Nodal EBV+ cytotoxic T-cell lymphoma: A literature review based on the 2017 WHO classification

Nodal Epstein-Barr virus (EBV)-positive cytotoxic T-cell lymphoma (CTL) is a primary nodal peripheral T-cell lymphoma (PTCL) characterized by a cytotoxic phenotype and EBV on the tumor cells. This disease reportedly accounts for 21% of PTCL not otherwise specified (NOS). However, few nodal EBV+ lymphomas have been documented in detail. Nodal EBV+ CTL and nasal-type NK/T-cell lymphoma (NKTL) both exhibit cytotoxic molecule expression and EBV positivity on the tumor cells; however, nodal EBV+ CTL is characterized as a systemic disease without nasopharyngeal involvement, and exhibits a CD8+/CD56- phenotype distinct from NKTL. The clinicopathological uniqueness of nodal EBV+ CTL is further supported by its T-cell origin in most reported cases. In the 2008 WHO classification, it was unclear whether nodal EBV+ CTL should be classified as PTCL or NKTL. However, based on additional data, the 2017 revision classifies nodal EBV+ CTL as PTCL. In the present review, we focus on the clinicopathological characteristics of nodal EBV+ CTL, discuss the relationship between chronic active EBV infection and nodal EBV+ lymphoma, and highlight future perspectives regarding the treatment of this disease.