Your pathology report for meningioma

By Jason Wasserman MD PhD FRCPC
December 1, 2025


A meningioma is a type of brain tumor that starts from cells in the meninges, the thin layers of tissue that cover and protect the brain and spinal cord. More specifically, meningiomas are thought to arise from meningothelial cells in the arachnoid mater, one of the protective layers.

Most meningiomas are benign (non-cancerous) and grow slowly. However, some can grow more quickly or come back after treatment and are considered more aggressive. The World Health Organization (WHO) classifies meningiomas as grades 1, 2, or 3 based on how the tumor appears under the microscope and its behavior.

Where do meningiomas occur?

Meningiomas can develop anywhere along the meninges. Common locations include the

  • Cerebral convexities (the outer surfaces of the brain).

  • Falx cerebri and venous sinuses (midline structures between the two brain hemispheres).

  • Olfactory groove (near the sense of smell).

  • Skull base, including sphenoid wing, parasellar and suprasellar regions, and optic nerve sheath.

  • Tentorium and posterior fossa (structures at the back and underside of the brain).

  • Spinal canal, especially the thoracic spine.

These locations affect symptoms and the complexity of surgery. Rarely, meningiomas can arise outside the central nervous system, such as in the lung.

What are the symptoms?

The symptoms of a meningioma depend on where the tumor is located, its size, and how quickly it grows. Because most meningiomas grow slowly, symptoms can develop gradually over months or years. Common symptoms include:

  • Headaches.

  • Seizures.

  • Weakness or numbness in an arm or leg.

  • Changes in vision or hearing, depending on the tumor’s site.

  • Balance problems or difficulty walking.

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

Some meningiomas are discovered incidentally when imaging is performed for other reasons, such as after trauma or for long-standing headaches.

How common is meningioma?

Meningioma is the most common primary brain tumor in adults. It accounts for more than one-third of all central nervous system tumors. The risk of meningioma increases with age, and the median age at diagnosis is around 66 years. Meningiomas are more common in women than in men, particularly for WHO grade 1 tumors. They are less common in children and young adults.

What causes meningioma?

For most people, the exact cause of a meningioma is unknown. Several risk factors have been identified:

  • Ionizing radiation. Radiation exposure, especially to the head during childhood, clearly increases the risk of meningioma.

  • Hormones. The higher incidence in women, the presence of hormone receptors in some tumors, and links with other hormone-related conditions suggest that estrogen and progesterone may play a role.

  • Inherited syndromes. Certain genetic conditions, such as neurofibromatosis type 2 (NF2), Gorlin syndrome, and syndromes involving genes such as BAP1, PTEN, SMARCE1, and others, can increase the risk of developing one or more meningiomas.

  • Family history. Having a close family member with a meningioma may increase an individual’s risk.

Most meningiomas, however, occur sporadically without a clear inherited cause.

How is this diagnosis made?

Imaging

Meningiomas are usually first suspected based on neuroimaging, most commonly MRI and CT scans. On MRI, a meningioma often appears as a well-defined, solid mass attached to the dura (the outermost layer of the meninges). It usually shows uniform contrast enhancement after gadolinium injection. A characteristic imaging feature is a “dural tail”, where the enhancement extends along the dura beyond the primary tumor.

Calcifications (areas of calcium) are common and are best seen on CT. Some meningiomas show swelling (edema) in the brain tissue around the tumor, which can be prominent in specific subtypes, such as secretory, microcystic, angiomatous, lymphoplasmacyte-rich, and higher-grade tumors. Imaging can suggest the diagnosis, and sometimes the likely grade, but a tissue sample is needed to confirm meningioma and determine its subtype and grade.

Biopsy and surgery

The diagnosis of meningioma is usually confirmed 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 examined under the microscope by a pathologist. The pathologist determines whether the tumor is a meningioma, describes its histologic subtype, and assigns a WHO grade based on specific features.

