Key features distinguishing post-transplantation lymphoproliferative disorders and acute liver rejection

Post-transplantation lymphoproliferative disorder (PTLD) and acute rejection are two serious complications of orthotopic liver transplantation that can have a similar histologic appearance. We undertook the present study to assess the best way to distinguish these two entities. We studied histologic features, immunophenotyping, and Epstein-Barr virus (EBV) status, as assessed by immunohistochemical stain and in situ hybridization (ISH), in three groups: Group I, 8 cases of PTLD post-orthotopic liver transplantation with liver involvement; Group II, 15 cases diagnosed with acute liver rejection (control group); and Group III, a subset of 6 biopsy specimens from 4 patients of Group I whose graft rejection was diagnosed within the 2 months preceding the diagnosis of PTLD. The mean proportion of plasma to plasmacytoid cells in most cases from Group I was more than 40%, whereas from Group II it was less than 25% (P = .0001). There was a higher number of B lymphocytes than T lymphocytes in Group I. The numbers of mitotic figures and immunoblasts were significantly different in the two groups (P < .0001 and P = .0005, respectively), being higher in the patients with PTLD. EBV immunostain was most specific for the diagnosis of PTLD (75% positive in Group I, negative in Group II). ISH for EBV-encoded RNA was positive in 87% of cases in Group I and only 6.6% of cases in Group II (P = .0005). In Group III, four of the six liver biopsy specimens had a low plasma cell count and were negative for EBV studies. The other two biopsy specimens in this group had 70 to 80% plasma cell infiltrate, in addition to positive EBV immunostain and ISH in one, for which tissue was available for study. We conclude that viral studies and assessment of the number of plasma cells and B lymphocytes can help to distinguish between acute rejection and early PTLD.