Case 1
A previously healthy 12-year-old female underwent orthotopic heart transplant (OHT) for dilated cardiomyopathy. Pre-transplant serologies were EBV donor positive/recipient negative. She received postoperative immunosuppression with anti-thymocyte globulin (ATG) and corticosteroids and was maintained on tacrolimus and mycophenolate mofetil (MMF). She presented approximately 38 months post OHT with altered mental status, weight loss, nausea and diarrhea. Central nervous system (CNS) imaging revealed a left temporal ring enhancing lesion which was found to be EBV Post-Transplant Lymphoproliferative disorder (PTLD). Serum EBV levels peaked at 11,848 copies/mL around time of diagnosis. Further imaging revealed a two cm lesion in the right hepatic dome and another one cm lesion in the right inferior hepatic lobe, presumed to be additional PTLD lesions (Fig 4). Immunosuppression was subsequently reduced, and she was started on PTLD directed chemotherapy with rituximab, methotrexate, cyclophosphamide, and triple intrathecal therapy10.
Repeat imaging one month following therapy showed interval improvement of her CNS PTLD, but demonstrated interval growth of the liver lesions, with increased FDG avidity on PET and newly visualized left kidney lesions (Fig 4). Due to the presumed discrepant response, an ultrasound-guided liver biopsy was performed which revealed hepatic EBV-SMT (Fig 1). At diagnosis, EBV PCR was negative in the peripheral blood with less than 200 copies/mL found in the cerebrospinal fluid; likely due from PTLD directed treatment effects. Her tacrolimus was changed to sirolimus and her mycophenolate was discontinued in an effort to reduce overall immunosuppression and provide potential antitumor effect through mammalian target of rapomycin (mTOR) inhibition7. She went on to receive 4,500 cGy whole brain radiation and EBV targeted cytotoxic T-lymphocyte (CTL) therapy11. CNS remission of her PTLD was achieved approximately 1.5 years after diagnosis and EBV liver lesions remain stable at approximately six years post EBV SMT diagnosis. She was restarted on tacrolimus due to mild acute cellular rejection and remains currently on a combination of sirolimus and tacrolimus for immunosuppression.