Answer

Post transplant lymphoproliferative disorder (PTLD), diffuse large B-cell lymphoma type, EBV negative

Discussion

Post-transplant lymphoproliferative disorder (PTLD) is a B-cell proliferation process due to therapeutic immunosuppression after organ transplantation. These patients may develop polyclonal polymorphic B-cell hyperplasia ; B cells from some of patients may undergo mutations which will render them monoclonal and give rise to frank lymphoma, higher risk with certain types of immunosuppressive drugs such as Calcineurin inhibitors (tacrolimus and cyclosporine) and anti-T cell antibodies (ATG, ALG and OKT3) [1]. While the majority (up to 80%) cases of PTLD are associated with EBV infection, there are cases with no evidence of EBV involvement. These EBV-negative PTLDs may comprise a distinct subgroup of PTLD: they tend to occur later after transplant (median of 50 months post transplant), to have a more malignant-appearing histology and to behave more aggressively, with a reported median survival of 1month. Even so, some of them may still respond to reduction of immunosuppression [2]. PTLD seemed to occur a little early (30 months) in this patient without EBV infection.There has been some controversy regarding EBV-negative PTLD listing as a distinct entity, because the etiology of EBV-negative PTLD is not fully understood. Other viruses, such as HHV8, HTLV-1, HCV, CMV and simian virus (SV40) infections, have been reported in association with EBV-negative PTLD [3]. In addition, other unknown viruses as well as chronic antigenic stimulation, such as that seen in transplantation patients, have been linked to EBV-negative PTLD. Therefore, although controversial, CMV and BKV, which shares important features with SV40 [4], may have contributed to the etiology in the present case. Since the etiology of the EBV-negative PTLD is not clear, this entity may be endowed with multiclonal potentiality, it would be of interesting to reexamine the subtype of PTLD at different stage of the disease. Different histological subtypes including polymorphic B-cell PTLD and monomorphic T-cell PTLD (ALK-positive ALCL) have been reported in the same lymph node in a patient who developed PTLD after liver transplantation in the absence of EBV infection [5].

References

1. Kataoka K, Seo S, Sugawara Y, Ota S, Imai Y, Takahashi T, Fukayama M, Kokudo N, Kurokawa M. Post-transplant lymphoproliferative disorder after adult-to-adult living donor liver transplant: case series and review of literature. Leuk Lymphoma. 2010 Aug;51(8):1494-501.
2. Loren AW, Porter DL, Stadtmauer EA, Tsai DE. Post-transplant lymphoproliferative disorder: a review. Bone Marrow Transplant. 2003 Feb;31(3):145-55.
3. Nelson BP, Nalesnik MA, Bahler DW, Locker J, Fung JJ, Swerdlow SH. Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity? Am J Surg Pathol. 2000 Mar;24(3):375-85.
4. Vilchez RA, Kusne S. Molecular and clinical perspectives of polyomaviruses: emerging evidence of importance in non-kidney transplant populations. Liver Transpl. 2006 Oct;12(10):1457-63.
5. Krzysztof Mucha, Bartosz Foroncewicz, Bogna Ziarkiewicz-Wróblewska, Marek Krawczyk, Jan Lerut and Leszek Pączek. Post-transplant lymphoproliferative disorder in view of the new WHO classification: a more rational approach to a protean disease? Nephrol Dial Transplant (2010) 25: 2089-2098.