Microscopic features

Under the microscope, meningiomas are tumors of meningothelial cells that often show round or oval nuclei and a moderate amount of cytoplasm. Many meningiomas form whorls, circular arrangements of cells, and psammoma bodies, small, lamellated calcifications.

Most WHO grade 1 meningiomas are relatively uniform and show low mitotic activity (few dividing cells). WHO grade 2 (atypical) and WHO grade 3 (anaplastic or malignant) meningiomas show increased cell density, more irregular nuclear features, higher mitotic activity, and sometimes necrosis (areas of dead tissue) or brain invasion.

Immunohistochemistry

Immunohistochemistry (IHC) uses antibodies linked to dyes to highlight specific proteins in tumor cells. In meningiomas, IHC helps confirm the diagnosis and rule out other tumors. Common markers include:

  • EMA (epithelial membrane antigen) and vimentin, which are often positive in meningiomas.

  • SSTR2A, a somatostatin receptor that is strongly and diffusely expressed in most meningiomas, can help distinguish them from other tumors.

Proliferation markers, such as Ki-67, are used to estimate the rate of tumor cell division. A higher Ki-67 index suggests a higher-grade tumor and a greater chance of recurrence.

Some special stains can act as surrogates for underlying genetic changes. For example:

  • Loss of nuclear SMARCE1 expression is seen in many clear cell meningiomas.

  • Loss of BAP1 expression is seen in some rhabdoid or high-grade meningiomas and is associated with more aggressive behavior.

These and other immunohistochemical findings are interpreted in conjunction with microscopic features and clinical information to arrive at the final diagnosis.

Histologic types of meningioma

Under the microscope, meningiomas can have different patterns and appearances. These patterns are called histologic subtypes. A histologic subtype is a way of describing how the tumor cells are arranged and what they look like under a microscope. For example, some tumors have many small calcifications, some have many blood vessels, and others have clear cells or secretory areas. These differences help pathologists classify the tumor more precisely.

Most histologic subtypes are considered WHO grade 1, meaning they are benign and slow-growing. A few subtypes, such as chordoid and clear cell meningiomas, are assigned WHO grade 2 because they are more likely to come back after treatment. Very aggressive tumors with highly abnormal cells and many dividing cells are classified as WHO grade 3. In this way, the histologic subtype is closely linked to the tumor’s grade, which tells doctors how the tumor is likely to behave and helps guide treatment.

Meningothelial meningioma (grade 1)

Meningothelial meningioma is the classic and most common subtype. The tumor is composed of meningothelial cells arranged in lobules with a syncytial pattern, in which cell borders are not sharply defined and the cells appear to blend. The nuclei can show “nuclear holes” and intranuclear pseudoinclusions, which are invaginations of cytoplasm into the nucleus. Whorls and psammoma bodies are less common than in some other subtypes. These tumors are usually WHO grade 1 and have an excellent prognosis when completely removed.

Fibrous meningioma (grade 1)

Fibrous meningioma is made of spindle-shaped cells arranged in bundles or fascicles within a collagen-rich background. The tumor can feel firm and fibrous. Whorls and psammoma bodies may be present. This subtype is usually WHO grade 1. Recurrence risk is low after complete removal, although tumors under challenging areas may be more complex to resect fully.

Transitional meningioma (grade 1)

Transitional meningioma shows a mixture of meningothelial and fibrous patterns. Areas with whorls and psammoma bodies are common. Because it combines features of meningothelial and fibrous subtypes, it is called “transitional.” Most transitional meningiomas are WHO grade 1 and behave benignly, especially when entirely excised.

Psammomatous meningioma (grade 1)

Psammomatous meningioma is characterized by numerous psammoma bodies, which are rounded calcifications. Tumor cells can be sparse and often resemble fibrous or transitional subtypes. This type usually occurs in the spine, particularly in middle-aged or elderly women. It is WHO grade 1 and generally has an excellent prognosis.

