Kaleem Zahid, Hassan Anjum, Pathan M Hanif, White Glenda
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Mo, USA.
Arch Pathol Lab Med. 2004 Feb;128(2):181-6. doi: 10.5858/2004-128-181-FCEOPB.
Posttransplant B-cell lymphoproliferative disorders (PTLDs) constitute a heterogeneous group that includes hyperplastic and unique polymorphic lesions at one end of the spectrum and monomorphic lymphoid proliferations indistinguishable morphologically from conventional B-cell non-Hodgkin lymphomas (NHLs) at the other end. Almost all the PTLDs are of B-cell origin, with only rare examples of T-cell phenotype described. Despite a plethora of information available on the morphologic spectrum, pathogenetic role of Epstein-Barr virus, and various treatment options, a detailed flow cytometric immunophenotypic evaluation of PTLDs is largely lacking.
To evaluate the immunophenotypic profiles of various PTLDs using multiparameter flow cytometric analysis to compare and contrast with conventional de novo B-cell lymphoproliferative disorders and to identify any immunophenotypic patterns useful in diagnosis.
We retrospectively analyzed data on the immunophenotype of 25 cases of pediatric and adult PTLD (12 cases of monomorphic PTLD [m-PTLD] and 13 cases of polymorphic PTLD [p-PTLD]) using multiparameter flow cytometry in addition to routine morphologic and immunohistochemical evaluation. The flow cytometric immunophenotypic data were also compared and contrasted with 334 cases of various de novo B-cell NHLs during the same period as a control group.
We observed a much higher incidence of lack of surface immunoglobulin light chains and CD20 expression in B-cell PTLDs using multiparameter flow cytometry in comparison with de novo B-cell NHL as a group (with the exception of small lymphocytic lymphoma). Four (16%) of 25 cases of PTLD (3 m-PTLD and 1 p-PTLD) showed almost complete lack (CD20%/CD19% ratio < 1:9) of CD20 expression in contrast to only 8 ( approximately 2%) of 334 cases of de novo B-cell NHL (P =.007). Several other cases of both m-PTLD and p-PTLD also showed partial and dim expression of CD20. Nine (36%) of 25 cases, including 5 cases of m-PTLD and 4 of p-PTLD, showed either an almost complete lack (light chains%/CD19% ratio < 1:9) or significant loss (>50% loss) of surface immunoglobulin light chains in contrast to less than 5% incidence of light-chain negativity in conventional de novo B-cell NHL. Immunoglobulin light-chain clonality was observed in 9 cases (5 m-PTLD and 4 p-PTLD). Seven cases (5 p-PTLD and 2 m-PTLD) had polyclonal expression of immunoglobulin kappa and lambda light chains. The m-PTLD showed expression patterns of CD5, CD10, and CD23 similar to their de novo counterparts.
Both polymorphic and monomorphic PTLDs show a higher incidence of lack of CD20 and surface immunoglobulin light-chain expression. The lack of CD20 expression in these lesions may have therapeutic implications, since anti-CD20 antibody has increasingly become an important modality in the treatment of B-cell lymphoproliferative disorders, including posttransplant disorders.
移植后B细胞淋巴组织增生性疾病（PTLDs）是一组异质性疾病，一端包括增生性和独特的多形性病变，另一端是形态上与传统B细胞非霍奇金淋巴瘤（NHLs）无法区分的单形性淋巴样增生。几乎所有的PTLDs都起源于B细胞，只有极少数T细胞表型的病例报道。尽管已有大量关于形态学谱、爱泼斯坦-巴尔病毒的致病作用以及各种治疗方案的信息，但对PTLDs进行详细的流式细胞术免疫表型评估在很大程度上仍很缺乏。
采用多参数流式细胞术分析评估各种PTLDs的免疫表型特征，与传统的原发性B细胞淋巴组织增生性疾病进行比较和对比，并确定任何有助于诊断的免疫表型模式。
我们回顾性分析了25例儿童和成人PTLD（12例单形性PTLD [m-PTLD]和13例多形性PTLD [p-PTLD]）的免疫表型数据，采用多参数流式细胞术，同时进行常规形态学和免疫组织化学评估。流式细胞术免疫表型数据也与同期334例各种原发性B细胞NHL作为对照组进行了比较和对比。
与原发性B细胞NHL组相比（小淋巴细胞淋巴瘤除外），我们通过多参数流式细胞术观察到B细胞PTLDs中表面免疫球蛋白轻链和CD20表达缺失的发生率更高。25例PTLD中有4例（16%）（3例m-PTLD和1例p-PTLD）显示CD20表达几乎完全缺失（CD20%/CD19%比值<1:9），而334例原发性B细胞NHL中只有8例（约2%）出现这种情况（P = 0.007）。m-PTLD和p-PTLD的其他几例病例也显示CD20部分和弱阳性表达。25例中有9例（36%），包括5例m-PTLD和4例p-PTLD，显示表面免疫球蛋白轻链几乎完全缺失（轻链%/CD19%比值<1:9）或显著丢失（>50%丢失），而传统原发性B细胞NHL中轻链阴性发生率不到5%。9例（5例m-PTLD和4例p-PTLD）观察到免疫球蛋白轻链克隆性。7例（5例p-PTLD和2例m-PTLD）免疫球蛋白κ和λ轻链呈多克隆表达。m-PTLD显示CD5、CD10和CD表型与原发性病例相似。
多形性和单形性PTLDs均显示CD20和表面免疫球蛋白轻链表达缺失的发生率较高。这些病变中CD20表达缺失可能具有治疗意义，因为抗CD抗体在治疗B细胞淋巴组织增生性疾病（包括移植后疾病）中越来越成为一种重要的治疗方式。
