Date Published: April 17, 2012
Publisher: Hindawi Publishing Corporation
Author(s): Hazem A. H. Ibrahim, Kikkeri N. Naresh.
Posttransplant lymphoproliferative disorders (PTLDs) are a group of diseases that range from benign polyclonal to malignant monoclonal lymphoid proliferations. They arise secondary to treatment with immunosuppressive drugs given to prevent transplant rejection. Three main pathologic subsets/stages of evolution are recognised: early, polymorphic, and monomorphic lesions. The pathogenesis of PTLDs seems to be multifactorial. Among possible infective aetiologies, the role of EBV has been studied in depth, and the virus is thought to play a central role in driving the proliferation of EBV-infected B cells that leads to subsequent development of the lymphoproliferative disorder. It is apparent, however, that EBV is not solely responsible for the “neoplastic” state. Accumulated genetic alterations of oncogenes and tumour suppressor genes (deletions, mutations, rearrangements, and amplifications) and epigenetic changes (aberrant hypermethylation) that involve tumour suppressor genes are integral to the pathogenesis. Antigenic stimulation also plays an evident role in the pathogenesis of PTLDs. Plasmacytoid dendritic cells (PDCs) that are critical to fight viral infections have been thought to play a pathogenetically relevant role in PTLDs. Furthermore, regulatory T cells (Treg cells), which are modulators of immune reactions once incited, seem to have an important role in PTLDs where antigenic stimulation is key for the pathogenesis.
Post-transplant lymphoproliferative disorders (PTLDs) are a group of diseases that range from benign polyclonal to malignant monoclonal lymphoid proliferations. They develop as a consequence of immunosuppression. PTLDs are characterised by the following: they are usually derived from B cells with preferential presentation as non-Hodgkin’s lymphoma (as against Hodgkin’s lymphoma), usually originate in extranodal sites, rarely affect skin, behave aggressively, and frequently harbour the Epstein-Barr virus (EBV) genome. Whilst most are high-grade B-cell non-Hodgkin’s lymphoma (NHLs), a few are classical Hodgkin’s lymphomas. Rare cases have also been shown to be either of T-cell or NK-cell lineages [1, 2].
PTLDs are classified as either early onset lesions which develop within one year, or late onset lesions, which develop more than one year after transplantation [7, 8].
The clinical manifestations vary from nonspecific symptoms in the form of fever, sweats, malaise, weight loss, and features of primary EBV infection in some patients, to sudden enlargement of tonsils, lymph nodes, or other extranodal lymphoid organs. Other organs such as the central nervous system, bone marrow, spleen, lung, small intestine, liver, and kidney may also be affected .
Clinicopathologic features of major types of posttransplant lymphoproliferative disorders are summarised in Table 2. The classification of PTLDs is currently based on the WHO classification of lymphoid neoplasms (Table 3). Three main pathologic subsets/stages of evolution are recognised: early, polymorphic, and monomorphic lesions .
The pathogenesis of PTLD is multifactorial. EBV plays an important role in driving the proliferation of EBV-infected B cells. It is widely perceived, however, that it is not solely responsible for the “neoplastic” state, and that accumulation of different aberrations in protooncogenes and suppressor genes, and hypermethylation of suppressor genes are integral parts of the pathogenesis  (Figure 2).
PTLDs are group of diseases that range from benign polyclonal to malignant monoclonal lymphoid proliferations. Genetic and epigenetic alterations as well as viruses, notably EBV, contribute towards the development of PTLDs. Common genetic rearrangements which are frequent in immune competent lymphoma are rare in PTLDs. Microenvironment-resident PDCs and Treg cells are likely to play a critical role in the pathogenesis of PTLDs. Therefore, further studies investigating the cytokines secreted by PDCs and Teg cells are required to substantiate and further clarify their precise role in the pathogenesis of PTLD.