High level MYC amplification in B-cell lymphomas: is it a marker of aggressive disease?

While MYC translocations in B-cell lymphoma (BCL) have been extensively studied, the significance of MYC amplification (MYC amp) is poorly understood. This study characterizes BCL showing MYC amp, defined as uncountable FISH signals. Retrospective analysis of all BCL FISH for MYC aberrations performed at our institution (1/2010–2/2018) identified 44/9715 (0.45%) cases with MYC amp. MYC amp probe signals appeared in a cloud-like distribution (70%) or in a single homogenous-staining-region (30%). In total 59% also had MYC separation by breakapart probe indicating concurrent MYC translocation. The most common morphology was large cell (82%) and diagnosis was diffuse large BCL (DLBCL, 50%). In total 88% were germinal center B-cell-like by Hans algorithm. In total 12/42 (29%) cases were “double-hit” by WHO criteria (DHL/THL) in addition to having MYC amp. The estimated 2-year overall survival (OS) of DLBCL cases with MYC amp was 80%. There was no significant difference in OS between DLBCL and DHL/THL among cases with MYC amp, suggesting a poor prognostic impact of MYC amp. However, when compared to a larger cohort of DLBCL and DHL/THL, MYC amp did not have prognostic significance. In summary, MYC amp in BCL is rare, most commonly occurs in DLBCL, and was not associated with survival in our cohort.