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

Abstract

Esthesioneuroblastoma (ENB) is a rare malignant tumour thought to derive from neuroendocrine cells of the olfactory epithelium on the basis of location, morphologic, immunophenotypic and ultrastructural features. In fact, well differentiated ENB is characterized by the presence of neuropil, Homer Wright and olfactory rosettes (Hyams et al, 1988), by a positive immunoreactivity for neuron-specific enolase, synaptophysin, chromogranin and neurofilaments and, ultrastructurally, by cytoplasmic processes, microtubules and dense core granules, all features consistent with an origin in the olfactory epithelium (Shanmugaratnam, 1991;Banerjee et al, 1992).The neuroectodermal origin of ENB has been subsequently strengthened by cytogenetic and molecular findings. The presence of t(11;22)(q24;q12) translocation, the chromosome hallmark of Ewing's sarcoma, in addition to the single case of mesenchymal chondrosarcoma, was detected repeatedly in three other tumours: peripheral neuroepithelioma, Askin tumour and ENB . The presence of a common cytogenetic marker strengthened the hypothesis that all these four tumours are developmentally related and that they represent phenotypic variations of the same pathogenetic theme; for this reason they are defined as primitive peripheral neuroectodermal tumours, Ewing's tumours (pPNETs-ETs). 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.However, these cytogenetic-molecular-based data have been recently challenged by the results of two other studies. In the first study (Nelson et al, 1995,) 18 out of 18 ENBs resulted nonimmunoreactively to the 12E7 monoclonal antibody, specific for the protein product of the MIC2 gene and known to reliably stain pPNETs-ETs, although not specifically (Chan et al, 1995). In the second study, 20 out of 20 ENBs were immunocytochemically MIC2-negative, and 11 of them were also EWS/FLI-1-negative for the presence of fusion transcripts. Furthermore one case, analysed by Southern blotting, did not show any EWS rearrangement (Argani et al, 1998).To address the point of whether ENB shares common markers with pPNETs-ETs, we analysed five frozen samples of ENB, by RT-PCR, dual colour fluorescence in situ hybridization (FISH) and Southern blot. RT-PCR was performed to verify the occurrence of the EWS/FLI-1 fusion transcript, of the EWS/ERG by RNA originated from the less frequent t(21;22)(q22;q12) translocation reported in pPNETs-ETs (Soren...

Sinonasal Malignancy: What’s New?

“…Following the results from a recent study by Logsdon et al [26] [14] comprises the olfactory neuroblastoma (esthesioneuroblastoma; ICD-O 9522/3). This tumor is of olfactory membrane origin and probably does not belong to the peripheral neuroectodermal tumor-Ewing's tumor, as 2 recent molecular biological studies have demonstrated [28,29]. Characteristically, this tumor has a lobular structure with well-defined groups of neuroblasts and neurofibrils separated by highly vascular fibrous stroma.…”

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

“…However, no statistically significant survival difference was found for these variables. 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].…”

Esthesioneuroblastoma: a meta-analysis and review

“…89 Studies with fluorescence in situ hybridisation 39,40 and RT-PCR 31,40 have not confirmed this translocation in ENB. ENB should therefore be seen as a distinct entity from PNET and the Ewing's sarcoma family of tumours.…”

“…These were supplemented by another 19 relevant publications found in references cited. 4,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] The studies were divided into three types, according to their principal objectives: origin and aetiology of ENB, 9,11,15,[17][18][19]21,24,[27][28][29][30][31][32][33][34][35][36][37][38][39][40] histopathological diagnosis; 10,[12][13][14]23,37,[41][42][43][44]…”