At the age of four, patient was doing well and screening bone marrow biopsy showed mildly hypocellular marrow without PTLD (Figure 3 ). Despite the persistent EBV viremia by serum PCR, EBV was negative by EBER in situ hybridization. Molecular testing did not identify a clonal population. However, cytogenetics revealed one cell with an abnormal female karyotype with trisomy 3, similar to that previously observed in this patient 47,XX,+3[1]/46,XX[19]. Although one abnormal cell is considered non-clonal, due to the similar trisomy 3 finding in the previous bone marrow this finding was communicated to the clinical team to alert them for the possibility of the residual PTLD.
Figure 3 . Patient 1: Bone marrow is negative for involvement by PTLD. Bone marrow biopsy shows mildly hypocellular marrow for age multilineage hematopoiesis (A. 100X and B. 400X). There is no morphologic support for involvement by PTLD.
At the age of 11 and 14 years imaging studies identified multiple new mesenteric FDG-avid mesenteric lymph nodes; however, tissue biopsy did not confirm recurrence of PTLD. Screening biopsies of the intestine did not demonstrate recurrence of the PTLD. Over the course of her disease, patient’s EBV viremia was addressed by the immunosuppression reduction, Ganciclovir, and Rituximab. Currently patient is doing well and does not show signs of acute rejection or recurrent PTLD.
Case 2 . The patient is a 9-year-old female born full term with a Hemoglobin (Hgb)C trait. At five weeks of age she started having cyanotic episodes and was diagnosed with left ventricular non-compaction dilated cardiomyopathy. Patient required an orthotopic heart transplant at the three months of age. Immunosuppression was mediated by the mycophenolate mofetil and tacrolimus (CellCept). Shortly after the cardiac allograft patient developed cytomegalovirus (CMV) infection. CMV viremia was successfully treated with Ganciclovir, with subsequent negative serology. At the eight months her mother noticed that she developed difficulty crawling and holding her head. At that time hydrocephalus was diagnosed and a ventriculoperitoneal shunt placed. Over the course of her clinical course patient was noted to have a marked neutropenia and reticulocytopenia refractory to the granulocyte colony stimulating growth factor Neupogen. By age four, patient required transfusion.
At age five, patient developed cervical lymphadenopathy. Although EBV viremia was noted, lymph node biopsy did not reveal PTLD. At age six, patient developed diffuse lymphadenopathy with multiple FDG-avid lymph nodes. At that time, an inguinal lymph node biopsy revealed near-total nodal effacement by a diffuse proliferation of mixed atypical lymphocytes, large transformed lymphocytes or immunoblasts, and numerous plasma cells, consistent with the involvement by polymorphous PTLD. Immunostains highlighted mixed lymphoplasmacytic cells with increased numbers of immunoblasts and polytypic plasma cells. Proliferation index was at 40%, and EBV-EBER was positive by in-situ hybridization. Concurrent flow cytometry did not detect any monotypic B-cells or pan T-cell aberrancy.