52. FGFR3-TACC3: Case report and review of a potentially targetable diagnostic marker in high grade gliomas

Abstract

Background: FGFR3-TACC3 fusion has been identified in IDH wild-type WHO grade III and IV astrocytomas, with an incidence of 2–3% in most case series and a range of 1–8%. These tumours have characteristic histopathological features and a poor prognosis. The aberrant CD34 immunohistochemical staining and glial and neuronal marker co-expression may lead to a misdiagnosis of a glioneuronal tumour with a better prognosis. An immunohistochemistry antibody to FGFR3 is commercially available which may serve as a more cost-effective screening test for identification of possible FGFR3-TACC3 cases. These tumours may also be amenable to treatment by FGFR tyrosine kinase inhibitors, or through inhibition of oxidative phosphorylation as a down-stream functional target of FGFR3-TACC3 fusion. Aims: A report highlighting common pitfalls in the diagnosis of high grade astrocytoma with FGFR3-TACC3 gene fusion. Methods: A single case study and review of the supporting literature. Results and conclusions: A 64-year-old male with a four month history of focal sensory abnormalities had a solitary 24 mm, intra-axial, contrast-enhancing left parietal lobe brain lesion on MRI. A stereotactic craniotomy and tumour resection was performed. Histopathology showed a malignant heterogeneous tumour. The cellular morphology included gemistocytic features, larger pleomorphic cells and numerous mitotic figures. Additional findings were psammomatous calcifications and thin-walled branching blood vessels with perivascular lymphoid cuffing. Many of the lesional cells co-expressed neuronal and glial protein markers on immunohistochemistry and there was also patchy aberrant CD34 staining. IDH1, IDH2 and BRAF genes were wild-type on molecular pathology testing. There was no loss of chromosome 1p or 19q or EGFR amplification by cytogenetic analysis. The Illumina TP170 next-generation sequencing assay identified a FGFR3-TACC3 gene fusion, a TERT promoter mutation (C250T) and a gain of FGFR3. The diagnosis of anaplastic astrocytoma, WHO grade III, IDH wild-type with FGFR3-TACC3 fusion, TERT promoter mutation and FGFR3 gain was made.