Epstein–Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach

• Published in: Pathology Vol. 52; no. 1; pp. 111 - 127
• Main Authors: Hue, Susan Swee-Shan, Oon, Ming Liang, Wang, Shi, Tan, Soo-Yong, Ng, Siok-Bian
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.01.2020
• Subjects: aggressive NK-cell leukaemia; childhood; chronic active EBV infection; differential diagnosis; Epstein–Barr virus-positive T-cell and NK-cell lymphoproliferative disease; extranodal NK/T cell lymphoma; haemophagocytic lymphohistiocytosis; Hydroa vacciniforme-like lymphoproliferative disorder; peripheral T-cell lymphoma; severe mosquito bite allergy; STCLC; differential diagnosis; Hydroa vacciniforme-like lymphoproliferative disorder; childhood; chronic active EBV infection; extranodal NK/T cell lymphoma; haemophagocytic lymphohistiocytosis; peripheral T-cell lymphoma; ENKTL; EBV-HLH; HV-LPD; ANKL; EBV-TNKLPD; Epstein–Barr virus-positive T-cell and NK-cell lymphoproliferative disease; CAEBV; severe mosquito bite allergy; Nodal TNKL; aggressive NK-cell leukaemia; SMBA
• ISSN: 0031-3025; 1465-3931; 1465-3931
• DOI: 10.1016/j.pathol.2019.09.011

Epstein–Barr virus (EBV)-positive T-cell and natural killer (NK)-cell lymphoproliferative diseases (EBV-TNKLPD) are a group of uncommon disorders characterised by EBV infection of T- and NK-cells. As a group, EBV-TNKLPD are more commonly encountered in Asians and Native Americans from Central and South America compared to Western populations. They encompass a spectrum of entities that range from non-neoplastic lesions such as EBV-associated haemophagocytic lymphohistiocytosis (EBV-HLH) to more chronic conditions with variable outcomes such as chronic active EBV infections (CAEBV) of T- and NK-cell type (cutaneous and systemic forms) and malignant diseases such as systemic EBV-positive T-cell lymphoma of childhood, aggressive NK-cell leukaemia, extranodal NK/T-cell lymphoma, nasal-type, and primary EBV-positive nodal T/NK-cell lymphoma. Due to their rarity, broad clinicopathological spectrum and significant morphological and immunophenotypic overlap, the diagnosis and precise classification of EBV-TNKLPD often pose a challenge to clinicians and pathologists. Correct classification of this group of rare diseases relies heavily on the age of onset, disease presentation, duration of symptoms and cell of origin (T- vs NK-cell lineage). In this review, we provide an update on the clinicopathological and molecular features of the various EBV-TNKLPD entities occurring in non-immunocompromised patients and present a practical algorithmic approach for the general pathologist who is confronted with these disorders in routine clinical practice.