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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.

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