How I diagnose high-grade B-cell lymphoma

Area of Science:

• Hematopathology
• Oncology
• Molecular Diagnostics

Background:

• High-grade B-cell lymphoma (HGBL) was introduced in the 2016 WHO classification, encompassing lymphomas with specific genetic rearrangements or high-grade morphology.
• Diagnostic criteria and nomenclature for HGBL have been updated in the 2022 WHO fifth edition (WHO-5) and International Consensus Classification (ICC) systems.
• Accurate diagnosis of HGBL is essential for guiding appropriate therapeutic strategies.

Purpose of the Study:

• To describe a diagnostic approach for high-grade B-cell lymphoma (HGBL).
• To highlight the importance of integrating morphology, immunophenotype, and genetic findings in HGBL diagnosis.
• To emphasize the correct nomenclature and classification of HGBL according to WHO-5 and ICC guidelines.

Main Methods:

• Presentation of two illustrative cases of HGBL.
• Case 1: HGBL with MYC and BCL6 rearrangements.
• Case 2: HGBL with MYC and BCL2 rearrangements and TdT expression, emphasizing differential diagnosis from other high-grade lymphomas and B-lymphoblastic leukemia/lymphoma (B-LBL/ALL).

Main Results:

• HGBL diagnosis necessitates a comprehensive integration of morphologic, immunophenotypic, and genetic data.
• Differential diagnosis must exclude other high-grade lymphomas such as Burkitt lymphoma, B-LBL/ALL, and blastoid mantle cell lymphoma.
• Consideration of HGBL/large B-cell lymphoma with 11q aberration is important in specific patient cohorts.

Conclusions:

• HGBL subclassification relies on distinct morphologic and genetic features.
• Nomenclature and definitions differ between WHO-5 and ICC classifications for HGBL.
• Distinguishing HGBLs from other mature B-cell lymphomas and B-LBL/ALL is critical for optimal patient management.