Rizkalla K S, Asfar S K, McLean C A, Garcia B M, Wall W J, Grant D R
Department of Pathology, University Hospital, London, Ontario, Canada.
Mod Pathol. 1997 Jul;10(7):708-15.
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.
移植后淋巴组织增生性疾病（PTLD）和急性排斥反应是原位肝移植的两种严重并发症，它们可能具有相似的组织学表现。我们开展本研究以评估区分这两种病变的最佳方法。我们研究了三组的组织学特征、免疫表型分析以及通过免疫组化染色和原位杂交（ISH）评估的 Epstein-Barr 病毒（EBV）状态：第一组，8 例原位肝移植后发生 PTLD 且肝脏受累；第二组，15 例诊断为急性肝排斥反应的病例（对照组）；第三组，从第一组的 4 例患者中选取的 6 份活检标本子集，这些患者在 PTLD 诊断前 2 个月内被诊断为移植排斥反应。第一组大多数病例中浆细胞与浆细胞样细胞的平均比例超过 40%，而第二组则低于 25%（P = 0.0001）。第一组中 B 淋巴细胞数量多于 T 淋巴细胞。两组中的有丝分裂象和免疫母细胞数量有显著差异（分别为 P < 0.0001 和 P = 0.0005），PTLD 患者中的数量更高。EBV 免疫染色对 PTLD 的诊断最具特异性（第一组 75%阳性，第二组阴性）。EBV 编码 RNA 的原位杂交在第一组 87%的病例中呈阳性，而在第二组仅 6.6%的病例中呈阳性（P = 0.0005）。在第三组中，6 份肝活检标本中有 4 份浆细胞计数低且 EBV 检测为阴性。该组另外两份活检标本有 70%至 80%的浆细胞浸润，其中一份除 EBV 免疫染色和原位杂交呈阳性外，还有可供研究的组织。我们得出结论，病毒学检测以及浆细胞和 B 淋巴细胞数量的评估有助于区分急性排斥反应和早期 PTLD。
