Primary Intrarenal Posttransplant Lymphoproliferative Disorder Detected by Surveillance Protocol Biopsy

Abstract

To the Editor: Moir et al. recently reported a case of Epstein–Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (PTLD), presenting as multiple cystic lesions, in a 67-year-old renal transplant recipient. The renal lesions were initially detected by ultrasound and computed tomography, and then investigated by renal biopsy. The authors concluded that this rare PTLD case underlines the need for a high index of clinical suspicion; they recommended that a biopsy be performed for abnormal pararenal allograft masses (1Moir JA Simms RJ Wood KM Talbot D Kanagasundaram NS Posttransplant lymphoproliferative disorder presenting as multiple cystic lesions in a renal transplant recipient.Am J Transplant. 2012; 12: 245-249Abstract Full Text Full Text PDF Scopus (2) Google Scholar). PTLD is estimated to occur in 1–5% of renal transplant recipients. Primary intrarenal localization is extremely rare and is generally diagnosed late, because of ambiguous clinical presentation (2Végso G Hajdu M Sebestyén A Lymphoproliferative disorders after solid organ transplantation-classification, incidence, risk factors, early detection and treatment options.Pathol Oncol Res. 2011; 17: 443-454Crossref PubMed Scopus (75) Google Scholar). We detected primary intrarenal lymphoplasmacellular early PTLD in a 5-year-old kidney transplant recipient by renal allograft protocol biopsy. At age 3, the boy underwent renal transplantation from a deceased donor because of end stage renal disease associated with Prune–Belly syndrome. Immunosuppressive therapy included daclizumab, steroids, tacrolimus, and mycophenolate mofetil. Pretransplant EBV serology was negative. The postoperative course was uncomplicated, and renal function recovered quickly. At posttransplant week 12th, the boy developed high blood EBV DNA load (8000 copies/104 lymphomonocytes), without clinical or biochemical signs of primary EBV infection. Immunosuppression was withdrawn, by minimizing tacrolimus and prednisone, and discontinuing mycophenolate. By posttransplant month 12, normal renal function (serum creatinine 45 umol/L) and an EBV DNA load of 1083 copies/104 lymphomonocytes were observed. According to our protocol, a surveillance renal allograft biopsy was performed, which revealed severe lymphomonocytes infiltration with CD3+ T lymphocytes, CD20+ B lymphocytes, CD79a+ plasma cells, and rare CD68+ monocytes. C4d staining was negative. EBV in situ hybridization showed numerous positive cells, consistent with EBV-associated intrarenal early PTLD (Figure 1). Rituximab therapy (375 mg/m2, 2 doses) was administered: the EBV DNA load became negative. Histologically, two control biopsies performed at 3 and 15 months after rituximab therapy were normal. This rare case confirms the need for careful vigilance for PTLD in renal transplant recipients, and emphasizes the role of surveillance protocol biopsy. PTLD diagnosis may be very difficult before mass lesion development, especially if the primary localization is the allograft itself and the patient is asymptomatic. Therefore, renal allograft protocol biopsy, performed at fixed time points in patients with normal renal function, may be a very useful tool for the early identification of not only immunological, but also nonimmunological renal lesions, of which PTLD represents an increasing cause of reduced graft and patient survival. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.