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

• Published in: Cancer science Vol. 109; no. 8; pp. 2599 - 2610
• Main Authors: Yamashita, Daisuke, Shimada, Kazuyuki, Takata, Katsuyoshi, Miyata‐Takata, Tomoko, Kohno, Kei, Satou, Akira, Sakakibara, Ayako, Nakamura, Shigeo, Asano, Naoko, Kato, Seiichi
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.08.2018
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - immunology; CD5 Antigens - immunology; Child; Child, Preschool; cytotoxic molecule; Epstein-Barr Virus Infections - immunology; Epstein‐Barr virus; Female; Herpesvirus 4, Human - immunology; Humans; Infant; Infant, Newborn; Killer Cells, Natural - immunology; Lymphoma, Extranodal NK-T-Cell - immunology; Lymphoma, T-Cell, Peripheral - immunology; Male; Middle Aged; onset age; Original; peripheral T‐cell lymphoma‐not otherwise specified; Prognosis; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell, alpha-beta - immunology; T-Lymphocytes, Cytotoxic - immunology; TCR phenotype; Young Adult; TCR phenotype; Epstein-Barr virus; peripheral T-cell lymphoma-not otherwise specified; cytotoxic molecule; onset age
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13652

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. This retrospective study revealed that nodal EBV‐negative CTL is heterogeneous, and there may be prognostically indolent subgroups defined by immunophenotype and genotype—ie, CD5+ TCRαβ and CD5+ NK‐cell types—which have not previously been highlighted.