Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms

Abstract

BACKGROUND: Posttransplantation lymphoproliferative disorders (PT-LPDs) are a clinicopathologically heterogeneous group of lymphoid proliferations of varied clonal composition, the majority of which are associated with Epstein-Barr virus (EBV) infection. The clonal content and clonal relatedness of 24 separate PT-LPD lesions occurring synchronously in one organ in a single patient were investigated. METHODS: Twenty-four separate PT-LPD lesions from the colon and mesentery of a 15-year-old male, developing 4 months after cardiac transplantation, were studied for clonality based on immunoglobulin heavy chain (IgH) gene rearrangements for the presence, clonality, and type of EBV infection and for the presence of c-myc, ras, and p53 gene alterations. Southern blot hybridization, polymerase chain reaction, and single strand conformation polymorphism assays were employed. RESULTS: All 24 lesions were histologically similar (polymorphic B-cell lymphomas) but exhibited varied clonality and were clonally distinct with respect to both IgH gene rearrangements and EBV infection. All lesions were infected with EBV type A. Structural alterations of oncogenes or tumor suppressor genes were not identified. CONCLUSIONS: Separate PT-LPD lesions occurring synchronously in a single organ or patient may be clonally distinct, suggesting that they represent multiple distinct primary lymphoid proliferations rather than metastatic disease as in conventional malignant lymphomas. This may explain partially the rapid development in some patients of a large PT-LPD tumor burden that may regress rapidly after reduction of immunosuppression.