Transdifferentiation of diffuse large B-cell lymphoma to a poorly differentiated neoplasm following CAR T-cell therapy

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...

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Bibliographic Details
Published inJournal of hematopathology Vol. 17; no. 3; pp. 149 - 153
Main Authors Padmanabha, Nandan, Weinstock, Matthew J., Xu, Sean, Lepe, Marcos, Garrett, Leslie A., Kappes, Ulrike P., Michaels, Phillip D.
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2024
Subjects
Case Report
Hematology
Medicine
Medicine & Public Health
Pathology
B-cell downregulation
NGS
CAR-T
Transdifferentiation
Diffuse large B-cell lymphoma
IGH::BCL2
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Summary: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.
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ISSN:1868-9256
1865-5785
1865-5785
DOI:10.1007/s12308-024-00592-9