Stuhlmann-Laeisz Christiane, Szczepanowski Monika, Borchert Alisa, Brüggemann Monika, Klapper Wolfram
Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrecht University, Kiel, Germany,
Virchows Arch. 2015 Jan;466(1):85-92. doi: 10.1007/s00428-014-1661-z. Epub 2014 Oct 23.
Although the vast majority of diffuse large B-cell lymphomas (DLBCL) are negative for the Epstein-Barr virus (EBV), a subset of DLBCL in immunocompetent patients carries EBV in the lymphoma cells and expresses EBV-encoded RNA and/or proteins. EBV-positive DLBCL are rare and represent either pyothorax associated DLBCL or EBV-positive DLBCL of the elderly. In all cases of EBV-positive DLBCL, EBV is detectable in virtually all lymphoma cells, indicating that EBV was present at an initial phase of lymphomagenesis. We identified four lymphomas with an unusual EBV expression pattern. The majority of B-cell blasts were EBV-negative, but accompanied by a small number (less than 10 % of all B-cells) of EBV-positive B-cells with blastic morphology. The median age of the patients was 56.5 years, and no clinically evident immunosuppression was reported. In one patient EBV-positive blasts occurred in the gastric mucosa which resembled an EBV-positive mucocutaneous ulcer. In all cases EBV-positive B-cells occurred in small loose clusters within or adjacent to an EBV-negative DLBCL. In one case we were able to study immunoglobulin gene rearrangement in microdissected EBV-positive B-cells and the EBV-negative lymphoma compartment. This revealed different rearrangement patterns in EBV-negative DLBCL than in EBV-positive peritumoral B-cells, without clonal relationship between these B-cell populations. Despite the molecular data being limited to one patient, we suggest that in close proximity to EBV-negative DLBCL intra- and peritumoral EBV-positive B-cells may occur, possibly due to local immune escape mechanisms. This represents a diagnostic pitfall.
尽管绝大多数弥漫性大B细胞淋巴瘤（DLBCL）的爱泼斯坦-巴尔病毒（EBV）检测呈阴性，但免疫功能正常患者中的一部分DLBCL在淋巴瘤细胞中携带EBV，并表达EBV编码的RNA和/或蛋白。EBV阳性的DLBCL较为罕见，包括与脓胸相关的DLBCL或老年EBV阳性DLBCL。在所有EBV阳性DLBCL病例中，几乎所有淋巴瘤细胞中均可检测到EBV，这表明EBV在淋巴瘤发生的初始阶段就已存在。我们鉴定出4例具有异常EBV表达模式的淋巴瘤。大多数B细胞母细胞EBV阴性，但伴有少量（占所有B细胞的不到10%）具有母细胞形态的EBV阳性B细胞。患者的中位年龄为56.5岁，未报告有明显的临床免疫抑制情况。1例患者的胃黏膜中出现了EBV阳性母细胞，类似于EBV阳性的黏膜皮肤溃疡。在所有病例中，EBV阳性B细胞均以小而松散的簇状出现在EBV阴性DLBCL内部或附近。在1例病例中，我们能够研究显微切割的EBV阳性B细胞和EBV阴性淋巴瘤区域中的免疫球蛋白基因重排。这显示出EBV阴性DLBCL与EBV阳性瘤周B细胞的重排模式不同，这些B细胞群体之间不存在克隆关系。尽管分子数据仅来自1例患者，但我们认为在EBV阴性DLBCL的瘤内和瘤周可能会出现EBV阳性B细胞，这可能是由于局部免疫逃逸机制所致。这是一个诊断陷阱。
