Your pathology report for atypical meningioma

By Jason Wasserman MD PhD FRCPC
December 2, 2025

An atypical meningioma is a type of meningioma that is more aggressive than a noncancerous meningioma (grade 1) but is less aggressive than the cancerous anaplastic meningioma (grade 3). Atypical meningiomas are classified as World Health Organization (WHO) grade 2.

Meningiomas arise from cells in the meninges, the thin layers of tissue that cover the brain and spinal cord. Most meningiomas are slow-growing and benign, but atypical meningiomas are more likely to recur (come back) after treatment, grow more quickly, and sometimes invade nearby brain tissue. Because of these features, they are considered an intermediate-grade tumor and require closer monitoring and, in some cases, additional therapy.

Where do atypical meningiomas occur?

Atypical meningiomas can arise anywhere along the meninges.

Common locations include:

  • The cerebral convexities (the outer surface of the brain).

  • The falx cerebri (the midline structure between the brain hemispheres).

  • The skull base, including areas around the eyes, nose, and ears.

  • The spinal canal, although less commonly.

Tumor location affects symptoms and how easily the tumor can be surgically removed.

What are the symptoms?

The symptoms associated with an atypical meningioma depend on the size and location of the tumor and how much it compresses nearby brain tissue.

Common symptoms include

  • Headaches.

  • Seizures.

  • Weakness or numbness in the arms or legs.

  • Changes in vision or hearing.

  • Balance difficulties.

  • Changes in personality, memory, or behavior, especially with frontal lobe tumors.

Because atypical meningiomas grow faster than WHO grade 1 meningiomas, symptoms may develop more quickly.

How common is atypical meningioma?

Atypical meningiomas account for 15–30% of all meningiomas, making them more common than anaplastic meningiomas but less common than benign meningiomas. They are more common in adults and may be slightly more common in men than in women.

What causes atypical meningioma?

Most atypical meningiomas arise sporadically, meaning they have no clear inherited cause. However, several risk factors are known:

  • Ionizing radiation. Prior radiation to the head, especially in childhood, increases the risk.

  • Genetics. Some inherited syndromes, including neurofibromatosis type 2 (NF2) and, less commonly, BAP1 tumor predisposition syndrome or SMARCE1-associated syndromes, can cause multiple or higher-grade meningiomas.

  • Hormones. The higher incidence in women, hormone receptor expression in some tumors, and associations with hormone-related conditions suggest hormones may play a role.

  • Genetic changes in the tumor itself. Atypical meningiomas tend to show more genetic changes than grade 1 meningiomas, including alterations in NF2 or mutations in genes such as AKT1, SMO, and TRAF7.

How is this diagnosis made?

Imaging

Meningiomas are usually first suspected based on neuroimaging, most commonly MRI and CT scans. Atypical meningiomas often appear as well-defined, contrast-enhancing, dural-based masses on MRI. Compared to grade 1 meningiomas, atypical tumors are more likely to show.

  • Irregular or lobulated borders.

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

  • Increased swelling (edema) around the tumor.

  • Areas of spontaneous necrosis, especially in larger tumors.

Although imaging provides important information, only a surgical specimen or biopsy confirms the grade.

Biopsy and surgery

Atypical meningiomas are usually diagnosed after surgical removal of all or part of the tumor. In some cases, a biopsy is performed if the tumor cannot be safely removed. A pathologist examines the tissue under the microscope to determine the tumor type, subtype, and WHO grade.

Microscopic features

When a pathologist examines an atypical meningioma under the microscope, they look for features suggesting the tumor is growing more rapidly or behaving more aggressively than a typical (grade 1) meningioma. These changes are found in the tumor cells (the actual meningioma cells) and in the tumor architecture (how the cells are arranged and how the tissue looks overall).

One of the most important microscopic findings in atypical meningioma is increased mitotic activity. Mitosis is the process by which cells visibly divide under the microscope. A high number of mitotic figures means the tumor cells are multiplying more rapidly than expected. In atypical meningioma, having four or more mitoses in ten high-power fields (a standard microscopic measurement) is one of the key diagnostic features.

Another important feature is brain invasion. In most meningiomas, the tumor pushes against the brain but does not invade it. In atypical meningioma, however, tumor cells can extend directly into the brain tissue, breaking through the thin layer normally separating the tumor from the brain. Brain invasion increases the risk of recurrence and automatically places the tumor into WHO grade 2.

Pathologists also look for high cellularity, which means the tumor contains a greater number of cells packed more tightly together than expected. The reverse situation—tumors with abundant background tissue and fewer cells—is more typical of grade 1 meningiomas.

