gingival changes are seen in about 25% of patients medicated with cyclosporine , but the rate may increase to greater than 60% in patients medicated with both cyclosporine and a calcium channel blocker4 - 6 ) . in renal allograft recipients , the incidence of post- transplantation lymphoproliferative disorder ( ptld ) is 2.3%7 ) , and its overall annual incidence is 0.5%8 ) . up to 40% of ptlds occur in extranodal sites such as the stomach , intestine , bone , central nervous system , eyes , and skin9 , 10 ) . the following case report relates a unique case of ptld in a renal transplant recipient who was receiving cyclosporine and a calcium channel blocker , which manifested as gingival hyperplasia . a male , 41 years old , visited the clinic in april 2002 after experiencing bleeding , pus discharge , edema , and pain of the gingivae over the previous three months ( figure 1a , 1b ) . he had previously been diagnosed with end stage renal failure because of iga nephropathy . additionally , continuous ambulatory peritoneal dialysis was initiated in january 1994 . the patient was maintained on medication consisting of 75 mg of cyclosporine twice daily , 12 mg of deflazacort once daily , and 750 mg of mycophenolate mofetile ( mmf ) administered twice daily . his post - operative progress was good until he developed gingival bleeding , discharged pus , and pain . three months before entering our clinic , he was admitted to the outpatient dental clinic for treatment of hyperplastic gingivae ( which at that time was considered to have been induced by cyclosporine ) . the lesion , however , did not improve despite scaling , oral antibiotics , and a reduction in the cyclosporine doses . moreover , the gingival hyperplasia exhibited focal papillary growth and bled in response to light pressure . he had also lost 5 kg of body mass over the preceding six months . a laboratory examination , including complete blood counts , blood chemistry , and urinary analysis , revealed that his hemoglobin concentration was 11.1 g / dl , blood urea nitrogen concentration was 27.5 mg / dl , and creatinine concentration was 1.46 mg / dl . the biopsy established the presence of leukemic cell infiltration including a malignant lymphoma or histiocytic tumor ( figure 3 ) . muramidase and immunohistochemical stains specific for lca ( figure 4a ) , l26 ( figure 4b ) , uchl1 , and cd68 revealed a large diffuse b cell type of malignant lymphoma . the latent membrane protein for the epstein - barr virus ( ebv - lmp ) immunohistochemical stain was positive ( figure 5 ) . in the initial stage of the lymphoma , computed tomography ( ct ) scan of the neck indicated a 21.5 cm enlarged lymph node present in the right submandibular area several enlarged lymph nodes were also in the bilateral parapharyngeal space . the final stage of the lymphoma was stage ii ( b ) according to the ann arbor staging system . the patient started chemotherapy with a chop regimen of 1087 mg of cyclophosphamide ( 750 mg / m ) , 72 mg of doxorubicin ( 50 mg / m ) , 2 mg of vincristine , and 100 mg of prednisolone . after three serial chop chemotherapies , a neck ct showed a marked regression of the right submandibular lesion but no clearly enlarged lymphadenopathy in the other neck areas . chop therapy and external radiotherapy of the gingivae was performed a total of six times . in 2004 , the patient 's gingivae were normal upon examination , and ct scans could not detect lymphadenopathy . presently , his renal function is good and is treated by daily doses of 100 mg azathioprine and 7.5 mg prednisolone . the clinical definition of gingival non - hodgkin 's lymphoma ( nhl ) varies , but it is usually described as an asymptomatic gingival enlargement or a mass of tissue that resembles a pyogenic granuloma10 ) . therefore , any diagnosis of ptld could be missed or delayed if the physicians do not consider the possibility of lymphoma when assessing gingival overgrowth in patients receiving immunosuppressive drugs . in our case , we initially suspected cyclosporine or nifedipine as causing the gingival hyperplasia . however , this lesion was aggravated in spite of withdrawing from the nifedipine , reducing the dosage of cyclosporine ( from 275 mg to 150 mg daily ) , and three months of conservative dental care . these findings suggested that other causes might have been responsible , and gingival biopsy eventually was revealed in nhl . in retrospect , several of the initial symptoms were more indicative of lymphoma than drug - induced gingival hyperplasia . first , the patient had lost 5 kg of body mass during the preceding three months . third , his gingival hyperplasia had progressed to a mass - like lesion that bled easily when touched . had the possibility of a hidden malignancy been considered , a careful physical examination may have detected the lymphoma . until now , only a few cases of gingival lymphoma or plasmacytoma in transplant patients10 - 14 ) have been reported . there was one case in a bone marrow transplant patient in 2000 and two cases after cardiac transplantations in 2004 . the major risk factors for ptld are the duration of immune suppression and the amount and number of immunosuppressive agents used4 , 11 , 15 ) . these agents induce abnormal lymphoid cell proliferation , which may vary from the polymorphic proliferation of b lymphocytes to monoclonal high - grade malignant lymphoma16 ) . our patient had received dual therapy ( cyclosporine and steroid ) for seven years , followed by a regimen of mmf added 14 months ago to prevent chronic allograft nephropathy . there is currently no evidence to indicate that mmf is directly associated with the observed increase in ptlds17 - 19 ) , but the elevated intensity of immunosuppression by mmf may be partly responsible for ptlds in this case . the roles of ebv and its complications in the development of lymphomas have been studied extensively20 - 23 ) . ptlds may be the result of primary or reactivated ebv infections in a host with impaired immunity22 ) . ebv infection is associated with 70% of b - cell ptld cases25 ) . in this case , we also confirmed the presence of ebv with in situ hybridization , since previous cases were usually associated with ebv . treatment of nhl in renal transplant recipients consists of reducing or withdrawing immunosuppressants and cytotoxic therapy ( including chemotherapy and radiotherapy ) . it has been reported that ptlds subsequent to bone marrow transplantation were successfully treated by administering rituximab for four weeks and reducing the immunosuppressive agent doses10 ) . other patients with ptld subsequent to cardiac transplantation were successfully treated by reducing the dose of the immunosuppressive agent11 ) . our patient was treated with conventional chop chemotherapy and radiotherapy because of the presence of several parapharyngeal lymphadenopathies and because a lack of response to a reduction in cyclosporine . the prognosis of primary diffuse oral lymphomas is less favorable than that of nodular lymphomas26 , 27 ) , but both disease staging and early diagnosis are important prognostic factors . a good prognosis for ptld is associated with early detection , localization to a single organ and treatment with cyclosporine , whereas late - onset ptld , dissemination of the disease , and cns or bone marrow involvement are associated with a poor prognosis28 ) . good and poor prognostic factors were present in our patient who had been treated with cyclosporine , but had developed late - onset ptld . in conclusion , non - hodgkin 's lymphoma should be considered as a possible cause of gingival hyperplasia when the lesion does not respond to conventional treatment and the morphology is atypical .
gingival hyperplasia is a frequent complication in transplant patients who receive cyclosporine or calcium channel blockers . 
 we studied an unusual case involving a renal transplant recipient with post - transplant non - hodgkin 's lymphoma that manifested as gingival hyperplasia . 
 we initially consider that it was a side effect of cyclosporine and nifedipine . 
 the lesion did not respond to dose reductions or the withdrawal of cyclosporine and nifedipine , and the gingival hyperplasia progressed in a localized fashion , becoming ulcerated and bleeding easily . 
 histological examination revealed the presence of malignant lymphoma .