Unraveling the many faces of angioimmunoblastic T-cell lymphoma: clinical, pathological, and molecular heterogeneity

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma originating from follicular helper T cells and characterized by profound clinical, pathological, and molecular heterogeneity. Despite advances in classification and diagnosis, therapeutic outcomes remain suboptimal, particularly in relapsed or refractory settings. In recent years, the evolution of risk stratification models and a deeper understanding of AITL’s molecular pathogenesis, including its unique pattern of clonal evolution, have paved the way for precision medicine. Notably, targeted treatment approaches, such as immunomodulatory agents, epigenetic therapies, kinase inhibitors, and immune checkpoint blockade, are demonstrating promising clinical efficacy, especially in patients harboring specific molecular aberrations. This review comprehensively summarizes the multilayered heterogeneity of AITL, emphasizes the role of immune and molecular profiling in informing therapeutic decisions, and outlines future directions for personalized, multi-agent treatment strategies aimed at overcoming resistance and improving survival.