Clinicopathologic correlates of L265P mutation and programmed cell death (PD-1) pathway in primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) patients have a poorer prognosis than systemic lymphoma. Gain-of-function c.794T > C (p. L265P) mutation and programed cell death-1 (PD-1) pathway alterations are potential targetable pathways. Our study objective was to determine the clinicopathologic correlates of mutation and PD-1 alterations in PCNSL and the impact of Epstein-Barr virus (EBV) infection. We studied 53 cases including 13 EBV-associated (EBV) PCNSL, 49% harbored mutation, none seen in EBV PCNSL. MYD88 protein expression did not correlate with mutation. T-cell and macrophage infiltration was common. All PD-L1-positive tumors were EBV. Two PD-L1 positive tumors showed 9p24.1/PD-L1 locus alterations by Fluorescence Hybridization. T cells and macrophages expressed PD-1 and/or PD-L1 in 98% and 83% cases, respectively. mutation or protein expression and PD-1 or PD-L1 expression did not predict outcome. We hypothesize that EBV PCNSL has a distinct activation mechanism, independent of genetic alterations.