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

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 (<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.

Aberrant Pattern of Cytokeratin Expression in Olfactory Neuroblastoma: A Potential Diagnostic Pitfall

“…In conclusion our case represents the first demonstration of a ''dot-like'' cytokeratin expression in an ONB, a feature hitherto undescribed to our knowledge and supplements the Literature data [2][3][4][5]. Pathologists should be aware of this potential diagnostic pitfall in distinguishing a high grade ONB from a high grade NEC, particularly in scanty & Martina Mandarano mandaranomartina@gmail.com biopsies [2], in which is crucial an integration of immunohistochemical data with careful interpretation of morphological features.…”

“…In their paper entitled ''Neuroendocrine Neoplasm of the Sinonasal Tract: Neuroendocrine Carcinomas and Olfactory Neuroblastoma'' Shah and Perez-Ordoñez [2] reported a cytokeratins positivity, observed in up to 30 % of ONBs, in accordance with other Authors who documented cytokeratins expression from 23 to 35 % of cases, both focal or diffuse with strongly intensity, but never showing a paranuclear or globoid stain (''dot-like'' pattern). This latter being an important difference respect to Neuroendocrine Carcinoma (NEC) [1][2][3][4][5]. Furthermore another recent article by Holbrook et al [6] demonstrated that cytokeratin 18 (CK18) was positive in ONB separating tumor cells into nests.…”

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

“…Contrary, mutations of TP53 were not found in any of 19 cases of ONB, but about the half of all cases showed p53 overexpression [37]. Another study revealed p53 aberrant expression in 16 out of 26 cases (62%) [38]. Nevertheless, recent studies have identified point mutations of TP53 in two cases of metastatic ONB [39, 40].…”

“…The limitation of their study was uneventful disease course amongst sample as the majority of patients did not show any recurrence and a small cohort size. Longer survival may be associated with an increased abundance of S-100 protein-positive cells and a low Ki-67 labeling index [38], and this may probably be associated with differentiation, as the number of sustentacular cells decreases with increased tumor grade.…”

“…First approach to this issue was made by Hirose et al, who used flow cytometry [38]. These authors analyzed 22 cases of ONB and assessed their ploidy and percentage of cells in S phase.…”