Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related to Ewing sarcoma.

Abstract

Olfactory neuroblastoma (ONB) is a malignant tumor of the nasal mucosa whose histogenesis is unclear. A relationship to neuroblastoma (NB), a pediatric tumor of the sympathetic nervous system, is based on morphologic similarities and the expression of similar neural antigens. However, the clinical presentation of ONB differs from that of NB, and MYCN amplification characteristic of NB is not observed. We have therefore examined the relationship of this malignancy to other classes of neural tumors. appear to act as aberrant transcription factors (10). Identification of EWS/FLI1 and EWS/ERG fusion transcripts by reverse transcription PCR (RT-PCR) has formed the basis of a sensitive and specific diagnostic test for pPNETs (11).Olfactory neuroblastoma (ONB) is a tumor of the nasal cavity that was first described in 1924 by Berger et al. (12). Since that time the histogenesis of this tumor has been vigorously debated, giving rise to a variety of other names, including esthesioneuroblastoma, olfactory neuroepithelioma, and others (13). A neural derivation is indicated ultrastructurally by the presence of dense core neurosecretory granules and neuritic processes within tumor cells and immunohistochemically by expression of neurofilament protein, neuron-specific enolase, and S-100 protein (14-17). Several anatomical origins of ONB have been suggested, including the sympathetic fibers of the anterior nasal cavity, the neuroectodermal cells of the olfactory placode, the sphenopalatine ganglion, and the organ of Jacobson (13). The proposed relationship to neuroblastoma (NB) implied in the name is based on morphologic similarities to primitive forms of NB, the identification of norepinephrine and dopamine ,B-hydroxylase (a key enzyme in the metabolic pathway of catecholamine synthesis) in a case of ONB (18), and a possible origin from sympathetic fibers of the nervus terminalis located in the anterior nasal cavity. Unlike NB, however, ONB rarely occurs in early childhood, tends to behave less aggressively than NB, and is rarely associated with catecholamine secretion (13,15). Moreover, the superior location of ONB within the nasal vault favors an origin from neuroectodermally derived cells of the olfactory placode. These clinicopathologic considerations have led to the alternative hypothesis that ONB is related to the pPNET family of primitive sarcomas.Although morphologically similar, a number of molecular features distinguish pPNETs and NBs. The t(11;22) and t(21;22) chromosomal translocations and gene fusions described for pPNETs have never been observed in NBs. Instead, these malignancies demonstrate amplification of the MYCN protooncogene in about 30% of the cases (19,20), and a similar proportion have allelic losses of the distal short arm of chromosome 1 (21,22). NBs are associated with catecholamine secretion, and expression of tyrosine hydroxylase, the ratelimiting enzyme in catecholamine biosynthesis, has been used diagnostically for the detection of residual NB cells (23

Esthesioneuroblastoma is not a member of the primitive peripheral neuroectodermal tumour-Ewing’s group

“…In ENB the t(11;22)(q24;q12) has been detected in two out three metastatic cell lines (Whang-Peng et al, 1987;Cavazzana et al, 1988) and the presence of trisomy 8, a second non-random chromosomal aberration in pPNET-ETs, has been found in one of three short-term cultures of primary ENB (VanDevanter et al, 1991). The cytogenetic results were further confirmed by the molecular analysis carried out by reverse transcription polymerase chain reaction (RT-PCR) on six primary ENBs (Sorensen et al, 1996). In four of them (two of which originated in the previously cited cell lines) (Cavazzana et al, 1988), the presence of EWS/FLI-1 fusion transcript (Sorensen et al, 1994) was identified.…”

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

“…Most ONBs do not exhibit balanced translocations and the presence of fusion genes in patient samples and cell lines [49, 50]. Early research improperly suggested ONB exhibiting a translocation (11;22)(q24;q12) and producing an EWS/FLI1 transcript, which might cause misclassification to primitive neuroectodermal tumors (PNETs) [51, 52]. …”

Neuroectodermal Neoplasms of the Head and Neck with Emphasis on Neuroendocrine Carcinomas

“…With the widespread emergence of molecular diagnostic techniques applicable to paraffinembedded tissue, it was initially suggested that ONB was a form of peripheral neuroectodermal tumor (PNET), based on the apparent finding of the t(11;22)(q24;q12) translocation characteristic of Ewing's sarcoma and PNET in some ONB (95). However, a more recent study performing RT-PCR on 11 ONBs failed to find the chimeric EWS/FLI1 transcript in any of these tumors (96).…”