Clinicopathological categorization of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disease: an analysis of 42 cases with an emphasis on prognostic implications

Leuk Lymphoma. 2017 Jan;58(1):53-63. doi: 10.1080/10428194.2016.1179297. Epub 2016 May 9.

Abstract

Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) include several overlapping EBV-related conditions with variably aggressive courses. For prognostic categorization, we retrospectively analyzed 42 EBV-T/NK-LPD cases. Male (79% [33/42]), young (≤40 years; 83% [35/42]) patients and T-cell lineage (81% [34/42]; CD8/CD4 = 1.8) were predominant. Clinicopathologically, three systemic and one cutaneous category were developed: hemophagocytic lymphohistiocytosis (HLH; 26% [11/42]), chronic active EBV infection (CAEBV; 31% [13/42]), systemic unclassifiable disease (24% [10/42]), and hydroa vacciniforme/hydroa vacciniforme-like lymphoma (HV/HVL; 19% [8/42]). Prognostically, cutaneous disease (HV/HVL) was better than systemic disease (p = 0.014; median, 285 vs. 10 months). In systemic diseases, HLH was worst (p = 0.002; 3[HLH] vs. 4[unclassifiable] vs. not reached [CAEBV]). Univariate survival analysis (n = 42) revealed cytopenia (≥one lineage; p < 0.001), onset age (>40 years; p = 0.001), T-cell lineage (p = 0.041), hemophagocytic histiocytes (p = 0.031), elevated lactate dehydrogenase (p = 0.020), and liver dysfunction (p = 0.023) predicted shorter survival. In multivariate analysis, T-cell lineage (p = 0.025 [HR =11.3]) and cytopenia (p = 0.028 [HR =5.4]) were independent prognostic factors. Therefore, EBV-T/NK-LPD could be classified into four prognostic categories.

Keywords: Chronic active EBV infection; EBV-positive T/NK-cell lymphoproliferative disorder; Epstein–Barr virus; hydroa vacciniforme-like lymphoma; systemic EBV-positive T-cell lymphoproliferative disease of childhood.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Cell Lineage / genetics
  • Child
  • Child, Preschool
  • Clonal Evolution
  • Epstein-Barr Virus Infections / virology
  • Female
  • Herpesvirus 4, Human
  • Humans
  • Infant
  • Infant, Newborn
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / pathology*
  • Killer Cells, Natural / virology
  • Lymphoproliferative Disorders / diagnosis*
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / mortality*
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Symptom Assessment
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology*
  • T-Lymphocyte Subsets / virology
  • Young Adult

Substances

  • Biomarkers