Unexpected favorable outcome in a patient with high grade B-cell lymphoma with abnormalities of MYC, BCL6 and BCL2 loci

摘要

High grade B-cell lymphoma (HGBCL) by WHO 2016 classification requires rearrangements ofMYCandBCL2and/orBCL6,practically covering the so called “double-hit” or “triple hit” lymphomas. We report a case of HGBCL “triple-hit” lymphoma in a 64-year old female. Cytogenetic and fluorescence in situ hybridization (FISH) studies revealed complex karyotype including rearrangement ofMYCto a novel, non-IGpartner on chromosome 18, and rearrangement ofBCL2, BCL6andIGHas well as ins(3)(q21q27.3q25.1) among other abnormalities. FISH studies showed five copies ofMYCand 3–8 copies ofBCL2. Gene expression analysis by RNA sequencing showed thatMYC, BCL2andMECOMgenes were overexpressed whereasBCL6was under-expressed.BCL6 was fused toMBNL1gene due to complex structural rearrangement. MYC was expressed in >70% of cells and BCL2 was diffusely but highly expressed by immunohistochemistry. No pathogenic mutations were identified by sequencing a 26-gene panel includingTP53.The patient has unexpectedly been in complete remission for 12 months after diagnosis after intensive chemotherapy including DA-EPOCH regimen despite having HGBCL. The prognostication of HGBCL patients may further be improved by the sub-categorization of these lymphomas on the basis of more detailed genomic markers than merely the WHO 2016 classification.