Clinicopathological Findings of Systemic Epstein-Barr-Positive CD8-positive T-lymphoproliferative Diseases in Younger and Older Patients 

Background: Systemic Epstein-Barr virus + CD8 + T-cell lymphoma (sEBV + CD8 + TCL) occurs in childhood and young adults, and exceptionally rare in older individuals. Methods: : We investigated clinicopathological features in 16 patients of various ages with systemic EBV + CD8 + T-lymphoproliferative diseases. Results: : Eight younger and four of eight older patients 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. Other two patients demonstrated EBV + node-based CD8 + large TCL without HLH, while the remaining two had 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%). Programmed cell death-ligand (PD-L)1 + tumor cells and strong reaction of PD-L1 + 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 cytotoxic therapies including etoposide, and the three underwent allogeneic stem cell transplantation (SCT). Conclusion: sEBV + CD8 + TCL was observed in younger and older patients with less history of sCAEBV. HLH, tumor cell atypia, immunohistological findings, and progressive clinical course were characteristic in sEBV + CD8 + TCL. Prompt cytotoxic treatments and SCT induced tumor regression in sEBV + CD8 + TCL patients.