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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.

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    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.[2,3,4] 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.[5,6,7,8,9,10,11] 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.

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