Angiomatous meningioma (grade 1)

Angiomatous meningioma contains many blood vessels that dominate the tumor, with meningioma cells squeezed between them. The vessels may be thick-walled and hyalinized (showing a glassy appearance). This subtype is WHO grade 1 but can be associated with significant brain edema (swelling) around the tumor. Prognosis is usually good after complete removal.

Microcystic meningioma (grade 1)

Microcystic meningioma has many small spaces (microcysts) between tumor cells, giving a loose, spongy appearance. Tumor cells often have thin, elongated processes. These tumors are typically benign (WHO grade 1), but like angiomatous and secretory meningiomas, they can be associated with prominent brain edema.

Secretory meningioma (grade 1)

Secretory meningioma is characterized by small gland-like spaces filled with eosinophilic (pink) secretions called pseudopsammoma bodies. These secretory areas often stain for epithelial markers such as CEA. This subtype is WHO grade 1 but can cause significant edema around the tumor. Despite impressive imaging findings, the prognosis is generally favorable when the tumor is entirely removed.

Lymphoplasmacyte-rich meningioma (grade 1)

Lymphoplasmacyte-rich meningioma has a prominent inflammatory infiltrate of lymphocytes and plasma cells that can overshadow the tumor cells. Tumor cells themselves are often typical meningothelial cells. This rare subtype is WHO grade 1 and may sometimes be difficult to distinguish from inflammatory conditions.

Metaplastic meningioma (grade 1)

Metaplastic meningioma shows areas where tumor cells resemble other tissue types, such as bone (osseous), cartilage (chondroid), fat (lipomatous), or xanthomatous (foamy) tissue. These changes are usually benign. Metaplastic meningiomas are WHO grade 1 and generally behave like other benign meningiomas.

Chordoid meningioma (grade 2)

Chordoid meningioma has cells arranged in cords or strands within a mucin-rich (myxoid) background and can resemble another tumor, chordoma. Chordoid meningioma may be associated with more frequent recurrence and is therefore assigned WHO grade 2, even if other features are otherwise low grade. Atypical (grade 2) behavior may require closer follow-up and, in some cases, additional treatment.

Clear cell meningioma (grade 2)

Clear cell meningioma is made of cells with clear cytoplasm due to glycogen and often shows a sheet-like growth pattern. These tumors may occur in the cerebellopontine angle or spinal canal and tend to affect younger patients. Clear cell meningioma has a higher risk of recurrence and is designated WHO grade 2, even in the absence of other atypical features.

Atypical meningioma (grade 2)

Atypical meningioma is defined by increased mitotic activity, brain invasion, or specific combinations of histologic features such as high cellularity, small cells with a high nucleus-to-cytoplasm ratio, prominent nucleoli, patternless or sheet-like growth, and spontaneous necrosis. These tumors have a significantly higher recurrence rate than grade 1 meningiomas and are classified as WHO grade 2. Prognosis is intermediate, and close monitoring is needed.

Anaplastic (malignant) meningioma (grade 3)

Anaplastic, or malignant, meningioma is the most aggressive subtype. It shows markedly abnormal cells, high mitotic activity, necrosis, and often invades the brain and surrounding structures. Molecular features such as TERT promoter mutations or CDKN2A/CDKN2B homozygous deletions can also qualify a tumor as WHO grade 3, even if microscopic features are borderline. These tumors are classified as WHO grade 3 and have a high risk of recurrence and metastasis. They often require combined surgery and radiation, and the prognosis is guarded.

WHO grade

WHO grade is a system that describes how aggressive a tumor is likely to be. It is based on how the tumor looks under the microscope (including its histologic subtype), how many cells are dividing, whether it invades the brain, and whether there are areas of necrosis (dead tissue). Grade is important because it helps predict the likelihood that the tumor will recur after treatment and how quickly it may grow.

