Molecular reprogramming in thymic neuroendocrine tumors: a narrative review

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Thymic neuroendocrine tumors (tNETs) are rare and heterogeneous neoplasms.
• Diagnosis and management are challenged by limited evidence and reliance on morphology.
• Molecular profiling is reshaping the understanding of tNET biology and clinical behavior.

Purpose of the Study:

• To synthesize recent molecular findings in tNETs.
• To propose an integrated framework combining morphology and molecular stratification for precision oncology.
• To review diagnostic algorithms and therapeutic strategies for tNETs.

Main Methods:

• Narrative review of literature from 2010-2025.
• Focus on histologic classification, molecular taxonomy, diagnostics, and therapeutics.
• Integration of genomic, epigenetic, and clinical study evidence.

Main Results:

• Copy number instability (CNI)-based classification and alterations in MEN1, TP53, and RB1 refine risk stratification.
• Everolimus and temozolomide show therapeutic promise; PRRT may be less effective.
• Epigenetic dysregulation and novel trial designs are key research areas.

Conclusions:

• Current knowledge integrates molecular diagnostics and therapeutics for tNETs.
• Key genetic/epigenetic alterations and future directions like liquid biopsy and AI are highlighted.
• Biomarker-driven approaches are essential for improving outcomes in ultra-rare tNETs.