1F). We selected the reduction of immunosuppression alone for the patient as the first-line treatment because the level of EBV-DNA in the blood was not high (1.2 × 102 copies/106 peripheral blood leukocytes) (Fig. 2), and she had no abnormal findings on clinical or imaging examinations. The dosages of

TACER and MMF were reduced to 5 and 500 mg/day, respectively (Fig. 2). MMF was later switched to 200 mg/day of mizoribine (Fig. 2) in anticipation of some antiviral effect. Follow-up biopsy to assess the treatment response at 1.5 years after transplantation revealed no histopathological findings characteristic of PTLD (Fig. 3). The blood EBV-DNA fluctuated at low levels RAD001 and stabilized thereafter within the normal range (Fig. 2). The patient has remained well with a normal graft function. The early detection and diagnosis of PTLD are not easy because clinical pictures of this disease are often uncharacteristic. There are many diagnostic measures for PTLD including physical examination, laboratory testing, and different imaging techniques; however, the final diagnosis is always based on histopathology.[2] According

to the latest WHO classification from 2008, four histological types of PTLD: (i) early lesions, (ii) polymorphic PTLD, (iii) monomorphic PTLD, and (iv) Hodgkin lymphoma-type PTLD, have been identified.[4] In the present case, 1 year protocol allograft biopsy detected plasmacytic hyperplasia that was a characteristic feature of ‘early lesions’ of PTLD. Such pathological change is sometimes MK-1775 cell line difficult to differentiate from that of plasma cell-rich or B-cell-rich acute rejection, but biopsy specimens of our case exhibited distinctive hallmarks of PTLD: relatively mild or no tubulitis and peritubular capillaritis in proportion to the extent of focally distributed tubulointerstitial infiltration. To identify the cause Oxalosuccinic acid of this plasmacytic hyperplasia, we applied in situ hybridization for EBER in the biopsy specimens in addition to histopathological and immunohistochemical identification of infiltrating cells. In situ hybridization for EBER also serves to distinguish

between cell invasion due to acute rejection and cell invasion in PTLD due to EBV infection.[5] In addition, analysis of EBV viral load in peripheral blood is useful for screening suspected cases of EBV disease.[6] With the early diagnosis of EBV-positive PTLD, examination of EBV load over time was available to monitor the patient for response to therapy against PTLD. Both the patient and the donor had been confirmed to be sero-positive for EBV before surgery. It has been reported that the risk of PTLD increases 10- to 50-fold if the recipient is sero-negative and the donor is sero-positive for EBV.[7] Protocol biopsy enabled us to initiate early treatment for the patient with asymptomatic PTLD by detecting the ‘early lesions’.