Histological examination has been the traditional means for

Histological examination has been the traditional means for diagnosis. Microscopic imaging of small, round, blue TWS119 accompanied by positive CD99 antigen expression supports a diagnosis of ES. CD-99 is a 32-kDa cell membrane glycoprotein which may inhibit cellular differentiation in ES via modulation of the MAPK pathway [43]. Unfortunately, CD99 expression is not entirely specific for ES, as it is also expressed in other primitive neuroectodermal tumors. A positive molecular EWSR1-FLI1 fusion transcript is considered an important diagnostic feature for PIEES [44]. While our series involved molecular confirmation by either FISH or RT-PCR, there were several cases in the literature in which the diagnosis was based only on histopathology and immunohistochemistry. The fidelity of the diagnosis could not be completely ascertained in such cases, although they were reported as Ewing’s sarcoma. It must also be remembered that peripheral primary neuroectodermal tumors (pPNETs) are virtually indistinguishable from Ewing’s sarcoma with a positive EWSR1-FLI1 fusion transcript and strong positivity for CD99. Given their similarity, it has been argued that they are the same pathologic lesion as extraosseous Ewing’s sarcoma, falling within the spectrum of “Ewing family of tumors (EFT)”. In light of these findings, several cases in the literature reported their findings as “Ewing’s sarcoma/pPNET”. It must be noted that, for the very same reason, we were unable to perform accurate histologic discrimination between the two types of tumors in our own series. In contrast to osseous Ewing’s sarcoma, we found most patients in our series to present in late adulthood (median age-31 years). We also found poor 5-year overall survival in our series (40%, Fig. 2B), whereas, in contrast, literature has previously suggested higher 5-year survival in extraosseous Ewing’s sarcomas (70%), even when compared to osseous lesions (62%) [3]. The pathogenesis of formation of an intradural tumor is unclear. Initially, several lines of evidence suggested a neural crest cell of origin for Ewings’s sarcoma based on expression of neuroectodermal markers on tumor cells [45,46]. However more recently, studies have shown that expression of EWSR1-FL11 fusion transcript upregulates expression of neural crest genes in bone marrow cells, fibroblasts and other cell types [[47], [48], [49]]. This suggests that expression of EWSR1-FL11 might play a larger role in Ewing’s sarcoma neural phenotype than cell of origin itself [50]. For surgical management, it has been shown that complete resection with negative margins of extraosseous ES confers a statistically significant survival advantage [51]. While there is no evidence specific to PIEES, it is worth noting anecdotally that of all death events reported in the literature, 60% (6/10) involved subtotal resection. The use of minimally invasive surgery for removal of intradural extramedullary lesions has been reported in the literature [52]. A significant proportion of patients in the literature review presented with acute decompensation due to intratumoral hemorrhage and intraoperatively, a high degree of vascularity was encountered in general, which is also an important consideration for surgical resection. Given the adhesive, infiltrative and vascular nature of the tumor, especially around nerve roots, the use of neuromonitoring such as EMG should be considered to avoid injury to the neural elements.