A 52-year-old man undergoes MRI for progressive headaches and focal neurological deficits. Imaging reveals a supratentorial mass with heterogeneous enhancement and central necrosis. Histopathology shows increased cellularity, mitotic figures, and microvascular proliferation. Which of the following is NOT a characteristic feature of glioblastoma multiforme (WHO Grade IV astrocytoma)?

Explanation

## Glioblastoma Multiforme (GBM) — WHO Grade IV Astrocytoma ### Key Pathological Features of GBM **Key Point:** Glioblastoma is the most aggressive primary CNS tumor, characterized by rapid growth, marked cellularity, and extensive infiltration into surrounding brain parenchyma. ### Hallmark Histological Features | Feature | Presence in GBM | Significance | |---------|-----------------|---------------| | Pseudopalisading necrosis | ✓ Yes | Tumor cells arrange around areas of ischemic necrosis | | Microvascular proliferation | ✓ Yes | Endothelial hyperplasia and new vessel formation | | High mitotic activity | ✓ Yes | Numerous mitotic figures; defines Grade IV | | Nuclear pleomorphism | ✓ Yes | Marked variation in nuclear size and shape | | Well-demarcated margin | ✗ NO | GBM infiltrates diffusely; no clear boundary | | Central necrosis | ✓ Yes | Due to rapid growth outpacing blood supply | ### Why Well-Demarcated Margin is INCORRECT **High-Yield:** GBM is characterized by **diffuse infiltration** into adjacent brain tissue. Tumor cells extend far beyond the contrast-enhancing region on imaging, making complete surgical resection impossible. This infiltrative nature is a key reason for poor prognosis and high recurrence rates. **Clinical Pearl:** The contrast-enhancing region on MRI represents only the most densely cellular portion; microscopic tumor extends into surrounding brain that appears normal on imaging. This is why even "gross total resection" leaves residual disease. ### Contrast with Lower-Grade Gliomas - **Grade II astrocytomas**: Well-differentiated, minimal atypia, low mitotic rate, infiltrative but slow-growing - **Grade III anaplastic astrocytomas**: Increased cellularity and mitotic activity, but lack pseudopalisading necrosis and microvascular proliferation - **Grade IV GBM**: All hallmarks present; most aggressive **Mnemonic: "GBM = PANDA"** — Pseudopalisading necrosis, Atypia (nuclear pleomorphism), Necrosis (central), Diffuse infiltration, Aggressive (high mitotic rate) ### Clinical Correlates **Key Point:** The infiltrative nature of GBM explains: - Poor prognosis (median survival ~15 months with standard therapy) - High recurrence rate even after aggressive resection - Difficulty in defining surgical margins intraoperatively - Need for adjuvant radiotherapy and chemotherapy [cite:Robbins 10e Ch 28]