Diffuse large B-cell lymphoma (DLBCL) is clinically and genetically heterogeneous. The existence of genetically defined subtypes with therapeutic implications is clear. Additional considerations that are yet to be fully resolved include defining boundaries between discrete classes, relevant molecular data types, and handling of unclassifiable/composite cases. In this review, we juxtapose points of view on the topic from experts in the field, outline practical workflow considerations, and distill lessons from clinical trials. These synthesize experimental design and analytic considerations that inform the development and evaluation of clinically relevant DLBCL subtyping approaches. SIGNIFICANCE: The most meaningful way to stratify DLBCL remains unresolved, and this represents a significant barrier to adopting a precision medicine paradigm.
Shipp et al. (2026) studied this question.