INTRODUCTION

Posttransplant lymphoproliferative disorder (PTLD) is a wellknown, serious complication of solid organ transplant recipients (OTRs) or bone marrow (hematopoietic stem cell) transplant recipients. The clinicopathological spectrum ranges from a mononucleosis-like illness or benign lymphoid hyperplasia to an aggressive malignant lymphoma. Although the skin may be involved as a component of disease dissemination, primary localized cutaneous disease is rare.

PATHOGENESIS

The etiology of PTLD is multifactorial. More than 95% of the world's population is infected by Epstein-Barr Virus (EBV). With primary infection, EBV establishes latency in memory B-cells. Immunocompetent individuals mount a humoral immune response producing antibodies that bind to viral membrane proteins and neutralize viral infectivity. A cellular immune response, composed of cytotoxic T-lymphocytes (CTL), is necessary to control primary and latent EBV-infected cells. In the latent state, viral proteins, Epstein-Barr nuclear antigen (EBNA) and latent membrane proteins (LMP), are produced and protect the B-cell from apoptosis while allowing for continued viral replication.

In the setting of immunosuppression, the normal CTL response to EBV antigens is impaired, allowing viral replication to continue unabated and leading to cell cycle dysregulation in B-cells and an uncontrolled lymphoproliferative response. When unregulated replication proceeds, the virus can infect adjacent host cells. Viral proliferation leads to expression of EBV-derived oncogenes including synthesis of EBNA and LMP. Persistent immunosuppression and additional mutations may result in transformation from an EBV-mediated polyclonal lymphoproliferative disorder to a true, potentially aggressive, monoclonal lymphoma.