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Updated: Jan 6, 2026
Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Diffuse glioma with FGFR3-TACC3 fusion in adults is not a homogenous clinicopathological and molecular entity
Xiaoli Su1,2, Jiawen Wu3, Pingling Wang1
1Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China.
Abstract:
Adult diffuse gliomas with FGFR3-TACC3 (F3T3) fusion are rare and highly heterogeneous central nervous system (CNS) tumors. Current research on the biological behavior of these tumors is limited, especially regarding whether histopathologically low-grade tumors are indolent or represent early-stage high-grade tumors, thereby posing challenges for grading. In this single-center study of 17 patients with adult F3T3 fusion diffuse gliomas (F3T3 gliomas), both low- and high-grade F3T3 gliomas presented distinctive recurrent histopathological features, such as oligodendrocyte-like cells, branched vessels and frequent calcifications. Molecularly, TERT promoter mutations and 7+/10- chromosomal alterations were common; one patient with recurrent glioma with histopathological features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) had additional CDK4 and MDM2 amplifications. Methylation profiling of 3 samples revealed varied results. A patient whose tumor had histopathological features consistent with PLNTY and a methylation subtype classified as the mesenchymal subtype of glioblastoma (GBM) experienced tumor recurrence 8 months after surgery. After 5-62 months of follow-up, seven patients relapsed, and six died; the primary tumors of the three patients with recurrence presented histopathological characteristics of low-grade glioma (LGG). GBM patients had worse overall survival than LGG patients (p = 0.035) but similar progression-free survival (p = 0.47), indicating that LGG patients may experience recurrence. For adults with tumors with histopathological features of PLNTY, further molecular and methylation analyses are needed for grading. If TERT promoter mutations are present, even with a PLNTY methylation profile, these tumors can still exhibit the biological behavior of high-grade gliomas.
Insights
Adult diffuse gliomas with FGFR3-TACC3 (F3T3) fusion are rare CNS tumors. Even low-grade F3T3 gliomas can recur, highlighting the need for molecular analysis for accurate grading and prognosis.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Genetics
Background:
- Adult diffuse gliomas with FGFR3-TACC3 (F3T3) fusion are rare and heterogeneous central nervous system (CNS) tumors.
- Limited research exists on the biological behavior of these tumors, particularly distinguishing indolent low-grade from early-stage high-grade tumors.
- Accurate grading poses challenges due to overlapping histopathological features.
Purpose of the Study:
- To investigate the histopathological and molecular characteristics of adult F3T3 fusion diffuse gliomas (F3T3 gliomas).
- To evaluate the clinical behavior, including recurrence and survival, of low-grade versus high-grade F3T3 gliomas.
- To determine the necessity of molecular and methylation profiling for accurate grading and prognosis in F3T3 gliomas, especially those with polymorphous low-grade neuroepithelial tumor of the young (PLNTY) features.
Main Methods:
- Single-center study of 17 adult patients with F3T3 gliomas.
- Histopathological analysis for recurrent features (oligodendrocyte-like cells, branched vessels, calcifications).
- Molecular analysis including TERT promoter mutations, chromosomal alterations (7+/10-), CDK4/MDM2 amplifications, and methylation profiling.
Main Results:
- Distinct histopathological features were observed in both low- and high-grade F3T3 gliomas.
- TERT promoter mutations and 7+/10- chromosomal alterations were common.
- Seven of 17 patients relapsed, and six died within 5-62 months; three recurrences originated from primary low-grade glioma (LGG) tumors.
- Glioblastoma (GBM) patients had worse overall survival than LGG patients (p=0.035), but similar progression-free survival (p=0.47).
- One patient with PLNTY features and a mesenchymal GBM methylation subtype experienced recurrence within 8 months.
Conclusions:
- Low-grade F3T3 gliomas can recur, necessitating further molecular and methylation analyses for accurate grading, especially for tumors with PLNTY features.
- The presence of TERT promoter mutations in PLNTY-like tumors indicates a potential for high-grade biological behavior, irrespective of methylation profile.
- Molecular profiling is crucial for understanding the behavior and prognosis of adult diffuse F3T3 fusion gliomas.
