Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare lymphoma with variable clinical outcomes, lacking molecular markers for prognostication and prediction of treatment response. We report a case of aggressive SDRPL showing progressive disease despite multimodality treatments. Next generation sequencing identified variants of BIRC3 (p.I427fs), CCND3 (p.H291fs), TP53 (p.V272L) and a deletion of RB1 (p.654_656del), together with the TP53 mutation progressing from heterozygous at diagnosis to homozygous during disease progression, hence, representing a possible marker of aggressive disease.Blood Cancer U
