Molecular Characterization of a Rare Glioblastoma Case With Atypical Histopathologic Features

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Radiology

Background:

• Diffuse gliomas can present with subtle or atypical imaging and histologic features.
• Accurate classification is essential for appropriate treatment and prognosis.
• Molecular diagnostics are increasingly important in glioma grading.

Purpose of the Study:

• To highlight the role of integrated molecular diagnostics in classifying a diffuse glioma with atypical features.
• To present a case of glioblastoma (GBM), IDH wild-type, grade 4, diagnosed based on molecular findings despite non-classic histology.
• To emphasize the importance of next-generation sequencing and methylation profiling in challenging glioma cases.

Main Methods:

• Review of neuroimaging (T2 FLAIR hyperintensity) and histopathology (atypical glial cells, Ki-67 index).
• Immunohistochemistry for IDH1 R132H mutation.
• Next-generation sequencing (NGS) for genetic alterations (TERT promoter, EGFR amplification, CDKN2A deletion).
• Methylation profiling for molecular subtyping and grading.

Main Results:

• The patient presented with stable, non-mass-like T2 FLAIR hyperintensity that later progressed.
• Histopathology showed atypical glial cells with low proliferation index and no necrosis or microvascular proliferation.
• Molecular analysis revealed TERT promoter mutation, EGFR amplification, and CDKN2A deletion, leading to a diagnosis of glioblastoma, IDH wild-type, WHO grade 4.
• The integrated molecular findings were essential for establishing the diagnosis despite atypical histologic features.

Conclusions:

• Integrated molecular diagnostics, including NGS and methylation profiling, are indispensable for accurate glioma classification, especially in cases with atypical histology.
• This case underscores that molecular data can override traditional histologic criteria for grading diffuse gliomas.
• Prompt and accurate diagnosis through molecular profiling facilitates appropriate therapeutic strategies, including surgery, radiotherapy, and chemotherapy.