Lymphoplasmacytic lymphoma associated with diffuse large B-cell lymphoma: Progression or divergent evolution?

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Lymphoplasmacytic lymphoma (LPL) is an indolent B-cell neoplasm frequently associated with the MYD88-L265P mutation.
• A subset of LPL cases (~10%) can transform into a more aggressive diffuse large B-cell lymphoma (DLBCL).
• Understanding the mechanisms of this transformation is crucial for patient management.

Purpose of the Study:

• To investigate the clinicopathological and molecular features of patients diagnosed with both LPL and DLBCL.
• To explore potential shared and divergent genetic alterations in paired LPL and DLBCL samples.
• To elucidate the mechanisms underlying DLBCL transformation in LPL.

Main Methods:

• Retrospective review of 7 patients with concurrent LPL and DLBCL diagnoses.
• Histopathological analysis and FISH studies for MYC, BCL2, and BCL6 gene rearrangements.
• MYD88-L265P mutation and IGH rearrangement analysis via PCR.
• Comprehensive mutational profiling using next-generation sequencing (NGS).

Main Results:

• The MYD88-L265P mutation was present in 6 of 7 cases, indicating its common role.
• IGH rearrangement analysis revealed overlapping features in some cases.
• Next-generation sequencing in three cases showed both shared and distinct mutations between LPL and DLBCL components.
• DLBCL transformation occurred simultaneously, after, or preceding LPL diagnosis.

Conclusions:

• The findings suggest that DLBCL can arise from LPL through multiple distinct molecular pathways.
• Shared MYD88 mutations indicate a common clonal origin in most cases.
• Divergent mutations highlight genetic evolution and potential acquisition of new alterations during transformation.