For meningiomas, the WHO grading system uses three primary grades:

  • WHO grade 1 (benign meningioma): Grade 1 tumors grow slowly and have low mitotic activity (few dividing cells). They do not show malignant features such as severe nuclear atypia, brain invasion, or widespread necrosis. Most common subtypes, including meningothelial, fibrous, transitional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, and metaplastic meningiomas, are usually WHO grade 1. These tumors have the lowest risk of recurrence, especially when they are entirely removed.

  • WHO grade 2 (atypical meningioma): Grade 2 tumors show more active growth and a higher risk of coming back. A tumor may be classified as grade 2 if it has increased mitotic activity, brain invasion, or a combination of specific microscopic features such as high cellularity, prominent nucleoli, sheeting (patternless growth), and spontaneous necrosis. Two subtypes, chordoid and clear cell meningioma, are always considered at least WHO grade 2 because they recur more often than typical grade 1 tumors. Patients with grade 2 meningiomas need closer follow-up and may receive radiation therapy after surgery.

  • WHO grade 3 (anaplastic or malignant meningioma): Grade 3 tumors are the most aggressive. They show marked anaplasia (very abnormal cells), very high mitotic activity, and often brain invasion and necrosis. In addition, certain genetic changes, such as TERT promoter mutations or homozygous deletion of CDKN2A and CDKN2B, are considered strong markers of malignant behavior and can support a WHO grade 3 diagnosis, even if some microscopic features are borderline. Grade 3 meningiomas have a high risk of recurrence and may spread beyond the brain. They usually require aggressive treatment and careful long-term monitoring.

The histologic subtype provides the basic tumor pattern, while the WHO grade combines this pattern with other microscopic and molecular features to estimate the tumor’s aggressiveness and guide treatment planning.

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 meningiomas, specific biomarkers help predict recurrence risk, support grading decisions, and may identify tumors that could benefit from targeted therapies or immunotherapy. Biomarkers can also help distinguish between different subtypes and identify tumors associated with inherited syndromes.

What types of biomarkers are tested?

Biomarker testing for meningioma typically involves molecular tests, such as next-generation sequencing and copy-number analysis. These tests look for mutations, deletions, amplifications, and gene fusions in tumor DNA. Some of the most clinically relevant biomarkers include changes in NF2, AKT1, TRAF7, SMO, PIK3CA, TERT promoter, CDKN2A/CDKN2B, SMARCE1, and BAP1. Immunohistochemistry can serve as a surrogate marker for some genetic alterations, such as SMARCE1 or BAP1 loss.

NF2

NF2 is a tumor suppressor gene located on chromosome 22 that helps control cell growth. Loss or mutation of NF2 is the most common genetic change in meningiomas, especially in convexity and spinal meningiomas. NF2 inactivation is an early event in tumor development and is associated with more complex genetic changes and a higher risk of progression in some cases.

NF2 status is assessed using molecular tests, such as next-generation sequencing and copy number analysis, to detect mutations and deletions involving chromosome 22q.

Your report may state whether NF2 is mutated, deleted, or intact, and this information may be included in the tumor’s molecular profile.

AKT1, SMO, PIK3CA, and TRAF7

AKT1, SMO, PIK3CA, and TRAF7 are genes involved in growth and signaling pathways. Mutations in these genes are common in skull-base meningiomas, particularly in meningothelial and secretory subtypes, and often occur in a mutually exclusive pattern with NF2 mutations. Tumors with these mutations tend to have more balanced genomes and may behave differently from NF2-mutant tumors.

These genes are evaluated using next-generation sequencing panels that simultaneously analyze multiple genes.

The pathology report will describe whether each gene is mutated or wild type (no mutation detected). The specific mutation may be listed, such as AKT1 p.E17K.

TERT promoter

The TERT promoter region controls expression of the TERT gene, which is involved in maintaining telomeres, the protective ends of chromosomes. TERT promoter mutations increase telomerase activity and are associated with more aggressive tumor behavior. In meningiomas, TERT promoter mutations are associated with a higher risk of recurrence, a shorter time to progression, and worse overall survival.

