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Novel Approaches in Molecular Characterization of Classical Hodgkin Lymphoma
Diede A G van Bladel1,2, Wendy B C Stevens3, Michiel van den Brand1,4
1Radboud University Medical Center, Department of Pathology, 6525 GA Nijmegen, The Netherlands.
Insights
Molecular analysis of classical Hodgkin lymphoma (cHL) aids diagnosis and understanding of pathogenesis. Next-generation sequencing techniques reveal clonal composition and genetic drivers, improving diagnostic accuracy for atypical cases.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Classical Hodgkin lymphoma (cHL) is a B-cell malignancy defined by specific genetic alterations in malignant cells.
- Molecular analysis of cHL provides insights into disease pathogenesis and clonal evolution.
- Diagnostic challenges arise from cHL's histological and clinical resemblance to other conditions.
Purpose of the Study:
- To review molecular analysis methods for cHL.
- To highlight the utility of clonality testing and mutation analysis in cHL diagnostics.
- To discuss the application of next-generation sequencing (NGS) in cHL research and clinical practice.
Main Methods:
- Detection of immunoglobulin and T cell receptor gene rearrangements for clonality assessment.
- Mutation analysis to identify genetic drivers of cHL.
- Application of next-generation sequencing (NGS) for comprehensive molecular profiling of cHL from tissue and cell-free DNA.
Main Results:
- Clonality testing is crucial for diagnosing atypical cHL and linking composite or sequential lymphoma presentations.
- Molecular insights have elucidated key signaling pathways (e.g., NF-κB, JAK/STAT) and immune evasion mechanisms in cHL.
- NGS-based techniques offer detailed characterization of clonal composition and genetic alterations in cHL.
Conclusions:
- Molecular techniques, particularly NGS, are indispensable for accurate cHL diagnosis and understanding its pathogenesis.
- Clonality assessment aids in differentiating cHL from reactive conditions and other lymphomas.
- Continued implementation of molecular analysis in research and diagnostics will advance cHL management.
Abstract:
Classical Hodgkin lymphoma (cHL) represents a B-cell lymphoproliferative disease characterized by clonal immunoglobulin gene rearrangements and recurrent genomic aberrations in the Hodgkin Reed-Sternberg cells in a reactive inflammatory background. Several methods are available for the molecular analysis of cHL on both tissue and cell-free DNA isolated from blood, which can provide detailed information regarding the clonal composition and genetic alterations that drive lymphoma pathogenesis. Clonality testing involving the detection of immunoglobulin and T cell receptor gene rearrangements, together with mutation analysis, represent valuable tools for cHL diagnostics, especially for patients with an atypical histological or clinical presentation reminiscent of a reactive lesion or another lymphoma subtype. In addition, clonality assessment may establish the clonal relationship of composite or subsequent lymphoma presentations within one patient. During the last few decades, more insight has been obtained on the molecular mechanisms that drive cHL development, including recurrently affected signaling pathways (e.g., NF-κB and JAK/STAT) and immune evasion. We provide an overview of the different approaches to characterize the molecular composition of cHL, and the implementation of these next-generation sequencing-based techniques in research and diagnostic settings.
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