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 withMYCandBCL2and/orBCL6rearrangements, high-grade B-cell lymphoma, not otherwise specified, and Burkitt lymphoma, together account for approximately 40% of B-cell non-Hodgkin lymphomas. Identification ofMYC,BCL2, andBCL6rearrangements 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 bothIGH/MYCdual-color dual-fusion (D-FISH) andMYCbreak-apart probes (BAP) as an initial probe set, followed byBCL2BAP (orIGH/BCL2D-FISH) andBCL6BAP if aMYCrearrangement is identified. In pediatric patients or aggressive B-cell lymphomas with Burkitt-like morphology, a complete analysis at the outset using BAP probes forMYC,BCL2(orIGH/BCL2D-FISH), andBCL6as well as D-FISH probes forIGH/MYC,IGK/MYC, andIGL/MYCis recommended.