Ependymal Tumors - Introduction

Ependymal Tumors

• 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

2021 WHO Classification

• 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

Supratentorial Ependymomas

• 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

Posterior Fossa Ependymomas

• 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

Spinal Ependymomas

• 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)

Histologic Patterns

• 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

Cytology

• 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

Immunophenotype

• 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

Treatment and Prognosis

• 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%