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

Priyanka A Pophali,Paul J Kurtin,Thomas Habermann,Raphael Mwangi,Reid G Meyer,Rebecca L King,Rhett P Ketterling,Lisa M Marinelli,Matthew J Maurer,Ellen D Mcphail

doi:10.1038/s41408-019-0271-z

Abstract

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.

Highlights

MYC is a multifunctional transcription factor that plays a significant role in tumorigenesis[1]
Of the 33 cases with LBCL morphology, Hans algorithm IHC was available for 26 cases: 23 (88%) were germinal center B-cell-like (GCB), and 3 (12%) were non-GCB
MYC IHC was available for 22 LBCL cases: 15/22 (68%) met the MYC positivity threshold of 40% or more; 6/22 (27%) cases had

Summary

Introduction

MYC is a multifunctional transcription factor that plays a significant role in tumorigenesis[1]. MYC rearrangements are characteristic of several types of B cell neoplasms. Diffuse large B cell (DLBCL) and high grade B cell lymphomas (HGBL) demonstrating MYC translocation with concurrent BCL2 and/or BCL6 rearrangements, colloquially called double and triple hit lymphomas (DHL and THL), have poor clinical outcomes[2]. The prognostic implications of DHL and THL underlie the 2017 World Health Organization (WHO) update, which includes the cytogenetically defined category of “High grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements” (DHL/THL) as its own distinct entity[3]. Cases without MYC rearrangements should be diagnosed as diffuse large B cell lymphoma (DLBCL) or high grade B cell lymphoma, not otherwise specified (HGBL, NOS)[3]

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