Supratentorial ependymoma, zinc finger translocation-associated fusion positive, with extensive synaptophysin immunoreactivity arising from malignant transformation of clear cell ependymoma: A case report

Abstract

Background: We describe a case of a supratentorial ependymoma, zinc finger translocation-associated (ZFTA) fusion positive with extensive synaptophysin immunoreactivity arising from malignant transformation of an ependymoma with clear cell features in a patient with long-term follow-up. Case Description: A 55-year-old woman presented with seizures and ataxia 15 years after an initial resection of a clear cell ependymoma, Grade 2. Imaging demonstrated an enhancing right paracentral mass and the patient underwent biopsy and resection. Microscopic analysis showed regions of the tumor with morphological and immunohistochemical features typical of ependymoma, including perivascular pseudorosettes and focal dot- like epithelial membrane antigen positivity, as well as high-grade features. In addition, the neoplasm contained large nodular regions of clear cells exhibiting extensive synaptophysin immunoreactivity, suggestive of neural differentiation, and only focally positive immunoreactivity for glial markers. Electron microscopy showed poorly formed and ill-defined junctional complexes, but no cilia, microvilli, or dense granules were seen. Molecular profiling revealed the presence of a fusion between ZFTA (previously known as C11orf95) and RELA fusion. Conclusion: We report a case of extensive synaptophysin immunoreactivity in a ZFTA-RELA fusion-positive ependymoma that had undergone malignant transformation from a clear cell ependymoma and has long-term follow-up, contributing to the assessment of prognostic significance of synaptophysin immunoreactivity in supratentorial ependymoma, ZFTA fusion positive.

Ependymoma‐like tumor with mesenchymal differentiation (ELTMD) with ZFTA:NCOA1 fusion: A diagnostic challenge

“…It is also postulated that the fusion leads to enhanced cytokine production and reduced cellular adhesion. 6 Apart from the common fusion partner for ZFTA (i.e., RELA), there are other less commonly reported fusion partners, including NCOA1, NCOA2, and MAML2. 2 A recent publication reported a novel fusion partner, DUX4.…”

“…12 There have been rare case reports of ependymomas with ZFTA fusion showing expression of neuroendocrine markers, such as synaptophysin, NeuN, and INSM1. 6 It is known that ZFTA zinc fingers in ZFTA:RELA fusions impact oncogenicity. 13 ZFTA:NCOA1/2 fusions have only one ZFTA zinc finger domain in the fusion protein, whereas all previously reported non-RELA ZFTA fusions had four ZFTA zinc fingers.…”

“…The activation of NF‐κB activates various proliferative and antiapoptotic genes, leading to carcinogenesis. It is also postulated that the fusion leads to enhanced cytokine production and reduced cellular adhesion 6 …”

“…The protein p65 is encoded by RELA , while L1CAM expression is linked to NF‐κB pathway activation 12 . There have been rare case reports of ependymomas with ZFTA fusion showing expression of neuroendocrine markers, such as synaptophysin, NeuN, and INSM1 6 …”