Abstract：
Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.
摘要：
细胞周期蛋白D1蛋白阳性弥漫性大B细胞淋巴瘤（DLBCL）的免疫表型为CD5（-）细胞周期蛋白D1（+）SOX11（-），大多数病例缺乏CCND1重排，并具有DLBCL的基因表达谱。很少,细胞周期蛋白D1蛋白阳性DLBCL携带CCND1重排，并检测到套细胞淋巴瘤（MCL）的一些典型遗传拷贝数特征。由于尚未进行基因表达研究，此类CCND1重排病例是否代表细胞周期蛋白D1蛋白阳性DLBCL或CD5/SOX11双负多形性MCL尚不清楚.迄今为止,没有CD5/SOX11双阴性MCL的报道。在这项研究中,我们收集了8例最初诊断为细胞周期蛋白D1蛋白阳性的DLBCL，包括四个有CCND1重排，四个没有。免疫组织化学，所有4例CCND1重排病例均有>50%的肿瘤细胞细胞周期蛋白D1阳性，而只有1例（25％）未重排的病例具有>50％的阳性肿瘤细胞。全基因组拷贝数分析，突变,基因表达谱显示CCND1重排病例与MCL相似，而CCND1非重排病例与DLBCL相似。尽管通过免疫组织化学SOX11阴性，与未重排的病例相比，CCND1重排的病例具有较高的SOX11mRNA水平的显着趋势（P=0.064）。这里,我们首次表明，在诊断为cyclinD1蛋白阳性DLBCL的病例中，CCND1重排可用于鉴定CD5/SOX11双阴性多形性MCL。>50％细胞周期蛋白D1蛋白阳性肿瘤细胞免疫组织化学和较高SOX11mRNA水平的病例更有可能发生CCND1重排，荧光原位杂交可用于检测重排。
