Acute Rejection Grading

Posttransplant Lymphoproliferative Disorder (PTLD)

Small bowel transplant recipients are at a relatively high risk of developing PTLD compared to the solid organ transplant population. Approximately 20% of patients receiving small bowel allografts develop PTLD. Onset of PTLD is 1 to 82 months after transplantation (median onset approximately 8 months) with 2/3 of the cases diagnosed within the first post-transplant year. PTLD is lethal in approximately 1/3 of the total morbid cases. Children are at significant higher risk than adults. The multivisceral allografts are also at a significantly higher risk to develop PTLD compared to the isolated small intestine. Since the frequency of PTLD can be reduced with modification of immunosuppressive regimen and adoption of the prophylactic/empirical anti-viral therapy, close monitoring of the EBV viremia with early diagnosis and treatment of EBV infection is important in reducing the risk of PTLD among the intestinal allograft recipients(1).

The main histological features of PTLD is proliferation of EBV-positive lymphoid cells with malignant potential. EBV infection manifests as a continum from lymphoid hyperplasia to frankly malignant lymphoid proliferation resembling non-Hodgkin's lymphoma. At the early phase of EBV infection, the tissue is expanded by scattered EBER-positive lymphocytes. With disease progression, the number of positive cells increases, lymphocytes become activated and transformed, and ultimately, tissue architecture is effaced by a malignant lymphoproliferative process. Finn et al has developed a quantitative method to grade EBV infection in small bowel allograft recipients(2). Although this method was used for pediatric population, it can also be easily applied to adult patients. This scheme is based on the numbers of EBV-positive cells by EBER in situ hybridization: Grade 1 - one to five EBER-positive cells/HPF with most cells being small lymphocytes and scattered mature plasma cells; Grade 2 - more than five EBER-positive cells/HPF with atypical features insufficient to warrant categorization as PTLD; Grade 3 - more than 15 EBER-positive cells/HPF with features of polymorphous PTLD; Grade 4 - more than 15 EBER-positive cells/HPF with features of monomorphic PTLD.

It is important to distinguish PTLD from rejection because many patients will respond to a reduction in immunosuppression alone. Other treatment options for PTLD include antiviral therapy or interferon-a.


1. Nalesnik, M., Jaffe, R., Reyes, J., Mazariegos, G., Fung, J. J., Starzl, T. E., and Abu-Elmagd, K. Posttransplant lymphoproliferative disorders in small bowel allograft recipients. Transplant Proc, 32: 1213, 2000.

2. Finn L, Reyes J, Bueno J and Yunis E. Epstein-Barr virus infections in children after transplantation of the small intestine. Am. J. Surg. Pathol. 22(3):299-309, 1998

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Last Modified: Thu Jun 18 10:14:08 EDT 2009