303 Synchronous Olfactory Neuroblastoma and Olfactory Carcinoma with Genetic Evidence of Common Clonal Origin

Introduction/Objective Olfactory neuroblastoma (ONB) is a malignant neuroectodermal neoplasm originating from the olfactory neuroepithelium capable of diverse differentiation, including epithelial differentiation. Whether cases with nonfocal epithelial differentiation represent a distinct entity, i.e., olfactory carcinoma (OC), remains under debate. Methods/Case Report A 63-year-old male presented with nasal obstruction. Imaging revealed two separate masses: one centered at the cribriform plate, and another centered in the left maxillary sinus and nasal cavity. The cribriform plate mass demonstrated sheets and nests of primitive cells with Homer Wright pseudorosettes and Flexner-Wintersteiner rosettes, diffuse synaptophysin positivity, and focal AE1/AE3 positivity, features consistent with ONB. The sinonasal mass showed similar morphology but with prominent glandular differentiation, patchy weak synaptophysin positivity, and nearly diffuse AE1/AE3 positivity, features consistent with OC. Next-generation sequencing detected two identical pathogenic SMARCA4 mutations shared by both masses, along with an additional pathogenic CTNNB1 mutation exclusive to the sinonasal mass. Microarray analysis revealed largely overlapping chromosomal alterations between the two, suggesting a common clonal origin. The sinonasal mass demonstrated more aggressive behavior than the cribriform plate mass on follow-up. Results NA Conclusion These findings provide the first genetic evidence that OC, at least in a subset of cases, may represent progressed ONB rather than a distinct pathological entity.