Prevalence and prognostic value ofMYD88andCD79Bmutations in ocular adnexal large B-cell lymphoma: a reclassification of ocular adnexal large B-cell lymphoma

Abstract

AimsTo (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.MethodsThis 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).ResultsTwo 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.ConclusionOA-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.

Ocular adnexal lymphoma: Subtype‐specific clinical and genetic features

“… Note : Modified from Kirkegaard et al 2016 (Paper I), Knudsen Kirkegaard et al 2017 (Paper II) and Kirkegaard et al 2021 (Paper III). With permissions from JAMA Ophthalmology and the British Journal of Ophthalmology. …”

“… Note : Modified from Kirkegaard et al 2021 (Paper III). With permission from the British Journal of Ophthalmology. …”

“…(d) cMYC immunostaining with the tumour cells showing a positive immunoreaction (bar: 50 μm). From Kirkegaard et al 2021 (Paper III). With permission from the British Journal of Ophthalmology.…”

“…Oncoprint chart showing molecular and phenotypic findings in 34 large B‐cell lymphomas of the ocular adnexal region. From Kirkegaard et al 2021 (Paper III). With permission from the British Journal of Ophthalmology.…”

“…Tick marks indicate censored data. Modified from Kirkegaard et al 2016 and Kirkegaard et al 2021. With permissions from JAMA Ophthalmology and the British Journal of Ophthalmology.…”