Atypical meningiomas may also show small cells with a high nuclear-to-cytoplasmic ratio, meaning the nucleus (the cell’s central control center) is large relative to the small amount of cytoplasm (the cell’s surrounding material). This “crowded” look suggests the cells are less mature and more aggressive.

Prominent nucleoli, which are round structures inside the nucleus, may be seen. Visible nucleoli often indicate increased protein production, which is commonly associated with faster-growing tumor cells.

Some atypical meningiomas grow in unstructured sheets rather than in organized patterns. This is called sheet-like growth and is another sign of abnormal behavior.

Finally, the presence of spontaneous necrosis, or areas where tumor cells have died without being injured during surgery, can also support the diagnosis. Necrosis suggests that the tumor may be growing so rapidly that parts of it outgrow their blood supply, leading to tissue death.

When one or more of these features are present, the tumor is diagnosed as an atypical (WHO grade 2) meningioma. These microscopic features help predict the likelihood of tumor recurrence and whether additional treatment may be recommended.

Immunohistochemistry

Immunohistochemistry (IHC) uses antibodies linked to dyes to highlight specific proteins in tumor cells. In atypical meningioma, IHC helps confirm the diagnosis and rule out other tumor types.

Common IHC findings include:

  • EMA and vimentin, which are often positive in meningiomas.

  • SSTR2A is strongly positive in most meningiomas and helps distinguish them from other brain tumors.

  • Ki-67, which shows how quickly tumor cells are dividing. A higher Ki-67 index supports a higher grade and increased risk of recurrence.

Some IHC stains can also act as surrogates for genetic changes:

  • Loss of H3K27me3 is seen in some higher-grade meningiomas and is associated with a higher chance of recurrence.

  • Loss of BAP1 expression is associated with more aggressive behavior and may indicate an underlying hereditary syndrome.

Histologic types of atypical meningioma

Meningiomas have many histologic subtypes, which describe the tumor’sappearance under the microscope. Most subtypes are WHO grade 1, meaning they are slow-growing and usually behave benignly. However, some subtypes are more likely to recur and are assigned WHO grade 2, even when they lack other atypical features. Atypical meningioma itself is defined by specific microscopic findings rather than a particular subtype.

Chordoid meningioma (WHO grade 2)

Chordoid meningioma contains tumor cells arranged in cords or strands within a mucin-rich (“myxoid”) background. Because this subtype has a higher risk of recurrence than typical grade 1 tumors, it is always classified as WHO grade 2, even if it lacks other atypical features.

Clear cell meningioma (WHO grade 2)

Clear cell meningioma is composed of cells with clear cytoplasm due to glycogen. These tumors often occur in the spine or cerebellopontine angle and tend to recur more often. For this reason, all clear cell meningiomas are assigned WHO grade 2.

Meningiomas with papillary and rhabdoid features

In the past, papillary and rhabdoid patterns were automatically considered high-grade. We now know these patterns can appear in tumors of different grades. They do not determine WHO grade on their own, but often occur together with other features seen in WHO grade 2 or grade 3 tumors. Pathologists evaluate these patterns carefully because they may signal a higher risk of recurrence.

WHO grade

WHO grade is a system that describes how aggressive a tumor is expected to be based on its microscopic appearance and, in some cases, its molecular (genetic) features. The World Health Organization assigns meningiomas a grade of 1-3.

Atypical meningiomas are WHO grade 2. Grade 2 is an intermediate grade between benign grade 1 tumors and malignant grade 3 tumors.

  • WHO grade 1 meningiomas are slow-growing tumors with a low risk of coming back after treatment. They have a typical appearance under the microscope and rarely invade the brain.
  • WHO grade 2 atypical meningiomas show signs of more aggressive behavior. These signs include increased mitotic activity, brain invasion, and specific unusual microscopic features such as crowded cells, prominent nucleoli, or spontaneous necrosis. Tumors that fall into the chordoid or clear cell subtypes are also automatically assigned grade 2 because these types have a higher recurrence risk, even when other atypical features are not present. Overall, atypical meningiomas recur more often than grade 1 tumors and may require closer follow-up and additional treatment such as radiation.
  • WHO grade 3 meningiomas are the most aggressive group. They exhibit rapid cell division, severe cellular abnormalities, and widespread invasion of surrounding tissues. These tumors almost always require combined treatment and close follow-up.

In recent years, molecular findings have also become important for determining WHO grade. For example, homozygous deletion of CDKN2A or CDKN2B (loss of both copies of these genes) or a TERT promoter mutation automatically supports a diagnosis of WHO grade 3, even if the microscopic features look closer to grade 2. This is because studies have shown that tumors with these genetic changes behave much more aggressively.

