A 52-year-old man from Delhi presents with a 3-month history of progressive headaches, morning vomiting, and recent onset seizures. MRI brain shows a large, heterogeneous mass in the right frontal lobe with significant perifocal edema and central necrosis. The tumor crosses the corpus callosum. On histopathology, the lesion shows high cellularity, marked nuclear pleomorphism, abundant mitotic figures (>10 per 10 HPF), and areas of pseudopalisading necrosis. Immunohistochemistry is positive for GFAP and p53. What is the most likely diagnosis?

Explanation

## Diagnosis: Glioblastoma Multiforme (WHO Grade IV) ### Clinical Presentation **Key Point:** The clinical triad of progressive headaches, morning vomiting (raised intracranial pressure), and seizures in a middle-aged adult is classic for a high-grade glioma. ### Imaging Findings **High-Yield:** The MRI features are pathognomonic for glioblastoma: - Large, heterogeneous mass (mixed signal intensity) - Significant perifocal edema (vasogenic edema from tumor neovascularization) - Central necrosis (hallmark of Grade IV tumors due to rapid growth outpacing blood supply) - Corpus callosum involvement ("butterfly" or infiltrative pattern common in glioblastoma) ### Histopathological Criteria for WHO Grade IV | Feature | Grade II | Grade III | Grade IV (GBM) | | --- | --- | --- | --- | | Cellularity | Low–moderate | High | Very high | | Nuclear pleomorphism | Mild | Moderate–marked | Marked | | Mitotic activity | 0–1 per 10 HPF | 5–10 per 10 HPF | >10 per 10 HPF | | Necrosis | Absent | Absent | Present (pseudopalisading) | | Vascular proliferation | Absent | Absent | Often present | **Key Point:** Pseudopalisading necrosis (tumor cells arranged radially around areas of ischemic necrosis) is a defining feature of glioblastoma and distinguishes it from Grade III astrocytoma. ### Immunohistochemistry - **GFAP-positive:** Confirms astrocytic differentiation - **p53-positive:** Indicates TP53 mutations, common in secondary glioblastomas and some primary GBMs **Clinical Pearl:** Glioblastoma is the most common primary malignant brain tumor in adults, with a median survival of 12–15 months despite multimodal therapy (surgery, radiation, temozolomide). ### Why Grade IV and Not Grade III? Grade III (anaplastic astrocytoma) lacks necrosis and pseudopalisading. The presence of >10 mitoses per 10 HPF and central necrosis mandates Grade IV classification. **Mnemonic — GBM Red Flags:** **NECROTIC** = Necrosis, Edema, Corpus callosum crossing, Rapid growth, Older age, Tumor burden, Imaging heterogeneity, Cellular pleomorphism [cite:Robbins 10e Ch 28]