B-cell posttransplant lymphoproliferative disorder isolated to the central nervous system is Epstein-Barr virus positive and lacks p53 and Myc expression by immunohistochemistry

Andrew Sundin; Bartosz J Grzywacz; Sophia Yohe; Michael A Linden; Elizabeth L Courville

doi:10.1016/j.humpath.2016.12.007

B-cell posttransplant lymphoproliferative disorder isolated to the central nervous system is Epstein-Barr virus positive and lacks p53 and Myc expression by immunohistochemistry

Hum Pathol. 2017 Mar:61:140-147. doi: 10.1016/j.humpath.2016.12.007. Epub 2016 Dec 16.

Authors

Andrew Sundin¹, Bartosz J Grzywacz², Sophia Yohe², Michael A Linden², Elizabeth L Courville³

Affiliations

¹ University of Minnesota Medical School, University of Minnesota, Minneapolis, MN 55455, USA.
² Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
³ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: [email protected].

PMID: 27993575
DOI: 10.1016/j.humpath.2016.12.007

Abstract

In this retrospective study from one institution, we performed a clinicopathological study of a cohort of patients with posttransplant lymphoproliferative disorder (PTLD) confined to the central nervous system. We also identified a comparison cohort of patients with de novo primary diffuse large B-cell lymphoma of the central nervous system. We performed a detailed morphologic review, evaluated Epstein-Barr virus (EBV) by in situ hybridization, and interpreted a panel of immunohistochemical stains in a subset of cases including Hans classification markers (CD10, BCL6, MUM1), p53, CD30, Myc, and BCL2. All 17 of the posttransplant and none of 11 de novo cases were EBV positive (P < .005). Morphologic patterns identified in the PTLD cases were monomorphic diffuse large B-cell lymphoma pattern (10 patients) and "T-cell-rich" pattern (7 patients). The monomorphic posttransplant cases were more likely to be Myc negative (P = .015) and CD30 positive (P < .005) than the de novo cases, and showed a similarly low rate of p53 positivity by immunohistochemistry. No prognostic factors for overall survival were identified. Central nervous system PTLD is EBV positive, typically lacks p53 and Myc expression by immunohistochemistry, and can present with numerous background T lymphocytes.

Keywords: Central nervous system lymphoma; Myc; PTLD; Posttransplant lymphoproliferative disorder; p53.

MeSH terms

Adolescent
Adult
Aged
B-Lymphocytes / chemistry*
B-Lymphocytes / immunology
B-Lymphocytes / pathology
B-Lymphocytes / virology
Biomarkers / analysis
Biopsy
Central Nervous System Neoplasms / chemistry*
Central Nervous System Neoplasms / immunology
Central Nervous System Neoplasms / pathology
Central Nervous System Neoplasms / virology
Central Nervous System Viral Diseases / immunology
Central Nervous System Viral Diseases / metabolism*
Central Nervous System Viral Diseases / pathology
Central Nervous System Viral Diseases / virology
Child
Epstein-Barr Virus Infections / immunology
Epstein-Barr Virus Infections / metabolism*
Epstein-Barr Virus Infections / pathology
Epstein-Barr Virus Infections / virology
Herpesvirus 4, Human / genetics
Herpesvirus 4, Human / isolation & purification*
Humans
Immunohistochemistry*
In Situ Hybridization
Lymphoma, Large B-Cell, Diffuse / chemistry*
Lymphoma, Large B-Cell, Diffuse / immunology
Lymphoma, Large B-Cell, Diffuse / pathology
Lymphoma, Large B-Cell, Diffuse / virology
Male
Middle Aged
Minnesota
Organ Transplantation / adverse effects*
Predictive Value of Tests
Proto-Oncogene Proteins c-myc / analysis
RNA, Viral / genetics
Retrospective Studies
T-Lymphocytes / chemistry
T-Lymphocytes / immunology
T-Lymphocytes / pathology
T-Lymphocytes / virology
Tumor Suppressor Protein p53 / analysis*
Young Adult

Substances

Biomarkers
MYC protein, human
Proto-Oncogene Proteins c-myc
RNA, Viral
TP53 protein, human
Tumor Suppressor Protein p53