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MRI Phenotype of RELA-fused Pediatric Supratentorial Ependymoma

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Abstract

Purpose

Epigenetic profiling has recently identified clinically and molecularly distinct subgroups of ependymoma. The 2016 World Health Organization (WHO) classification recognized supratentorial ependymomas (ST-EPN) with REL-associated protein/p65 (RELA) fusion as a clinicopathological entity. These tumors represent 70% of pediatric ST-EPN characterized by recurrent C11orf95-RELA fusion transcripts, which lead to pathological activation of the nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NF-κB) signaling pathway. Cyclin-dependent kinase inhibitor 2A (CDKN2A) inactivation has also been reported to correlate with poor prognosis. Here, we systematically describe magnetic resonance imaging (MRI) characteristics of RELA-fused ST-EPN, with respect to CDKN2A deletion status.

Methods

Our cohort of patients with ST-EPN (n = 57) was obtained from the database of the German Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), and tumors were diagnosed according to the 2016 WHO classification. Molecular characterization identified 47 RELA-fused tumors. We analyzed the preoperative MRI according to standardized criteria, and comparison was performed between CDKN2A altered (n = 21) and CDKN2A wild type (n = 26) tumors.

Results

The RELA-fused ST-EPN showed a spectrum of predominantly hemispheric tumors with cysts and necrosis. Statistical analysis on CDKN2A status revealed significant differences in terms of younger manifestation age (p =0.002) and more intratumoral hemorrhage in T2-weighted imaging (T2WI) (p =0.010) in wild type tumors; however, the location was not a parameter for differentiation.

Conclusion

This study first provides comprehensive MRI data for RELA-fused ST-EPN as a distinct entity, with further interest on CDKN2A genomic status. Patient stratification by morphological MRI alone seems difficult at present. The results may support ongoing research in ST-EPN within the framework of the radiogenomics concept.

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Acknowledgements

This work was supported by the German Childhood Cancer Foundation.

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Authors and Affiliations

  1. Reference Center for Neuroradiology, Institute for Diagnostic and Interventional Neuroradiology, University Hospital of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany

    Johannes Nowak, Carolin Seidel, Annika Hohm & Monika Warmuth-Metz

  2. Department of Diagnostic and Interventional Radiology, University Hospital of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany

    Johannes Nowak & Henner Huflage

  3. Department of Neuropathology, Brain Tumor Reference Center of the DGNN, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Stephanie Theresa Jünger & Torsten Pietsch

  4. Departments of Radiology and Pathology, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth St, MA 02129, Charlestown, USA

    Lindsey A. Vandergrift

  5. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Katja von Hoff & Stefan Rutkowski

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  1. Johannes Nowak
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Correspondence to Johannes Nowak.

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Conflict of interest

J. Nowak, S.T. Jünger, H. Huflage, C. Seidel, A. Hohm, L.A. Vandergrift, K. von Hoff, S. Rutkowski, T. Pietsch and M. Warmuth-Metz declare that they have no competing interests.

Caption Electronic Supplementary Material

62_2018_704_MOESM1_ESM.jpg

Fig. S1: Representative histology and immunohistochemical reaction for p65RelA and p16 protein expression in two cases with RELA-positive anaplastic ependymomas (WHO grade III). HE (Hematoxylin/Eosin) histology shows vascular proliferations in both cases (arrows). Both samples display the characteristic nuclear accumulation of p65RelA. Case #1 lost p16 protein indicating CDKN2A gene loss. p16 is only detected in normal cells such as endothelial cells (arrow). In contrast, case #2 shows retained p16 expression in the tumor cell nuclei (arrow)

62_2018_704_MOESM2_ESM.jpg

Fig. S2: MR images of two RELA-fused ST-EPN with and without CDKN2A deletion. Patient 1 (A–C, CDKN2A deleted = del, GE Signa 1.5 T), manifestation age: 9yr 7 m, with no signs for hemorrhage. Patient 2 (D–F, CDKN2A wild type = WT, Siemens Vision 1.5 T), manifestation age: 5yr 5 m, shows signs for hemorrhage in T2WI (white arrow in E), confirmed in T1 (D) and T2* (F)

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Nowak, J., Jünger, S.T., Huflage, H. et al. MRI Phenotype of RELA-fused Pediatric Supratentorial Ependymoma. Clin Neuroradiol 29, 595–604 (2019). https://doi.org/10.1007/s00062-018-0704-2

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