Novel insights into the pathogenesis of T-cell lymphomas.

T-cell lymphomas are a heterogeneous group of rare malignancies with overlapping clinical, immunologic, and histologic features. Recent advances in our understanding of T-cell differentiation based on gene expression profiling, next-generation sequencing, and transgenic mouse modeling studies have better elucidated the pathogenetic mechanisms underlying the diverse biology of T-cell lymphomas. These studies show that although genetic alterations in epigenetic modifiers are implicated in all subtypes of T-cell lymphomas, specific subtypes demonstrate enrichment for particular recurrent alterations targeting specific genes. In this regard, RHOA and TET2 alterations are prevalent in nodal T-cell lymphomas, particularly angioimmunoblastic T-cell lymphomas, peripheral T-cell lymphomas (PTCLs) not otherwise specified, and nodal PTCLs with T-follicular helper phenotype. JAK-STAT signaling pathways are mutationally activated in many extranodal T-cell lymphomas, such as natural killer/T-cell and hepatosplenic T-cell lymphomas. The functional significance of many of these genetic alterations is becoming better understood. Altogether these advances will continue to refine diagnostic criteria, improve prognostication, and identify novel therapeutic targets, resulting in improved outcomes for patient with T-cell lymphomas.