Histopathologic Classification of Childhood Ependymal Tumors

In the most recent World Health Organization (WHO) classification of brain tumors, ependymal tumors are classified into four main subtypes:[1]

• Subependymoma (WHO Grade I).

• Myxopapillary ependymoma (WHO Grade I).

• Ependymoma (WHO Grade II). Variants include cellular, papillary, tanycytic, clear cell, and mixed.

• Anaplastic (also known as malignant) ependymoma (WHO Grade III).

The subependymoma is a slow-growing benign neoplasm, typically attached to the ventricle wall, and is composed of glial tumor cell clusters embedded in a fibrillary matrix. The myxopapillary ependymoma arises almost exclusively in the location of the conus medullaris, cauda equina, and filum terminale of the spinal cord, and is characterized histologically by tumor cells arranged in a papillary manner around vascularized myxoid stromal cores.

The ependymoma, which is considered a Grade II neoplasm originating from the walls of the ventricles or from the spinal canal, is composed of neoplastic ependymal cells. Ependymomas are subdivided, based on histological findings, into four subtypes:

• Cellular ependymoma — the most common subtype; usually demonstrates significant cellularity without an increase in mitotic activity.
• Papillary ependymoma — forms linear, epithelial-like surfaces along cerebrospinal fluid exposures.
• Clear cell ependymoma — displays an oligodendroglial-like appearance with perinuclear halos; this variant is preferentially located in the supratentorial compartment of the brain.
• Tanycytic ependymoma — the rarest form of Grade II ependymoma; most commonly found in the spinal cord; tumor cells are arranged in fascicles of variable width and cell density and poorly intertwined.

The anaplastic ependymoma is considered a malignant glioma of ependymal differentiation and, compared to the Grade II ependymomas, shows increased cellularity and increased mitotic activity, often associated with microvascular proliferation and pseudopalisading necrosis.

In children, approximately 65% to 75% of ependymomas arise in the posterior fossa. Believed to arise from radial glia cells, supratentorial and infratentorial ependymomas have different genomic, gene expression, and immunohistochemical signatures.[2-4] Supratentorial tumors are characterized by neuronal differentiation.[3]

Subependymomas and myxopapillary ependymomas are usually considered to be different than the Grade II and Grade III ependymomas. In Grade II and Grade III ependymomas, the relationship between histological features and survival has varied between studies, although most recent larger studies and meta-analyses have demonstrated that histological grade is an independent predictor of event-free survival.[5-11] A single institution study suggests that patients with clear-cell ependymomas may be at higher risk for treatment failure than patients with other forms of Grade II ependymomas;[12] however, confirmation is required in the larger group of unselected patients.

Ependymoblastomas, which generally behave more like medulloblastomas or cerebral neuroectodermal tumors, are considered separate entities from ependymomas and are now classified with the embryonal tumors.[1,5] (Refer to the PDQ summary on Childhood Central Nervous System Embryonal Tumors for more information.)

The pathologic classification of pediatric brain tumors is a specialized area that is undergoing evolution; review of the diagnostic tissue by a neuropathologist who has particular expertise in this area is strongly recommended.

1. Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007. 
   
   
2. Taylor MD, Poppleton H, Fuller C, et al.: Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8 (4): 323-35, 2005.  [PUBMED Abstract]
   
   
3. Andreiuolo F, Puget S, Peyre M, et al.: Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro Oncol 12 (11): 1126-34, 2010.  [PUBMED Abstract]
   
   
4. Grill J, Bergthold G, Ferreira C: Pediatric ependymomas: will molecular biology change patient management? Curr Opin Oncol 23 (6): 638-42, 2011.  [PUBMED Abstract]
   
   
5. Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007.  [PUBMED Abstract]
   
   
6. Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 19 (6): 1497-502, 1990.  [PUBMED Abstract]
   
   
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8. Chiu JK, Woo SY, Ater J, et al.: Intracranial ependymoma in children: analysis of prognostic factors. J Neurooncol 13 (3): 283-90, 1992.  [PUBMED Abstract]
   
   
9. Pollack IF, Gerszten PC, Martinez AJ, et al.: Intracranial ependymomas of childhood: long-term outcome and prognostic factors. Neurosurgery 37 (4): 655-66; discussion 666-7, 1995.  [PUBMED Abstract]
   
   
10. Tihan T, Zhou T, Holmes E, et al.: The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factors. Mod Pathol 21 (2): 165-77, 2008.  [PUBMED Abstract]
    
    
11. Shu HK, Sall WF, Maity A, et al.: Childhood intracranial ependymoma: twenty-year experience from a single institution. Cancer 110 (2): 432-41, 2007.  [PUBMED Abstract]
    
    
12. Fouladi M, Helton K, Dalton J, et al.: Clear cell ependymoma: a clinicopathologic and radiographic analysis of 10 patients. Cancer 98 (10): 2232-44, 2003.  [PUBMED Abstract]