MOLECULAR-GENETIC ANALYSIS DEMONSTRATES THAT MULTIPLE POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS OCCURRING IN ONE ANATOMIC SITE IN ASINGLE PATIENT REPRESENT DISTINCT PRIMARY LYMPHOID NEOPLASMS

Background. Posttransplantation lymphoproliferative disorders (PT-LPDs ) are a clinicopathologically heterogeneous group of lymphoid prolifer ations of varied clonal composition, the majority of which are associa ted with Epstein-Barr virus (EBV) infection. The clonal content and cl onal relatedness of 24 separate PT-LPD lesions occurring synchronously in one organ in a single patient were investigated. Methods. Twenty-f our separate PT-LPD lesions from the colon and mesentery of a 15-year- old male, developing 4 months after cardiac transplantation, were stud ied for clonality based on immunoglobulin heavy chain (IgH) gene rearr angements for the presence, clonality, and type of EBV infection and f or the presence of c-myc, ras, and p53 gene alterations. Southern blot hybridization, polymerase chain reaction, and single strand conformat ion polymorphism assays were employed. Results. All 24 lesions were hi stologically similar (polymorphic B-cell lymphomas) but exhibited vari ed clonality and were clonally distinct with respect to both IgH gene rearrangements and EBV infection. All lesions were infected with EBV t ype A. Structural alterations of oncogenes or tumor suppressor genes w ere not identified. Conclusions. Separate PT-LPD lesions occurring syn chronously in a single organ or patient may be clonally distinct, sugg esting that they represent multiple distinct primary lymphoid prolifer ations rather than metastatic disease as in conventional malignant lym phomas. This may explain partially the rapid development in some patie nts of a large PT-LPD tumor burden that may regress rapidly after redu ction of immunosuppression.