Supplemental Digital Content is available in the text. In the era of precision medicine, accurate and reproducible assignment of cell-of-origin (COO) in diffuse large B-cell lymphoma patients has become important. The Lymph2Cx assay is accurately determining COO by analyzing RNA expression of 20 selected genes while the Hans algorithm based on immunohistochemistry is the most popular method for routine daily diagnosis. However, there are discrepancies between the 2 methods, which need to be evaluated for better correlation. We prospectively analyzed 156 cases of diffuse large B-cell lymphoma, not otherwise specified to analyze the characteristics of discrepancy groups of COO determined by Lymph2Cx and Hans algorithm. We investigated the pattern and cause of discrepancy of COO assigned by the 2 methods. Hans algorithm classified 50 cases (32%) as germinal-center B-cell-like (GCB) type and 106 cases (68%) as non-GCB type. Lymph2Cx assay assigned 43 cases (28%) as GCB type, 94 cases (60%) as activated B-cell-like type, and 19 cases (12%) as intermediate/unclassified type. The agreement rate was 86% after exclusion of unclassified type. With regard to the clinicopathologic factors related with discrepancy between Hans algorithm and Lymph2Cx assay, endoscopic biopsy of the gastrointestinal tract (4/11, 36%) showed higher discrepancy rate (P=0.052). Immunophenotypically, CD10−/BCL6+/MUM1− GCB type and CD10−/BCL6+/−/MUM1+ (=30%, low level expression) non-GCB type exhibited a significantly higher discrepancy rate (6/13, 46%; 4/13, 31%) (P=0.0001). Activated B-cell-like subgroup via Lymph2Cx assay predicted poor progression-free survival (mean survival duration 28.6 mo, P=0.049) compared with the GCB and unclassified type. Hans algorithm revealed no significant difference in progression-free survival and overall survival (P=0.122 and 0.121). These results suggest that when assigning COO via Hans algorithm, CD10−/BCL6+/MUM1− GCB type and CD10−/BCL6+/MUM1+ (=30%, low level) non-GCB type require careful interpretation, especially if the MUM1 staining is weak and heterogeneous in the biopsied specimen.

中文翻译：

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Lymph2Cx 检测和 Hans 算法在确定弥漫性大 B 细胞淋巴瘤的细胞来源方面的比较，未另作说明

补充数字内容在文本中可用。在精准医学时代，对弥漫性大 B 细胞淋巴瘤患者进行准确和可重复的来源细胞 (COO) 分配变得重要。Lymph2Cx 检测通过分析 20 个选定基因的 RNA 表达来准确确定 COO，而基于免疫组织化学的 Hans 算法是最常用的常规日常诊断方法。但是，这两种方法之间存在差异，需要对其进行评估以获得更好的相关性。我们前瞻性地分析了 156 例未特别指定的弥漫性大 B 细胞淋巴瘤，以分析 Lymph2Cx 和 Hans 算法确定的 COO 差异组的特征。我们调查了两种方法分配的 COO 差异的模式和原因。Hans 算法将 50 例（32%）分类为生发中心 B 细胞样（GCB）类型，106 例（68%）为非 GCB 类型。Lymph2Cx 检测将 43 例 (28%) 指定为 GCB 型，94 例 (60%) 为活化 B 细胞样型，19 例 (12%) 为中间/未分类类型。剔除未分类类型后一致率为86%。关于与 Hans 算法和 Lymph2Cx 检测差异相关的临床病理因素，胃肠道内镜活检 (4/11, 36%) 显示更高的差异率 (P=0.052)。免疫表型上，CD10-/BCL6+/MUM1- GCB 型和 CD10-/BCL6+/-/MUM1+（=30%，低水平表达）非 GCB 型表现出显着更高的差异率（6/13、46%；4/13 , 31%) (P=0.0001)。与 GCB 和未分类类型相比，通过 Lymph2Cx 测定激活的 B 细胞样亚组预测无进展生存期较差（平均生存期为 28.6 个月，P=0.049）。Hans 算法显示无进展生存期和总生存期无显着差异（P=0.122 和 0.121）。这些结果表明，当通过 Hans 算法分配 COO 时，CD10-/BCL6+/MUM1- GCB 类型和 CD10-/BCL6+/MUM1+（=30%，低水平）非 GCB 类型需要仔细解释，尤其是在 MUM1 染色较弱的情况下和活检标本中的异质性。