Molecular reprogramming in thymic neuroendocrine tumors: a narrative review.

Background and Objective: Thymic neuroendocrine tumors (tNETs) are rare and heterogeneous neoplasms with limited evidence to guide diagnosis and management. Traditional classifications rely heavily on morphology, but recent advances in molecular profiling have begun to reshape understanding of their biology and clinical behavior. This narrative review synthesizes recent molecular findings in tNETs and proposes an integrated framework that combines traditional morphology with molecular stratification to guide precision oncology. Methods: We performed a narrative review of the current literature on tNETs, focusing on histologic classification, molecular taxonomy, diagnostic algorithms, and therapeutic strategies. Special emphasis was placed on integrating emerging evidence from genomic, epigenetic, and clinical studies published between 2010 and 2025. Key Content and Findings: Molecular frameworks such as copy number instability (CNI)-based classification, together with recurrent alterations in Conclusions: This review integrates current knowledge of tNETs with recent advances in molecular diagnostics and therapeutic strategies. By highlighting key genetic and epigenetic alterations, as well as future directions such as liquid biopsy, artificial intelligence, and novel trial designs, we emphasize the need for biomarker-driven approaches to improve outcomes in this ultra-rare disease.