Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study

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Abstract
Background. Olfactory neuroblastoma is an uncommon neuroectodermal tumor of the upper nasal cavity, microscopic features of which are not always homogeneous. No morphologic features have been found to correlate reliably with prognosis. Methods. Twenty‐six olfactory neuroblastomas occurring in 14 females and 12 males, ages 18–78 years, were studied by immunohistochemistry, electron microscopy, and DNA flow cytometry. Survival rates were statistically analyzed relative to several variables. Results. Microscopically, 22 tumors formed a morphologic spectrum intermediate between paraganglioma (PG) and neuroblastoma (NB). Others included two ganglioneuroblastomas (GNB), one lesion exhibited biphasic (neuronal and epithelial) differentiation, and one tumor showed predominantly epithelial features. Immunoreactivity for neuronal and neuroendocrine markers included synaptophysin in 77%, neurofilament protein in 38%, class III beta‐tubulin in 81%, and chromogranin A in 77%. In 88% of cases, elongated S‐100 protein‐positive cells surrounded tumor lobules. Cytokeratin and epithelial membrane antigen immunoreactivity were noted in six (23%) and two (8%) tumors, respectively. Aberrant p53 expression was detected in 16 tumors (62%). The Ki‐67 labeling index (LI) varied from 0%–43.8% (mean, 7.4%). Ultrastructurally, 80–230 nm dense core granules were noted within perikarya and as in microtubule‐containing processes in all of the 11 tumors studied by electromicroscopy. Lobules of seven tumors were surrounded by electron‐dense sustentacular cells. Epithelial tumors exhibited obviously epithelial features in addition to neuronal differentiation. DNA flow cytometry demonstrated a high incidence of polyploidy and aneuploidy (78%) and a wide range of percent S phase fractions (1.5%–21.8%; mean, 9.0%). The study showed that longer survival rates are related significantly to (1) the occurrence of metastases which was linked to tumor subtype, (2) to a higher incidence of S‐100 protein‐positive cells, and (3) to a low (Conclusions. The present study indicates that (1) although typical olfactory neuroblastomas exhibit PG/NB differentiation, they more closely resemble PG, (2) occasional tumors show GNB and/or epithelial differentiation, and (3) survival rates may correlate with S‐100 protein immunoreactivity and Ki‐67 LI.