PTLD Arising in Solid Organ Transplant Recipients

The overall incidence of PTLD after SOT is ~1.5% but varies from 0.3% to 12.5% depending on the organ transplanted and the immunosuppressive regimen, with a higher incidence in children than adults. Extensive studies of PTLD occurring in SOT recipients (primarily heart, kidney, and lung recipients) have shown that most of these lesions can be separated into three categories based on morphologic and molecular genetic criteria. These categories correlate with the biologic behavior of the lesions. Because of the special clinical setting, that is, iatrogenic immunosuppression that can be modulated, a unique classification scheme was originally developed by Nalesnik et al.,7 to describe the clinical course and outcome of SOT PTLD patients, and subsequently modified by Knowles, et al.8 (Table 34-6).

This classification divides cases into three major categories (Table 34-6). Plasmacytic hyperplasia (PH) lesions show retention of the overall architecture of the tissue. Genotypically, these lesions are usually polyclonal based on IGH rearrangement studies, or have small monoclonal/ oligoclonal populations. The majority of PH cases are EBV positive and do not contain structural alterations of known oncogenes or tumor suppressor genes. Furthermore,exam-ination of EBV antigen expression shows that PH lesions express LMP1 and in some instances EBNA2, indicating

Table 34-6. Solid Organ Posttransplantation Lymphoproliferative Disorders



Ig Genes


Onco/TS Genes

Clinical Outcome

Plasmacytic hyperplasia

Retention of architecture;


Poly-, oligo-, monoclonal



plasma cells, lymphocytes

Latency II, III


Disruption of architecture;






hetergeneous cell

Latency II, III



population;+/- necrosis,


Non-Hodgkin lymphoma/

Malignant lymphocytes or





multiple myeloma

plasma cells

Latency I

TS, tumor suppressor; Ig, immunoglobulin.

that they exhibit either the latency types II or III patterns of EBV gene expression.

The second category is the polymorphic PTLD lesions that histologically show destruction of the underlying architecture and are composed of a heterogeneous (polymorphic) cell population. At the genetic level these lesions are monoclonal based both on immunoglobulin studies and the presence of clonal EBV. Polymorphic PTLD lacks structural alterations in oncogenes and tumor suppressor genes except for the presence of BCL6 gene mutations, which are present in approximately half of the cases studied.9 Lesions containing the wild-type configuration of the BCL6 gene regress following a reduction in immunosuppression, while those lesions containing BCL6 gene mutations exhibit more aggressive behavior, requiring clinical intervention (Table 34-6). Polymorphic PTLD, like PH, exhibit the latency types II or III patterns of EBV gene expression. Type II and III latencies include expression of the transforming but immunogenic LMP and EBNA viral proteins, suggesting that reconstitution of an immune response in the host is more likely to result in elimination of these infected cells.

The third category is the monomorphic PTLD (malignant lymphoma/multiple myeloma) lesions that are composed of cytologically malignant cells and should be classified according to the WHO classification. They are monoclonal based both on IGH rearrangement and EBV studies. Additionally, they contain structural alterations in oncogenes and tumor suppressor genes frequently involved in lymphomagenesis, such as TP53 and MYC.8 In contrast to the other SOT PTLD, these lesions often exhibit the latency type I pattern of EBV gene expression, suggesting that they are less dependent on EBV and that they may no longer be recognized by the immune system even after immune reconstitution.

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