Clinicopathological findings of systemic Epstein-Barr virus-positive T-lymphoproliferative diseases in younger and older adults

BACKGROUND: Systemic Epstein-Barr virus(+) T-cell lymphoma (sEBV(+) TCL) occurs in childhood and young adults, and is exceptionally rare in older adults. METHODS: We investigated clinicopathological features in 16 patients of various ages with systemic EBV(+) CD8(+) T-lymphoproliferative diseases. RESULTS: Eight younger patients and four of eight older adults had sEBV(+) CD8(+) TCL, with invasion by medium-sized to/or large atypical lymphocytes primarily in bone marrow and lymph nodes, hemophagocytic lymphohistiocytosis (HLH), and progressive clinicopathological course. A further two patients demonstrated EBV(+) node-based CD8(+) large TCL without HLH, while the remaining two had the systemic form of chronic active EBV infection (sCAEBV) with CD8(+) small lymphocytes. Past history of sCAEBV-like lesions was observed in one sEBV(+) TCL patient (8.3%). Immunohistologically, in 12 sEBV(+) TCL patients, atypical lymphocytes were positive for phosphate signal transducer and activator of transcription 3 (66.7%), CMYC (83.3%), and p53 (75%). Strong reactions of programmed cell death-ligand (PD-L)1(+) tumor or non-neoplastic cells were detected in nine sEBV(+) TCL patients (75%). Clonal peaks of the T-cell receptor (TCR) γ gene were detected in eight sEBV(+) TCL patients by polymerase chain reaction. Four younger patients in sEBV(+) TCL (33.3%) are in remission with chemotherapies including etoposide, and three of the four underwent allogeneic stem cell transplantation (SCT). CONCLUSION: sEBV(+) CD8(+) TCL was observed in younger and older adults with less history of sCAEBV. HLH, tumor cell atypia, immunohistological findings, and progressive clinical course were characteristic of sEBV(+) CD8(+) TCL. Prompt chemotherapy and SCT induced tumor regression in sEBV(+) CD8(+) TCL patients.