Intracranial Ewing sarcoma: four pediatric examples

Abstract

Background: Ewing sarcoma typically arises in bone and is unrelated to intraparenchymal small blue cell embryonal central nervous system (CNS) tumors previously designated primitive neuroectodermal tumors (PNETs). When the CNS is impacted, it is usually secondary to local extension from either the epidural space, skull, or intracranial or spinal metastases. Primary examples within the cranial vault are rare, usually dural-based, and are largely case reports in the literature. We detail four pediatric patients with solitary, primary intracranial Ewing sarcoma, all manifesting the archetypal EWRS1 gene rearrangement that confirms diagnosis.

Procedure: Neurosurgical Department records, spanning 21 years (1995-2016), were reviewed to identify patients. Demographics, clinical history, pathological/genetic features, and clinical course were retrieved from the medical record and personal files of the authors.

Results: Four patients, one male and three females, age 5 to 16 years, were identified. One presented in extremis from a large lesion, two with soft tissue masses, and the fourth as an incidental finding after being involved in a motor vehicle collision. Three had clear bony involvement: a 10-year-old girl with a large left temporal lesion had clear origin in the skull, with spiculated calcified striations throughout the mass; a 9-year-old girl presented with a bony left petrous apex mass; and a 16-year-old girl presented with a left temporal mass with extension to the dura and underlying bone erosion. Only the 5-year-old boy had a large left frontoparietal mass traversing the falx with no bony contact. All four tumors manifested the diagnostic EWSR1 mutation and were treated with an Ewing sarcoma regimen. Outcomes were variable, with one patient showing progressive metastatic disease and death 3 years after presentation, one patient with disease-free survival 10.5 years after completion of therapy, and one alive and well at the completion of therapy 1 year after diagnosis. One patient completed therapy recently with post-therapy scans showing no evidence of disease.

Conclusion: Testing for the EWSR1 mutation confirms the diagnosis of Ewing sarcoma and excludes other types of embryonal CNS tumors. Long-term disease-free survival is possible with adherence to the appropriate therapeutic regimen after gross surgical resection.

Keywords: EWSR1 gene; Intracranial Ewing sarcoma; PNET; Pediatric brain tumor.

Fig. 1

a Images from Case 1 of a 16-year-old female presenting with a left temporal lobe tumor. Non-contrast axial CT. b Post-contrast coronal CT demonstrating bony involvement along the intracranial surface of the inferior left temporal bone

Fig. 2

a Images from Case 2 of a 10-year-old female presenting with a left temporal lobe tumor. Extensive remodeling of the intracranial surface of the left temporal bone is observed. Coronal T1-weighted MRI with contrast. b Axial T1-weighted MRI with contrast. c Coronal non-contrast CT. d Axial non-contrast CT

Fig. 3

a Images from Case 3 of a 5-year-old male presenting with a left parietal lobe tumor with transfalcine extension. Coronal pre-contrast T1-weighted MRI. b Coronal post-contrast T1-weighted MRI. c Sagittal post-contrast T1-weighted MRI

Fig. 4

a Images from Case 4 of a 9-year-old female presenting with a left petrous apex tumor. Axial non-contrast CT. b Coronal non-contrast CT. c Axial T1-weighted post-contrast MRI. d Coronal T1-weighted post-contrast MRI

Fig. 5

a H&E staining showing small blue cell tumor with scant cytoplasm and evident mitoses. b Immunohistochemical stain for CD99 showing strong expression in cell membranes. c FISH showing EWSR1 rearrangement