2026 Proffered Presentations
S187: MAPPING THE TUMOR ECOSYSTEM OF JUVENILE NASOPHARYNGEAL ANGIOFIBROMA THROUGH SINGLE-CELL TRANSCRIPTOMICS
Heidi Martini-Stoica, MD, PhD1; Brittany T Rupp2; Miek Kunz1; Alessandra Livraghi-Butrico2; Kenichi Okuda2; Wanda K O'Neal2; Hong Dang2; Brian D Thorp, MD1; Cristine Klatt-Cromwell, MD1; Charles S Ebert, MD, MPH1; Brent A Senior, MD1; Jackson R Vuncannon, MD1; Adam J Kimple, MD, PhD1; Kevin M Byrd, DDS, PhD2; 1University of North Carolina; 2Virginia Commonwealth University
Juvenile nasopharyngeal angiofibroma (JNA) is a rare but locally aggressive vascular tumor of adolescent males, often arising from the sphenopalatine foramen. Despite its distinctive demographic and anatomic features, the biological basis of JNA pathogenesis is poorly understood, and its management remains primarily surgical. To investigate the molecular underpinnings of JNA, we applied single-cell RNA sequencing to JNA tumors, adjacent mucosa, and control sinonasal tissue to define the tumor ecosystem at single-cell resolution. Our analysis revealed a complex fibrovascular network, including endothelial, fibroblast, pericyte, vascular smooth muscle, and neural crest–like populations. Compared to normal tissue, JNA showed expansion of neural crest–like cells and robust activation of angiogenesis, extracellular matrix, and cell migration, which are features consistent with a highly proliferative, vascularized phenotype. Endothelial cells in JNA downregulated adaptive immune pathways, indicating an immunosuppressed tumor microenvironment that may influence recurrence and therapeutic response. Cell–cell interaction analyses identified fibroblasts as central mediators of the tumor niche, extensively engaging endothelial cells, pericytes, vascular smooth muscle cells, and neurons/neural-like cells. Drug2cell mapping identified FDA-approved VEGF/VEGFR inhibitors (bevacizumab, tivozanib, lenvatinib) as potential therapeutic candidates for JNA. Together, these data provide the first high-resolution map of the JNA tumor ecosystem, highlight its neurovascular origin and angiogenic dependence, and nominate VEGF signaling as a targetable pathway.