Morscio Julie, Bittoun Emilie, Volders Nathalie, Lurquin Eveline, Wlodarska Iwona, Gheysens Olivier, Vandenberghe Peter, Verhoef Gregor, Demaerel Philippe, Dierickx Daan, Sagaert Xavier, Janssens Ann, Tousseyn Thomas
1Department of Imaging and Pathology, Lab for Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium.
2Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
J Hematop. 2016 May 21;9:113-120. doi: 10.1007/s12308-016-0273-8. eCollection 2016.
Up to 10 % of chronic lymphocytic leukemia (CLL) patients present with aggressive secondary B-cell lymphoma (most frequently diffuse large B-cell lymphoma, DLBCL) which may be clonally related to the CLL (i.e., Richter transformation, RT, 80 % of the cases) or de novo (20 % of the cases). Several genetic lesions associated with RT have already been identified, but the potential role of the Epstein-Barr virus (EBV) has been largely overlooked. In this study, we describe six CLL patients who developed a secondary EBV-positive (EBV) B-cell lymphoma (five DLBCL, one Hodgkin lymphoma) and compare their clinicopathological characteristics to ten CLL patients with EBV-negative (EBV) secondary B-cell lymphomas (all DLBCL). All 16 patients had a history of iatrogenic immunosuppression or chemotherapy. Eighty percent had received fludarabine as part of the CLL treatment. Most secondary lymphomas were clonally related to the previous CLL (3/4 EBV, 7/7 EBV cases tested). Notably EBV RT was associated with a trend for older age at onset (median 72 vs. 63 years, value >0.05), longer interval between CLL and RT diagnosis (median 4.2 vs. 2.9 years, value >0.05), and shorter overall survival (median 4 vs. 10 months, value >0.05). These differences were not significant, probably due to small sample size. Immunohistochemical profiling suggested more frequent overexpression of TP53 and MYC in EBV compared to EBV secondary lymphoma. Based on this small retrospective single center series, we hypothesize that EBV RT may constitute a separate subgroup of RT. Larger series are required to validate this suggestion.
高达10%的慢性淋巴细胞白血病（CLL）患者会出现侵袭性继发性B细胞淋巴瘤（最常见的是弥漫性大B细胞淋巴瘤，DLBCL），其可能与CLL存在克隆相关性（即里氏转化，RT，80%的病例）或为新发（20%的病例）。已经确定了几种与RT相关的基因损伤，但爱泼斯坦-巴尔病毒（EBV）的潜在作用在很大程度上被忽视了。在本研究中，我们描述了6例发生继发性EBV阳性（EBV+）B细胞淋巴瘤的CLL患者（5例DLBCL，1例霍奇金淋巴瘤），并将他们的临床病理特征与10例EBV阴性（EBV-）继发性B细胞淋巴瘤的CLL患者（均为DLBCL）进行比较。所有16例患者都有医源性免疫抑制或化疗史。80%的患者在CLL治疗过程中接受过氟达拉滨治疗。大多数继发性淋巴瘤与先前的CLL存在克隆相关性（检测的3/4例EBV+、7/7例EBV-病例）。值得注意的是，EBV+ RT与发病年龄较大的趋势相关（中位年龄72岁对63岁，P值>0.05），CLL与RT诊断之间的间隔时间更长（中位时间4.2年对2.9年，P值>0.05），总生存期更短（中位时间4个月对10个月，P值>0.05）。这些差异不显著，可能是由于样本量较小。免疫组织化学分析表明，与EBV-继发性淋巴瘤相比，TP53和MYC在EBV+中更频繁地过度表达。基于这个小样本回顾性单中心系列研究，我们推测EBV+ RT可能构成RT的一个单独亚组。需要更大规模的系列研究来验证这一观点。