Understanding the WHO grade helps your healthcare team estimate the likelihood of recurrence and determine whether surgery alone is appropriate or whether radiation therapy and closer follow-up are needed.

Biomarkers for atypical meningioma

Biomarkers are specific genetic or protein changes in tumor cells that provide information about prognosis and help guide management. In atypical meningioma, biomarkers help predict recurrence risk and identify tumors more likely to behave aggressively.

What types of biomarkers are tested?

Biomarker testing for atypical meningioma typically includes molecular testing, such as next-generation sequencing and copy-number analysis. Biomarkers known to influence behavior include NF2, AKT1, SMO, PIK3CA, KLF4, TRAF7, and high-risk features such as TERT promoter mutations or CDKN2A/CDKN2B deletions.

TERT promoter

The TERT promoter controls the expression of the TERT gene, which helps maintain telomeres—the protective ends of chromosomes. Mutations in the TERT promoter are associated with more aggressive behavior, earlier recurrence, and shorter survival in meningioma.

Pathologists use DNA sequencing to examine the promoter region of the TERT gene. Your report will state whether a TERT promoter mutation is present. If present, even in a tumor that otherwise appears grade 2, it may behave more like a grade 3 tumor.

CDKN2A and CDKN2B

CDKN2A and CDKN2B are genes that help regulate the cell cycle. When both copies are lost (homozygous deletion), tumor cells grow more freely. These deletions are found more often in higher-grade tumors and predict a high risk of recurrence.

These genes are evaluated using copy-number analysis or next-generation sequencing to detect deletions. The report will state whether the genes are intact or show homozygous deletion. Even in an atypical meningioma, a homozygous deletion increases the risk of progression.

NF2

NF2 is the most frequently mutated gene in all meningiomas, particularly those arising at the convexity or in the spine. NF2 loss is usually an early event and is often accompanied by additional genetic changes in atypical and anaplastic tumors.

NF2 status is assessed with next-generation sequencing and copy number testing. Your report will describe NF2 as mutated, deleted, or normal (wildtype).

SMO, AKT1, TRAF7, and PIK3CA

These genes are involved in cell growth and signaling pathways. They are more common in skull-base meningiomas, especially the meningothelial and secretory subtypes. Although these mutations are more often associated with grade 1 tumors, they help define molecular subgroups of meningiomas and may influence behavior and treatment.

Next-generation sequencing panels are used to evaluate multiple genes at once, including SMO, AKT1, TRAF7, and PIK3CA. The report will state whether the tumor has a mutation in one of these genes. These mutations do not automatically determine WHO grade but can help characterize the tumor.

H3K27me3

H3K27me3 is a chemical modification of a histone protein involved in regulating gene expression. Loss of H3K27me3 is associated with a higher risk of recurrence in atypical meningioma.

H3K27me3 status is assessed using immunohistochemistry. The report will state whether H3K27me3 is retained or lost. Loss is considered a high-risk feature.

Prognosis

Atypical meningioma has an intermediate prognosis. It is less aggressive than anaplastic meningioma (grade 3) but more likely to recur than grade 1 meningioma.

  • After complete surgical removal, recurrence rates are 29–52%.

  • After partial removal, recurrence is more common.

  • Additional treatment, such as radiation therapy, may be recommended to reduce the risk of recurrence.

Molecular features such as TERT promoter mutation, CDKN2A/CDKN2B deletion, and loss of H3K27me3 are associated with a higher risk of recurrence and can help refine prognosis.

What happens after the diagnosis?

After an atypical meningioma is diagnosed, your healthcare team will review imaging, pathology findings, and molecular results to decide on the best treatment plan. Surgery is the primary treatment, and doctors aim to remove the tumor completely when possible. If complete removal is not feasible or if high-risk features are present, radiation therapy is often recommended to lower the chance of recurrence.

Regular follow-up with MRI is essential because atypical meningiomas can return months or years after initial treatment. The timing and frequency of follow-up scans depend on WHO grade, extent of removal, and molecular results.

Questions to ask your doctor

  • What is the WHO grade and histologic subtype of my tumor?

  • Was the tumor completely removed during surgery?

  • Did the tumor invade brain tissue?

  • Were any high-risk molecular features identified, such as TERT mutation or CDKN2A/CDKN2B deletion?

  • Do you recommend radiation therapy in addition to surgery?

  • How often will I need follow-up MRIs?

  • What symptoms should I watch for that might suggest recurrence?

  • Are clinical trials or targeted therapies available for my tumor?

A+ A A-