Anaplastic Meningioma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
April 27, 2026

Anaplastic meningioma is the most aggressive form of meningioma, classified as World Health Organization (WHO) grade 3. Meningiomas develop from meningothelial cells in the meninges, the thin layers of tissue that cover and protect the brain and spinal cord. Like all meningiomas, anaplastic meningiomas are dural-based tumors — they grow attached to the dura (the tough outer layer of the meninges) and sit on the surface of the brain rather than within it. This extra-axial location is important because it means the tumor can usually be separated from the brain at surgery, which remains the cornerstone of treatment. However, unlike lower-grade meningiomas, anaplastic meningiomas grow quickly, frequently invade the underlying brain, have a high likelihood of recurrence after treatment, and, in a small number of cases, can spread to other parts of the body.

Anaplastic meningioma can arise as a high-grade tumor from the start — called a de novo anaplastic meningioma — or can develop when a previously diagnosed grade 1 or grade 2 meningioma acquires additional genetic changes over time and transforms into a more aggressive tumor. This distinction matters because patients with a prior history of a lower-grade meningioma who are now told the tumor has progressed to grade 3 are in a different clinical situation than patients diagnosed with grade 3 from the outset.

This article will help you understand the findings in your pathology report — what each term means and why it matters for your care. For a broader overview of meningioma, including all grades, histologic subtypes, and locations, see the main meningioma article. For information about grade 2 meningioma, see the article on atypical meningioma.

What are the symptoms of anaplastic meningioma?

The symptoms of anaplastic meningioma depend on where the tumor is growing, its size, and how quickly it grows. Because anaplastic meningiomas grow faster than grade 1 or grade 2 meningiomas, symptoms often develop or worsen more rapidly, over days to weeks rather than months or years.

Common symptoms include:

• Headaches — often progressive, and sometimes worse in the morning.
• Seizures — particularly for tumors over the surface of the brain.
• Weakness or numbness on one side of the body — usually on the opposite side to the tumor.
• Changes in vision, hearing, or speech — depending on the tumor’s location and which nerves or brain areas are compressed.
• Balance problems or difficulty walking.
• Changes in personality, behavior, or memory — particularly with frontal lobe tumors.
• Rapidly worsening neurological symptoms — a pace of worsening that is faster than expected for a meningioma may prompt imaging that reveals a recurrence or malignant transformation.

Anaplastic meningiomas can arise anywhere along the meninges. The most common locations are the cerebral convexities (the outer surface of the brain), the falx cerebri (the midline fold between the two halves of the brain), the skull base, and, less commonly, the spinal canal. Tumors at the skull base or near critical nerves and blood vessels are often more difficult to remove completely, which has important implications for treatment and prognosis.

What causes anaplastic meningioma?

For most people diagnosed with anaplastic meningioma, no single identifiable cause is found. Like other meningiomas, anaplastic meningiomas develop through a series of genetic changes that accumulate in meningothelial cells over time. Anaplastic meningiomas tend to have the most complex genetic profiles among meningioma grades, often including multiple mutations, copy-number changes, and large-scale chromosomal alterations.

Several factors are known to increase the risk:

• Ionizing radiation — prior radiation to the head, especially at high doses or in childhood, increases the risk of meningioma and is associated with higher-grade tumors.
• Prior lower-grade meningioma — a significant proportion of anaplastic meningiomas arise from the malignant transformation of a previously diagnosed grade 1 or grade 2 tumor. This is why long-term monitoring after any meningioma diagnosis is important.
• Male sex — unlike grade 1 meningiomas, which are far more common in women, anaplastic meningiomas are slightly more common in men.

A small number of anaplastic meningiomas develop in the setting of an inherited condition. Inherited conditions are caused by a genetic change that is present in every cell of the body from birth and can be passed from parent to child. Inherited conditions associated with anaplastic meningioma include:

• Neurofibromatosis type 2 (NF2) — caused by a change in the NF2 gene. People with NF2 often develop multiple meningiomas across all grades, vestibular schwannomas, and other nervous system tumors, typically at a younger age than sporadic cases.
• BAP1 tumor predisposition syndrome — caused by a change in the BAP1 gene. This syndrome predisposes to rhabdoid and high-grade meningiomas as well as mesothelioma, melanoma of the eye and skin, and kidney cancer. When loss of BAP1 protein is identified in the tumor, germline testing is recommended.

Germline (inherited) genetic testing and genetic counseling are recommended when a patient has multiple meningiomas, when an anaplastic meningioma is diagnosed at a young age, or when tumor molecular testing identifies loss of BAP1 or other features suggesting an inherited condition.

