Epstein-Barr virus-positive peripheral T cell lymphoma

Source:  Epstein-Barr virus-positive peripheral T cell lymphoma    Tag:  ebv positive lymphoma

Epstein-Barr Virus–positive nodal peripheral T cell lymphomas: clinicopathologic and gene expression profiling study
Sang Yun Haa, Jiyeon Sungb, Hyunjung Juc, Kennosuke Karubed, Soek Jin Kime, Won Seog Kime, Masao Setod, Young-Hyeh Koa, ,
a Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
b Department of Pathology, School of Medicine, Kyung Hee University, Seoul, Korea
c Experimental Pathology Center, Samsung Biomedical Research Institute, Seoul, Korea
d Division of Molecular Medicine, Aichi Cancer Center Research Institute, Aichi, Japan
e Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Summary
Epstein-Barr virus-positive peripheral T cell lymphoma, not otherwise specified (EBV+ PTCL-NOS), in which virtually all neoplastic T cells harbor EBV, is a very rare disease with poor prognosis. To analyze the clinicopathologic characteristics and gene expression profile, we retrospectively collected six cases of EBV+ PTCL-NOS with no known primary immunodeficiency. The patients were 5 men and 1 woman, their age ranging from 48 years to 88 years (median 61.5 years). Lymphadenopathy was the most common presentation. Four patients had underlying disease, including HBV carrier, HCV infection, diabetes mellitus, and prostate cancer. All patients showed fatal clinical course in spite of chemotherapy. Histopathologically, monotonous infiltration of atypical lymphocytes of small to medium size was shown in four patients and medium to large tumor cells in two patients. Five patients showed CD4-/CD8+/bF-1+ phenotype with TIA-1 expression. In gene expression analysis using mRNA microarray, genes differentially expressed in EBV+ PTCL-NOS compared to normal reactive lymph nodes included 1,515 genes (Mann Whitney U test p < 0.05, folder change ≥4 times). Enriched functional annotation terms by DAVID were mostly related to immune response, defense response, cell-to-cell signaling, and membrane signaling. Especially, the genes involved in B cell differentiation or activation were mostly down-regulated, and T cell activation was mostly suppressed by down-regulation of activation genes and up-regulation of regulatory genes. Genes associated with cytotoxic activity were mostly up-regulated. Based on its peculiar clinical, histopathologic, and gene expression findings in EBV+ PTCL-NOS, we suggest EBV+ PTCL-NOS as a distinct disease entity from PTCL-NOS. In this study, the finding that most significantly enriched the functional term was immune response, suggesting a specific relation between EBV infection and alteration of immune response in the patients with EBV+ PTCL-NOS.

Keywords
EBV; peripheral T cell lymphoma; gene expression