**10. DLBCL vs. PTLD**

1982 to 2009, with a 1.1% overall incidence among pediatric transplant heart-lung recipients, 14% of our pediatric renal PTLD patients, 1.6% among kidney recipients, and 0.71% pediatric liver-transplant recipients, as reported in a single institution study. BL-PTLD is a more aggressive type of PTLD and does not respond to a trial of decreased immunosuppression like P-PTLD and some M-PTLDs. BL-PTLD does require cessation of conventional immunosuppression during treatment with multiagent lymphoma-specific chemotherapy. Bone marrow involvement remains a poor prognostic factor, despite the use of lymphoma-specific

BL after organ transplantation is often found in extra-nodal sites; it involves the central nervous system more frequently than it does in immunocompetent patients. In 70% of BL occurring after organ transplantation, genes or gene products related to EBV can be demonstrated within the tumor cells. The EBV status of the tumor is of important prognostic significance: EBV-positive BL occurring in organ transplant patients usually responds well to reduction or cessation of immunosuppressive therapy; in some cases permanent complete remissions can be achieved even without chemotherapy. In contrast, patients with EBV-negative BL have a very poor prognosis and rarely respond even to aggressive chemotherapy protocols [23].

The etiology of posttransplant T-cell lymphomas remains unclear. Similarities with posttransplant B-cell proliferations are the predominant extranodal presentation and the finding that the time of occurrence is influenced by the type of immunosuppression. In contrast with posttransplant B-cell proliferations, only a minority of the cases are associated with EBV. Most tumors appear to be monoclonal. Prognosis is generally poor, but tumor presentation with localized disease might have a somewhat better prognosis. Ambiguity about the pathogenesis of T-PTLD and the lack of accepted diagnostic criteria may contribute to the rarity and inconsistent characterization of T-PTLD in the literature. While there is a general impression that T-PTLD is very difficult to cure, several recently reported cases demonstrate that these tumors can be very treatment responsive with the use of different chemotherapy regimens than those typically used to treat B-PTLD, such as the intensive ALL-type treatments we employed, and/ or the use of different strategies for immunosuppression. Most T-PTLDs are not EBV-driven; thus, reduction of immunosuppression may not be effective as a sole treatment strategy and

may be less critical for management of T-PTLD than it is in EBV-driven B-PTLDs.

strategies of treatment may be needed compared to B-lineage PTLD [25, 26].

T-PTLD cases may sometimes exhibit a bimodal response to therapy, with initial eradication of the bulk nodal disease with regimens typically used to treat ALL but persistence of lowlevel clonal T cells in the marrow, CSF, and lung. Due to small patient numbers, different

PTLD that resembles Hodgkin lymphoma (HL-PTLD) has been reported infrequently. These cases have variable numbers of Reed-Sternberg-like (RS-like) cells and highlight differences in the phenotype that may distinguish these from true Hodgkin lymphoma (HD). These

chemotherapy in these cases [20–24].

402 Organ Donation and Transplantation - Current Status and Future Challenges

**9.2. T cell PTLD**

**9.3. HL-PTLD**

Within the PT-DLBCL series, EBV (+) cases were different from EBV (−) cases. The fact that all EBV (+) PT-DLBCL cases are of activated B-cell (ABC) origin whereas 45% EBV (−) PT-DLBCL cases were of GCB origin might contribute to the observed difference in survival. Overall, EBV (−) PT-DLBCL was similar to DLBCL arising in immunocompetent individuals regarding median age at diagnosis (63 versus 65 years). The amount of stromal infiltration was significantly higher in IC-DLBCL than PT-DLBCL (12/13 and 12/33 cases contained ≥15% stroma, respectively, P = 0.0012). Geographical necrosis was almost exclusively observed in EBV (+) PT-DLBCL (46%), compared to EBV (−) PT-DLBCL (11%). In contrast, there was no obvious difference in the absolute amount of stromal infiltration between both groups. IDO1 was variably expressed in the tumor and/or stromal cells of 7/22 EBV(+) PT-DLBCL. The Epstein–Barr virus broad latency profile (LMP1+/EBNA2+) was most frequently expressed in PT-DLBCL (n = 13/22; 59%) and associated with a more elaborate inflammatory response than intermediate latency (LMP1+/EBNA2−).
