title: Nasal T/natural killer (NK)-cell lymphomas are derived from Epstein-Barr virus-infected cytotoxic lymphocytes of both NK- and T-cell lineage.
abstract: The cellular nature of nasal T/natural killer (NK)-cell lymphomas (NLs) remains controversial. It is still debatable whether these represent T-cell lymphomas with extensive loss of surface antigens or are, in fact, true NK-cell lymphomas. They are associated closely with Epstein-Barr virus (EBV), to the extent that EBV-encoded small non-polyadenylated RNAs (EBER) expression can be used as a marker for the neoplastic cells. The cell lineage of this group of lymphomas was examined further by correlating immunophenotype, genotype and EBV status with the expression of cytotoxic granule-associated proteins, perforin and T-cell intracellular antigen-1 (TIA-1) in 13 cases of NL. Combined immunophenotypic and gene rearrangement analyses demonstrated that NLs can be identified clearly as either NK-cell or T-cell tumours. Nasal NK-cell lymphomas lacked clonal rearrangement of both T-cell receptor (TCR) gamma and immunogloulin heavy chain (IgH) genes and were either CD3(Leu4)-CD56+ (8 cases) or CD3(Leu4)+CD56+ (2 cases), whereas nasal T-cell lymphomas had rearranged TCRgamma and germ-line IgH genes and were either CD3(Leu4)+CD56+ (2 cases) or CD3(Leu4)+CD56- (1 case). Immunohistochemical (IH) studies showed that both perforin and TIA-1 were expressed universally in NL, irrespective of NK- or T-cell lineage. Dual labelling of TIA-1 by IH and EBER by in situ hybridisation demonstrated that the granule proteins were expressed predominantly by the EBER+ tumour cells. Our results indicate that NLs are derived from EBV-infected cytotoxic lymphocytes of both NK- and T-cell lineage. We postulate that cytotoxic lymphocytes generated during the cellular immune response to EBV infection or re-activation at the nasal region themselves may become targets for EBV infection and subsequent transformation.
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong.
authors.forename: A K
authors.initials: AK
authors.lastname: Chiang
authors.forename: A C
authors.initials: AC
authors.lastname: Chan
authors.forename: G
authors.initials: G
authors.lastname: Srivastava
authors.forename: F C
authors.initials: FC
authors.lastname: Ho
mesh_terms: D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D005838:Genotype; D004854:Herpesvirus 4, Human; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D008562:Membrane Glycoproteins / Q000032:analysis*; D008565:Membrane Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D009669:Nose Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D054353:Perforin; D010641:Phenotype; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000032:analysis*; D012269:Ribosomal Proteins; D000074019:T-Cell Intracellular Antigen-1; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology* / Q000821:virology*
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D054353:Perforin; C067169:RPL22 protein, human