Your pathology report for anaplastic meningioma

by Jason Wasserman MD PhD FRCPC
December 2, 2025

Anaplastic meningioma is an aggressive type of meningioma. Meningiomas are tumors that start from the meninges, the thin layers of tissue that cover and protect the brain and spinal cord. Anaplastic meningioma is the highest-grade meningioma and is classified as World Health Organization (WHO) grade 3.

While most meningiomas are slow-growing and benign, anaplastic meningiomas grow more quickly, are more likely to invade nearby brain tissue, and have a higher risk of coming back after treatment. They can also spread (metastasize) to other parts of the body, although this is still rare.

Where do anaplastic meningiomas occur?

Anaplastic meningiomas can arise in many of the same locations as other meningiomas. They are often found on the surface of the brain (the convexities), along the falx cerebri (the midline fold between the two brain hemispheres), or near the skull base, including areas around the eyes, nose, and ears. They can also occur in the spinal canal, although this is less common.

Because of their location, anaplastic meningiomas may compress nearby brain tissue, nerves, or blood vessels, leading to a variety of symptoms.

What are the symptoms?

Symptoms depend on the tumor’s size and location, and on how quickly it is growing. Common symptoms include:

  • Headaches that may worsen over time.

  • Seizures.

  • Weakness or numbness in an arm or leg.

  • Changes in speech, vision, or hearing.

  • Problems with balance or walking.

  • Changes in personality, behavior, or memory, especially when the tumor is in the frontal lobes.

Because anaplastic meningiomas grow faster than typical (grade 1) meningiomas, symptoms may progress more rapidly.

How common is anaplastic meningioma?

Meningioma is the most common primary brain tumor in adults, but anaplastic meningioma is uncommon, making up only about 1–3% of all meningiomas. Anaplastic meningiomas can arise “de novo” (as a high-grade tumor from the start) or develop from a previously diagnosed lower-grade meningioma that has progressed over time.

What causes anaplastic meningioma?

For most people, the cause is not known. However, several factors increase the risk of developing meningiomas in general, and some are more associated with higher-grade tumors, including anaplastic meningioma.

  • Ionizing radiation. Previous radiation to the head, especially in childhood, increases the risk of developing meningioma and may be associated with higher grades.

  • Inherited syndromes. Conditions such as neurofibromatosis type 2 (NF2) and BAP1 tumor predisposition syndrome can increase the risk of multiple or aggressive meningiomas. These are caused by genetic changes passed down in families.

  • Genetic changes in the tumor. Anaplastic meningiomas often show more complex genetic abnormalities than lower-grade meningiomas, including alterations in genes that control cell growth and DNA repair.

In many patients, anaplastic meningioma is thought to arise from a pre-existing WHO grade 1 or grade 2 meningioma that has acquired additional genetic changes over time.

How is this diagnosis made?

Imaging

Imaging tests such as MRI and CT are usually the first step in evaluating a suspected meningioma. On MRI, anaplastic meningiomas often appear as dural-based masses that enhance strongly with contrast. Compared to lower-grade meningiomas, anaplastic meningiomas may show:

  • More irregular borders.

  • Signs of brain invasion, where the tumor appears to extend into the brain tissue.

  • Areas of necrosis (dead tissue) inside the tumor.

  • More extensive surrounding brain swelling (edema).

Although imaging can suggest a higher-grade meningioma, the final diagnosis and grade require examination of tumor tissue.

Biopsy and surgery

The diagnosis of anaplastic meningioma is usually made after surgery to remove all or part of the tumor. In some cases, a smaller biopsy is performed if the tumor cannot be safely removed. The tissue is then examined under the microscope by a pathologist, a doctor who specializes in diagnosing disease using tissue and cells.

The surgeon and pathologist work together to determine the extent of resection (how much of the tumor was removed) and to provide information that helps guide further treatment.

Microscopic features

Under the microscope, anaplastic meningioma shows clear features of malignancy. Compared to WHO grade 1 and grade 2 meningiomas, anaplastic meningiomas have:

  • Very high mitotic activity, meaning many cells are actively dividing.

  • Markedly abnormal cell appearance (anaplasia), with large, irregular nuclei and prominent nucleoli.

  • Often necrosis, areas where tumor cells have died.

  • A tendency to invade adjacent brain tissue and other structures.

The tumor cells may resemble those seen in other aggressive cancers, such as carcinoma or high-grade sarcoma. Because some anaplastic meningiomas can look very different from typical meningiomas, immunohistochemistry and molecular tests are often used to confirm the diagnosis.

