posttransplant lymphoproliferative disorders ( ptld ) are a rare , but serious complication following transplantation . occurring exclusively in iatrogenically immunosuppressed patients , there is an overall incidence of 15% in solid organ transplant ( sot ) recipients and 1% in hematopoietic stem cell transplant ( hsct ) recipients . late - onset ptld , as seen in our patient 8 years after transplantation , is often associated with more monoclonal lesions and consequently have a worse prognosis . the term ptld represents a spectrum of b - cell hyperproliferative states that can be classified as early lesions and polymorphic and monomorphic ptld , all of which are associated with epstein - barr virus ( ebv ) . monomorphic ptld is further divided into burkitt 's lymphoma / burkitt's - like lymphoma , diffuse large b - cell lymphoma ( dlbcl ) and classic hodgkin's - like lymphoma . the occurrence of ptld in solid organ allograft recipients can be quite varied in clinical presentation , histopathological characteristics and frequency . a variety of lymphomas can develop as ptld , although burkitt 's lymphoma appears infrequently and remains poorly understood in this clinical setting . in this report , we describe a case of burkitt 's lymphoma presenting as ptld following kidney and pancreas transplantation . the recipient was 39 years old and displayed gastrointestinal involvement by burkitt 's lymphoma several years following transplant . the tumor displayed the typical histological features of burkitt 's lymphoma but was negative for ebv . this report demonstrates that burkitt's - type lymphomas can develop in the posttransplant setting and that these tumors contain morphologic , cytofluorographic and molecular features identical to burkitt 's lymphomas that occur in non - transplant patients . we would recommend ptld - burkitt 's lymphomas behave aggressively and require intensive chemotherapeutic intervention . our patient is a 39-year - old man with an extensive past medical history including diabetes mellitus , below knee amputation in 2007 , end - stage renal disease , and simultaneous kidney and pancreas transplantation in 2003 . the patient went home and developed nausea , vomiting , and diarrhea with right lower quadrant pain . he had a right cervical submandibular mass and fullness in the right upper quadrant of his abdomen . he denied any constitutional symptoms , any obstructive symptoms , weight loss or gastrointestinal bleeding . he presented with a right submandibular swelling 3 cm in diameter , with a healing ulcerative lesion without any tenderness . his physical examination showed stable vital signs : temperature : 97.4f ; blood pressure : 136/76 mm hg ; pulse : 95 beats per min ; weight : 206.7 pounds ; weight loss : 7.30 pounds . he had no hepatosplenomegaly , no bleeding , no surgical scars and no other cervical , axillary or inguinal lymphadenopathy . the computed tomography ( ct ) on 08/16/2010 showed a soft tissue mass measuring 11  10 cm in the right lower quadrant region . the patient had a needle - guided biopsy of the mass which showed diagnosis of burkitt 's lymphoma with t(8;14 ) . pathology from fine needle aspiration showed medium - sized cells with speckled chromatin and multiple small conspicuous nucleoli ( fig . 1 ) . molecular cytogenetic analysis ( fluorescence in situ hybridization ) revealed a significant number of myc / igh fusion events ( fig . immunohistochemistry showed that the tumor cells were strongly positive for cd20 , consistent with mature b - cell lineage ( fig . ki-67 proliferation index was 100% by mib-1 immunohistochemistry , consistent with the diagnosis of burkitt 's lymphoma ( fig . . ebv by in situ hybridization was negative in this tumor , which is atypical of classical ptld that are positive for ebv ( fig . he had a bilateral bone marrow biopsy on 08/26/2010 , and then underwent staging workup including neck , chest , abdominal and pelvic ct on 08/27/2010 . he received treatment as per burkitt 's protocol along with aggressive hydration and was monitored closely for tumor lysis syndrome . he had partial bowel obstruction at the time of diagnosis , which improved over the period of a few days . the patient was diagnosed with burkitt 's lymphoma involving the right submandibular gland and the right ileocolic mass as well . the symptoms of bowel obstruction improved with conservative management . the patient was started on chemotherapy in view of the diagnosis of burkitt 's lymphoma . his