Most meningiomas are not cancer. They are the most common type of brain tumor, making up more than a third of all primary tumors in the central nervous system, and the large majority are slow-growing and classified as benign.1Europe PMC. Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions But the word “benign” can be misleading here, because meningiomas exist on a spectrum. The World Health Organization divides them into three grades, and where a particular tumor falls on that scale determines whether it behaves more like a nuisance or more like a genuine malignancy.
How the WHO Grading System Works
The WHO classifies meningiomas into three tiers based on what the tumor cells look like under a microscope, how fast they are dividing, and increasingly, what their DNA reveals. Grade I tumors are labeled benign. Grade II tumors are called atypical. Grade III tumors are anaplastic, and these are the ones that qualify as truly malignant.2PubMed Central. Extracranial metastases of anaplastic meningioma About 80 percent of meningiomas fall into Grade I. The remainder split between Grade II and Grade III, with anaplastic tumors accounting for roughly two to three percent of all meningiomas.
The dividing line between grades rests on several features pathologists look for in the tissue removed during surgery. One of the most important is the mitotic index, which measures how many cells are actively dividing in a given area. Grade I tumors have few dividing cells. Grade II tumors show more, and a meta-analysis confirmed that a higher mitotic index correlates with a significantly greater chance of recurrence after surgery.3PubMed. Mitotic Index and Progression-Free Survival in Atypical Meningiomas Grade III tumors have the highest counts, along with features like tissue death within the tumor and invasion into surrounding brain. These are the tumors that can spread to the lungs, liver, bone, and skin, though such distant spread remains uncommon even among them.2PubMed Central. Extracranial metastases of anaplastic meningioma
In 2021, the WHO added molecular criteria alongside the traditional microscope-based approach. A tumor that looks low-grade under the microscope can now be upgraded to Grade III if it carries a specific genetic deletion called CDKN2A/B homozygous deletion, which is strongly tied to early recurrence and aggressive behavior.4Europe PMC. CDKN2A/B homozygous deletion is associated with early recurrence in meningiomas This was a significant shift in how meningiomas are diagnosed: a tumor’s genetic profile can now override what the pathologist sees on the slide.
Why “Benign” Does Not Mean “Harmless”
A Grade I meningioma will not metastasize to distant organs, but it can still cause real problems. These tumors grow from the membranes surrounding the brain and spinal cord, and even slow growth in a confined space like the skull can press on critical structures. Symptoms range from headaches and vision changes to seizures and personality shifts, depending on where the tumor sits. Some meningiomas grow through the skull bone itself and into the tissue beneath the scalp, even when they are histologically benign.5Europe PMC. Brain meningioma invading and destructing the skull bone: replacement of the missing bone in vivo
Grade I meningiomas also recur. The recurrence rate depends heavily on how completely the tumor was removed and on certain microscopic features. In one study of 150 Grade I patients, a higher cell-division marker, skull base location, and incomplete removal were all independent predictors of recurrence.6PubMed Central. Atypical Histological Features as Risk Factors for Recurrence in Newly Diagnosed WHO Grade I Meningioma Another study found that Grade I patients whose tumors had a proliferation index above a certain threshold faced a recurrence risk comparable to patients who had an incomplete resection.7PubMed Central. WHO Grade I Meningioma Recurrence: Identifying High Risk Patients Using Histopathological Features and the MIB-1 Index So even within the “benign” category, some tumors act more aggressively than others. The grade gives you a general picture, but it is not the whole story.
What Drives a Meningioma to Become More Aggressive
The most common genetic abnormality found in meningiomas involves the NF2 gene, which produces a tumor-suppressor protein called Merlin. When this gene is lost or mutated, cells lose an important brake on growth.8PubMed Central. Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis NF2 alterations are found across all grades but are known to initiate events that lead to more aggressive tumor behavior. Interestingly, the prognostic impact of NF2 loss depends on tumor location: it predicts recurrence in tumors above the tentorium (the upper brain compartment) but may actually signal a better prognosis in tumors below it.9PubMed Central. Clinical significance of NF2 alteration in grade I meningiomas revisited; prognostic impact integrated with extent of resection, tumour location, and Ki-67 index
Beyond NF2, researchers have identified several molecular pathways involved in the transition from low-grade to high-grade disease. These include deletions on chromosome 1p, mutations in CDKN2A/B (the genetic marker now used for automatic Grade III classification), changes in a gene called TERT that controls how cells maintain their ability to keep dividing, and the activity of a transcription factor called FOXM1.10Journal of Cancer. Malignant Transformation of Meningiomas Understanding these pathways matters because they are beginning to inform treatment decisions, and they help explain why two tumors that look the same under the microscope can behave very differently over time.
Can a Benign Meningioma Turn Into Cancer
It is rare, but it does happen. In a large study tracking over 1,300 patients who had surgery for Grade I meningiomas and then experienced a recurrence, about one percent underwent histological transformation, meaning their tumor came back at a higher grade than it was originally. This corresponded to a risk of roughly 0.12 percent per patient-year of follow-up.11Scientific Reports. Histological transformation in recurrent WHO grade I meningiomas Most of the upgrades were from Grade I to Grade II, but a smaller number jumped to Grade III. Some tumors progressed in stages across multiple surgeries, going from I to II to III over years.
