Primary nasopharyngeal non-Hodgkin lymphoma and its relationship with Epstein-Barr virus infection

To investigate the immunophenotypes of primary nasopharyngeal non-Hodgkin lymphoma (NPL) and their relationship to Epstein-Barr virus (EBV) infection.

The clinical data and biopsies of 73 patients with NPL were collected in Guangzhou. In situ hybridization was performed to detect the EBV-encoded small non-polyadenylated nuclear RNAs (EBERs) on biopsy slides. Immunohistochemistry was used to classify the immunophenotypes of NPL and detect EBV antigen expression.

Forty-four (60.27%) of the 73 NPLs were of B cell lineage (CD79alpha(+)/CD3(-)/CD56(-)) while the 29 others (39.73%) were of non-B cell lineage. Seventy-three NPLs could be classified into 3 major immunophenotypes: B cell (CD79alpha(+)/CD3(-)/CD56(-), 44 cases), peripheral T cell (CD79alpha(-)/CD3(+)/CD56(-), 22) and NK/T cell (CD79alpha(-)/CD3(+)/CD56(+), 7). The percentages of EBV infection differed among the 3 major immunophenotypes (B cell: 11.36%, 5/44; peripheral T cell: 81.82%, 18/22; NK/T cell: 100%, 7/7). Both CD56(-) positive and CD56(-) negative immunophenotypes could further be divided into 4 subtypes: CD8(-)/CD4(-), CD8(+)/CD4(-), CD8(-)/CD4(+) and CD8(+)/CD4(+). All the CD8(-)/CD4(-) NPLs with CD56(-) positivity (7) or CD56(-) negativity (2) were infected with EBV. The neoplastic cells of a nasopharyngeal Burkitt's lymphoma expressed EBV nuclear antigen 1 (EBNA1) and EBV RNA (EBERs) only. In the other 29 EBV-infected NPLs, most of the lymphoma cells harboring EBV also expressed EBNA1 and EBERs; 21 of the 29 NPLs had a considerable number of neoplastic cells expressing latent membrane protein 1 (LMP1) (21/29, 72.41%) and 23 of 29 NPLs expressed latent membrane protein 2A (LMP2A) (23/29, 79.31%). A few lymphoma cells in 17 (17/29, 58.62%), 23 (23/29, 79.31%) and 22 NPLs (22/29, 75.86%) expressed Zta (Bam HI Z transactivator), viral capsid antigen (VCA) and membrane antigen (MA), respectively.

The prevalence ratio of the 3 immunophenotypes, namely, B cell, peripheral T cell and NK/T cell lymphoma, is about 6:3:1. However, the EBV infection ratio is reversed, 1:8:10. All the NK/T cell (CD56(+)) and peripheral immature T cell (CD3(+)/CD8(-)/CD4(-)) NPLs were EBV-infected. Except for one Burkitt's lymphoma, the EBV harbored in both B cell and non-B cell NPLs was mainly latent infection, type II, expressing EBNA1, LMP1 and LMP2A. However, the EBV found in a few lymphoma cells could become replicative, expressing lytic proteins.