Epstein - Barr virus positive T and NK-cell lymphoproliferations: Morphological features and differential diagnosis

Semin Diagn Pathol. 2020 Jan;37(1):32-46. doi: 10.1053/j.semdp.2019.12.004. Epub 2019 Dec 17.


The spectrum of Epstein-Barr virus (EBV)-positive T and NK-cell lymphoproliferations is broad and ranges from reactive self-limited disorders to neoplastic processes with a fulminant clinical course. EBV plays an important role promoting lymphomagenesis, although the precise mechanisms remain elusive. EBV-positive lymphoproliferative disorders (LPD) are more common in East Asia (China, Japan, Korea and Taiwan), and Latin America suggesting a strong genetic predisposition. The revised 2016 World Health Organization (WHO) lymphoma classification recognizes the following malignant NK- and T-cell lymphomas; extranodal NK/T-cell lymphoma, nasal type (ENKTCL), aggressive NK-cell leukemia (ANKL), and the provisional entity within the group of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) "primary EBV-positive nodal T or NK cell lymphoma". Disorders presenting mainly in children and young adults include chronic active EBV infection (CAEBV) - systemic and cutaneous forms - which are not considered malignant disorders but were included in the WHO classification for the first time because of the differential diagnosis with other T- or NK-cell lymphomas. CAEBV, cutaneous form, includes hydroa vacciniforme-like LPD (HV-LPD) and severe mosquito bite allergy (SMBA). Finally, systemic EBV-positive T-cell lymphoma of childhood was recognized as lymphoma because of its fulminant clinical course. Given the shared pathogenesis of these disorders, overlapping features are common demanding a close clinical, morphological and molecular correlation for an accurate diagnosis. This review summarizes the clinical, histopathological and molecular features of EBV-associated T and NK-cell LPD, highlighting the main features that might aid in the differential diagnosis.

Keywords: Aggressive NK-cell leukemia; Chronic active EBV infection; EBV lymphoproliferations; Extranodal NK/T-cell lymphoma nasal type; Hydroa vacciniforme-like T-NK-cell LPD; NK-cell; Primary EBV-positive nodal T/NK cell lymphoma; Severe mosquito bite allergy; Systemic EBV T-cell lymphoma of the childhood; T-cell.

Publication types

  • Review

MeSH terms

  • Epstein-Barr Virus Infections / complications*
  • Humans
  • Killer Cells, Natural / pathology*
  • Killer Cells, Natural / virology
  • Lymphoproliferative Disorders / pathology*
  • Lymphoproliferative Disorders / virology*
  • T-Lymphocytes / pathology*
  • T-Lymphocytes / virology