Sinonasal POU2AF3 (COLCA2)-rearranged carcinomas: a study of 11 aggressive tumors with findings supporting classification as solid adenoid cystic carcinoma.

POU class 2 homeobox associated factor (POU2AF3) is a gene that has been associated with increased risk of colon cancer. Recently, colleagues have reported recurrent EWSR1/FUS::POU2AF3 fusions in undifferentiated spindle cell/round cell sarcomas with a predilection for the sinonasal tract. We report 11 sinonasal POU2AF3-rearranged carcinomas that are distinct from the EWSR1/FUS::POU2AF3 sarcomas. The tumors affected mostly in men (median age: 46 years) and arose in the sinonasal tract (median size: 6 cm). Clinical follow-up on 9 patients showed 6 patients developed distant metastases with a latency from the time of presentation to 16 months. Four patients died of disease, 4 were alive with disease, and 1 was alive with no evidence of disease. Most tumors showed histologic features consistent with solid adenoid cystic carcinoma (AdCC), comprising basaloid cells growing in solid nests or sheets. All showed varying extent of duct formation. Pankeratin, CK7, CD117, and CK5/6 were expressed in all tested tumors; most were also positive for S100 protein and SOX10. RNA sequencing revealed EP300::POU2AF3 (n = 6), EWSR1::POU2AF3 (n = 3), CREBBP::POU2AF3 (n = 1), and CHD7::POU2AF3 (n = 1). Most also harbored NOTCH1 mutations (6/9). MYB RNA expression was elevated by RNA sequencing and/or RNA in situ hybridization in 7/7 tested cases. Our findings support that a subset of sinonasal solid AdCC harbors POU2AF3 rearrangements, and these tumors pursue an aggressive clinical course. Diffuse expressions of pankeratin, S100 protein, SOX10, CK7, and/or CD117 provide a useful immunoprofile that reflects the diffuse overgrowth of neoplastic ductal cells in AdCC and distinguishes them from the EWSR1/FUS::POU2AF3 sarcomas.