KRAS Footprints in the Skin: Leveraging Targeted Therapy for Unresectable Intra-Cerebral AVM.

A 15-year-old female with a longstanding, unresectable intracerebral arteriovenous malformation (AVM) involving the bilateral thalami and basal ganglia presented with progressive neurologic decline. Given the inaccessibility of the intracranial lesion, a lipomatous scalp nodule overlying the AVM was biopsied for molecular testing and revealed a somatic mosaic KRAS p.G12D variant, the most common variant detected in sporadic brain AVMs. Targeted therapy with the MEK inhibitor trametinib was initiated, but the treatment course was complicated by cutaneous toxicity and ongoing neurologic deterioration. This case illustrates that extracranial tissue in the skin can serve as a surrogate for molecular diagnosis in unresectable brain AVMs, underscoring the diagnostic and therapeutic importance of dermatologic assessment in complex vascular anomalies.