====== WHO Grade 3 Meningioma ======

**WHO Grade 3 meningiomas**, also known as **anaplastic or malignant meningiomas**, are the most aggressive subtype. They exhibit high mitotic activity, marked anaplasia, and often infiltrate brain or extracranial tissues. These tumors carry a high risk of recurrence, progression, and metastasis.

===== Definition =====
A **WHO Grade 3 meningioma** is diagnosed based on one or more of the following:
  * **Mitotic index ≥20 mitoses per 10 high-power fields (HPF)**
  * **Frankly malignant cytology resembling carcinoma, sarcoma, or melanoma**
  * **Histological subtypes classified as Grade 3**:
    - **Papillary meningioma**
    - **Rhabdoid meningioma**
    - **Anaplastic meningioma**

===== Histopathological Features =====
  * Marked nuclear atypia and pleomorphism
  * Extremely high cellularity
  * Prominent nucleoli
  * Extensive necrosis and brain invasion
  * High mitotic count (≥20/10 HPF)
  * Architectural disruption (sheet-like growth)

===== Molecular Features =====
  * Frequent chromosomal losses: 1p, 6q, 14q, 18q
  * **CDKN2A/B homozygous deletion** is strongly associated with anaplastic behavior
  * DNA methylation profiling may reveal high-risk epigenetic subgroups
  * TERT promoter mutations are associated with poor prognosis

===== Clinical Behavior =====
  * **Highly aggressive**, often with rapid recurrence despite treatment
  * May recur within months after surgery
  * Potential for **extracranial metastasis** (lungs, liver, bone)
  * More frequent in **non-skull-base** locations

===== Treatment =====
  * **Maximal safe surgical resection** is the first step
  * **Adjuvant radiotherapy** is **strongly recommended**, even after gross total resection
  * **Chemotherapy** or targeted therapies may be considered in recurrent or refractory cases, though evidence is limited
  * Enrollment in clinical trials is often appropriate

===== Prognosis =====
  * **Poor prognosis**, with 5-year overall survival around **30–50%**
  * Recurrence rate approaches **100%** in many series
  * Close surveillance with **frequent MRI** (e.g., every 3–6 months) is mandatory
  * Survival correlates with:
    - Extent of resection
    - Molecular profile (e.g., CDKN2A/B status)
    - Response to radiotherapy

===== References =====
  * WHO Classification of Tumours Editorial Board. *WHO Classification of Tumours of the Central Nervous System*, 5th ed. IARC, 2021.
  * Goldbrunner R, et al. EANO guidelines for the diagnosis and treatment of meningiomas. *Lancet Oncol*. 2016.
  * Sahm F, et al. DNA methylation-based classification and grading of meningiomas. *Acta Neuropathol*. 2017.
  * Driver J, et al. A molecularly integrated grade for meningioma. *Neuro Oncol*. 2022.