Abstract:
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.
摘要:
嵌合抗原受体T细胞(CAR-T)疗法是精准医学的最新进展,对于复发性或难治性B细胞恶性肿瘤患者具有可喜的结果。然而,罕见的治疗后形态学,免疫表型,和基因组改变可以发生。本研究将介绍一例弥漫性大B细胞淋巴瘤(DLBCL)患者,该患者在子宫内接受了抗CD19CAR-T治疗,该疾病显示转分化为分化不良的恶性肿瘤,但未能表达任何谱系特异性标记。在免疫组织化学中,与低分化子宫肿瘤相比,利用荧光原位杂交(FISH)和靶向下一代测序(NGS)来全面表征诊断性DLBCL样本.对诊断性DLBCL和低分化肿瘤的分析证明了克隆关系的证据,并揭示了与CAR-T抗性相关的突变的获得。此外,观察到B细胞相关抗原的下调,强调了与CAR-T规避的机械联系,并证明了诊断混乱。此病例说明了采用多种诊断方式阐明靶向治疗后B细胞淋巴瘤与低分化肿瘤之间的病理联系的实用性。