This is one reason why long-term follow-up imaging matters even after a seemingly complete removal of a benign meningioma. The absolute risk is low, but it is not zero, and catching a grade increase early changes the treatment approach considerably.
Risk Factors and the Hormone Connection
Meningiomas are roughly twice as common in women as in men, and hormones appear to be part of the reason. About two-thirds of all meningiomas occur in women, and the tumors frequently enlarge or become symptomatic during pregnancy or during certain phases of the menstrual cycle.12Journal of Neurosurgery. Estrogen and progesterone receptors in meningiomas A significant fraction of meningioma tissue carries progesterone receptors, which helps explain this hormonal sensitivity.
Hormone replacement therapy has been linked to increased meningioma risk. A large study found that women who used hormone therapy for more than ten years had about 70 percent higher odds of developing a meningioma compared to non-users, with the risk being especially pronounced for combined estrogen-progestagen regimens.13PubMed. Hormone replacement therapy increases the risk of cranial meningioma The connection to certain anti-androgen medications is even stronger. Cyproterone acetate, a drug used for conditions ranging from severe acne to prostate cancer, carried a dramatically elevated meningioma risk at high cumulative doses, with one cohort study showing a hazard ratio above 20 for the highest dose category.14PubMed. Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study This finding led several countries to restrict the drug’s use.
Despite these hormonal links, a small study examining estrogen-only hormone therapy in women who already had incidental meningiomas found that tumors in the treatment group were actually smaller and grew more slowly than those in the untreated group.15PubMed Central. Estrogen hormone replacement therapy in incidental intracranial meningioma: a growth-rate analysis The authors described these as preliminary results, and the finding should not be taken as medical advice, but it highlights the complexity: not all hormonal exposure carries the same risk, and the interplay between different hormones and meningioma biology is still being worked out.
Ionizing radiation is the other well-established risk factor. People who received radiation to the head during childhood, whether for a previous cancer or for conditions like scalp ringworm (which was treated with radiation decades ago), have a significantly higher lifetime risk of developing meningiomas, often years or decades later.
How Treatment Differs by Grade
For Grade I meningiomas that cause symptoms, surgery is the primary treatment, and it can be curative when the tumor and its attachment to the surrounding membrane are completely removed. The extent of removal is tracked using a classification that assigns grades based on how thoroughly the surgeon resected the tumor and its dural origin. Complete removal with excision of the underlying membrane yields the best results: recurrence rates as low as 5 percent in one series, compared to 35 percent when only partial removal was possible.16Journal of Neurosurgery. Relevance of Simpson grading system and recurrence-free survival after surgery for World Health Organization Grade I meningioma This relationship held for tumors in different locations, including both skull base and convexity tumors.
When complete removal is not achievable, or for tumors in locations where surgery carries high risk, focused radiation such as Gamma Knife radiosurgery is an effective tool. Long-term studies show good tumor control for Grade I meningiomas treated this way, especially for residual tumor after surgery or for tumors that are not causing swelling in the surrounding brain.17PubMed Central. Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma
For Grade II and III tumors, the picture changes. Surgery is still the starting point, but the recurrence rates are higher, and radiation therapy after surgery is more commonly recommended. Gamma Knife radiosurgery for recurrent or residual higher-grade meningiomas has shown a local tumor control rate of about 50 percent, which is substantially lower than for Grade I tumors, and roughly a fifth of patients in one series developed radiation-related side effects.18PubMed. Role of gamma knife radiosurgery for recurrent or residual World Health Organization grade II and III intracranial meningiomas Grade III meningiomas in particular tend to recur despite aggressive treatment, and options become limited after surgery and radiation have been tried.
What Happens When Standard Treatment Stops Working
For meningiomas that keep coming back despite surgery and radiation, drug treatments have historically been disappointing. But several newer approaches are being tested. Drugs that block the growth of blood vessels feeding the tumor, particularly bevacizumab, have shown the most promise. Two prospective trials and several retrospective studies suggest this drug can shrink tumors and reduce the swelling around them, with patients who have Grade II or III disease appearing to benefit more than those with Grade I tumors.19PubMed. Systemic therapy for relapsed/refractory meningioma: Is there potential for antiangiogenic agents?
Beyond bevacizumab, early-phase trials are exploring therapies that target specific molecular pathways active in meningiomas, including drugs that block cell-division machinery and immune checkpoint inhibitors. Some patients with recurrent high-grade meningiomas have experienced prolonged disease control with immunotherapy, though these are still early findings from small studies.20PubMed. Emerging targeted therapies in meningiomas The molecular profiling discussed earlier is what makes these targeted approaches possible: knowing which genetic alterations a tumor carries helps clinicians match it to the right drug.
