Definition
A lymphoid proliferation arising in a recipient of solid organ or bone marrow allogeneic transplantation (including umbilical cord blood transplantation2).
EBV is thought to be causal in most cases. However, about 20% of cases (50% of renal transplantation cases) are EBV-negative; these cases tend to occur late after transplantation. Most PTLD are of host origin but about 10% arise from donor lymphoid cells; those arising from donor cells most commonly arise after lung and liver transplantation and involve the allograft. PTLD in the context of bone marrow transplant is of donor origin.
A few cases of similar EBV-positive B-cell lymphoproliferative disorder have been described as a sequel to chemotherapy with fludarabine for low-grade B-cell lymphoma. At least in some cases, they regress spontaneously1.
The mean time to the development of PTLD after grafting is variable:
25% of cases involve the allograft. Azathioprine immunosuppression is associated with extranodal PTLD of the allograft and of the CNS. Cyclosporine and Tacrolimus are associated with nodal and gastrointestinal PTLD, less often CNS disease. Bone marrow, liver and lungs may also be involved. Involvement of the peripheral blood is rare.
plasmacytic hyperplasia and infectious mononucleosis-like PTLD: may arise at any time, most often in the first two years. They occur in younger recipients, including children. These conditions usually involve lymph nodes, tonsils or adenoids. There is preservation of nodal sinuses or tonsilar crypts and, in some cases, of reactive follicles. Plasmacytic hyperplasia shows numerous plasma cells and some immunoblasts. IM-like lesions show paracortical expansion by immunoblasts, T-cells and plasma cells. The immunoblasts are EBV-LMP+.
polymorphic PTLD: Most often arises in the first year. There is a polymorphic infiltrate of immunoblasts, plasma cells and intermediate-size lymphoid cells overrunning the nodal architecture or forming an extranodal mass. Reed-Sternberg-like cells may be present. Necrosis may be seen. There may be a continuum to monomorphic PTLD. The cells are a mix of B and T cells. The immunoblasts are EBV-LMP+ in most cases.
monomorphic PTLD: Most often arises in the first year. The morphology is that of a lymphoma and should be classified accordingly, but with PTLD appearing in the diagnosis. "Monomorphic" indicates that most of the cells appear transformed, not that the infiltrate is monotonous. Most cases express EBNA2 and LMP-1. B-cell monomorphic PTLD may show EBV-induced up-regulation of CD43 and CD45RO. Many cases are CD30+.
DLBCL; constitutes the majority of cases of monomorphic PTLD. Most are of immunoblastic type, some centroblastic or anaplastic.
plasma cell myeloma; rare
plasmacytoma-like lesions; may occur in the gastrointestinal tract, lymph nodes or other extranodal sites.
peripheral T-cell lymphoma; includes cases resembling Subcutaneous panniculitis-like T-cell lymphoma, Hepatosplenic T-cell lymphoma, NK/T-cell lymphomas, T-cell large granular lymphocyte leukaemia and Peripheral T cell lymphoma, unspecified. They express T-cell antigens including CD4 or CD8, and may express CD30 or CD56. EBV status varies. They are often unresponsive to reduced immunosuppression.
Hodgkin lymphoma and Hodgkin lymphoma-like PTLD. HL-like PTLD resembles that seen in association with HIV and with methotrexate. HL expresses CD15 and CD30. HL-like PTLD expresses B-cell antigens. HL and HL-like PTLD are almost always EBV-positive.
others
The overall mortality of PTLD is 60% in the context of solid organ allografts and 80% in bone marrow allograft recipients.
plasmacytic hyperplasia and infectious mononucleosis-like PTLD: often regresses spontaneously or with reduced immunosuppression. May progress to polymorphic or monomorphic PTLD. IM-like PTLD may sometimes be fatal.
polymorphic PTLD regresses in a variable proportion of cases on reduction of immunosuppression.
monomorphic PTLD;
World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.
This page last revised 10.4.2006.
©SMUHT/PW Bishop