Post-transplant Lymphoproliferative Disorder, Early Lesions and Polymorphic



Post-transplant Lymphoproliferative Disorder, Early Lesions and Polymorphic


C. Cameron Yin, MD, PhD

Pei Lin, MD










Polymorphic post-transplant lymphoproliferative disorder (PTLD) involving the rectum. Note the mixture of cell types present.






Polymorphic PTLD involving the rectum. In situ hybridization for Epstein-Barr virus (EBV) encoded small RNA (EBER) is positive in many cells.


TERMINOLOGY


Abbreviations



  • Post-transplant lymphoproliferative disorder (PTLD)


Definitions



  • Plasmacytic or lymphoid proliferations occurring as result of immunosuppression following solid organ or bone marrow transplantation



    • Early lesions are PTLDs characterized by architectural preservation of involved site


    • Polymorphic lesions are PTLDs that efface architecture but are morphologically heterogeneous and do not fulfill criteria for any known lymphoma type


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Epstein-Barr virus plays a central role



    • 80% of all PTLDs are EBV(+)



      • Usually type A


    • Serum EBV antibody titers and blood EBV DNA load increase prior to onset of PTLD


    • Number of EBV(+) cytotoxic T cells drops prior to onset of PTLD


    • Treatment with EBV-specific T cells induces remission or responses in some patients


    • Analysis of EBV terminal repeat regions by Southern blot analysis has shown monoclonal form of virus



      • Indicates presence of EBV before monoclonal expansion began


    • EBV can transform germinal center (GC) B cells



      • Extended half-life of EBV-infected B cells increases likelihood of acquiring additional molecular aberrations that confer a growth advantage


Pathogenesis



  • Arise from GC or post-GC B cells



    • In solid organ allograft recipients, most PTLDs are of host origin


    • In bone marrow or stem cell allograft recipients, most PTLDs are of donor origin


  • Iatrogenically decreased host immunosurveillance


  • Risk factors for PTLD in general



    • EBV seronegativity before transplant


    • Degree of overall immunosuppression


    • Type of immunosuppression



      • Higher risk with tacrolimus, OKT3 monoclonal antibody, or antithymocyte globulin


    • Type of organs transplanted



      • Most common in intestinal and multiorgan transplant recipients


      • Lowest in renal transplant recipients


      • May be attributable to differences in immunosuppressive regimens used


    • Age



      • Pediatric patients have a higher incidence of PTLD


      • Most likely related to more frequent EBV seronegativity prior to transplant


    • Additional risk factors for patients who receive autologous bone marrow or stem cell transplants



      • HLA-mismatched allograft


      • T-cell-depleted allograft


      • Immunosuppressive therapy for graft vs. host disease


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Frequency of PTLD is related to type of transplant and associated immunosuppression



      • Kidney: 1-3% of all transplant patients


      • Liver: 1-3% of all transplant patients


      • Heart: 1-6% of all transplant patients


      • Heart-lung: 2-6% of all transplant patients


      • Lung: 4-10% of all transplant patients



      • Small intestine: ˜ 20% of all transplant patients


  • Age



    • Predicted by age of patient population undergoing transplant



      • Younger patients are at increased risk of developing PTLD


Site



  • Early lesions



    • Primarily involving lymph nodes


    • Tonsils, adenoids


  • Polymorphic



    • Lymph nodes


    • Extranodal masses can occur

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Post-transplant Lymphoproliferative Disorder, Early Lesions and Polymorphic

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