Andrew W. Allbee1, James Gerson2, Guang Yang1 and Adam Bagg1 1Division of Hematopathology, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; 2Department of Hematology and Medical Oncology, Larner College of Medicine, University of Vermont Medical Center, Burlington, Vermont 05405, USA Corresponding author: adambaggpennmedicine.upenn.edu

We present a unique case of a single patient presenting with two mutationally distinct, PD-L1+ diffuse large B-cell lymphomas (DLBCLs). One of these DLBCLs demonstrated exceptionally high mutational burden (eight disease-associated variants and 41 variants of undetermined significance) with microsatellite instability (MSI) and an acquired PMS2 mutation with loss of PMS2 protein expression, detected postchemotherapy. This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs. Appropriate testing may be predictive of outcome and inform the utility of targeted therapy in these genetically diverse and historically treatment-refractory malignancies.

Received October 31, 2023. Accepted November 28, 2023.