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Publication
Clinicopathologic correlates of MYD88 L265P mutation and programmed cell death
(PD-1) pathway in primary central nervous system lymphoma.
Authors Sethi TK, Kovach AE, Grover NS, Huang LC, Lee LA, Rubinstein SM, Wang Y, Morgan
DS, Greer JP, Park SI, Ann Thompson-Arildsen M, Yenamandra A, Vnencak-Jones CL,
Reddy NM
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Leukemia & lymphoma
Year 2019
Date Published 12/1/2019
Volume : Pages 60 : 2880 - 2889
PubMed Reference 31184237
Abstract Primary central nervous system lymphoma (PCNSL) patients have a poorer prognosis
than systemic lymphoma. Gain-of-function MYD88 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 MYD88 mutation and PD-1 alterations in PCNSL and the impact of Epstein-Barr
virus (EBV) infection. We studied 53 cases including 13 EBV-associated (EBVpos)
PCNSL, 49% harbored MYD88 mutation, none seen in EBVpos PCNSL. MYD88 protein
expression did not correlate with MYD88 mutation. T-cell and macrophage
infiltration was common. All PD-L1-positive tumors were EBVpos. Two PD-L1
positive tumors showed 9p24.1/PD-L1 locus alterations by Fluorescence In Situ
Hybridization. T cells and macrophages expressed PD-1 and/or PD-L1 in 98% and
83% cases, respectively. MYD88 mutation or protein expression and PD-1 or PD-L1
expression did not predict outcome. We hypothesize that EBVpos PCNSL has a
distinct activation mechanism, independent of genetic alterations.




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