Abstract
Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (≥40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply to CNS DLBCL due to differences in disease biology.
Highlights
Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) arising in the brain or an intraocular location
We evaluated MYC protein expression in conjunction with a variety of morphologic, immunophenotypic, genetic, and clinical parameters in a large single-center series of CNS DLBCL to determine whether MYC protein expression could serve as a prognostic or theranostic biomarker
MYC overexpression (>40%) was noted in 73% of our cases, which is slightly lower that the frequency recently reported by Brunn et al (92%) but still higher than that described in systemic DLBCL [9, 10, 12]
Summary
Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) arising in the brain or an intraocular location. CNS DLBCL is rare, accounting for ,1% of all non-Hodgkin lymphomas and approximately 3% of all primary brain neoplasms [2]. Compared to systemic DLBCL, CNS DLBCL has a poor prognosis, and it remains unclear whether this reflects a location specific or microenvironmental effect, inherent aggressive biology of the tumor, or a combination of these factors. The cell-of-origin (COO) of CNS DLBCL is thought to be a late germinal center B-cell based on immunophenotypic analysis, gene expression profiling, and molecular characterization of the immunoglobulin genes [3, 4]. The biology of CNS DLBCL is poorly understood due to its rarity and, in part, due to difficulty in obtaining sufficient tumor samples
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