[Diffuse large B-cell lymphoma-NOS , high-grade B-cell lymphomas and Burkitt lymphoma: Updates]

Cyto-morphological analysis, combined with the study of genetic rearrangements, is central to the classification of aggressive B-cell lymphomas in WHO-5. Cytology distinguishes large-cell morphology from Burkitt-type or blastic cells, the latter two defining high-grade morphology. DLBCL-NOS is defined by large-cell morphology and may harbor isolated or combined MYC and BCL6 rearrangements. In contrast, the association of MYC and BCL2 excludes the diagnosis of diffuse large B cell lymphoma NOS (DLBCL-NOS) and defines a high-grade B-cell lymphoma. An isolated MYC rearrangement is associated with poor prognosis, particularly when involving the IGH locus or when associated with TP53 mutations. Double MYC/BCL6 rearrangements represent a heterogeneous group classified as DLBCL-NOS or high-grade B cell lymphoma NOS (HGBL-NOS) depending on morphology. High-grade B-cell lymphomas with MYC/BCL2 double rearrangements show highly aggressive clinical behavior and resistance to standard therapy. The 11q aberration defines a distinct entity lacking MYC rearrangement. This entity must be differentiated from Burkitt lymphoma. Burkitt lymphoma is strictly defined by an isolated IG/MYC rearrangement. Any association with BCL2 or BCL6 excludes the diagnosis of Burkitt lymphoma. Hierarchical analysis of MYC, BCL2, BCL6 rearrangements and 11q aberration is therefore essential. It directly impacts diagnosis, prognostic stratification, and therapeutic management.