Olfactory Neuroblastoma With Divergent Differentiation: Contemporary Management of Unusual Pathology and Literature Review

Olfactory neuroblastoma (ON; Esthesioneuroblastoma) is a malignant tumor that arises from the olfactory neuroepithelium. Very rarely, ON can histologically display a biphenotypic pattern, with only 7 cases reported in the literature to date. We describe a case of this poorly understood entity and review the patient's histology, pathology, and treatment. An 85-year-old man presented with endoscopy and imaging findings of a sinonasal mass arising from the olfactory cleft. Biopsy and further pathological review established Hyams grade 3 and Kadish stage C tumor. The patient underwent combined endoscopic and open-approach resection due to the involvement of the nasal bone and subsequent adjuvant radiation therapy. Specimen contained Flexner-Wintersteiner rosettes and stained positive for the neuroendocrine marker synaptophysin consistent with ON. A second, epithelial component pattern of goblet cells and mucin was observed suggesting divergent differentiation. We are the first group to report next-generation sequencing of this tumor, which revealed a pathogenic mutation in PIK3CA and a likely pathogenic variant in RUNX1 (AML1). ON with divergent differentiation is very rare, and more robust studies characterizing molecular drivers and pathology may aid in clinical management.