Abstract
It has been reported that in-frame FGFR3-TACC3 fusions confer to glioblastomas, IDH-wild type (GBMs, IDHwt) some unusual morphologic features, including monomorphous rounded cells with ovoid nuclei, nuclear palisading, endocrinoid network of “chicken-wire” vessels, microcalcifications and desmoplastic stroma, whose observation may predict the molecular profile of the tumor. We herein present a case of recurrent GBMs, IDHwt, exhibiting some of the above-mentioned morphological features and a molecularly-proven FGFR3-TACC3 fusion. A 56-year-old man presented to our hospital for a recurrent GBM, IDHwt, surgically treated at another center. Histologically, the tumor, in addition to the conventional GBM morphology, exhibited the following peculiar morphologic features: (1) monomorphous neoplastic cells with rounded nuclei and scant pale cytoplasm; (2) thin capillary-like vessels with “chicken-wire” pattern; (3) nuclear palisading; (4) formation of vague perivascular pseudorosettes; (5) spindled tumor cells embedded in a loose, myxoid background. Based on this unusual morphology, molecular analyses were performed and an FGFR3 exon17-TACC3 exon 10 fusion was found. The present case contributes to widening the morphologic spectrum of FGFR3-TACC3-fused GBM, IDHwt and emphasizes that pathologists, in the presence of a GBM, IDHwt with unconventional morphology, should promptly search for this fusion gene.
Highlights
Adult glioblastomas, IDH-wild type comprise a molecularly and histopathologically heterogeneous spectrum of neoplasms, characterized by poor prognosis and frequent resistance to the conventional radio-chemotherapy treatments [1,2,3]
FGFR3-TACC3 fusions are oncogenic drivers that were first reported in GBMs and bladder urothelial carcinomas [17]; in more detail, this unusual fusion was first detected on a series of
The present paper reports an additional case of a recurrent GBM, IDHwt, and FGFR3-TACC3 fused with emphasis on the potential correlation between histopathology and molecular status
Summary
IDH-wild type comprise a molecularly and histopathologically heterogeneous spectrum of neoplasms, characterized by poor prognosis and frequent resistance to the conventional radio-chemotherapy treatments [1,2,3]. Fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil 3 (TACC3) gene fusion was identified as a rare molecular feature in grade 1 to 4 adult diffuse gliomas lacking IDH1/2 mutations but always carrying TERT promoter mutations or CDKN2A loss in about 75% of cases [9, 10]. In the last few years, Bielle et al have described a series of 30 adult high-grade diffuse gliomas, harboring an in-frame FGFR3-TACC3 fusion and exhibiting the conventional molecular alterations of GBMs, IDHwt, but peculiar histopathologic features; interestingly, the following unusual morphological features were found: “monomorphous ovoid nuclei, nuclear palisading, and thin parallel cytoplasmic processes, an endocrinoid network of thin capillaries) associated with frequent microcalcifications and desmoplasia” [14]. Chromosome 10q loss without chromosome seven gain was detected, while no EGFR, MDM2, and CDK4 amplification nor CDKN2A homozygous deletion were found in the analyzed sample
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