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Acta Neuropathol. 2019 Nov 2. doi: 10.1007/s00401-019-02090-0. [Epub ahead of print]

Molecular characterization of histopathological ependymoma variants.

Author information

1
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. ju.neumann@uke.de.
2
II. Medizinische Klinik und Poliklinik, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
3
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.
4
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
5
Institute of Neuropathology, University Hospital Münster, Münster, Germany.
6
Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.
7
German Center for Neurodegenerative Diseases, Munich, Germany.
8
Department of Neuropathology, Institute of Pathology, University Hospital, Heidelberg and Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
10
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
11
Institute of Pathology, University of Basel, Basel, Switzerland.
12
Department of Neuropathology, Institute of Pathology, University of Würzburg, Würzburg, Germany.
13
Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
14
Division of Pediatric Neuro-Oncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
15
Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
16
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
17
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. u.schueller@uke.de.
18
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. u.schueller@uke.de.
19
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany. u.schueller@uke.de.

Abstract

According to the WHO classification, ependymal tumors are classified as subependymomas, myxopapillary ependymomas, classic ependymomas, anaplastic ependymomas, and RELA-fusion-positive ependymomas (RELA-EPN). Among classic ependymomas, the WHO defines rare histological variants, i.e., the clear cell, papillary, and tanycytic ependymoma. In parallel, global DNA methylation patterns distinguish nine molecular groups, some of which tightly overlap with histopathological subgroups. However, the match of the aforementioned histological variants to DNA methylation classes remains unclear. We analyzed histomorphology, clinical parameters, and global DNA methylation of tumors with the initial histological diagnoses of tanycytic (n = 12), clear cell (n = 14), or papillary ependymoma (n = 19). Forty percent of these tumors did not match to the epigenetic profile of ependymomas, using a previously published DNA methylation-based classifier for brain tumors. Instead, they were classified as low-grade glioma (n = 3), plexus tumor (n = 2), CNS high-grade neuroepithelial tumor with MN1 alteration (n = 2), papillary tumor of the pineal region (n = 2), neurocytoma (n = 1), or did not match to any known brain tumor methylation class (n = 8). Overall, integrated diagnosis had to be changed in 35.6% of cases as compared to the initial diagnosis. Among the tumors molecularly classified as ependymoma (27/45 cases), tanycytic ependymomas were mostly located in the spine (5/7 cases) and matched to spinal or myxopapillary ependymoma. 6/8 clear cell ependymomas were found supratentorially and fell into the methylation class of RELA-EPN. Papillary ependymomas with a positive ependymoma match (12/19 cases) showed either a "papillary" (n = 5), a "trabecular" (n = 1), or a "pseudo-papillary" (n = 6) growth pattern. The papillary growth pattern was strongly associated with the methylation class B of posterior fossa ependymoma (PFB, 5/5 cases) and tumors displayed DNA methylation sites that were significantly different when compared to PFB ependymomas without papillary growth. Tumors with pseudo-papillary histology matched to the methylation class of myxopapillary ependymoma (4/6 cases), whereas the trabecular case was anatomically and molecularly a spinal ependymoma. Our results show that the diagnosis of histological ependymoma variants is challenging and epigenetic profiles may improve diagnostic accuracy of these cases. Whereas clear cell and papillary ependymomas display correlations between localization, histology, and methylation, tanycytic ependymoma does not represent a molecularly distinct subgroup.

KEYWORDS:

Clear cell; Ependymoma; PFB; Papillary; RELA; Tanycytic

PMID:
31679042
DOI:
10.1007/s00401-019-02090-0

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