Diagnostic Implications of NGS-Based Molecular Profiling in Mature B-Cell Lymphomas with Potential Bone Marrow Involvement

Background: Methods such as cytogenetics and immunocytology/immunohistology provide essential diagnostic insights but may be limited in ambiguous cases of mature B-cell lymphoma. Next-generation sequencing (NGS) has emerged as a potential tool to improve diagnostics. Methods: We validated the analyt...

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Bibliographic Details
Published in:Diagnostics (Basel) Vol. 15; no. 6; p. 727
Main Authors: Strasser, Bernhard, Mustafa, Sebastian, Seier, Josef, Wimmer, Erich, Tomasits, Josef
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 14.03.2025
MDPI
Subjects:
B-cell lymphoma
Bone marrow
Classification
Cytogenetics
Decision making
Development and progression
Ethylenediaminetetraacetic acid
Gene mutations
Genes
Genetic testing
Genetics
Hybridization
Kinases
Lymphoma
Lymphomas
Medical prognosis
Medical research
Medicine, Experimental
molecular diagnostics
Morphology
Mutation
next-generation-sequencing
NGS
Reproducibility
Risk assessment
Tumors
California
United States > US
Switzerland
molecular diagnostics
NGS
B-cell lymphoma
next-generation-sequencing
ISSN:2075-4418, 2075-4418
Online Access:Get full text
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Summary:Background: Methods such as cytogenetics and immunocytology/immunohistology provide essential diagnostic insights but may be limited in ambiguous cases of mature B-cell lymphoma. Next-generation sequencing (NGS) has emerged as a potential tool to improve diagnostics. Methods: We validated the analytical performance of a lymphoid customized NGS panel. Clinical validation was conducted in 226 patients with suspected mature B-cell lymphoma with potential bone marrow involvement across multiple clinically relevant scenarios. Results: NGS (1) achieved 100% sensitivity and specificity with high reproducibility (r = 0.995), confirming its analytical performance. (2) It reliably detected WHO-classified markers, including BRAF mutations in all hairy cell leukemia cases, MYD88/CXCR4 mutations in lymphoplasmacytic lymphoma, and absence of BRAF mutations in splenic B-cell lymphoma with prominent nucleoli. (3) In lymphoma exclusion diagnostics, NGS identified mutations in previously undiagnosed cases, including a BCORL1 mutation leading to reclassification as marginal zone lymphoma. (4) Among 105 confirmed lymphomas, 65% harbored mutations, with detection rates highest in HCL and LPL (100%) and CLL (62%), while follicular lymphoma showed no detectable mutations. (5) In cases with non-interpretable cytogenetics, NGS detected pathogenic variants in 61% of patients, compensating for inconclusive findings. (6) In cases with limited morphological assessment, NGS identified relevant mutations in 70%, outperforming cytogenetics (30%; p = 0.0256, OR = 5.44). Conclusions: NGS enhances the diagnostic accuracy of mature B-cell lymphomas by complementing traditional methods, refining WHO-classified subtypes, and improving detection in cases with inconclusive cytogenetics or morphology. NGS may reduce the need for unnecessary bone marrow re-punctures by providing additional information in ambiguous cases.
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ISSN:2075-4418
2075-4418
DOI:10.3390/diagnostics15060727