This is a prospective and retrospective observational study. The primary objective is to identify new prognostic biomarkers for DLBCL patients in terms of progression-free survival (PFS) and able to add predictive capacity to recognized important clinical factors. The secondary objectives are: * to identify new biomarkers associated with overall survival (OS) and objective response rate (ORR) * to characterize tissue and circulating immune microenvironment of DLBCL patients by bulk and single cell transcriptomics; * to assess the correlation between the expression of immune checkpoint genes and mRNA signature; * to describe the mutational status of a panel of genes relevant to DLBCL pathogenesis;. * to assess the correlation between protein expression, mutational status and the messenger RNA (mRNA) signature. * to investigate the association between radiomic features obtained from PET images and patient and tumour characteristics and clinical outcomes (PFS, OS, ORR). For each enrolled patient, immunohistochemical determinations will be performed: Cell of origin (COO) (Germinal Cell -GC- or activated B-cell - ABC- type according with Hans algorithm ), evaluation of cluster of differentiation antigen 20 (CD20), cluster of differentiation antigen 5 (CD5), cluster of differentiation antigen 10 (CD10), Bcl6, Bcl2 (cut off\>50%), Multiple Myeloma 1 / Interferon Regulatory Factor 4 protein (MUM1/IRF4), c-myc (cut off\>40%) and Ki67, fluorescence in situ hybridization (FISH) for c-myc and if rearranged, for Bcl2 e Bcl6 ). Moreover, paraffin embedded (FFPE) tumor specimens will be collected for RNA extraction and mRNA expression mutational and proteomics analysis, centralized at IRST-IRCCS.