A 45-year-old man undergoes MRI for progressive headaches and is found to have a diffuse infiltrative tumor of the cerebral white matter with T2/FLAIR hyperintensity. Histopathology shows uniform fibrillary astrocytes with moderate nuclear pleomorphism and rare mitoses. Which WHO grade is most likely?

Explanation

## Grading of Astrocytomas (WHO Classification) **Key Point:** WHO Grade II diffuse astrocytoma is characterized by uniform fibrillary astrocytes with mild-to-moderate nuclear pleomorphism and **absent or rare mitoses**. The absence of necrosis and microvascular proliferation distinguishes it from higher grades. ### WHO Grading Criteria for Astrocytomas | WHO Grade | Tumor Type | Cellularity | Nuclear Pleomorphism | Mitoses | Necrosis | Vascular Proliferation | Prognosis | |---|---|---|---|---|---|---|---| | I | Pilocytic astrocytoma | Low | Minimal | Absent | Absent | Absent | Excellent | | II | Diffuse astrocytoma | Moderate | Mild–moderate | Rare or absent | Absent | Absent | 5–10 yr median | | III | Anaplastic astrocytoma | High | Marked | Brisk | Absent | Often present | 2–3 yr median | | IV | Glioblastoma | Very high | Marked | Abundant | Present | Present | <1 yr median | **High-Yield:** The **absence of mitoses** is the critical feature that excludes Grade III (anaplastic astrocytoma) and Grade IV (glioblastoma). Grade II tumors are infiltrative and diffuse, ruling out pilocytic astrocytoma (Grade I), which is typically circumscribed and occurs in children/young adults. **Clinical Pearl:** Grade II diffuse astrocytomas often undergo malignant transformation to Grade III or IV over time (median 5–10 years). Patients require long-term imaging surveillance and may benefit from early adjuvant therapy in some cases. **Mnemonic:** **"Rare Mitoses = Grade II"** — If mitoses are rare or absent in a diffuse astrocytoma, think Grade II; if brisk, think Grade III; if abundant with necrosis, think Grade IV.