High-Grade Astrocytoma With Piloid Features: An Aggressive Clinicogenomic Entity Distinct From Pilocytic Astrocytoma

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Genomics

Background:

• High-grade astrocytoma with piloid features (HGAP) is an aggressive glioma with unique molecular alterations.
• Distinguishing HGAP from pilocytic astrocytoma (PA) is crucial for accurate diagnosis and treatment.

Purpose of the Study:

• To clarify the clinical, pathological, and genomic differences between pediatric PA, adult PA, and HGAP.
• To provide evidence supporting HGAP's recognition as a distinct aggressive entity.

Main Methods:

• Retrospective analysis of 100 PA cases (pediatric and adult) and 25 HGAP cases.
• Next-generation sequencing and immunohistochemistry for molecular profiling.

Main Results:

• HGAP predominantly affects adults, exhibits high-grade features, and harbors distinct molecular alterations (e.g., CDKN2A/B deletions, NF1 mutations).
• HGAP patients show significantly shorter progression-free and overall survival compared to PA patients.
• Adult PAs, excluding HGAP, show distinct features from pediatric PAs but similar prognoses.

Conclusions:

• HGAP is a clinically aggressive and molecularly distinct high-grade glioma, separable from PA.
• Its unique genetic drivers and poor prognosis warrant recognition as a new entity.
• Accurate molecular profiling is essential for HGAP diagnosis, management, and development of targeted therapies.