Ancillary Studies in the Diagnostic Evaluation of Large B-Cell Lymphoma

Context.— Large B-cell lymphoma classification has changed significantly over the decades, evolving from a purely morphologic categorization to one using sophisticated ancillary studies including molecular analysis, immunohistochemistry, and cytogenetics, in addition to morphology and clinical presentation. Objective.— To discuss and interpret the key ancillary studies required for subclassification in 2019 and review the differential diagnosis of diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Data Sources.— Recent literature on the subcategories of large B-cell lymphoma is reviewed, along with relevant updates from the 2016 World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues, with an emphasis on Epstein-Barr virus–positive lymphoproliferative disorders, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and large B-cell lymphoma with IRF4 rearrangement. Conclusions.— Cases with DLBCL, NOS histology can be further subclassified on the basis of cell of origin studies, Epstein-Barr virus–encoded small RNAs, MYC and BCL2 and/or BCL6 rearrangement studies, and other relevant cytogenetic and immunohistochemical studies. The diagnosis of DLBCL, NOS is therefore a diagnosis of exclusion.