Table 2.
Genetic findings and biomarkers with potential relevance in aggressive / large B-cell lymphomas
| Disease entity | Genetic alterations and biomarkers | Diagnostic and clinical relevance |
|---|---|---|
|
DLBCL, NOS - germinal center B-cell type (GCB) - activated B-cell type (ABC) |
“Cell of origin” by immunohistochemistry or GEP, no “double hit” by FISH | Diagnostic, required for subtyping and separation from HGBL |
| Molecular subtypes by mutation profiling | Panel sequencing, LymphGen algorithm [87, 114] or similar; prognostic and in part predictive | |
| EBV+ DLBCL, NOS | EBV association | EBER1 ISH, diagnostic |
| High-grade BCL | ||
| - with MYC and BCL2-R |
- MYC-R and BCL2-R - CREBBP, BCL2, KMT2D, EZH2 mutations |
Diagnostic, required (FISH) |
| - with MYC and BCL6-R |
MYC-R and BCL6-R - Heterogeneous mutations |
Diagnostic, required (FISH) |
| - NOS | MYC-R in subset | Diagnosis of exclusion |
| Burkitt lymphoma | MYC-R with IGH, IGK or IGL genes | Diagnostic |
| - ID3, TCF3, DDX3X, CCND3, GNA13, TP53 | Optional, for difficult cases; TP53 mutations prognostic | |
| - EBV association +/- | Desirable | |
| Large/HG B-cell lymphoma with 11q aberration | 11q23.2-q23.3 gain/11qter loss (including ETS1 and FLI1) | Diagnostic, required (FISH, array CGH or similar) |
| GNA13, DDX3X, BTG2 mutations | ||
| Large B-cell lymphoma with IRF4-R* | IRF4-R and/or IRF4 mutations | Diagnostic, required; IRF4 mutations in cases with cryptic translocation |
HGBL, high-grade B-cell lymphoma; ISH, in situ hybridization; FISH, fluorescence in situ hybridization
*not considered an aggressive lymphoma by ICC