In the current World Health Organization classification, terminal deoxynucleotidyl transferase (TdT) expression in a high grade/large cell B-cell lymphoma (LBCL) indicates a B-lymphoblastic lymphoma/leukemia (B-LBL), although TdT expression in what appear to be mature LBCL or following mature B-cell neoplasms is reported. The frequency of TdT+ LBCL, how to best categorize these cases, and their clinicopathologic features, molecular landscape, and relationship to classic B-LBL remain to be better defined. TdT expression was therefore assessed in 258 LBCL and the results correlated with the cytologic, phenotypic, and cytogenetic findings. Targeted mutational analysis, review of prior biopsies, and assessment of clinical associations was performed in the 6 cases with >10% TdT+ cells. All 6 TdT+ LBCL were blastoid-appearing, CD34-, MYC+, BCL2+, and had MYC rearrangements (R) (5/6 with BCL2 and/or BCL6-R). 5/6 had a prior TdT- LBCL and/or follicular lymphoma and all had an aggressive course. Fifteen nonsynonymous variants in 11 genes were seen in the 4/5 tested cases with mutations. TdT+ and TdT- areas in 1 case showed identical mutations. The mutational profiles were more like those reported in germinal center B-cell type-diffuse LBCL rather than B-LBL. Evolution from preceding TdT- lymphomas was nondivergent in 1/3 tested cases and partially divergent in 2. The clinicopathologic and cytogenetic features of these 6 cases were similar to those found in a meta-analysis that included additional cases of TdT+ LBCL or B-LBL following follicular lymphoma. Thus, TdT+, CD34- large B-cell neoplasms with MYC rearrangements and often a "double hit" are rare, frequently a transformational event and aggressive but are distinct from classic B-LBL.

中文翻译：

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TdT+ 大 B 细胞淋巴瘤的突变情况支持它们与 B 淋巴细胞肿瘤的区别：一种罕见且具有攻击性的实体的多参数研究。

在目前的世界卫生组织分类中，高级别/大细胞 B 细胞淋巴瘤 (LBCL) 中的末端脱氧核苷酸转移酶 (TdT) 表达表明 B 淋巴细胞淋巴瘤/白血病 (B-LBL)，尽管 TdT 在似乎有报道为成熟 LBCL 或以下成熟 B 细胞肿瘤。TdT+ LBCL 的频率，如何最好地对这些病例进行分类，以及它们的临床病理学特征、分子景观以及与经典 B-LBL 的关系仍有待更好地定义。因此，在 258 个 LBCL 中评估了 TdT 表达，结果与细胞学、表型和细胞遗传学发现相关。在 6 例 TdT+ 细胞 > 10% 的病例中进行了靶向突变分析、对先前活检的回顾和临床关联评估。所有 6 个 TdT+ LBCL 均出现胚芽样，CD34-、MYC+、BCL2+、并且有 MYC 重排 (R) (5/6 与 BCL2 和/或 BCL6-R)。5/6 有既往 TdT-LBCL 和/或滤泡性淋巴瘤，并且都具有侵袭性病程。在具有突变的 4/5 测试病例中，发现了 11 个基因中的 15 个非同义变体。1 例 TdT+ 和 TdT- 区域显示相同的突变。突变谱更像生发中心 B 细胞型弥漫性 LBCL 而不是 B-LBL 中报道的那些。在 1/3 的测试病例中，从先前 TdT 淋巴瘤的演变是非分歧的，在 2 例中部分分歧。这 6 例病例的临床病理学和细胞遗传学特征与包括额外 TdT+ LBCL 或 B-LBL 病例的荟萃分析中发现的相似滤泡性淋巴瘤后。因此，具有 MYC 重排和通常“双重打击”的 TdT+、CD34- 大 B 细胞肿瘤是罕见的，