Division of Hematopathology, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Department of Hematology and Medical Oncology, Larner College of Medicine, University of Vermont Medical Center, Burlington, Vermont 05405, USA.
Cold Spring Harb Mol Case Stud. 2024 Jan 10;9(4). doi: 10.1101/mcs.a006318. Print 2023 Dec.
We present a unique case of a single patient presenting with two mutationally distinct, PD-L1 diffuse large B-cell lymphomas (DLBCLs). One of these DLBCLs demonstrated exceptionally high mutational burden (eight disease-associated variants and 41 variants of undetermined significance) with microsatellite instability (MSI) and an acquired mutation with loss of PMS2 protein expression, detected postchemotherapy. This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs. Appropriate testing may be predictive of outcome and inform the utility of targeted therapy in these genetically diverse and historically treatment-refractory malignancies.
我们呈现了一个独特的病例，该病例中的单一患者同时患有两种突变明显不同的 PD-L1 弥漫性大 B 细胞淋巴瘤（DLBCL）。其中一个 DLBCL 具有极高的突变负担（八种疾病相关变异和 41 种意义未明的变异），表现出微卫星不稳定性（MSI）和后天获得性 PMS2 蛋白表达缺失的突变，这些改变是在化疗后检测到的。本报告强调了在单独克隆扩展中可能存在的肿瘤异质性的程度，以及可能的综合征性 B 细胞肿瘤，支持这样一种观点，即尽管罕见，但在 DLBCL 中应更常规地考虑 PD-L1 表达和相关的高突变负担状态（如错配修复基因失活/微卫星不稳定）。适当的检测可能具有预后预测价值，并为这些遗传多样性和历史上难治性恶性肿瘤的靶向治疗提供信息。
