Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
J Hematop. 2024 Sep;17(3):149-153. doi: 10.1007/s12308-024-00592-9. Epub 2024 Jun 15.
Chimeric antigen receptor T-cell (CAR-T) therapy is a recent advancement in precision medicine with promising results for patients with relapsed or refractory B-cell malignancies. However, rare post-therapy morphologic, immunophenotypic, and genomic alterations can occur. This study is to present a case of a patient with diffuse large B-cell lymphoma (DLBCL) who underwent anti-CD19 CAR-T therapy with disease in the uterus that showed transdifferentiation to a poorly differentiated malignant neoplasm that failed to express any lineage specific markers. In immunohistochemistry, fluorescence in situ hybridization (FISH) and targeted next-generation sequencing (NGS) were utilized to fully characterize the diagnostic DLBCL sample in comparison to the poorly differentiated neoplasm of the uterus. Analysis of the diagnostic DLBCL and the poorly differentiated neoplasm demonstrated evidence of a clonal relationship as well as revealing acquisition of mutations associated with CAR-T resistance. Furthermore, downregulation of B-cell associated antigens was observed, underscoring a mechanistic link to CAR-T evasion as well as demonstrating diagnostic confusion. This case illustrates the utility of employing multiple diagnostic modalities in elucidating a pathologic link between a B-cell lymphoma and poorly differentiated neoplasm following targeted therapy.
嵌合抗原受体 T 细胞（CAR-T）疗法是精准医学的一项最新进展，为复发或难治性 B 细胞恶性肿瘤患者带来了希望。然而，罕见的治疗后形态学、免疫表型和基因组改变可能会发生。本研究介绍了一例接受抗 CD19 CAR-T 治疗的弥漫性大 B 细胞淋巴瘤（DLBCL）患者，其子宫内的疾病发生了转分化，表现为低分化恶性肿瘤，未能表达任何谱系特异性标志物。在免疫组织化学、荧光原位杂交（FISH）和靶向下一代测序（NGS）中，与子宫内的低分化肿瘤相比，对诊断性 DLBCL 样本进行了全面特征描述。对诊断性 DLBCL 和低分化肿瘤的分析表明存在克隆关系，并揭示了与 CAR-T 耐药相关的突变获得。此外，还观察到 B 细胞相关抗原的下调，强调了与 CAR-T 逃逸的机制联系，并证明了诊断上的混淆。该病例说明了在靶向治疗后阐明 B 细胞淋巴瘤和低分化肿瘤之间病理联系时，采用多种诊断方式的实用性。
