High-grade B-cell lymphomas: Double hit and non-double hit.

Area of Science:

• Hematology
• Oncology
• Pathology

Background:

• High-grade B-cell lymphoma (HGBL) comprises approximately 2% of non-Hodgkin lymphomas.
• Patients with HGBL often exhibit refractory or relapsed disease after standard treatments.
• The classification of HGBL has undergone significant revisions in recent decades.

Purpose of the Study:

• To provide an updated review of high-grade B-cell lymphoma (HGBL).
• To focus on clinicopathologic features, diagnosis, molecular genetics, and pathogenesis of HGBL subgroups.
• To discuss diagnostic approaches, differential diagnoses, and challenges, particularly with B lymphoblastic leukemia/lymphoma.

Main Methods:

• Review of current literature and classification systems (WHO-HAEM5, ICC).
• Analysis of clinicopathologic, molecular genetic, and pathogenetic features of HGBL subtypes.
• Discussion of diagnostic strategies and differential diagnosis considerations.

Main Results:

• The 5th edition of the World Health Organization classification (WHO-HAEM5) defines two main HGBL types: DLBCL/HGBL with MYC and BCL2 rearrangements, and HGBL, not otherwise specified (HGBL-NOS).
• WHO-HAEM5 reclassified certain DLBCL/HGBL with MYC and BCL6 rearrangements into DLBCL or HGBL-NOS based on morphology.
• The International Consensus Classification (ICC) recognizes the WHO-HAEM5 categories and adds HGBL with concurrent MYC and BCL6 rearrangements as a provisional entity.

Conclusions:

• Recent classifications refine the understanding of HGBL, impacting diagnosis and treatment.
• Accurate classification based on morphology and molecular genetics is essential for managing HGBL.
• Distinguishing HGBL from B lymphoblastic leukemia/lymphoma remains a critical diagnostic challenge.