A nodal γ/δ T-cell lymphoma with an association of Epstein-Barr virus

The postthymic gamma/delta T-cell lymphoma is rare, and most occur as extranodal tumors, e.g., in hepatosplenic or cutaneous forms. We here report an unusual nodal case that initially presented as a T-zone lymphoma. The neoplasm recurred as systemic lymphadenopathy 25 months after complete remission with terminal high-grade transformation. Phenotypic analysis showed CD1-, CD2+, CD3+, CD4-, CD5-, CD7+, CD8+, CD10-, CD16-, CD19-, CD20-, CD21-, CD25-, CD56-, CD57-, T-cell receptor (TCR) alpha/beta antigens negative, TCR gamma/delta antigens positive, and an HLA-DR+ phenotype. Cytogenetic studies showed clonal chromosomal translocations involving chromosomes 1, 5, 6, 8, 15, and X in eight of 15 cells; t(X;5;1)(q13;q13;p22) and t(6;15;8)(p22;q26;q13). Genotypic analysis showed the same clone, characterized by the TCR gamma-chain gene rearrangement pattern, to be present in both initial and recurrent tumors. The lymphoma cells were also demonstrated to express the latent membrane protein-1 by immunohistochemistry and EBV-encoded small RNAs by in situ hybridization. Southern blot analysis using the probe of the terminal repeat demonstrated incorporation of multiple copies of EBV in the recurrent tumor. However, the initial lesion, which contained a smaller number of EBV-positive cells, showed no such evidence of clonal proliferation. These data suggest that EBV may be associated with high-grade transformation, although its exact role in lymphomagenesis remains uncertain. The present study also adds to our understanding of the clinicopathologic spectrum of gamma/delta T-cell neoplasia.