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MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system.

Gill KZ, Iwamoto F, Allen A, Hoehn D, Murty VV, Alobeid B, Bhagat G - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, United States of America.

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.

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Representative examples of patterns of CNS DLBCL infiltration and MYC protein expression.H&E-stained section of a CNS DLBCL exhibiting a diffuse pattern of infiltration (A), CD20 expression (B), and MYC expression by 80% of neoplastic cells (C). H&E-stained section of a CNS DLBCL exhibiting a perivascular pattern of infiltration (D), CD20 expression (E), and MYC expression by 30% of neoplastic cells (F). All photomicrographs were taken at 40x magnification.
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pone-0114398-g002: Representative examples of patterns of CNS DLBCL infiltration and MYC protein expression.H&E-stained section of a CNS DLBCL exhibiting a diffuse pattern of infiltration (A), CD20 expression (B), and MYC expression by 80% of neoplastic cells (C). H&E-stained section of a CNS DLBCL exhibiting a perivascular pattern of infiltration (D), CD20 expression (E), and MYC expression by 30% of neoplastic cells (F). All photomicrographs were taken at 40x magnification.

Mentions: Forty-seven (80%) cases were classified as centroblastic, two of which exhibited signet ring cell features; 2 (3%) were immunoblastic; 1 (2%) was anaplastic; four (7%) exhibited plasmacytoid morphology; and 5 (8%) had morphologic features intermediate between DLBCL and Burkitt lymphoma (representative cases are illustrated in Figure 1). Twelve cases (20%) showed a perivascular pattern of infiltration, and the remainder showed a diffuse pattern (representative examples are shown in Figure 2).


MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system.

Gill KZ, Iwamoto F, Allen A, Hoehn D, Murty VV, Alobeid B, Bhagat G - PLoS ONE (2014)

Representative examples of patterns of CNS DLBCL infiltration and MYC protein expression.H&E-stained section of a CNS DLBCL exhibiting a diffuse pattern of infiltration (A), CD20 expression (B), and MYC expression by 80% of neoplastic cells (C). H&E-stained section of a CNS DLBCL exhibiting a perivascular pattern of infiltration (D), CD20 expression (E), and MYC expression by 30% of neoplastic cells (F). All photomicrographs were taken at 40x magnification.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257680&req=5

pone-0114398-g002: Representative examples of patterns of CNS DLBCL infiltration and MYC protein expression.H&E-stained section of a CNS DLBCL exhibiting a diffuse pattern of infiltration (A), CD20 expression (B), and MYC expression by 80% of neoplastic cells (C). H&E-stained section of a CNS DLBCL exhibiting a perivascular pattern of infiltration (D), CD20 expression (E), and MYC expression by 30% of neoplastic cells (F). All photomicrographs were taken at 40x magnification.
Mentions: Forty-seven (80%) cases were classified as centroblastic, two of which exhibited signet ring cell features; 2 (3%) were immunoblastic; 1 (2%) was anaplastic; four (7%) exhibited plasmacytoid morphology; and 5 (8%) had morphologic features intermediate between DLBCL and Burkitt lymphoma (representative cases are illustrated in Figure 1). Twelve cases (20%) showed a perivascular pattern of infiltration, and the remainder showed a diffuse pattern (representative examples are shown in Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, United States of America.

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.

Show MeSH
Related in: MedlinePlus