Watch-and-Wait for Meningiomas Found by Accident
A growing number of meningiomas are discovered incidentally, when someone gets a brain scan for an unrelated reason like a headache, a fall, or dizziness. These tumors are often small and causing no symptoms, which raises a question that does not have a tidy answer: should you treat it or just watch it?
Major guidelines from European and North American neuro-oncology organizations recommend periodic imaging and clinical assessment as the first-line approach for incidental meningiomas.21Neuro-Oncology Advances. The management of incidental meningioma: An unresolved clinical conundrum The intervals and duration of monitoring vary, reflecting the reality that the evidence base here is thin. Prognostic tools have been developed that combine MRI features, tumor volume, and patient characteristics to estimate the risk of rapid growth and help personalize the decision, but none are universally adopted yet.
Long-term follow-up of incidentally found meningiomas shows that the majority do grow over time, but many eventually plateau. In one prospective study tracked over 12 years, growth decelerated on average after about a year and a half and became statistically insignificant after eight years. About two-thirds of tumors showed this self-limiting growth pattern.22PubMed Central. Growth dynamics of incidental meningiomas: A prospective long-term follow-up study A separate analysis of over 200 untreated meningiomas found that about 59 percent grew during the observation period, while 14 percent actually shrank and 27 percent showed no change at all.23Neuro-Oncology Advances. Growth dynamics of untreated meningiomas
For older adults in particular, the decision gets even more nuanced. A multicenter study comparing focused radiation to observation in patients over 65 with incidental meningiomas found that radiation achieved tumor control in about 97 percent of cases compared to roughly 72 percent with observation alone. But the observation group had no new neurological deficits, while a small percentage of those treated with radiation did.24Neurosurgery. Comparison of Active Surveillance to Stereotactic Radiosurgery for the Management of Elderly Patients With an Incidental Meningioma When a tumor is not causing symptoms and the patient has other health concerns, the risk-benefit calculation tilts toward watching rather than treating. A related multicenter study concluded that if surveillance is the chosen approach, radiation should be recommended when tumor growth is detected on imaging, before symptoms appear.25PubMed. Stereotactic radiosurgery versus active surveillance for asymptomatic, skull-based meningiomas: an international, multicenter matched cohort study
How Imaging Is Changing the Game
Standard MRI has been the backbone of meningioma diagnosis and monitoring for decades, but a newer type of scan is proving useful for tricky cases. Meningiomas tend to produce high levels of a protein called a somatostatin receptor on their surface. PET scans that use a radioactive tracer designed to bind to this receptor can pick up meningioma tissue with high sensitivity, even in locations where MRI struggles, such as the skull base or areas where bone is involved.26PubMed. The Value of SSTR PET for Detection, Definition, and Ongoing Management of Meningioma
This type of PET imaging is also useful for distinguishing meningioma from other conditions that can mimic it on MRI, and for planning radiation therapy more precisely. Because Gamma Knife and other focused radiation techniques depend on accurately defining the tumor’s edges, adding this receptor-based imaging to MRI has improved the reliability of treatment planning, especially for recurrent tumors or those with complex skull involvement.27PubMed Central. Somatostatin Receptor Targeted PET-Imaging for Diagnosis, Radiotherapy Planning and Theranostics of Meningiomas: A Systematic Review of the Literature The same receptor that makes these tumors visible on PET scans may eventually serve as a target for therapy as well, an approach called theranostics that uses the imaging tracer to both find the tumor and deliver radiation directly to it.
Living With a Meningioma After Treatment
Even when treatment goes well, the aftermath of a meningioma diagnosis can affect quality of life in ways that do not always show up on a scan. Patients with meningiomas, including those with minimal symptoms, report significantly lower quality of life compared to healthy individuals across physical, mental, and social domains.28PubMed Central. Health-related quality of life in meningioma Risk factors for worse outcomes include larger tumors, higher histological grade, seizures, and tumor location near critical brain areas. Treatment tends to improve these scores, but they may remain lower than normal long-term.
A systematic review of long-term survivors found persistent physical symptoms like headaches, fatigue, and vision problems; emotional issues including depression and anxiety at elevated rates; and social consequences such as difficulty returning to work and social isolation.29Neuro-Oncology Advances. Long-term health-related quality of life in meningioma survivors: A mixed-methods systematic review A focused study quantified some of this: about two-thirds of patients showed measurable cognitive impairment, roughly a quarter had moderate to severe depressive symptoms, and nearly half were unable to return to work. Younger patients and those with faster mental processing speeds were more likely to get back to their jobs.30PubMed. Long-term neurocognitive, psychological, and return to work outcomes in meningioma patients
These findings are worth knowing because the label “benign brain tumor” can set expectations that do not match reality. People sometimes assume that if a tumor is not cancer, recovery should be straightforward. For many meningioma patients, it is not. Cognitive rehabilitation, mental health support, and realistic conversations about what to expect after surgery are all part of good care, even for Grade I tumors. The tumor’s grade tells you a lot about how it will behave biologically, but it tells you less about how the person living with it will feel day to day.