Histological features in pediatric central nervous system tumors with FGFR alterations. 2020

Ahmed Gilani, and Kurtis Davies, and Bette Kleinschmidt-DeMasters
University of Colorado Anschutz Medical Campus, United States.

BACKGROUND Identification of genetic alterations in central nervous system (CNS) tumors provides diagnostic and prognostic information and allows identification of potential therapeutic targets. Next-generation sequencing (NGS) technologies currently used for molecular testing are costly and remain largely limited to major academic centers or reference labs. Identification of histologic or immunohistochemical correlates for particular molecular alterations can serve as surrogates and can help triage cases for subsequent NGS-based confirmation. Recently, adult IDH-wildtype adult glioblastomas (GBMs) with fibroblast growth factor receptor (FGFR) gene alterations were reported to show palisading monomorphic cells, delicate arcuate vasculature, and microcalcifications. We explored whether pediatric tumors with FGFR fusion also show these histologic features and whether these features could predict the presence of this gene alteration. METHODS We reviewed pediatric CNS tumors with FGFR-fusions to retrospectively determine the presence/absence of the above-mentioned histological features in fusion-positive tumors. RESULTS 10 pediatric tumors with FGFR fusions were identified. Pediatric tumors demonstrated histologic and tumor type diversity, with diagnoses of pilocytic/pilomyxoid astrocytoma, pediatric-type oligodendroglioma, anaplastic astrocytoma, polymorphous low-grade neuroepithelial tumor of the young, rosette-forming glioneuronal tumor, and extraventricular neurocytoma. CONCLUSIONS Pediatric FGFR-fused CNS tumors demonstrate histologic features similar to their adult counterparts but also exhibit significant morphologic variability. As such, this histologic variability prevents the prediction of FGFR fusion and necessitates molecular testing for the identification of this alteration.

UI MeSH Term Description Entries
D008297 Male Males
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012189 Retrospective Studies Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. Retrospective Study,Studies, Retrospective,Study, Retrospective
D016543 Central Nervous System Neoplasms Benign and malignant neoplastic processes that arise from or secondarily involve the brain, spinal cord, or meninges. CNS Neoplasm,CNS Neoplasms,Central Nervous System Neoplasm,Central Nervous System Tumor,Neoplasms, Central Nervous System,Primary Central Nervous System Neoplasm,Central Nervous System Neoplasms, Primary,Central Nervous System Tumors,Primary Central Nervous System Neoplasms,Tumors, Central Nervous System,Neoplasm, CNS,Neoplasms, CNS
D017468 Receptors, Fibroblast Growth Factor Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity. FGF Receptor Complex,FGF Receptor Complexes,FGF Receptors,Fibroblast Growth Factor Receptors,Receptors, FGF,FGF Receptor,Fibroblast Growth Factor Receptor,Heparin-Binding Growth Factor Receptor,Heparin Binding Growth Factor Receptor,Receptor, FGF
D050596 Oncogene Fusion The GENETIC RECOMBINATION of the parts of two or more GENES, including an ONCOGENE as at least one of the fusion partners. Such gene fusions are often detected in neoplastic cells and are transcribed into ONCOGENE FUSION PROTEINS. Oncogene Fusions

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