immunosuppression was maintained in view of chemotherapy and the use of prednisone during burkitt 's protocol . the patient tolerated chemotherapy well and had marked reduction in the abdominal and right submandibular masses . the patient received 6 cycles of chemotherapy which involved high - dose methotrexate , rituximab , doxorubicin and vincristine . repeat ct and pet scans after completion of 2 cycles of chemotherapy and at completion of all planned cycles of chemotherapy showed that our patient had no evidence of hypermetabolic disease and continues to be in remission more than 2 years after his original diagnosis . ebv selectively infects b cells , remaining latent in the memory b - cell reservoir for the duration of the host 's life . the main viral genes involved in the transformation and persistence of infected b cells are lmp1 and lmp2a . through self - aggregation on the surface of the infected b cell , lmp2a and lmp1 provide tonic signals leading to the proliferation of transformed memory b cells that remain in the host for life . lmp1 and other ebv proteins such as ebna 2 , are highly antigenic , marking the infected b cells for destruction by cytotoxic t cells ( ctls ) in the healthy individual . however , in transplant recipients undergoing immunosuppression , ctls are immobilized , allowing for the proliferation and immortalization of infected b cells . sot patients , on the other hand , are immunosuppressed for life in order to ensure continuous proper function of the transplanted organ . in sot patients , a variety of lymphomas can develop as ptld , although some types appear infrequently and remain poorly understood . the tumors display the typical histological features of burkitt 's lymphoma and are markedly positive for ebv . contrary to common belief , strong bcl2 ihc expression is possible in typical burkitt 's lymphoma in adults and can not be absolutely relied upon to distinguish between burkitt 's lymphoma and dlbcl . furthermore , the combination of a strong expression of bcl-2 and ebv - positive status of the tumor found in our dlbcl patient suggests the disruption of an apoptotic pathway by ebv , promoting survival signals of the infected b cells . our burkitt's - ptld case had unique clinical and pathological characteristics that may challenge the clinical and pathological diagnosis and need to be recognized and managed in a timely manner . the patient presented with an exceptionally late onset of the disease ( 10 years ) and was ebv negative . ebv - positive ptld cases tend to occur earlier ( median interval 610 months ) than ebv - negative cases ( median interval 45 years ) , which are also more likely to be of monomorphic - type or frank lymphoma . ptld are associated with ebv reactivation in a setting of decreased host t - cell immune surveillance , leading to ebv - infected b - lymphocyte proliferation with eventual malignant lymphoma . the majority of ebv infections that occur after transplantation , especially in adults , are clinically silent reactivations . studies have shown a positive correlation between the degree of ebv dnaemia after transplantation and the development of ptld , which has significant implications for the importance of monitoring viral load after transplantation . in a study done by holman et al . , the risk of ptld in viremic patients significantly increased with the peak quantity of ebv dnaemia . correspondingly , more sot patients also developed ptld than did hsct patients , and also significantly later than hsct recipients . the median length of time between transplant and diagnosis of ptld for sot patients is 2.8 years versus 121 days for hsct patients . since the occurrence of ptld is significantly related to the viral load , constant monitoring and quantification of ebv - dna load is utilized as a prognostic marker for the development of ptld [ 68 ] . our patient presented with an extremely rare , aggressive burkitt 's lymphoma / leukemia - ptld . although the majority of monomorphic ptld fall into the category of dlbcl these include low - grade b - cell lymphoma , plasma cell myeloma , hodgkin 's lymphoma or hodgkin 's lymphoma - like ptld as well as various t - cell lymphomas with or without ebv infection . our case showed morphological and immunophenotypical characteristics of burkitt 's lymphoma , with t(8;14 ) involving rearrangement of myc gene [ 9 , 10 ] . compared to the general population , organ transplant patients have a 3060-fold increased risk of developing non - hodgkin 