2021 NPA-02

This case was originally published in 2021. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.

The patient is a 54-year-old man with no significant past medical history who presented with left-sided pectoral-distribution sensory numbness and burning sensation. MRI (Image A) of the spine showed an ovoid, enhancing spinal cord lesion measuring 13 x 9 x 5 mm at the cervicothoracic junction. He underwent laminectomy and resection of the mass.

Tissue Site
Spinal cord

The whole slide image provided is an H&E-stained slide of a resection from the spinal cord lesion.

H&E-stained sections show a moderately cellular glial tumor composed of cells with fibrillary to epithelioid features (Image B, Image C, and Image D). Both perivascular pseudorosettes and rare true ependymal rosettes are seen. Mitotic activity is low, and neither palisading necrosis nor microvascular proliferation is identified. Tumor cells are immunoreactive for GFAP (Image E) and demonstrate paranuclear dot-like staining with EMA (Image F). The Ki-67 proliferative index is low (Image G). This entity is histologically best categorized as ependymoma, World Health Organization (WHO) grade 2.

Ependymomas are uncommon tumors that may occur anywhere along the ventricular system or in the spinal cord. Although only 10% of ependymomas occur in the spinal cord, they are the most common neuroepithelial neoplasm of the spinal cord in adults. Intramedullary cervical or cervicothoracic locations are the typical sites. Clinically, spinal ependymomas often present with pain and sensory or motor deficits based on the tumor location. On imaging, they appear well-circumscribed, are contrast-enhancing, and are T1-hypointense and T2-hyperintense.

Grossly, spinal ependymomas are well-demarcated, tan-white, soft, and spongy. Microscopically, they are composed of variably epithelioid glial cells with round to oval nuclei and speckled chromatin, situated in a fibrillary background. Perivascular pseudorosettes and true ependymal rosettes are key histologic features. Ependymomas typically show diffuse immunoreactivity for GFAP, with accentuation of staining in perivascular pseudorosettes; EMA often shows focal paranuclear dot- or ring-like immunoreactivity. Unlike most other gliomas, immunostaining for SOX10 is characteristically negative. High nuclear:cytoplasmic ratio, high mitotic count, microvascular proliferation, and palisading necrosis are considered anaplastic features.

Ependymal tumors have traditionally encompassed four histologic groups: subependymoma, myxopapillary ependymoma, ependymoma, and anaplastic ependymoma. More recently, molecular analyses of ependymal tumors have revealed at least nine molecular subgroups, which tend to better correlate with prognosis than the conventional histologic classification. Each CNS compartment – supratentorial, posterior fossa, and spinal cord – harbors at least three molecular subgroups. The spinal cord ependymoma subgroups can generally be stratified based on morphology and include those with classic or anaplastic morphology, those with myxopapillary morphology, and those with subependymal morphology. The group with classic or anaplastic histomorphology most commonly harbors NF2 mutations and can occur in children and adults. This group also displays chromosomal gains of 7 and 12 and losses of 13, 14, and 22. A small subset of spinal cord ependymomas instead demonstrate MYCN amplification; these tumors typically show anaplastic features, have a poor prognosis, and thus should be distinguished from the more common and less aggressive NF2-mutated spinal cord ependymomas. The group with myxopapillary histomorphology has genome-wide polyploidy and occurs in adults. The group with subependymal histomorphology harbors 6q deletion and occurs in adults.

Apart from the small group of MYCN-amplified tumors, ependymomas occurring in the spinal cord generally have a good outcome compared to those in other locations. Gross total resection is the most important prognostic factor in spinal cord ependymomas. In pediatric patients with spinal ependymomas, those with tumors in the upper thoracic or cervical spinal cord have shown better progression free and overall survival. In adults, those with lower spinal cord tumors, many of which are myxopapillary ependymomas, have a shorter progression free survival and higher recurrence rate. As such, WHO grade 2 designation is now advised for myxopapillary ependymoma. Because a risk of CSF dissemination exists for all newly diagnosed ependymomas, radiographic staging of the remaining CNS should be considered, if not previously performed. Lesional cells can rarely be identified by CSF cytologic analysis, particularly if it is of the myxopapillary or anaplastic group.

The differential diagnosis for intramedullary spinal tumors includes not only ependymoma, but also astrocytomas (both diffuse and pilocytic) and hemangioblastoma. Schwannoma and meningioma are typically intradural and extramedullary but may be considered in the differential diagnosis of myxopapillary ependymoma. All lack true ependymal rosettes, but small foci that mimic perivascular pseudorosettes are occasionally present in pilocytic astrocytoma and other gliomas. Distinctive features of pilocytic astrocytoma include biphasic architecture with compact eosinophilic areas containing Rosenthal fibers and loose myxoid areas. The cells of pilocytic astrocytoma are immunoreactive for GFAP, OLIG2, and SOX10. While very rare in the spinal cord, the pilomyxoid variant of pilocytic astrocytoma characteristically displays an angiocentric growth pattern which can superficially mimic the perivascular pseudorosettes of ependymoma. Diffuse astrocytoma is composed of infiltrative glial cells that are immunoreactive for OLIG2 and SOX10, and are variably reactive for GFAP. Hemangioblastoma is a vascular tumor that is immunoreactive for inhibin, GLUT-1, and vascular markers such as CD31 and CD34. Schwannoma is a peripheral nerve sheath tumor with hyper- and hypocellular areas, nuclear palisading, and immunoreactivity for S100 and SOX10. Meningioma is composed of meningothelial cells commonly arranged in lobules or whorls and is immunoreactive for EMA and SSTR2A.

• Ependymomas are the most common intramedullary spinal cord neoplasm in adults, most often occurring in the cervicothoracic spine.
• Key histologic features include perivascular pseudorosettes and true ependymal rosettes, although the latter are seen less often.
• Classic spinal ependymomas in adults are associated with chromosomal gains of 7 and 12 and losses of 13, 14, and 22 (on which the NF2 gene is located).
• Gross total resection is an important prognostic factor in spinal ependymomas.
• Spinal ependymomas generally have a better prognosis than posterior fossa and supratentorial ependymomas.

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