Challenges in evaluating high-grade pancreato-hepato-biliary neuroendocrine tumors

We read with great interest and commend Tasneem <i>et al</i> for their valuable study on pancreato-hepatobiliary neuroendocrine tumors diagnosed <i>via</i> endoscopic ultrasound-guided biopsy. While the study offers important insights, we raise concerns regarding lesion classification, the lack of correlation between tumor size and aggressiveness, and the limited predictive value of individual clinical factors. Notably, many extra-pancreatic lesions may represent metastases rather than primary tumors. We advocate for a more comprehensive risk stratification approach and suggest incorporating novel molecular markers and analysis of the tumor microenvironment. Larger prospective studies are essential to enhance understanding and management of these rare and heterogeneous neoplasms.