Algorithm for the diagnostic workup of aggressive B-cell lymphomas. The current algorithm for diagnosing aggressive large B-cell lymphomas starts with a biopsy collection from a lymph node (excision or needle biopsy) or a biopsy of an extranodal site. The diagnosis of the different lymphoma entities is based on a combination of morphology, immunophenotype, EBER in situ hybridization, FISH analysis, and B-cell clonality analysis. Advances in the understanding of DLBCL herald a transition to a molecular genetic classification (red arrow). This genetic classification is based on mutational profile, somatic copy number alterations, and structural variants. The depicted molecular subtypes were identified in 3 different studies indicating that these subgroups reflect true biological differences.^131,132,134 On the basis of these molecular studies, a predictor model was developed that dissects the cell-of-origin and stratifies further the molecular classification into 7 genetic subtypes with apparently clinical relevance.¹³³ The acronyms indicate the names given in the different studies to the same identified biological group.