World Health Organization Classification of Tumors of the Central Nervous System 2021
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.
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).
Spinal cord ependymoma
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.