How common is anaplastic meningioma?

Anaplastic meningioma is rare, accounting for approximately 1–3% of all meningiomas. Because meningioma itself is the most common primary brain tumor in adults, even a small percentage translates to a meaningful number of patients annually. Anaplastic meningiomas can arise at any age but are most often diagnosed in adults over 50. They are slightly more common in men than in women.

How is the diagnosis made?

The diagnosis of anaplastic meningioma usually begins when imaging of the brain — most often magnetic resonance imaging (MRI) — reveals a dural-based mass with features suggesting a high-grade tumor. On MRI, anaplastic meningiomas typically appear as strongly contrast-enhancing masses attached to the dura. Compared with lower-grade meningiomas, they are more likely to show irregular or lobulated borders, evidence of brain invasion (where the tumor extends into the underlying brain tissue), prominent surrounding swelling (edema), and internal areas of necrosis (dead tissue) visible as non-enhancing zones within the tumor. CT scanning may reveal tumor calcification or erosion of the overlying skull bone. Although these imaging features suggest a high-grade tumor, the grade can only be determined by examining tumor tissue under the microscope.

The diagnosis is confirmed after a tissue sample is examined by a pathologist. In most cases, tissue is obtained during surgery to remove the tumor. A neurosurgeon opens the skull through a craniotomy and removes as much of the tumor as can safely be taken out. When a tumor cannot be safely removed — for example, because it is deeply located or involves critical nerves and blood vessels — a smaller stereotactic biopsy is performed to obtain enough tissue for diagnosis and molecular testing.

Under the microscope, anaplastic meningioma has the features of an overtly malignant tumor. The cells show marked anaplasia — meaning the nuclei are large, vary greatly in shape and size, and often contain very prominent nucleoli (small dense structures inside the nucleus). Mitotic activity is high, defined by the WHO 2021 classification as 12.5 or more mitotic figures per square millimeter (standardized from the older threshold of 20 per 10 high-power fields to reduce variability between microscopes). Necrosis — areas where tumor cells have died — is common and often extensive. The tumor typically invades the underlying brain tissue. In some anaplastic meningiomas, the cells have lost so much of their normal appearance that the tumor resembles other types of aggressive cancer, such as carcinoma or sarcoma. In these cases, immunohistochemistry is essential to confirm the meningothelial origin of the tumor.

To confirm the diagnosis, the pathologist uses immunohistochemistry (a laboratory test that uses antibodies to detect specific proteins in the tumor cells). SSTR2A, a somatostatin receptor that is consistently expressed by meningothelial cells, is the most useful single marker for confirming the diagnosis. EMA and vimentin are also typically positive, although EMA expression may be weaker in higher-grade tumors. Ki-67, a marker of how rapidly tumor cells are dividing, is substantially elevated in anaplastic meningioma and supports the high-grade classification. Molecular testing, described in the biomarker section below, is also a routine part of the workup.

WHO grade

Anaplastic meningioma is always WHO grade 3, the highest grade assigned to meningioma. A meningioma is classified as grade 3 when it shows overtly malignant microscopic features — primarily a mitotic count of 12.5 or more mitotic figures per square millimeter, marked anaplasia of the tumor cells, and usually necrosis and brain invasion. Grade 3 can also be assigned when molecular testing identifies either a TERT promoter mutation or homozygous deletion of CDKN2A and/or CDKN2B, even when the microscopic features might otherwise suggest grade 2. This means a tumor’s final grade is sometimes not settled until molecular results are available.

It is important to understand that the distinction between grade 2 and grade 3 is not always a sharp line in clinical practice — some tumors have features overlapping both grades, and the molecular findings can be the deciding factor. Your pathology report should document which specific criteria led to the grade 3 classification, whether that was microscopic features alone, molecular findings alone, or both.

Extent of resection (Simpson grade)

For anaplastic meningioma, the extent of surgical removal is one of the strongest predictors of outcome and directly determines the urgency and type of radiation therapy recommended afterward. The pathology and operative reports often describe the extent of resection using the Simpson grade, a five-point scale where lower numbers indicate more complete removal:

• Simpson grade 1 — complete removal of the tumor together with the attached dura and any involved bone.
• Simpson grade 2 — complete removal of the tumor, with coagulation (cautery) of the attached dura.
• Simpson grade 3 — complete removal of the tumor, but the attached dura is left in place, untreated.
• Simpson grade 4 — partial removal of the tumor.
• Simpson grade 5 — biopsy or decompression only.