TERT promoter mutations are detected using targeted sequencing methods that analyze the TERT promoter region.

Your report will indicate whether a TERT promoter mutation is present. When present, this finding supports assigning a higher WHO grade (often grade 3) and suggests a more aggressive clinical course.

CDKN2A and CDKN2B

CDKN2A and CDKN2B are tumor suppressor genes that regulate the cell cycle. Homozygous deletion (loss of both copies) of these genes allows cells to divide more freely and is associated with aggressive behavior in meningiomas.

These genes are evaluated using copy-number analysis or other molecular techniques that detect deletions.

The report will describe whether CDKN2A and CDKN2B are intact or show homozygous deletion. Homozygous deletion is considered a high-risk feature and can support a diagnosis of WHO grade 3 meningioma.

SMARCE1

SMARCE1 is a gene involved in chromatin remodeling, which affects how DNA is packaged and how genes are turned on or off. Mutations in SMARCE1 are strongly associated with clear cell meningioma, especially in younger patients.

SMARCE1 status can be assessed by DNA sequencing to detect mutations and by immunohistochemistry to evaluate nuclear expression of the SMARCE1 protein.

Loss of nuclear SMARCE1 staining in tumor cells supports a diagnosis of clear cell meningioma. The report may also state whether a SMARCE1 mutation was identified.

BAP1 and PBRM1

BAP1 and PBRM1 are tumor suppressor genes that are involved in chromatin regulation. Loss or mutation of BAP1 is associated with rhabdoid and some high-grade meningiomas and is linked to the BAP1 tumor predisposition syndrome, which includes a risk of other cancers. PBRM1 mutations are enriched in papillary meningiomas and may be associated with aggressive behavior.

These genes can be evaluated by next-generation sequencing for mutations and by immunohistochemistry to assess protein expression in tumor cell nuclei.

The report may describe loss of BAP1 expression or PBRM1 mutation as high-risk features associated with more aggressive meningiomas. Loss of BAP1, particularly, supports a more malignant behavior and may prompt closer follow-up.

Prognosis

The prognosis for meningioma depends on many factors, including WHO grade, histologic subtype, tumor location, extent of surgical removal, and molecular features.

  • WHO grade 1 tumors generally have an excellent prognosis, especially when completely removed, but they can recur, especially in difficult locations.

  • WHO grade 2 tumors have a higher risk of recurrence and may require radiation therapy after surgery.

  • WHO grade 3 tumors are aggressive, often recur quickly, and carry a higher risk of metastasis and mortality.

Molecular features such as TERT promoter mutations, CDKN2A/CDKN2B deletions, and complex chromosomal changes are associated with worse outcomes and can help refine prognosis within each grade.

What happens after the diagnosis?

After a meningioma is diagnosed, your care team will discuss treatment options with you. In many cases, the main treatment is surgery to remove as much of the tumor as safely possible. For tumors that cannot be fully removed, or for higher-grade tumors, radiation therapy may be recommended. Some patients may be monitored with regular imaging if the tumor is small, not causing symptoms, or located in an area where surgery would be risky.

It is increasingly important that meningiomas undergo molecular testing for biomarkers such as TERT promoter status and CDKN2A/CDKN2B deletion, especially in atypical or anaplastic tumors or those that behave aggressively. These results can influence grading, prognosis, and eligibility for clinical trials or targeted therapies. Your doctors will also consider factors such as your age, general health, and preferences when planning treatment and follow-up.

Questions to ask your doctor

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

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

  • Are there any high-risk features, such as brain invasion, high mitotic count, or necrosis?

  • Were any molecular changes, such as TERT promoter mutation, CDKN2A/CDKN2B deletion, or NF2 mutation, identified?

  • Do you recommend radiation therapy or other treatments in addition to surgery?

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

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

  • Are there any clinical trials or targeted therapies that might be appropriate for my type of meningioma?

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