Glioblastoma, IDH-Wild Type With FGFR3-TACC3 Fusion: When Morphology May Reliably Predict the Molecular Profile of a Tumor. A Case Report and Literature Review

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.

Keywords: FGFR3-TACC3 fusion; IDH-wildtype; diagnosis; glioblastoma; high-grade glioma; molecular biology; unusual morphological features.

Figure 1

(A) Preoperative axial section of a T1 w MRI after gadolinium injection revealing a left parieto-occipital recurrent lesion with infiltration of the splenium of the corpus callosum. (B) Postoperative axial section of a T1 w MRI after gadolinium injection revealing the complete resection of the enhancing nodule.

Figure 2

(A) Low magnification showing the conventional morphology of WHO grade IV glioblastoma, IDH-wild type: a moderately cellular astrocytic tumor with foci of pseudopalisading necrosis (hematoxylin and eosin; original magnification 150x); (B) Tumor exhibits, as an unusual morphologic feature, more bland-looking areas composed of monomorphous round-shaped cells and thin capillary-like vessels with “chicken-wire” pattern, arranged in an endocrinoid pattern (insert); these features are also found close to foci of microvascular proliferation [hematoxylin and eosin; original magnifications 150x and 300x (insert)]; (C) Tumor areas with nuclear palisading (lines) are seen (hematoxylin and eosin; original magnification 150x); (D) Spindled neoplastic cells set in a loose, myxoid background, imparting to the tumor a focal “tissue culture-like” morphology (hematoxylin and eosin; original magnification 300x).

Figure 3

Representation of the FGFR3-TACC3 fusion gene identified by Next Generation Sequencing in a GBM IDHwt patient. Visualization of RNA sequencing reads supports the fusion junction between FGFR3 exon 17 and TACC3 exon 10.