Aggressive B-cell Diagnostic Algorithm

Morphology: diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), or

BLYMF / B-Cell Lymphoma, FISH, Tissue break-apart FISH probe (BAP) and IGH/MYC dual fusion FISH (D-FISH) probe

Positive for MYC Positive for MYC Negative for MYC rearrangement rearrangement but negative rearrangement and/or positive and negative for IGH/MYC fusion for IGH/MYC fusion for IGH/MYC fusion

FISH: BCL2 and BCL6 BAP. FISH: BCL2 and BCL6 BAP Add IGK/MYC and IGL/MYC D-FISH only if pediatric patient and/or high suspicion for Burkitt lymphoma Morphology: DLBCL vs HGBCL Burkitt lymphoma likely excluded, however, ■ Consider CMAPT / Chromosomal Microarray, Tumor, Formalin-Fixed Negative for BCL2 and Positive for BCL2 and/or DLBCL HGBCL, not Paraffin-Embedded for 11q23 BCL6 rearrangements BCL6 rearrangements otherwise specified aberrancy and 11q24-ter deletion ■ Consider D-FISH for IGK/ Morphology: DLBCL vs High-grade B-cell lymphoma, Cell of origin (COO) MYC and IGL/MYC to exclude HGBCL vs Burkitt lymphoma with MYC and BCL2 and/or (IHC) a MYC rearrangement BCL6 rearrangements (CD10, BCL6, MUM1) and double completely, especially in expresser IHC (BCL2 and MYC) a pediatric patient

HGBCL vs Burkitt lymphoma DLBCL

IHC: CD10, CD43, BCL2, COO IHC (CD10, Double expresser IHC: BCL6, MUM1, MYC BCL6, MUM1) and BCL2 and MYC double expresser IHC (BCL2 and MYC) COO IHC: CD10

Any other BCL2+ and MYC+ All others CD10+, CD43+, Positive Negative BCL6+, MUM1–, phenotype MYC+, BCL2– Germinal center BCL6 Double expresser Not a double B-cell phenotype expresser Probably Burkitt HGBCL, not lymphoma, particularly otherwise if IG/MYC identified. specified Positive Negative Confirm with morphology and clinical. MUM1 Non-germinal center B-cell phenotype

Positive Negative

Non-germinal center Germinal center B-cell phenotype B-cell phenotype

© Mayo Foundation for Medical Education and Research (MFMER). All rights reserved. 9/2018