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 (< 10%) Ki-67 labeling index.
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.
Cancer 1995; 76:4-19.