Coexisting FGFR3 p.K650T mutation in two FGFR3-TACC3 fusion glioma cases

To the editor, Chromosomal translocations leading to oncogenic fusions are increasingly being recognized as molecular drivers of gliomas [9]. Approximately 3% of glioblastomas (GBMs) carry a fusion involving fibroblast growth factor receptors (FGFR1/FGFR3) with the transforming acidic coiled-coil domains of TACC1 or TACC3. FGFR3-TACC3 fusion gliomas exhibit characteristic, histologic features, including monomorphous ovoid nuclei, nuclear palisading, perivascular pseudorosettes, an endocrinoid (“chicken-wire”) capillary network, microcalcifications and FGFR3 expression [1]. FGFR3-TACC3 fusion gliomas are IDH1/IDH2-wildtype, and frequently (~ 75% of cases) have TERT promoter mutations or CDKN2A loss [1]. The histologic features of FGFR3-TACC3 fusion glioma are similar to those in the recently described polymorphous low-grade neuroepithelial tumor of the young (PLNTY) [2, 4]. In fact, the majority of PLNTYs in some series carry the FGFR3-TACC3 fusion. Although rare reports of PLNTY occurring in adults exist, the majority of PLNTYs occur in young patients [7]. Although FGFR3TACC3 fusion gliomas share histologic features with PLNTY, and may also express CD34, the former typically exhibits high-grade features consonant with glioblastoma and has a mean age at diagnosis of 62 years [1]. Here we describe two cases of infiltrating glioma with histologic features of FGFR3-TACC3 fusion glioma. Molecular characterization confirmed the presence of FGFR3p.K650 T, TERT promoter mutation, and FGFR3-TACC3 fusion in both cases. The cases call attention to an association between the FGFR3p.K650 T mutation and FGFR3-TACC3 fusion.