gunawardana, C. Gould, H. Oey, K. Bednarska, S. Delecluse, R. U. Trappe, L. Merida de Long, M. B. Sabdia, G. Bhagat, G. Hapgood, E. BlythL. Clancy, J. Wight, E. Hawkes, L. M. Rimsza, A. Maguire, K. Bojarczuk, B. Chapuy, C. Keane

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression (eg, posttransplant lymphoproliferative disorders or HIV [AIDS-related PCNSL]). These cases are poorly characterized, have dismal outcome, and are typically Epstein-Barr virus (EBV)-associated (ie, tissue-positive). We used targeted sequencing and digital multiplex gene expression to compare the genetic landscape and tumor microenvironment (TME) of 91 PCNSL tissues all with diffuse large B-cell lymphoma histology. Forty-seven were EBV tissue-negative: 45 EBV HIV PCNSL and 2 EBV HIV+ PCNSL; and 44 were EBV tissue-positive: 23 EBV+ HIV+ PCNSL and 21 EBV+ HIV PCNSL. As with prior studies, EBV HIV PCNSL had frequent MYD88, CD79B, and PIM1 mutations, and enrichment for the activated B-cell (ABC) cell-of-origin subtype. In contrast, these mutations were absent in all EBV tissue-positive cases and ABC frequency was low. Furthermore, copy number loss in HLA class I/II and antigen-presenting/processing genes were rarely observed, indicating retained antigen presentation. To counter this, EBV+ HIV PCNSL had a tolerogenic TME with elevated macrophage and immune-checkpoint gene expression, whereas AIDS-related PCNSL had low CD4 gene counts. EBV-associated PCNSL in the immunosuppressed is immunobiologically distinct from EBV HIV PCNSL, and, despite expressing an immunogenic virus, retains the ability to present EBV antigens. Results provide a framework for targeted treatment.

Original languageEnglish (US)
Pages (from-to)1468-1477
Number of pages10
Issue number11
StatePublished - Mar 18 2021

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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