Abstract

Fusion proteins are known drivers of cutaneous epithelioid vascular proliferations, notably FOS and FOSB fusions in epithelioid hemangiomas. However, no fusion genes have been reported in cases of CEAN. Herein we report a case of an otherwise healthy 2-year-old boy with a bleeding solitary raised nodule on the naris. Excision histology demonstrated a pauci-inflammatory proliferation, well-circumscribed in the superficial dermis. The endothelial lesional cells appeared epithelioid with occasional intracytoplasmic vacuoles, forming thin vascular channels. Immunohistochemically, the endothelial lesional cells were strongly positive for ERG, CD31, and, intriguingly, ALK. GLUT1 and HHV8 immunostains were negative. Fluorescence in situ hybridization (FISH) analysis further confirmed the presence of ALK gene rearrangement. The patient remains disease-free 5 months after excision. This is the first reported case of CEAN associated with activating gene rearrangement in the literature, also constituting the first reported activating ALK gene rearrangement in cutaneous epithelioid vascular proliferations. Our finding further expands the molecular characterization of such tumors, provides new evidence for classification, and identifies a novel actionable therapeutic target with ALK inhibitors for potential clinical indications.