Immunohistochemistry

Immunohistochemistry (IHC) uses antibodies linked to dyes to highlight specific proteins in cells. In anaplastic meningioma, IHC helps confirm that the tumor is a meningioma and not another type of cancer, and it can provide clues about prognosis.

Typical immunohistochemical findings include

  • EMA (epithelial membrane antigen) and vimentin positivity support a meningioma diagnosis, although EMA may be weaker in higher-grade tumors.

  • SSTR2A (somatostatin receptor 2A) positivity in most meningiomas helps to distinguish them from other tumors.

  • Ki-67 (a proliferation marker) shows a high index in anaplastic tumors, reflecting rapid growth.

Special IHC stains can act as surrogates for genetic changes

  • Loss of BAP1 expression in the nucleus is seen in some rhabdoid or high-grade meningiomas and is associated with aggressive behavior and a possible underlying hereditary syndrome.

  • Loss of H3K27me3 (a histone modification) is found in a subset of high-grade meningiomas and is associated with worse prognosis.

IHC results are combined with routine microscopic findings and molecular tests to make the final integrated diagnosis.

WHO grade

WHO grade is a way of describing how aggressive a tumor is expected to be. Meningiomas are graded 1-3. Anaplastic meningioma is always WHO grade 3, the highest grade.

  • WHO grade 1 meningiomas are benign and slow-growing, with a relatively low risk of recurrence when completely removed.

  • WHO grade 2 (atypical) meningiomas have higher mitotic activity, may invade the brain, or show other atypical features, and have a higher risk of recurrence.

  • WHO grade 3 (anaplastic/malignant) meningiomas exhibit clear malignant features, including very high mitotic counts, marked anaplasia, necrosis, and brain invasion.

Notably, specific molecular changes, such as a TERT promoter mutation or homozygous deletion of CDKN2A and/or CDKN2B, can support a diagnosis of WHO grade 3 even if some histologic features are borderline. WHO grade is one of the strongest predictors of prognosis and guides recommendations for surgery, radiation, and follow-up.

Biomarkers

Biomarkers are specific genetic or protein changes in tumor cells that provide information about how the tumor behaves and how it may respond to treatment. In anaplastic meningioma, biomarkers help confirm the diagnosis, refine the WHO grade, estimate the risk of recurrence, and identify tumors that may respond to targeted therapies or immunotherapy. Biomarker testing is critical in high-grade meningiomas because these tumors have a higher chance of coming back or spreading.

What types of biomarkers are tested?

Biomarker testing in anaplastic meningioma typically relies on molecular tests, such as next-generation sequencing and copy-number analysis. These tests look for mutations, deletions, and other changes in genes that regulate cell growth, DNA repair, and chromatin structure. Immunohistochemistry can also serve as a surrogate marker for some genetic changes, such as BAP1 or SMARCE1 loss.

TERT promoter

The TERT promoter is a region of DNA that controls expression of the TERT gene, which helps maintain telomeres, the protective caps at the ends of chromosomes. Mutations in the TERT promoter increase telomerase activity, allowing tumor cells to divide indefinitely. In meningiomas, TERT promoter mutations are strongly associated with more aggressive behavior, earlier recurrence, and shorter overall survival, and they support a diagnosis of WHO grade 3.

TERT promoter mutations are detected using targeted DNA sequencing of the promoter region in tumor tissue.

Your report will state whether a TERT promoter mutation is present or absent. The presence of a TERT promoter mutation is considered a high-risk feature and supports classification as an anaplastic (grade 3) meningioma.

CDKN2A and CDKN2B

CDKN2A and CDKN2B are tumor suppressor genes that encode proteins that control the cell cycle. When both copies of CDKN2A and/or CDKN2B are lost (a “homozygous deletion”), cells can grow and divide much more easily. In meningiomas, homozygous deletion of CDKN2A and/or CDKN2B is associated with aggressive behavior and supports assigning WHO grade 3, even if the microscopic appearance is not frankly anaplastic.

These genes are evaluated using copy number analysis or other molecular methods that detect deletions in tumor DNA.

The report will indicate whether CDKN2A and CDKN2B are intact or show homozygous deletion. A homozygous deletion is considered a high-risk feature and can, by itself, justify WHO grade 3 status.

