Update: Ependymoma RELA fusion positive

Ependymoma RELA fusion positive

Ependymoma RELA fusion-positive is a accepted variant of ependymoma, only recognised in the World Health Organization Classification of Tumors of the Central Nervous System 2016 1).

Epidemiology

They are the most common type of supratentorial ependymoma in children, and not found in the posterior fossa or spinal cord.

Two-thirds of supratentorial (ST) ependymomas harbor oncogenic fusions of RELA.

Outcome

The protein product is the principal effector of canonical Nuclear factor kappa signaling. RELA fusion proteins activate signaling for tumor proliferation and malignant progression, resulting in poorer prognoses in these patients compared to those in patients with other ST ependymomas.

In a study, Nakamura et al. encountered a case of C11orf-RelA fusion-positive ST anaplastic ependymoma that was diagnosed in first tumor resection surgery of multi-staged gross total resection with molecular evidence. In ependymomas, regardless of tumor location or pathological grade, subtotal resection is associated with higher rates of mortality compared with GTR 2).

In posterior fossa ependymoma group A (PF-EPN-A) tumors, telomerase activity varied and was significantly associated with dismal overall survival, whereas telomerase reactivation was present in all supratentorial RelA fusion-positive (ST-EPN-RELA) ependymomas 3).

Pathology

These tumours can be both grade II or III and demonstrate a variety of histological morphologies, although clear cells and prominent vascularity are common.

The presence of the RELA fusion gene can be assessed with FISH.

Immunophenotype

GFAP positive

EMA positive

L1CAM positive correlates closely with the presence of RELA fusion not exclusive to ependymomas.

Treatment

Actinomycin D could constitute a promising therapeutic option for Ependymoma RELA fusion positive, whose tumours frequently exhibit p53 inactivation 4).

Case reports

2017

A case of aggressive anaplastic ependymoma arising in the right frontoparietal lobe, which had genetically 1q25 gain, CDKN2A homozygous deletion, and L1CAM overexpression. The patient was a 10-year-old boy who underwent four times of tumor removal and seven times of gamma knife surgery. Metastatic loci were scalp and temporalis muscle overlying primary operation site, lung, liver, buttock, bone, and mediastinal lymph nodes. He had the malignancy for 10 years and died. This tumor is a representative case of Ependymoma RELA fusion positive, showing aggressive behavior 5).

1)

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016 Jun;131(6):803-20. doi: 10.1007/s00401-016-1545-1. Epub 2016 May 9. Review. PubMed PMID: 27157931.

2)

Nakamura T, Fukuoka K, Ikeda J, Yoshitomi M, Udaka N, Tanoshima R, Tateishi K, Yamanaka S, Ichimura K, Yamamoto T. Encouraging option of multi-staged gross total resection for a C11orf-RelA fusion-positive supratentorial anaplastic ependymoma. Brain Tumor Pathol. 2017 Oct;34(4):160-164. doi: 10.1007/s10014-017-0297-5. Epub 2017 Aug 22. PubMed PMID: 28831588.

3)

Gojo J, Lötsch D, Spiegl-Kreinecker S, Pajtler KW, Neumayer K, Korbel P, Araki A, Brandstetter A, Mohr T, Hovestadt V, Chavez L, Kirchhofer D, Ricken G, Stefanits H, Korshunov A, Pfister SM, Dieckmann K, Azizi AA, Czech T, Filipits M, Kool M, Peyrl A, Slavc I, Berger W, Haberler C. Telomerase activation in posterior fossa group A ependymomas is associated with dismal prognosis and chromosome 1q gain. Neuro Oncol. 2017 Sep 1;19(9):1183-1194. doi: 10.1093/neuonc/nox027. PubMed PMID: 28371821; PubMed Central PMCID: PMC5570194.

4)

Tzaridis T, Milde T, Pajtler KW, Bender S, Jones DT, Müller S, Wittmann A, Schlotter M, Kulozik AE, Lichter P, Peter Collins V, Witt O, Kool M, Korshunov A, Pfister SM, Witt H. Low-dose Actinomycin-D treatment re-establishes the tumoursuppressive function of P53 in RELA-positive ependymoma. Oncotarget. 2016 Sep 20;7(38):61860-61873. doi: 10.18632/oncotarget.11452. PubMed PMID: 27556362; PubMed Central PMCID: PMC5308696.

5)

Kim SI, Lee Y, Kim SK, Kang HJ, Park SH. Aggressive Supratentorial Ependymoma, RELA Fusion-Positive with Extracranial Metastasis: A Case Report. J Pathol Transl Med. 2017 Nov;51(6):588-593. doi: 10.4132/jptm.2017.08.10. Epub 2017 Nov 15. PubMed PMID: 29161788.

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