Because anaplastic meningiomas recur at high rates even after the most complete surgery, a Simpson grade 1 or 2 resection is strongly preferred when safely achievable. For skull-base tumors or tumors involving dural sinuses and critical nerves, complete removal is often not possible, and a planned partial resection followed by radiation is the standard approach.

Biomarker and molecular testing

Molecular testing is a standard part of the workup for every anaplastic meningioma. The results confirm the grade, characterize the tumor’s biological behavior, identify features that may indicate an inherited condition, and in some cases reveal targets for clinical trials.

TERT promoter mutation

Mutations in the TERT promoter region increase telomerase activity, allowing tumor cells to divide indefinitely. TERT promoter mutations are found in about 20–25% of grade 3 meningiomas — a much higher frequency than in grade 1 or grade 2 tumors — and are one of the two molecular changes that can automatically assign a tumor to grade 3 regardless of its microscopic appearance. Their presence is associated with shorter time to recurrence and worse overall survival. Testing is performed using targeted DNA sequencing.

CDKN2A and CDKN2B

CDKN2A and CDKN2B are tumor suppressor genes. When both copies of either gene are lost (homozygous deletion), cells divide more easily and the tumor behaves aggressively. Homozygous deletion of CDKN2A and/or CDKN2B is the second molecular change that can assign grade 3, and is found in a significant proportion of anaplastic meningiomas. Testing is performed using next-generation sequencing with copy-number analysis or fluorescence in situ hybridization (FISH). Loss of the p16 protein on immunohistochemistry can serve as a surrogate marker for CDKN2A deletion.

BAP1

The BAP1 gene is a tumor suppressor involved in chromatin regulation and DNA repair. Loss of BAP1 protein expression on immunohistochemistry is associated with rhabdoid morphology, aggressive behavior, and a significantly higher risk of recurrence. Because BAP1 loss may indicate an underlying BAP1 tumor predisposition syndrome — which also increases the risk of mesothelioma, eye melanoma, and kidney cancer — germline testing is recommended whenever BAP1 loss is identified in a meningioma.

H3K27me3 loss

H3K27me3 is a chemical modification on a histone protein that helps control gene expression. Loss of H3K27me3 protein on immunohistochemistry is not a formal WHO grading criterion but is an important prognostic marker: meningiomas that have lost H3K27me3 have shorter time to recurrence and worse overall survival than those that retain it. Your pathology report may describe H3K27me3 as retained or lost.

NF2

NF2 gene alterations are the most common genetic change across all meningioma grades. Their presence does not change the grade in isolation but is routinely reported as part of the molecular profile and can prompt consideration of germline testing when features of neurofibromatosis type 2 are present.

Other molecular changes

Anaplastic meningiomas often harbor additional changes in genes involved in chromatin remodeling and cell cycle control, including PBRM1, ARID1B, and others. Large-scale chromosomal losses — particularly of chromosomes 1p, 10, and 14q — are common and contribute to the complex molecular profile of grade 3 tumors. These findings may be reported on next-generation sequencing panels and are relevant to understanding the tumor’s biology, though they do not currently change treatment outside of clinical trials.

DNA methylation profiling

DNA methylation profiling compares the tumor’s methylation pattern to a large reference database and can identify molecular risk groups that predict recurrence more accurately than WHO grade alone. This testing is increasingly used in specialized centers to characterize high-grade meningiomas, resolve borderline cases, and identify patients appropriate for specific clinical trials.

For more information about biomarkers and molecular testing across all cancer types, visit the Biomarkers and Genetic Testing section.

What is the prognosis?

Anaplastic meningioma has the worst prognosis of any meningioma grade. Even with aggressive surgery and radiation, the tumor frequently recurs, often multiple times and with shorter intervals between recurrences. Median overall survival after diagnosis is approximately 2–3 years. Five-year survival is approximately 30–40%, though outcomes vary substantially depending on surgical completeness, molecular profile, and patient age and overall health.

Several features are associated with worse outcomes:

• Incomplete surgical removal — Simpson grade 3 or 4 resection is associated with a much shorter time to recurrence than gross total resection.
• TERT promoter mutation — associated with shorter survival even among grade 3 tumors.
• Homozygous CDKN2A/B deletion — similarly associated with an aggressive clinical course.
• Loss of H3K27me3 — predicts earlier recurrence.
• Loss of BAP1 — associated with rhabdoid morphology and aggressive behavior.
• Skull-base location — makes complete removal less achievable.
• Malignant transformation from prior lower-grade tumor — recurrent transformed tumors tend to have complex molecular profiles and may be more resistant to treatment than de novo grade 3 tumors.
• Older age and poor overall health — reduce tolerance for aggressive surgery and radiation.

