Ependymal Tumors

Study Notes

Represent a broad group of gliomas that manifest morphologic and ultra-structural evidence of ependymal differentiation
Account for 5% to 9% of all primary brain tumors in adults, 6% to 12% in children, and up to 30% in infants
Originate from radial glial-like stem cells lining the wall of the ventricles or the wall of the spinal canal
Can occur along the entire neuroaxis

Ependymomas categorized based on location and molecular alteration into molecular groups across the supratentorial, posterior fossa, and spinal compartments
Two molecularly defined types of supratentorial ependymoma (with ZFTA or YAP1 fusion)
Two molecularly defined types of posterior fossa ependymoma (PFA and PFB)
One spinal ependymoma defined by the presence of MYCN amplification

ZFTA fusion-positive ependymomas: more common (25-58% of all supratentorial ependymomas in adults and 66-84% in children)
Homozygous deletion of CDKN2A/B can have a negative impact on prognosis
YAP1 fusion-positive ependymomas: rare, tend to occur primarily in young children, and show more indolent behavior

PFA ependymoma: characterized by loss of H3K27me3 due to overexpression of EZHIP or H3 p.K27M mutation
PFB ependymoma: characterized by retention of nuclear histone H3K27me3, and exhibits a characteristic DNA methylation profile

Frequently show loss of chromosome 22q and mutations of NF2
Associated with a favorable outcome in children and adults
Patients with neurofibromatosis type 2 develop spinal ependymomas (often multiple)

Papillary variant: characterized by papillary structures with gliofibrillary stroma
Tanycytic variant: characterized by a predominance of epithelial-like (cuboidal to columnar) cells lining papillae and fingerlike projections
Other rare patterns: extensive tumor cell vacuolation and signet ring formation, extensive hyalinization/sclerosis, lipomatous metaplasia, widespread pleomorphic giant cells, and melanotic differentiation

Ependymomas are cellular tumors that smear in fibrillar tissue fragments with discohesive sheets of relatively small and uniform cells
Pseudorosettes are responsible for the "arboreal" or "caterpillar" appearance seen in smears
Anaplastic (WHO grade 3) ependymomas show crowded tissue fragments with tumor cells displaying dark and irregular nuclei

Ependymomas typically express S100 protein, GFAP, and vimentin
EMA often shows a characteristic dot-like perinuclear or ring-like pattern of cytoplasmic positivity
CD99, D2-40 (podoplanin), and CD56 (NCAM) are also frequently positive

Complete surgical resection and second-look surgery for resection of residual tumor are increasingly advocated
Postoperative radiotherapy is considered the standard of care for lowering risk of recurrence
Poor prognostic factors include a fourth ventricular location, grade 3 tumors (formerly known as anaplastic), and incomplete resection
Children have a worse prognosis (both fourth ventricular location and anaplastic variant are more common in children)
Overall, the 5-year survival rate in children ranges from 50% to 75%