Spatial transcriptomic profiling: The “Next Generation Diagnosis” distinguishing between EBV+ lymphoproliferations with Hodgkin‐like features

Introduction: Epstein-Barr virus positive (EBV+) lymphoproliferative disorders (LPD) with Hodgkin-like features include indolent, localised conditions such as EBV+ mucocutaneous ulcer (EBVMCU) through to systemic lymphomas, classical Hodgkin lymphoma (EBVcHL) and diffuse large B-cell (EBVDLBCL). The diagnostic distinction between these LPD is imperative guide management, but can prove problematic, owing the dearth of reliable markers. biological underpinning resulting in close pathological similarities different clinical behaviours also uncertain. Methods: Utilising immunohistochemistry CD30 CD68 sampling, Nanostring GeoMX spatial transcriptomic characterisation whole transcriptome HRS/HRS-like macrophage compartments was performed EBVMCU (n = 6; 27 regions interest (ROI)), EBVcHL 8; 11 ROI) EBVDLBCL 12 on formalin fixed paraffin embedded (FFPE) tissue sections. Differential gene expression set enrichment analyses were identify characteristic signatures explore novel discriminators LPD. Results: Dimensionality reduction (tSNE) based profiles showed that EBVMCU, cHL clustered distinctly from one another. using a linear mixed effects model analysis revealed pathways discriminate distinguished HRS-like compartment by upregulation involved T-reg differentiation (odds ratio (OR) 40; p 0.0001), interleukin 2 (OR 0.0001) interferon response signalling, whilst distinctive negative regulation T-cell activation 80; 0.00001) IL10 production < 0.0001). cells HRS CHL chemotaxis 120; migration 0.00001), interferon-alpha 0.0004) interferon-beta responses 0 0.0004). Conclusion: Gene profiling diagnostically discriminates EBVDLBCL. findings demonstrate scope for transcriptomics FFPE represent “Next Generation Diagnosis” Cellular Pathology. research funded by: Jean Shanks/The Pathological Society UK Keywords: Diagnostic Prognostic Biomarkers, lymphoma, Genomics, Epigenomics, Other -Omics No conflicts interests pertinent abstract.