The Biological Basis of Histologic Transformation.

Histologic transformation of follicular lymphoma remains the leading cause of follicular lymphoma-related mortality in the rituximab era. Both the diverse timing of transformation and heterogeneity in associated genomic events suggest that histologic transformation may itself comprise distinct disease entities. Successive indolent and transformation episodes occur by divergent clonal evolution from an inferred common progenitor cell, representing a potential therapeutic target. Existing biological knowledge largely pre-dates anti-CD20 therapy, and further prospective validation is essential. Inclusion of transformation cases in clinical trials incorporating biomarker discovery, and an integrated understanding of the genetic and microenvironmental factors underpinning transformation, may unearth renewed clinical opportunities.