case_images: PMC4729030_01
case_images: a Coronal T2 FLAIR highlights the intra-parenchymal location of the complex tumor resection bed and associated edema. b Axial post contrast T1 MRI showing peripheral ring enhancement and progression from previous post-surgical imaging (right). c H&E sections showing a hypercellular fibrillary neoplasm with morphological atypia, mitoses, and endothelial proliferation. Necrosis was also present (not shown). The tumor showed diffuse expression of the glial markers Olig2, Sox2 and GFAP. Immunoreactivity with antibody against the R132H IDH1 mutation. ATRX immunostaining highlighting loss within the tumor and normal retained expression in a adjacent vessel. Immunohistochemistry with the STAT6 antibody showing strong nuclear expression in 15-20 % of tumor nuclei (inset) consistent with previous described function of NAB2-STAT6 fusion event. d Schematic demonstrating the locations of common NAB2-STAT6 rearrangements in solitary fibrous tumor (SFTs), the presented case GBM and other STAT6 rearrangements reported in GBMs
case_images: 13000_2016_455_Fig1_HTML.jpg
case_images: PMC4729030_01_13000_2016_455_Fig1_HTML.jpg
case_images: Fig1
case_images: A previously healthy 29-year-old male presented to an outside hospital with a symptomatic intra-axial enhancing right parietal brain lesion necessitating surgical management and adjuvant temozolomide (Fig. 1a, b). Histology showed a densely cellular infiltrating glial neoplasm comprised of severely atypical cells with mitoses, vascular proliferation and necrosis consistent with GBM (Fig. 1c). MIB1 proliferation index of >30 % (Fig. 1c). MGMT methylation testing revealed that the tumor was positive for promoter methylation. TP53 (p.Y126_splice), ATRX (p.R1302fs*), HNF1A (p.R263H) and NF1 (p.H2592del) variants, several variants of unknown significance, and a NAB2-STAT6 fusion involving exon 3 of NAB2 and exon 18 of STAT6 (Fig. 1d, Table 1). This rearrangement has not previously been reported outside the context of solitary fibrous tumors (SFTs). SFTs, fusion products are variable, but typically involve exons 6/7 of NAB2 and exons 17/18 of STAT6 (Fig. 1d). Similar to the functional consequence of this fusion product in SFTs, we confirmed that this novel NAB2-STAT6 fusion detected in our GBM patient resulted in strong STAT6 nuclear localization (Santa Cruz, catalog #sc-621), however this was present in only a subpopulation of cells (Fig. 1c).