's lymphoma . burkitt 's lymphoma after organ transplantation is often found at extranodal sites ; it involves the central nervous system in immunocompromised patients more frequently than it does in immunocompetent patients . in 70% of burkitt 's lymphoma 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 burkitt 's lymphoma 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 , ebv - negative burkitt 's lymphoma has a very poor prognosis and hardly responds even to aggressive chemotherapy protocols . late - onset ptld , as seen in our patient , is often associated with more monoclonal lesions and consequently , carries a worse prognosis . the term ptld represents a spectrum of b - cell hyperproliferative states that can be classified as early lesions and polymorphic and monomorphic ptld , all of which are associated with ebv . this final category of monomorphic ptld is further divided into burkitt 's lymphoma / burkitt's - like lymphoma , dlbcl and classic hodgkin's - like lymphoma . our case contrasts the rare occurrence of burkitt 's lymphoma as ptld with more common dlbcl as ptld . the typical immunophenotype of burkitt 's lymphoma is igm+/cd10+/bcl-2-/bcl-6 + with a ki-67 proliferation index > 95% [ 12 , 13 ] . all cases of burkitt 's lymphoma , in both immunocompetent and immunosuppressed hosts , have a myc gene translocation . treatment for ptld includes pharmacologic , biologic , and newly emerging cell - based therapies . antiviral therapies such as acyclovir and ganciclovir have commonly been used to treat ptld . while they effectively decrease viral shedding in early - onset ebv infections , there is insufficient evidence to show that they are effective against the latent phase of ebv , namely the development of ptld . additionally , intravenous immunoglobulins have also been used , but their efficacy against ptld remains unknown . immunosuppression reduction ( ir ) therapy remains the current first - line treatment for aggressive ptld , such as the monoclonal lymphomas seen in our patient . early - onset ptld patients tend to have a better outcome than those who present with late - onset ptld . in aggressive ptld refractory to treatment , immunosuppression is discontinued altogether . for localized ptld , however , in view of diffuse proliferation of infected b cells , chemotherapy for advanced ptld is similar to treatment of lymphoma with chop - like chemotherapy . immunotherapy with anti - b - cell antibodies is now surfacing as a first - choice therapy after the failure of ir therapy alone to achieve complete remission . in a case , complete remission of an intra - graft ptld was achieved through the use of rituximab along with ir therapy and chemotherapy without graft loss . it was suggested that the immunosuppressive effects of rituximab may have partially compensated for the detrimental impact of ir therapy on graft function . this complementary role of rituximab is what allowed for the ir therapy during chemotherapy . ir , antiviral medications or cmv - immunoglobulin for ebv prevention , immunosuppression withdrawal , anthracycline - based chemotherapy for control of localized or systemic clonal disease or resection of primary ptld are various strategies for the treatment of ptld . overall , chemotherapy has been shown to have a response rate of 70% in the treatment of malignant ptld . the current recommendation for treating ptld , whether it is the rare burkitt 's lymphoma variation or common dlbcl , ebv - positive or ebv - negative , is a sequential combination of rituximab and chemotherapy . in conclusion , further investigations are needed to better understand the role of ebv infection in the pathogenesis of the different forms of ptld in immunosuppressed patients .
posttransplant lymphoproliferative disorders ( ptld ) are a rare , but serious complication following transplantation . 
 late - onset ptld are often associated with more monoclonal lesions and consequently have a worse prognosis . 
 there are only isolated case reports of burkitt 's lymphoma presenting as ptld 
 . we present an extremely rare , aggressive burkitt 's lymphoma years after kidney and pancreas transplantation which was successfully treated with combination chemotherapy along with withdrawal of immunosuppression . 
 the patient remains in complete remission more than 2 years after his diagnosis . 
 we also provide a succinct review of treatment of various ptld and discuss the role of epstein - barr virus infection in the pathogenesis of ptld .