A practical approach to FISH testing for MYC rearrangements and brief review of MYC in aggressive B-cell lymphomas

Aggressive B-cell lymphomas, including the WHO diagnoses of diffuse large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high-grade B-cell lymphoma, not otherwise specified, and Burkitt lymphoma, together account for approximately 40% of B-cell non-Hodgkin lymphomas. Identification of MYC, BCL2, and BCL6 rearrangements in these neoplasms is critical for diagnostic, prognostic, and therapeutic purposes. Herein, we address technical issues surrounding identification of these genetic abnormalities, discuss their diagnostic, prognostic, and therapeutic implications, and present an algorithm for use of interphase FISH in the work-up of aggressive B-cell lymphomas. To maximize sensitivity while still limiting cost, it is recommended that interphase FISH be performed in all B-cell lymphomas with large cell or high-grade morphology using both IGH/MYC dual-color dual-fusion (D-FISH) and MYC break-apart probes (BAP) as an initial probe set, followed by BCL2 BAP (or IGH/BCL2 D-FISH) and BCL6 BAP if a MYC rearrangement is identified. In pediatric patients or aggressive B-cell lymphomas with Burkitt-like morphology, a complete analysis at the outset using BAP probes for MYC, BCL2 (or IGH/BCL2 D-FISH), and BCL6 as well as D-FISH probes for IGH/MYC, IGK/MYC, and IGL/MYC is recommended.