PMC7738346_01
Pre-operative T1-weighted (A) and T2-weighted (B) magnetic resonance images showing a solid cystic mass with heterogeneous hyperintensity and surrounding edema. Histologically, the tumor was comprised of poorly differentiated/undifferentiated cells with neuropils and proliferated endothelial cells, but no typical true rosettes (C). Some tumor cells were small, round, and poorly-differentiated, whereas some cells presented with atypia as well as rough and dark chromatin. Mitotic figures and apoptotic bodies were easily identified under HPF x400 (D). Immunohistochemically, the tumor cells were synaptophysin positive (E), and the Ki67 index was >50% (F). The C19MC locus showed no alteration (G) compared with the positive amplification positive control (H).
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Brain magnetic resonance imaging (MRI) scans revealed a solid cystic mass with lesions in the left temporal lobe-basal ganglia-corona radiate, midline shifted to the right, and nodules in the left parietal lobe (maximum diameter, 75 mm) ( Figures 1A, B ). The tumor was comprised of diffuse undifferentiated embryonal cells with neuropils, but no true rosettes ( Figures 1C, D ). By immunochemistry, cells were negative for glial fibrillary acidic protein (GFAP) and strongly positive for synaptophysin (Syn) ( Figure 1E ). The Ki67 proliferation index was high (>50%) ( Figure 1F ), and fluorescence in situ hybridization (FISH) results showed no change in the copy number at the 19q13.42 C19MC locus ( Figures 1G, H ).
Next generation sequencing (NGS) revealing (A) a CIC-LEUTX gene fusion in exon 20 of the CIC gene and exon 3 of the LEUTX gene, (B) a germline NBN c.C127T variant, and (C) a somatic TSC2 c.G2714A variant (D). (E) Copy number variation (CNV) of the CIC gene was highest in the whole genome. (F) The CIC gene was amplified 4.85-fold on chromosome 19. (G) The unaffected father of the patient carried the heterozygous NBN c.C127T mutation, (H) whereas the healthy mother did not.
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We found a fusion of CIC-LEUTX genes with breakpoints located in exon 20 of the CIC gene and exon 3 of the LEUTX gene ( Figures 2A, B ). In addition, a somatic mutation in the TSC2 gene ( Figure 2C ) and a germline mutation in the NBN gene ( Figure 2D ) were also identified. Copy number variation (CNV) showed the CIC gene to be amplified 4.85-fold on chromosome 19 ( Figures 2E, F ). Further studies by Sanger sequencing revealed that the patient's father, and not his mother, was a carrier of the NBN heterozygous mutation ( Figures 2G, H ).