Biphenotypic Sinonasal Sarcoma With a Novel PAX3::MAML2 Fusion

Biphenotypic sinonasal sarcoma (BSNS) is a rare, low-grade spindle cell sarcoma of the sinonasal tract. It is characterized by dual neural and myogenic differentiation and classically shows fusions involving PAX3. MAML3, a co-activator in the Notch signaling pathway, is the most common fusion partner of PAX3. Here, we describe the first reported case, to our knowledge, of BSNS harboring a novel PAX3::MAML2 fusion in a polypoid lesion arising from the left ethmoid of a 61-year-old man. Microscopically, the tumor demonstrated bland spindle cell morphology. The cells were arranged in small fascicles and a vaguely whorled pattern without mitotic activity or cellular atypia. Immunohistochemistry displayed characteristic co-expression of S100 and smooth muscle actin as well as patchy nuclear positivity for beta-catenin. SOX10, AE1/AE3, EMA, and CD34 were negative. Ki-67 was expressed in less than 1% of tumor cells, consistent with a low-grade lesion. The RNA sequencing identified a novel PAX3::MAML2 fusion transcript. MAML2 fusion is commonly associated with other head and neck neoplasms, including mucoepidermoid carcinoma and NR1D1-rearranged tumors. These findings highlight the value of comprehensive fusion testing in BSNS and emphasize the evolving fusion landscape in this entity and related tumors.