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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Sep 24, 2016; 6(3): 505-516
Published online Sep 24, 2016. doi: 10.5500/wjt.v6.i3.505
Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders
Julie Morscio, Thomas Tousseyn
Julie Morscio, Department for Imaging and Pathology, Translational Cell and Tissue Research, 3000 Leuven, Belgium
Thomas Tousseyn, Department of Pathology, University Hospitals Leuven, 3000 Leuven, Belgium
Author contributions: Morscio J wrote the paper; Tousseyn T revised the paper.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Thomas Tousseyn, MD, PhD, Department of Pathology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. thomas.tousseyn@uzleuven.be
Telephone: +32-16-336582 Fax: +32-16-336622
Received: April 23, 2016
Peer-review started: April 24, 2016
First decision: June 6, 2016
Revised: July 8, 2016
Accepted: August 17, 2016
Article in press: August 18, 2016
Published online: September 24, 2016
Processing time: 153 Days and 10.7 Hours
Abstract

Post-transplant lymphoproliferative disorder (PTLD) is an aggressive complication of solid organ and hematopoietic stem cell transplantation that arises in up to 20% of transplant recipients. Infection or reactivation of the Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, in combination with chronic immunosuppression are considered as the main predisposing factors, however insight in PTLD biology is fragmentary. The study of PTLD is complicated by its morphological heterogeneity and the lack of prospective trials, which also impede treatment optimization. Furthermore, the broad spectrum of underlying disorders and the graft type represent important confounding factors. PTLD encompasses different malignant subtypes that resemble histologically similar lymphomas in the general population. Post-transplant diffuse large B-cell lymphoma (PT-DLBCL), Burkitt lymphoma (PT-BL) and plasmablastic lymphoma (PT-PBL) occur most frequently. However, in many studies various EBV+ and EBV- PTLD subtypes are pooled, complicating the interpretation of the results. In this review, studies of the gene expression pattern, the microenvironment and the genetic profile of PT-DLBCL, PT-BL and PT-PBL are summarized to better understand the mechanisms underlying post-transplantation lymphomagenesis. Based on the available findings we propose stratification of PTLD according to the histological subtype and the EBV status to facilitate the interpretation of future studies and the establishment of clinical trials.

Keywords: Epstein-Barr virus, Post-transplant lymphoproliferative disorder, Immunodeficiency, Diffuse large B-cell lymphoma, Burkitt lymphoma, Plasmablastic lymphoma

Core tip: At the moment different post-transplant lymphoproliferative disorders (PTLD) are grouped in broad categories (early, polymorphic, monomorphic and Hodgkin-like PTLD) and the Epstein-Barr virus (EBV) status is not taken into account. However, increasing evidence demonstrates that different malignant PTLD and EBV+ and EBV- lesions are clinically and biologically distinct, stressing the need for subtype-specific management. We propose that in future studies patients should be stratified according to the histological lymphoma subtype and the EBV status to minimize bias and to simplify the establishment and analysis of clinical trials.