Arteriovenous Malformations as Neoplastic-Like Lesions: Molecular Underpinnings and Implications for the...

Arteriovenous malformations (AVMs) are high-flow vascular anomalies traditionally treated as congenital structural lesions with embolization or surgical resection. However, recurrence after embolization alone exceeds 90%, underscoring incomplete understanding of their biology. Next-generation sequencing has identified somatic gain-of-function mutations in KRAS, MAP2K1, BRAF, and HRAS as drivers of sporadic AVMs. Confined to lesional endothelial cells, these mutations activate RAS/MAPK signaling and support a neoplastic-like rather than purely structural disease model. This has therapeutic implications: MEK inhibitors, particularly trametinib, have shown angiographic and clinical responses in refractory AVMs. Interventional radiologists can obtain draining vein liquid-biopsy samples during embolization for molecular genotyping; embolization may increase circulating cell-free DNA yield. This review summarizes the molecular rationale, targeted therapy evidence, and integration of genotyping into embolization workflows to enable combined treatment strategies.Level of Evidence: No level of evidence assigned (Review Article).