The pathogenesis of formation of an intradural tumor
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 SP 141 [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 [, , ]. This suggests that expression of EWSR1-FL11 might play a larger role in Ewing’s sarcoma neural phenotype than cell of origin itself .
For surgical management, it has been shown that complete resection with negative margins of extraosseous ES confers a statistically significant survival advantage . 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 . 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.
In terms of adjuvant therapies, the roles of radiation therapy and chemotherapy are still being established. In their meta-analysis of extradural ES, Saeedinia et al. . found a survival advantage at 1-year when both modalities were administered together versus singularly. However, this advantage was lost at the 2-year follow-up. Radiation to the spine remains a challenge for management. The safety threshold for radiation to the spinal cord is 50–55 Gy to minimize the risks of myelopathy, deformity, fracture, fibrosis and secondary malignancies . However, this safety threshold is below the optimal dose 56–60 Gy recommended to treat osseous ES without surgical resection, and thus it might pose a sub-therapeutic risk in PIEES with gross residual disease . Apart from gross residual disease, the possibility of microscopic seeding from a friable tumor needs to be taken into consideration while considering the optimal course for adjuvant radiotherapy . Advances in understanding the potential benefits of preoperative radiation, and the applicability of stereotactic radiosurgery in lesional targeting are exciting areas of investigation which will help advance the management of these lesions.
Although the optimal chemotherapy regime to treat PIEES is unknown, current recommendations for osseous ES have also been suggested as the initial regime for PIEES. This includes alternating cycles of vincristine, doxorubicin, and cyclophosphamide with ifosfamide and etoposide . A number of clinical trials are underway investigating regimes that may provide greater control for metastatic disease in osseous ES, which may have some role in managing PIEES recurrence later on since these areas are well supplied by spinal arteries [57,58]. However, in cases such as Cases 1 and 3 in our series, where metastases to the brain occur, the potential benefit of the same chemotherapy regime will be reduced due to the need to penetrate the blood brain barrier (BBB). Limited evidence from literature for other extraosseous Ewing’s sarcomas also indicates that adjuvant chemotherapy and radiotherapy may improve survival . The small sample size in our review supplemented with the heterogeneity in reporting precluded outcome comparisons between different treatment modalities.
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