Ependymoma classification

Ependymoma classification

World Health Organization Classification of Tumors of the Central Nervous System 2021 stratifies ependymoma (EPN) into nine molecular subgroups according to the anatomic locations which outperform histological grading.

Supratentorial ependymoma

Supratentorial ependymoma ZFTA fusion-positive

Supratentorial ependymoma YAP1 fusion-positive

Posterior fossa ependymoma

Posterior fossa ependymoma group PFA

Posterior fossa ependymoma group PFB

Spinal ependymoma

Spinal ependymoma MYCN-amplified

Myxopapillary ependymoma

Subependymoma

Chinnam et al. aimed at molecularly reclassifying 200 EPN using immunohistochemistry (IHC) and sequencing for ZFTA fusions in supratentorial (ST) EPN. Further, they assessed the utility of L1CAM, cyclinD1, and p65 markers in identifying ZFTA fusion. Demographic profiles, histologic features, molecular subgroups, and clinical outcomes were retrospectively analyzed. IHC for L1CAM, cyclinD1, p65, H3K27me3, and H3K27M and sequencing for ZFTA fusion was performed. ZFTA fusions were identified in 44.8% of ST EPN. p65 displayed the highest specificity (93.8%), while L1CAM had the highest sensitivity (92.3%) in detecting ZFTA fusions. The negative predictive value approached 96.6% and sensitivity improved to 96.2% with combinatorial IHC (L1CAM, cyclinD1, p65). H3K27me3 loss (PF-A) was noted in 65% PF EPN. Our results provide evidence that a combination of two or three (L1CAM, p65, and cyclinD1) can be used as surrogate markers for predicting fusion. ZFTA fusion, and its surrogate markers in ST, H3K27me3 and younger age (< 5 years) in PF showed a significant correlation with PFS and OS on univariate and Kaplan-Meier analysis. On multivariate analysis, H3K27me3 loss and younger age group are associated with poor clinical outcomes 1).

Intracranial ependymoma.

Spinal cord ependymoma.

see Ependymal tumors classification.


In a review, Lee et al. describe the genetic differences between spinal ependymomas and their intracranial counterparts to better understand their prognosis. From the literature review, many studies have reported that spinal cord ependymoma might be associated with NF2 mutation, NEFL overexpression, Merlin loss, and 9q gain. In myxopapillary ependymoma, NEFL and HOXB13 overexpression were reported to be associated. Prior studies have identified HIC-1 methylation, 4.1B deletion, and 4.1R loss as common features in intracranial ependymoma. Supratentorial ependymoma is usually characterized by NOTCH-1 mutation and p75 expression. TNC mutation, no hypermethylation of RASSF1A, and GFAP/NeuN expression may be diagnostic clues of posterior fossa ependymoma. Although MEN1, TP53, and PTEN mutations are rarely reported in ependymoma, they may be related to a poor prognosis, such as recurrence or metastases. Spinal ependymoma has been found to be quite different from intracranial ependymoma in genetic studies, and the favorable prognosis in spinal ependymoma may be the result of the genetic differences. A more detailed understanding of these various genetic aberrations may enable the identification of more specific prognostic markers as well as the development of customized targeted therapies 2).

Ependymoblastoma, an aggressive embryonal tumor containing multilayered (ependymoblastic) rosettes in addition to primitive small round blue cells, is now considered a form of primitive neuroectodermal tumor.

Histopathological classification is not sufficient to show variable outcomes, and fails to show prognostic markers of the diverse outcomes; hence, it is essential to understand biological mechanisms.

see Perivascular Pseudorosettes.


1)

Chinnam D, Gupta K, Kiran T, Saraswati A, Salunke P, Madan R, Kumar N, Radotra BD. Molecular subgrouping of ependymoma across three anatomic sites and their prognostic implications. Brain Tumor Pathol. 2022 Mar 29. doi: 10.1007/s10014-022-00429-2. Epub ahead of print. PMID: 35348910.
2)

Lee CH, Chung CK, Ohn JH, Kim CH. The Similarities and Differences between Intracranial and Spinal Ependymomas : A Review from a Genetic Research Perspective. J Korean Neurosurg Soc. 2016 Mar;59(2):83-90. doi: 10.3340/jkns.2016.59.2.83. Epub 2016 Feb 29. Review. PubMed PMID: 26962412.

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