J Pathol Transl Med.  2017 Jul;51(4):352-358. 10.4132/jptm.2017.03.15.

Epstein-Barr Virus–Associated Lymphoproliferative Disorders: Review and Update on 2016 WHO Classification

• Kim HJ
• Ko YH
• Kim JE
• Lee SS
• Lee H
• Park G
• Paik JH
• Cha HJ
• Choi YD
• Han JH
• Huh J
• Hematopathology Study Group of the Korean Society of Pathologists

• KMID: 2392574
• DOI: http://doi.org/10.4132/jptm.2017.03.15

Abstract

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin's lymphoma, and immune-deficiency associated LPDs (post-transplant and human immunodeficiency virus-associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

Keyword

Epstein-Barr virus; Lymphoproliferative disorders

MeSH Terms

B-Lymphocytes
Burkitt Lymphoma
Classification*
Diagnosis
Herpesvirus 4, Human
Humans
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoproliferative Disorders*
T-Lymphocytes
World Health Organization

Figure

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  Fig. 1. Mucocutaneous ulcer (Courtesy of Dr. J.H. Paik). (A) This 70-year-old female presented with a sore throat, painful swelling saliva, and tonsillar enlargement with a discrete ulcer. (B) The scanning power view shows a dense infiltrate beneath the ulcer. (C) Medium sized atypical lymphocytes are observed. (D) Epstein-Barr virus (EBV)–in-situ hybridization positive cells are aggregated in the ulcer bed. (E) CD20 immunostaining disclosed overlapping with EBV-positive cells. (F) The large atypical cells are diffusely and strongly positive for CD20.

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  Fig. 2. Chronic active Epstein-Barr virus (EBV) infection of a T-cell or natural killer cell type, systemic (Courtesy of Dr. Y.H. Ko). (A) A 21-yearold man presented with severe oral ulcer, recurrent pneumonia, thrombocytopenia, and elevated liver enzymes for 2 years. Liver biopsy reveals atypical T lymphocytes infiltrating the sinusoidal and hepatic lobules. (B) EBV-encoded small RNA (EBER) in-situ hybridization exhibits positive signals in these T cells. (C) Bone marrow biopsy shows small lymphocytic infiltrate. (D) CD3 is expressed in most lymphocytes. (E) EBER in-situ hybridization also shows positive signals in T cells.

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