Reappraisal of nodal Epstein‐Barr Virus‐negative cytotoxic T‐cell lymphoma: Identification of indolent CD5⁺ diseases

Abstract

Nodal cytotoxic molecule (CM)‐positive peripheral T‐cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein‐Barr virus (EBV)‐negative CTL to 48 patients with EBV‐positive CTL. The two groups did not differ in histopathology, T‐cell receptor (TCR) expression or rearrangement incidences, or survival curves. However, patients with EBV‐negative CTL less frequently showed hepatic involvement (P = .007), B symptoms (P = .020), hemophagocytosis (P = .024), and detectable CD4 (P = .002) and CD5 (P = .009). Univariate and multivariate analyses identified three factors that independently predicted favorable survival, onset age <60 years (P = .002), CD5 expression (P = .002), and mixed morphology (P = .013), TCRαβ was not an independent predictor (P = .30), but was strongly linked with long survivorship among patients younger than 60 years old. A prognostic model incorporating these factors worked well for prognostic delineation, independently of the International Prognostic Index (P = .007 vs P = .082) and Prognostic Index for PTCL (P = .020 vs P = .15). Moreover, this constellation of findings indicated two nodal indolent diseases: CD5+ TCRαβ (n = 13), and CD5+ NK‐cell type lacking TCR expression or clonal TCRγ rearrangement (n = 4). The survival curves for these two groups were significantly superior to others (n = 29, P < .001). These diseases appear to be unique in their indolent clinical behavior, and should be managed differently from other diseases.

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

“…Nodal EBV + CTL can develop across a wide range of ages, in infants to the elderly, but it predominantly affects middle-aged and elderly people, with a reported median age of 61-64 years. 3,6,10,14 Male predominance has been described, with a M:F ratio of 1.5-3.8:1. 3,6,7,10 Some cases may be associated with autoimmune diseases and immunosuppressive treatment.…”

“…3,6,10,14 Male predominance has been described, with a M:F ratio of 1.5-3.8:1. 3,6,7,10 Some cases may be associated with autoimmune diseases and immunosuppressive treatment. 7…”

“…We also discuss future perspectives regarding the treatment of nodal EBV + disease. Nodal CTL without EBV-harboring tumor cells is beyond the scope of the present review, but it will be discussed in a future review, including the subject of indolent CD5 + cytotoxic nodal T/ NK-cell lymphoproliferative disease affecting patients <60 years old, which was newly identified by Yamashita et al 3…”

Approach to nodal-based T-cell lymphomas

“…Independent of the viral association, a cytotoxic immunophenotype is generally indicative of a poor prognosis in PTCL-NOS. 107,108 Accordingly, a molecular subgroup of PTCL-NOS defined by a cytotoxic signature was also found to be associated with a poorer survival. 109…”

Humanized Mice Are Precious Tools for Preclinical Evaluation of CAR T and CAR NK Cell Therapies

“…Chen et al [ 26 ] adapted a similar approach by targeting CD5, a marker expressed at the surface of a majority of T-cell malignancies including T-ALL and T cell lymphomas [ 100 , 101 ]. Anti-CD5 CAR NK cells inhibited and controlled cancer progression in xenograft mouse models of T-ALL but failed though to eradicate established tumor cells [ 26 ].…”