Advances in peripheral T cell lymphomas: pathogenesis, genetic landscapes and emerging therapeutic targets

Abstract

Peripheral T cell lymphomas (PTCLs) are a biologically diverse and aggressive group of non-Hodgkin lymphomas that originate from mature T cells, often presenting with complex clinical and morphological features. This review explores the challenges in diagnosing and classifying PTCLs, focusing on the intricate biology of the more common nodal entities. Advances in molecular diagnostics, such as mutational and gene expression profiling, have improved our understanding. However, the rarity and morphological variability of PTCLs continue to complicate the definition of biologically and clinically meaningful entities, as well as the application of current diagnoses in daily practice; these advancements have not yet translated into improved clinical outcomes. Standard therapies fail in most cases and lead to poor prognoses, highlighting the urgent need for improved therapeutic strategies. Precise characterisation of PTCL advances refined classification and supports the development of more targeted and effective treatments. Recent approaches have focused on biology-based risk stratification, either within specific entities or in an entity-agnostic manner. This development aims for improved treatment selection or even personalised treatment based on genetic, epigenetic and functional profiles.