Olfactory Neuroblastoma

Olfactory neuroblastoma (ONB) is a malignant neuroectodermal tumor that typically occurs in the superior nasal cavity. It is a distinct entity with features that include nesting, low-grade stippled nuclei, and neurofibrillary stroma with formation of pseudorosettes. It has a distinctive immunoprofile that includes keratin negativity, neuroendocrine marker positivity, and S100 positive sustentacular cells, which surround the nests of tumor in a supportive manner. Although the typical clinicopathologic features leave little room for misinterpretation, the wide variability in this tumor may cause diagnostic difficulty. This includes immunophenotypic diversity or patchy staining with immunomarkers, wide spectrum of grade and histology, posttreatment changes, and occasional divergent differentiation. In addition, problems in sampling, preservation, and clinical localization may make the diagnosis more challenging. A large group of tumors may show morphologic overlap with ONB, with some mimicking low-grade tumors, whereas others mimic high-grade tumors. This differential diagnosis has important treatment and prognostic implications. Further complicating the issue is that many of the mimics themselves may show great morphologic and immunophenotypic variability. This manuscript will review the typical clinical and pathologic features of ONB, address the great variability of ONB in our experience, will focus on the differential diagnosis and report on recent findings in these tumors including molecular genetics where applicable.