Abstract
Although ependymomas (EPNs) have similar histopathology, they are heterogeneous tumors with diverse immunophenotypes, genetics, epigenetics, and different clinical behavior according to anatomical locations. We reclassified 141 primary EPNs from a single institute with immunohistochemistry (IHC) and next-generation sequencing (NGS). Supratentorial (ST), posterior fossa (PF), and spinal (SP) EPNs comprised 12%, 41%, and 47% of our cohort, respectively. Fusion genes were found only in ST-EPNs except for one SP-EPN with ZFTA-YAP1 fusion, NF2 gene alterations were found in SP-EPNs, but no driver gene was present in PF-EPNs. Surrogate IHC markers revealed high concordance rates between L1CAM and ZFTA-fusion and H3K27me3 loss or EZHIP overexpression was used for PFA-EPNs. The 7% cut-off of Ki-67 was sufficient to classify EPNs into two-tiered grades at all anatomical locations. Multivariate analysis also delineated that a Ki-67 index was the only independent prognostic factor in both overall and progression-free survivals. The gain of chromosome 1q and CDKN2A/2B deletion were associated with poor outcomes, such as multiple recurrences or extracranial metastases. In this study, we propose a cost-effective schematic diagnostic flow of EPNs by the anatomical location, three biomarkers (L1CAM, H3K27me3, and EZHIP), and a cut-off of a 7% Ki-67 labeling index.
Highlights
IntroductionEpendymomas (EPNs) are uncommon neuroepithelial malignancies, constituting approximately 2% of the central nervous system (CNS) tumors and about 6.8% of all gliomas [1]
Ependymomas (EPNs) are uncommon neuroepithelial malignancies, constituting approximately 2% of the central nervous system (CNS) tumors and about 6.8% of all gliomas [1]. They can occur at any age and are the third most common CNS tumors in children [2]. 2016 World Health Organization (WHO) classification subdivided EPNs mostly based on histology and included only one genetically defined EPN subtype, EPN, RELA fusion-positive [3], and it has been noted that the WHO grades do not reflect biological behavior and patient outcomes [4]
All PF-EPN; group A (PFA)-EPNs occurred in children (0– to 16-year-old, median: 2.8-year-old), except for one clear cell PFA-EPN, occurring in a 38-year-old woman, while 100% of PFB-EPNs and 89% of SP-EPNs occurred in adults
Summary
Ependymomas (EPNs) are uncommon neuroepithelial malignancies, constituting approximately 2% of the central nervous system (CNS) tumors and about 6.8% of all gliomas [1]. The cIMPACT- update 7 and the 2021 WHO classification of tumors of the CNS classify EPNs by a combination of anatomic site, molecular genetics, epigenetics, and histological features [6, 7]. According to these updates, anatomic sites, e.g., ST, PF, and SP, should add to the diagnostic term, EPN. Histology- or molecularly defined EPN grades still have pitfalls as there are no clear criteria established for WHO grades 2 and 3
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