Hepatosplenic gamma delta T-cell lymphoma: relation to Epstein-Barr virus and activated cytotoxic molecules

Aims: Hepatosplenic gamma delta T-cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopen ia, Epstein-Barr virus (EBV) infection and activated cytotoxic molecules (g ranzyme and perforin) are uncommon in hepatosplenic gamma delta CTL. EBV in fection and activated cytotoxic molecules are occasionally detected in non- hepatosplenic gamma delta TCL, We describe the clinicopathological features of three Japanese cases who were not immunodeficient. Methods and results: All cases showed gamma delta T-cell type (CD2+, CD3+, T-cell receptor (TCR)delta-1+, beta F1-). Two cases expressed natural kille r (NK) cell-associated antigens (CD8-, CD16+, CD56+; CD8-, CD16-, CD56+), a nd one expressed CD8 (CD8+, CD16-, CD56-). All cases expressed cytotoxicity -associated molecules (perforin, granzyme B, TIA-1 and Fas ligand). However , perforin and Fas ligand were not detected in one case. In-situ hybridizat ion analysis with EBER probes revealed strong nuclear positivity in all neo plastic cells. In addition, two cases showed clonal bands of the EBV termin al repeat (TR) gene. Cytologically, instead of the presence of monomorphic medium-sized cells, our three cases showed pleomorphic medium-sized and lar ge cells. Conclusions: Our gamma delta TCL cases were clinicopathologically considere d to be compatible with hepatosplenic gamma delta T-cell lymphoma. However, with regard to EBV association, activated cytotoxic profile and cytologica l features they resembled non-hepatosplenic gamma delta TCL. EBV may play a role in this disease by inducing cellular activation.