A 42-year-old man from Delhi presents with a 6-month history of progressive headaches, morning vomiting, and recent onset focal seizures. MRI brain shows a well-demarcated, non-enhancing lesion in the left temporal lobe with surrounding vasogenic edema. On histopathology, the tumor shows uniform cells with round nuclei, scant cytoplasm, and numerous mitotic figures. Immunohistochemistry is positive for GFAP and negative for IDH1 R132H mutation. What is the most likely diagnosis?

Explanation

## Clinical Presentation and Imaging Findings The patient presents with classic features of a high-grade glioma: progressive headaches, morning vomiting (suggesting increased intracranial pressure), and focal seizures. The MRI shows a non-enhancing lesion with vasogenic edema — a pattern typical of WHO Grade II–III diffuse gliomas. ## Histopathological Analysis **Key Point:** The critical finding is the presence of **numerous mitotic figures** with uniform cellularity and GFAP positivity (confirming astrocytic origin), but **absence of necrosis and microvascular proliferation**. | Feature | Grade II | Grade III | Grade IV | |---------|----------|-----------|----------| | Mitotic activity | Absent/rare | Brisk (≥4 per 10 HPF) | Abundant | | Necrosis | Absent | Absent | Present | | Microvascular proliferation | Absent | Absent | Present | | Enhancement on MRI | No | Variable | Yes (ring-like) | | IDH1 mutation | Often present | Often present | Rare in primary | ## Molecular Marker Interpretation **High-Yield:** The **negative IDH1 R132H mutation** suggests a primary glioblastoma rather than secondary progression from a lower-grade tumor. However, the **absence of necrosis and microvascular proliferation** excludes WHO Grade IV glioblastoma. The brisk mitotic activity (Grade III criterion) combined with GFAP positivity and absence of Grade IV features (necrosis, vascular proliferation) defines **Anaplastic Astrocytoma (WHO Grade III)**. ## Why Not Grade IV? Glioblastoma requires EITHER necrosis OR microvascular proliferation; this tumor has neither. The imaging shows non-enhancement, which is atypical for GBM. ## Clinical Significance **Clinical Pearl:** Anaplastic astrocytomas have a median survival of 2–3 years with treatment, compared to <1 year for GBM. Accurate grading is essential for prognostication and treatment planning (radiotherapy + chemotherapy vs. surgery alone). **Mnemonic: GAMA** — **G**rade III = **A**naplastic, **M**itotic activity present, **A**strocytoma (GFAP+).