Pathology of Supratentorial Ependymomas in Children

Pathophysiology

• Ependymal cells are cell of orgin: Cells that line the ventricular system of the brain are the cells of origin for ependymomas.
• Most originate in ventricles: Common locations for ependymomas are the fourth, third, and lateral ventricles of the brain.
• Parenchymal ependymomas may be developmental in nature: Sometimes ependymal cells that fail to migrate to their programmed location remain in the brain parenchyma, giving rise to these tumors.

Molecular/Genetic Pathology

Genomic analysis established several characteristic locations and grade-specific differences in tumor karyotype and gene expression. The most common expressions seen are:

• Chromosome 22, loss: Loss of this chromosome is especially common in adults with spinal cord tumors. The NF2 gene is also on chromosome 22 (12).
• Chromosome 1q, gain: Gains in this chromosome are most common in children with high-grade tumors (13).
• Chromosome 12q, gain, and losses of 6q and 13: These are also characteristic of intracranial ependymoma (14).

Histopathology

Cell of origin

• Glial cell of origin: The cell of origin is a glioma cell, and the tumor is described under the broad category of “neuroepithelial cell tumor.” This cell gives rise to the ependymal epithelial layer lining the ventricular system of the brain and the central canal of the spinal cord.

Gross morphology

• Well-demarcated tumors: Ependymomas are usually solid, well-circumscribed tumors (15).
• Hemorrhage and by-products: Areas of calcifications, cysts, and often hemorrhage exist.
• Sharp margin: There is usually limited infiltration into surrounding structures.

Grading

The WHO classification recognizes three grades of ependymoma (15):

• Grade 1: Subependymoma and myxopapillary ependymoma
• Grade 2: Cellular ependymoma, papillary ependymoma, and clear cell ependymoma
• Grade 3: Anaplastic (malignant) ependymoma.

Histological Features of Supratentorial Ependymomas

• Perivascular pseudorosettes of neoplastic cells that encircle blood vessels are the hallmark for this tumor.

Ependymoma: H&E stain shows perivascular pseudorosettes.

• Intermediate- to high-grade: Supratentorial ependymomas are commonly grade 2, but 30% are grade 3 (6, 15).
• Benign histology: Benign tumors often have moderate cellularity, low mitotic activity, occasional nuclear atypia, and foci of necrosis and calcification.
• Malignant histology: Malignant tumors show anaplasia, high cellularity, marked mitotic activity, more nuclear atypia, prominent vascular proliferation and necrosis.

Anaplastic ependymoma: H&E stain shows high cellularity, marked mitotic activity, and vascular proliferation.