Despite the serious prognosis, treatment meaningfully prolongs survival and can control symptoms for extended periods. Advances in radiation techniques, surgical approaches, and — increasingly — clinical trials of targeted and immune-based therapies are expanding the options available to patients.

What happens after the diagnosis?

Anaplastic meningioma is managed by a multidisciplinary team that typically includes a neurosurgeon, a neuro-oncologist, a radiation oncologist, a neuropathologist, and a neuroradiologist. Other members of the team may include a neurologist for seizure management, a neuro-ophthalmologist for tumors near the optic nerves, an endocrinologist for tumors near the pituitary gland, rehabilitation specialists, and palliative care, which is often introduced early and alongside active cancer-directed treatment. A geneticist or genetic counselor is involved when an inherited condition is suspected.

Surgery

Maximal safe surgical removal is the first step in treatment and the single most important factor influencing the risk of recurrence. A Simpson grade 1 or 2 resection — complete removal, including the attached dura — is the goal whenever it is safely achievable. For skull-base tumors or tumors involving dural sinuses or critical cranial nerves, planned subtotal removal followed by radiation is the standard approach. Repeat surgery is often considered when the tumor recurs and the location and the patient’s overall condition permit it.

Radiation therapy

Radiation therapy is recommended for nearly all patients with anaplastic meningioma, regardless of the extent of surgical removal, because of the high recurrence risk even after complete resection. Radiation can be delivered in two main ways:

• Fractionated radiation — multiple smaller doses given over several weeks, typically to the tumor bed and a surrounding margin. This is the standard approach for most anaplastic meningiomas, particularly larger tumors or those near critical structures where dose distribution is important.
• Stereotactic radiosurgery — a single high dose of very focused radiation delivered in one session. Used for smaller residual tumors or for recurrent disease in a favorable location.

For patients whose tumor recurs after initial radiation, re-irradiation may be considered depending on the dose previously delivered, the time elapsed since prior treatment, and the proximity of critical structures. The decision involves careful planning with the radiation oncologist.

Systemic therapy

No systemic therapy is currently approved as a standard treatment for anaplastic meningioma. For recurrent disease that cannot be managed with further surgery or radiation, options sometimes used include bevacizumab (a drug that reduces tumor blood vessel growth), somatostatin analogues, hydroxyurea, and interferon-alpha, although evidence for these agents is limited. Clinical trials testing targeted therapies, immunotherapy (including checkpoint inhibitors), and tumor-treating fields (TTFields) are ongoing and represent the most promising avenue for patients with recurrent or refractory disease. Molecular testing of the tumor — including TERT promoter status, CDKN2A/B deletion, BAP1 status, and comprehensive next-generation sequencing — is important for determining eligibility for these trials.

Follow-up

Long-term and close follow-up with regular MRI scans is essential for all patients with anaplastic meningioma. Because these tumors recur at high rates, surveillance imaging is typically performed every 3–4 months during the first two years after treatment, with adjustments based on stability and risk profile. Long-term effects of the tumor and its treatment — including seizures, cognitive changes, hormonal effects, and the late effects of radiation — are managed by the multidisciplinary team. Palliative care, focusing on symptom management, quality of life, and emotional and spiritual support, is an important part of care from diagnosis onward and is not limited to the end of life.

Questions to ask your doctor

• Is this a de novo anaplastic meningioma, or has a prior lower-grade meningioma transformed to grade 3?
• What microscopic and molecular features led to the grade 3 diagnosis — was it high mitotic activity, a TERT promoter mutation, CDKN2A/B deletion, or a combination?
• What was the Simpson grade of my surgery? Was the tumor completely removed, including the attached dura?
• Is there any residual tumor visible on post-operative imaging?
• Were any high-risk molecular features identified, such as BAP1 loss or H3K27me3 loss?
• Do you recommend radiation therapy, and if so, what type — fractionated radiation or stereotactic radiosurgery — and to what area?
• Should I be referred for genetic counseling or germline genetic testing?
• Are there clinical trials available for my molecular profile, and should I be referred to a specialized center?
• How often will I need MRI scans, and what will you be watching for?
• What symptoms should I watch for that might indicate the tumor is growing or coming back?
• How will any seizures be managed, and will I be able to drive?
• What are the expected effects of radiation on cognitive function, and are there strategies to minimize them?
• When would repeat surgery or re-irradiation be considered if the tumor recurs?
• What supportive care and palliative care services are available, and when should we involve palliative care?

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