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, 20 (9), 1472-82

Epstein-Barr Virus-Associated Lymphoproliferative Disease in Non-Immunocompromised Hosts: A Status Report and Summary of an International Meeting, 8-9 September 2008

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Epstein-Barr Virus-Associated Lymphoproliferative Disease in Non-Immunocompromised Hosts: A Status Report and Summary of an International Meeting, 8-9 September 2008

J I Cohen et al. Ann Oncol.

Abstract

Background: Recently novel Epstein-Barr virus (EBV) lymphoproliferative diseases (LPDs) have been identified in non-immunocompromised hosts, both in Asia and Western countries. These include aggressive T-cell and NK-cell LPDs often subsumed under the heading of chronic active Epstein-Barr virus (CAEBV) infection and EBV-driven B-cell LPDs mainly affecting the elderly.

Design: To better define the pathogenesis, classification, and treatment of these disorders, participants from Asia, The Americas, Europe, and Australia presented clinical and experimental data at an international meeting.

Results: The term systemic EBV-positive T-cell LPD, as adopted by the WHO classification, is preferred as a pathological classification over CAEBV (the favored clinical term) for those cases that are clonal. The disease has an aggressive clinical course, but may arise in the background of CAEBV. Hydroa vacciniforme (HV) and HV-like lymphoma represent a spectrum of clonal EBV-positive T-cell LPDs, which have a more protracted clinical course; spontaneous regression may occur in adult life. Severe mosquito bite allergy is a related syndrome usually of NK cell origin. Immune senescence in the elderly is associated with both reactive and neoplastic EBV-driven LPDs, including EBV-positive diffuse large B-cell lymphomas.

Conclusion: The participants proposed an international consortium to facilitate further clinical and biological studies of novel EBV-driven LPDs.

Figures

Figure 1.
Figure 1.
A healthy Epstein–Barr virus (EBV) seropositive individual and a patient rapidly recovering from infectious mononucleosis have diverse CD8+ T cells that recognize a variety of EBV peptides, while a patient with persistent infectious mononucleosis has a limited diversity of CD8+ T cells that recognize few viral peptides. Labels on pie charts indicate individual EBV peptides recognized by CD8+ T cells [11].
Figure 2.
Figure 2.
Epstein–Barr virus (EBV)-positive large B-cell lymphoma of the elderly. (A) Large lymphoid cells predominate and in (B) express CD20. (C) Some cells have more pleomorphic features, and CD30 is often positive. (D) EBV encoded RNA (EBER) highlights atypical cells.
Figure 3.
Figure 3.
Hydroa vacciniforme-like lymphoma. (A) Sun-exposed areas of the skin exhibit a papulovesicular eruption, with ulceration and crusting. (B) The infiltrate is present in the superficial dermis. (C) Lymphoid cells are positive with EBER in situ hybridization. (D) Lymphoid cells are small to medium in size; clonal TCR gene rearrangement was shown by PCR studies.
Figure 4.
Figure 4.
Generation of cytotoxic T cells that recognize EBV LMP2. Autologous dendritic cells and EBV-transformed B cells [lymphoblastoid cell line (LCL)] are infected with adenovirus expressing LMP2 (Ad5f35). These cells are used to present LMP2 to peripheral blood mononuclear cells (PBMCs). After stimulation of PBMCs with irradiated adenovirus-infected dendritic cells and LCLs in the presence of IL-2, LMP2-specific autologous cytotoxic T cells (CTLs) are obtained [58].

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