Aims To (1) reclassify ocular adnexal large B-cell lymphomas (OA-LBCLs) per 2016 WHO lymphoma classification and (2) determine the prevalence of MYD88 and CD79B mutations and their association with clinical parameters among OA-LBCLs.
Methods This study is a retrospective analysis of all OA-LBCLs diagnosed in Denmark between 1980 and 2018. Medical records and tissue samples were retrieved. Thirty-four OA-LBCLs were included. Fluorescence in situ hybridisation and Epstein-Barr-encoded RNA in situ hybridisation were used for the reclassification. Mutational status was established by allele-specific PCR and confirmed by Sanger sequencing. Primary endpoints were overall survival, disease-specific survival (DSS) and progression-free survival (PFS).
Results Two LBCL subtypes were identified: diffuse large B-cell lymphoma (DLBCL) (27 of 32; 84%) and high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (5 of 32; 16%). cMYC/BCL2 double-expressor DLBCLs had a poorer DSS than non-double-expressor DLBCLs (5-year DSS, 25% vs 78%) (HR 0.23; 95% CI 0.06 to 0.85; p=0.014). MYD88 mutations were present in 10 (29%) of 34 lymphomas and carried a poorer PFS than wild-type cases (5-year PFS, 0% vs 43%) (HR 0.78; 95% CI 0.61 to 0.98; p=0.039). CD79B mutations were present in 3 (9%) of 34 cases.
Conclusion OA-LBCL consists mainly of two subtypes: DLBCL and HGBL with MYC and BCL2 and/or BCL6 rearrangements. MYD88 mutations are important drivers of OA-LBCL. MYD88 mutations, as well as cMYC/BCL2 double-expressor DLBCL, appear to be associated with a poor prognosis. Implementing MYD88 mutational analysis in routine diagnostics may improve OA-LBCL prognostication.
Data availability statement
Data are available upon reasonable request. Data are available on request from the authors.
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Contributors Study concept and design: MKK, LDS, STP, SH. Acquisition, analysis, or interpretation of data: MKK, MM, PRGE. Drafting of the manuscript: MKK. Critical revision of the manuscript for important intellectual content: MM, LDS, STP, PRGE, SH. Statistical analysis: MKK. Obtained funding: MKK, MM, STP. Study supervision: LDS, STP, SH. Guarantor: SH.
Funding This work was supported by grants from the Synoptik Foundation, the Lymph&Co Foundation, Arvid Nielsson’s Foundation, the Danish Eye Research Foundation, the Medical Sciences Part of the Faculty of Health and Medical Sciences’ Foundation for Scientifically Employed Candidates and Students at the University of Copenhagen Foundation (Grant Number 2019–0090), Ms. Amalie Jørgensen’s Memorial Grant, and Else and Mogens Weddell-Weddellsborg’s Foundation (Grant Number 11-20-2).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.