Malignant Transformation of a Radiation-Naïve Sinonasal Tract Angiofibroma: Clinicopathologic and Molecular Characterization of an Exceptionally Delayed Transformation.

Sinonasal tract angiofibroma (formerly juvenile nasopharyngeal angiofibroma) is a rare benign but locally aggressive vascular tumor that predominantly affects adolescent males. Malignant transformation is exceedingly uncommon and has historically been reported following radiation therapy, with only two cases described in radiation-naïve patients. We report a 56-year-old male with a history of sinonasal tract angiofibroma diagnosed at age 11 and recurrent at age 54, who developed sarcomatous transformation more than four decades after the initial diagnosis and just two years after developing a first overtly non-sarcomatous recurrence. The most recent surgical resection and histopathologic evaluation demonstrated a hypercellular, spindle cell proliferation with hyperchromasia, conspicuous mitoses and a herringbone architectural pattern distinct from angiofibroma. Molecular analysis revealed a shared CTNNB1 variant and TERT promoter mutation in both the recurrent angiofibroma and subsequent malignancy, with additional NRAS and STK11 alterations in the sarcoma, supporting clonal evolution. This case underscores the possibility for delayed recurrence and subsequent radiation- naïve malignant transformation, along with molecular mechanisms, and highlights the necessity for long-term clinical surveillance in patients with sinonasal tract angiofibroma.