NF2

NF2 is a tumor suppressor gene located on chromosome 22. Loss or mutation of NF2 is among the most common genetic changes in meningiomas and is observed across all grades, including anaplastic tumors. NF2 loss is an early event and often accompanied by additional genetic changes in higher-grade meningiomas.

NF2 status is assessed by next-generation sequencing and copy-number analysis to detect mutations and deletions on chromosome 22.

Your report may describe NF2 as mutated, deleted, or wildtype. While NF2 loss alone does not determine grade, it often appears in the background of more complex, high-grade genetic profiles.

BAP1

BAP1 is a tumor suppressor gene involved in chromatin regulation and DNA repair. Loss of BAP1 function is associated with rhabdoid and other aggressive meningiomas and may occur as part of the BAP1 tumor predisposition syndrome, where individuals are at risk for other cancers such as uveal melanoma and mesothelioma.

BAP1 can be evaluated by DNA sequencing and immunohistochemistry to determine whether the BAP1 protein is present in tumor cell nuclei.

Your report may state that BAP1 expression is lost in tumor cells, suggesting a BAP1 alteration. This is associated with more aggressive behavior and often supports a high-grade classification.

PBRM1

PBRM1 is another gene involved in chromatin remodeling. PBRM1 mutations have been reported in papillary and rhabdoid meningiomas and may be linked to more aggressive behavior.

PBRM1 is assessed by next-generation sequencing to detect mutations and, sometimes, by immunohistochemistry to evaluate protein expression.

The report may describe PBRM1 mutation or loss of PBRM1 expression as a high-risk molecular feature in anaplastic meningioma.

H3K27me3

H3K27me3 (often written as H3K27me3 or H3 p.K27me3) refers to a specific chemical modification on a histone protein, which helps control how tightly DNA is packaged. Loss of this modification has been observed in a subset of high-grade meningiomas and is associated with a higher risk of recurrence and shorter survival.

Loss of H3K27me3 is detected by immunohistochemistry, which shows the absence of nuclear staining in tumor cells while normal cells retain staining.

The report will state whether H3K27me3 expression is retained or lost. Loss is described as a marker of more aggressive biological behavior.

Prognosis

Anaplastic meningioma has a poorer prognosis than lower-grade meningiomas. Even after surgery and radiation, the tumor often comes back (recurs), sometimes multiple times. The risk of spread beyond the brain or spine, while still low overall, is higher than in grade 1 or grade 2 meningiomas.

Factors that influence prognosis include:

  • WHO grade (anaplastic = grade 3).

  • Extent of surgical removal (gross total resection versus subtotal).

  • Presence of high-risk molecular features such as TERT promoter mutation and CDKN2A/CDKN2B deletion.

  • Tumor location and the ability to safely remove all visible tumor.

Despite the aggressive nature of anaplastic meningioma, newer approaches, including advanced radiation techniques, repeat surgeries, and clinical trials of targeted or immune-based therapies, are offering more options for some patients.

What happens after the diagnosis?

After an anaplastic meningioma is diagnosed, your healthcare team will discuss a treatment plan tailored to your situation. Surgery to remove as much of the tumor as possible is usually the first step. Because these tumors are aggressive, radiation therapy is often recommended after surgery to reduce the risk of recurrence. In some cases, especially when the tumor cannot be removed entirely or comes back after treatment, additional options such as stereotactic radiosurgery, repeat surgery, chemotherapy, or enrollment in a clinical trial may be considered.

The tumor must be evaluated with molecular testing to assess biomarkers, including TERT promoter status, CDKN2A/CDKN2B deletion, BAP1, and H3K27me3. These results help refine the grade, estimate prognosis, and may determine eligibility for clinical trials or targeted therapies.

You will need regular follow-up with MRI scans and neurological examinations to monitor for recurrence or progression. Supportive care, including seizure management, rehabilitation, and symptom control, is also an important part of treatment.

Questions to ask your doctor

  • Is my tumor an anaplastic meningioma, and what does WHO grade 3 mean in my case?

  • Was the tumor completely removed, or is there residual tumor remaining?

  • Did the pathologist identify any high-risk molecular features, such as a TERT promoter mutation or a CDKN2A/CDKN2B deletion?

  • Do I need radiation therapy, and if so, what type and for how long?

  • Are there any clinical trials or targeted therapies that may be appropriate for me?

  • How often will I need MRI scans and follow-up visits?

  • What symptoms should I watch for that might indicate the tumor has returned or progressed?

  • Should my family members consider genetic counseling or testing based on my tumor’s features?

A+ A A-