Multifocal primary central nervous system Ewing sarcoma presenting with intracranial hemorrhage and leptomeningeal dissemination: illustrative case

Abstract

Background: Ewing sarcoma is a neoplasm within the family of small round blue cell tumors and most frequently arises from skeletal bone. Primary involvement of the central nervous system in these lesions is extremely rare, with an incidence of 1%.

Observations: A case is presented of a 34-year-old man who presented with left facial numbness, multiple intracranial lesions, a lumbar intradural lesion, and diffuse spinal leptomeningeal involvement. A lumbar laminectomy and biopsy were performed, which revealed the diagnosis of extraskeletal Ewing sarcoma/primitive neuroectodermal tumor. The patient had a rapidly progressive clinical decline despite total neuroaxis radiation and multiple lines of chemotherapeutic treatments, eventually dying from his disease and its sequelae 6 months after diagnosis.

Lessons: The authors' review of 40 cases in the literature revealed only 2 patients with isolated intraaxial cranial lesions, 4 patients with cranial and spine involvement, and an additional 34 patients with spine lesions. The unique characteristics of this patient's case, including his presentation with diffuse disease and pathology that included a rare V600E BRAF mutation, are discussed in the context of the available literature.

Keywords: BRAF; CNS = central nervous system; CSF = cerebrospinal fluid; CT = computed tomography; ES = Ewing sarcoma; Ewing sarcoma; GFAP = glial fibrillary acidic protein; MRI = magnetic resonance imaging; cPNET = central primitive neuroectodermal tumor; intracranial; oncology; spine.

FIG. 1.

Non-contrast CT scans of the brain showing a hyperdense intraaxial lesion in the right frontal medial orbital gyrus (A, arrow), and adjacent cerebral edema (B).

FIG. 2.

T1 postcontrast MRI of the brain. A: Rim-enhancing right frontal lesion with an associated hemorrhagic component with mild mass effect, shown in coronal, sagittal, and axial planes. B: Enhancing lesion within the left Meckel’s cave (arrows), shown in coronal, sagittal, and axial planes.

FIG. 3.

Sagittal slices from MRI of the lumbar spine, with sequences of T2 (A), T1 without contrast (B), and T1 with contrast (C). There is a contrast-enhancing soft tissue epidural mass filling the thecal sac and compressing the adjacent conus medullaris (arrows) and, below that, the nerve roots of the cauda equina.

FIG. 4.

Histopathological characteristics of resected lumbar intradural tumor—extraskeletal ES/PNET. Original magnifications ×400. Hematoxylin and eosin–stained images (A and B) show a small blue cell tumor, with variably round to spindle-shaped nuclei, karyorrhexis, brisk mitotic activity, and a patchy neutrophilic infiltrate. Immunohistochemical stains were performed, and the tumor cells show membranous expression of CD99 (C) and nonreactivity for CAM5.2 (D), GFAP (E), and synaptophysin (SYN) (F). SYN highlights entrapped axons within the involved nerve root.