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.

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:
  1. Papillary meningioma
  2. Rhabdoid meningioma
  3. Anaplastic meningioma

• 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)

• 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

• 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

• 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

• 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:
  1. Extent of resection
  2. Molecular profile (e.g., CDKN2A/B status)
  3. Response to radiotherapy

• 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.