Supratentorial tumor resembling anaplastic ependymoma in an adolescent

• DOI: 10.1111/bpa.13137
• Publication Date: 2023-01-19T17:31:32Z
• Authors: Margarita Zaytseva; Ludmila Papusha; Agnesa Panferova; Andge Valiakhmetova; Anastasia Shekhtman; Sergey Obydennyi; Igor Kireev; Galina Novichkova; Alexander Druy
• Keywords: Synaptophysin; Ependymoma; Chromogranin A

An 11-year-old previously healthy girl presented with acute cerebral symptoms in the form of headache and vomiting two to three times a day, bringing relief. MRI brain revealed pathological cystic formation left frontoparietal region, an oval shape clear, partly uneven outlines total size 35 × 44 31 mm, intensively accumulating contrast agent along periphery. The lesion exerted pronounced mass effect, displacing median structures right by 9 mm squeezing lateral ventricle (Figure 1). patient underwent gross resection. spinal cord showed no metastatic spread tumor. Cytological examination cerebrospinal fluid malignant cells. received proton therapy on resected tumor bed focal dose 59.4 Gy. Follow-up 11C-methionine PET/CT scans verified remission main disease, lasting 1.6 years (Box Access at https://isn-slidearchive.org/?col=ISN&fol=Archive&file=BPA-22-06-167.svs Morphological composed ovoid cells abundant eosinophilic cytoplasm, forming perivascular pseudorosettes suggesting differential diagnosis between ependymoma astroblastoma. high mitotic activity (up 5 figures 10 visual fields magnification 400×), microvascular proliferation necrosis, Figure 2A. Immunohistochemically, tested positive for GFAP, S100, dot-like EMA, Synaptophysin preserved INI1 expression, 2B. Single nuclei were Olig2. Immunohistochemical tests Chromogranin A, Myelin Basic Protein, Neurofilament, Desmin, Myogenin, MyoD1 negative. Ki67 index reached 20%. morphological immunohistochemical findings suggested anaplastic ependymoma. putative supratentorial was questioned genetic tissue, which identified ZFTA::RELA or YAP1::MAMLD1 fusions PCR. High-throughput genomic sequencing mutations established clinical diagnostic significance H3F3A, BRAF, IDH1/2, TP53, PDGFRA, TERT, CDKN2A/B. DNA methylation profiling thereafter performed, but results intermediate confidence; classified as Neuroepithelial Tumor, PATZ1 fusion-positive borderline score (0.79052) according DKFZ Brain Tumor Classifier version v12.5. highly recurrent MN1::PATZ1 fusion subsequently RNA (TruSeq exome, Illumina), 2D. chimeric oncogene related copy number variations (chromothripsis) Chromosome 22. Given light microscopic appearance suggestive ependymal differentiation, ultrastructural studies performed. Transmission electron microscopy loose arrangement matrix containing dense collagen fibrils 2C). Even hypercellular regions corresponding microscopy, cell-to-cell contacts/junctions not observed. Lumina, cilia, microvilli typical differentiation present. Unusual neoplasm glial (?) harboring fusion, NEC. tumors (NET-PATZ1) are extremely rare, recently recognized, predominantly pediatric CNS tumors. Histologically, these exhibit hypercellularity, rounded spindle cell morphologies, variable nuclear shapes cytoplasm. is typically moderate occasionally high. majority NET-PATZ1 present endothelial about one-third them show necrosis recognized astroblastoma-like pseudorosettes. Despite range histopathology, common signature helps identify [1]. Chromosomal rearrangements involving specific NET-PATZ1. 5′-partner genes rearranged neoplasms (EWSR1 MN1), encode transcription activation domain emerging oncoprotein, also astroblastoma (MN1::BEND2, less frequently EWSR1::BEND2) intracranial myxoid mesenchymal FET-CREB (EWSR1::ATF1, EWSR1::CREB1, EWSR1::CREM) [1, 2]. In contrast, 3′-partner disease-specific: BEND2 found astroblastoma, whereas act oncogenic drivers regardless 5′-fusion partner. Identical have been individual cases extracranial round sarcomas, may coexpression myogenic neurogenic markers (S100, SOX10, GFAP). Although PATZ1-fusion extra-CNS share histopathological features, cellular origin remains uncertain, wavering glioneuronal [2]. our case, investigation absence submicroscopic features addition loosely embedded collagenous stroma, more neoplasms, however On basis layered information complying WHO CNS5, high-throughput molecular technologies apart from examination, primary studied case refined. At time integrated this unusual puzzling completed, had commenced radiotherapy accordance limited regarding long-term prognosis tumors, it decided proceed complete performed equipment supported Nikon Center Excellence Belozersky Institute Physico-Chemical Biology Lomonosov Moscow State University Development program (PNR 5.13). study Foundation support development field Pediatric Hematology, Oncology Immunology "Science Children." investigations Russian Science grant 21-75-00109. authors declare that research conducted any commercial financial relationships could be construed potential conflict interest. Independent Ethics Committee Scientific Council Dmitry Rogachev National Medical Research approved study. Written voluntary consent participation obtained legal representative. confirm data supporting available within article. Raw author, upon reasonable request (see Box