MOLECULAR PATHOLOGY OF POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS

Posttransplantation lymphoproliferative disorders (PT-LPDs) represent a heterogeneous group of Epstein-Barr virus (EBV) associated lymphoid proliferations occurring in the setting of immunosuppression associate d with solid organ transplantation. Some PT-LPDs regress after a reduc tion in immunosuppression, whereas others progress despite aggressive therapy. Previously defined histopathologic categories do not correlat e with clonality, and neither histopathology nor clonality has reliabl y predicted their clinical behavior. Recently, correlative clinical, m orphological, and molecular genetic analysis has suggested that PT-LPD s are divisible into three distinct clinically relevant categories as follows: (1) plasmacytic hyperplasia: most commonly arise in the oroph arynx or lymph nodes, are nearly always polyclonal, usually contain mu ltiple EBV infectious events or only a minor cell population infected by a single form of EBV, and lack oncogene or tumor suppressor gene al terations; (2) polymorphic lymphoproliferative disorders: may arise in lymph nodes or extranodal sites including the gastrointestinal tract and lungs, are nearly always monoclonal based on the presence of clona l immunoglobulin gene rearrangements, usually contain a single form of EBV, and lack oncogene or tumor suppressor gene alterations; and (3) malignant lymphoma or multiple myeloma: present with widely disseminat ed disease frequently including the bone marrow, are monoclonal based on clonal immunoglobulin gene rearrangements, contain a single form of EBV, and contain alterations of one or more oncogenes or tumor suppre ssor genes (c-myc, ras, p53). Thus, protooncogene and tumor suppressor gene alterations appear to be associated with disease progression and an often fatal clinical outcome. Furthermore, multiple PT-LPD lesions occurring in the same individual but in multiple anatomic sites, eith er simultaneously or dysynchronously over time, may show distinct clon al immunoglobulin gene rearrangement patterns and evidence of infectio n by different forms of EBV, suggesting that each lesion represents a distinct clonal neoplasm that may show distinctive clinical behavior. Therefore, whenever possible, a biopsy of each one of the several PT-L PD lesions occurring in an individual should be obtained to derive a t rue assessment of the pathobiological nature and clinical aggressivene ss of an individual's disease. Copyright (C) 1997 by W.B. Saunders Com pany.