Can a Glioma Be Benign? A Look at Glioma Grades

Some gliomas are indeed benign, but the word “benign” applies cleanly to only a narrow slice of glioma diagnoses. The World Health Organization grades gliomas on a scale from 1 to 4, and grade 1 tumors, the kind most common in children, often behave like textbook benign growths: slow, well-defined, and curable with surgery alone. Once you move to grade 2, though, the picture shifts. These tumors are called “low-grade,” and while they grow slowly, many carry a real risk of transforming into aggressive cancers over time. The grading system, the molecular biology underneath it, and the age of the patient all shape whether a given glioma deserves the reassuring label of “benign.”

How the WHO Grading System Works

The WHO classifies brain tumors on a four-tier scale. Grade 1 tumors are slow-growing, typically well-circumscribed, and often curable. Grade 2 tumors grow slowly but tend to infiltrate surrounding brain tissue. Grade 3 tumors show features of active, abnormal cell division. Grade 4 tumors are the most aggressive, with rapid growth, areas of dead tissue, and new blood vessel formation. For gliomas specifically, grade 1 and grade 2 are grouped under the umbrella of “low-grade,” while grades 3 and 4 are “high-grade.”

The classification has changed substantially in recent years. The 2021 fifth edition of the WHO system overhauled how gliomas are categorized, placing much greater weight on molecular features rather than relying almost entirely on what the tumor looks like under a microscope. Genetic markers now help determine both the tumor type and its grade, which means two tumors that look identical under the microscope might receive different grades depending on their molecular profile.¹ Adult diffuse gliomas, in particular, are now graded partly through molecular markers, and entirely new categories of pediatric gliomas have been recognized.²

Grade 1 Gliomas and the Case for “Truly Benign”

If any glioma earns the label “benign” without an asterisk, it is pilocytic astrocytoma. This is the most common brain tumor in children, classified as WHO grade 1, and it tends to form a discrete mass that does not infiltrate deeply into surrounding tissue. The ten-year survival rate exceeds 95%, and many patients are effectively cured after complete surgical removal.³ When a surgeon can take the whole tumor out, recurrence is uncommon, and many of these patients go on to live normal lives.

Another grade 1 glioma worth knowing is subependymal giant cell astrocytoma, or SEGA, which arises almost exclusively in people with a genetic condition called tuberous sclerosis complex. SEGA is considered benign, but its location near the fluid-filled chambers of the brain means it can cause dangerous pressure buildup if it blocks the flow of cerebrospinal fluid. Treatment options include surgery and a class of drugs called mTOR inhibitors. Everolimus, one such drug, has been shown to shrink these tumors and is now approved for this use in the US and Europe.⁴

Even among grade 1 tumors, location matters enormously. Optic pathway gliomas, for example, are low-grade tumors that grow along the nerves connecting the eyes to the brain. They are frequently linked to another genetic condition, neurofibromatosis type 1. The tumor itself may be histologically benign, but because of where it sits, it can impair vision, disrupt hormonal function, and affect development in children.⁵ So “benign” on a pathology report does not always translate to “harmless” in a patient’s life.

Why “Low-Grade” Does Not Always Mean “Benign”

Grade 2 gliomas are where the language gets slippery. Doctors call them “low-grade,” and patients understandably hear that as reassuring. But most grade 2 gliomas are diffuse, meaning the tumor cells spread into the brain tissue around them like fingers, making a clean surgical removal much harder. These tumors affect mostly young adults and represent a genuinely different biological situation from grade 1 tumors.⁶

The critical distinction is this: grade 1 gliomas are usually cured by surgery; grade 2 gliomas are usually managed over time. The word “managed” is doing a lot of work in that sentence. It means ongoing MRI surveillance, potential additional surgeries, and often radiation or chemotherapy at some point. Calling a grade 2 diffuse glioma “benign” would mislead a patient about the likely trajectory of their disease.

Molecular Markers That Shape the Outlook

The 2021 WHO classification made molecular genetics central to how gliomas are understood, and for good reason. Two genetic features in particular have a major influence on prognosis in grade 2 gliomas: mutations in the IDH genes (IDH1 or IDH2) and a chromosomal abnormality called 1p/19q codeletion. Tumors that carry both of these markers tend to respond better to treatment and have significantly longer survival times. One study found that patients with both IDH mutation and 1p/19q codeletion had a median survival of about 15.6 years, significantly better than any other molecular subgroup of grade 2 glioma.⁷

On the other end of the spectrum, grade 2 gliomas that lack IDH mutations (called “IDH wild-type”) tend to behave more aggressively, and under the 2021 classification, many of these tumors are now reclassified as grade 4 regardless of what they look like under the microscope. This is a major shift: a tumor that might have been labeled “low-grade” a decade ago based on its appearance could now be designated the highest grade based on its genetics. The molecular markers also shape the immune environment of the tumor in ways that may affect future immunotherapy approaches.⁸

The Risk of Transformation

One of the most unsettling aspects of low-grade gliomas is that they can transform into high-grade tumors over time. A diffuse grade 2 glioma that sits quietly for years can acquire new genetic alterations and begin growing aggressively. A systematic review and meta-analysis identified several factors that predict this transformation: the molecular markers mentioned above (IDH status and 1p/19q codeletion), the size of the tumor before and after surgery, how much of the tumor was removed, and whether the tumor shows contrast enhancement on MRI.⁹

At the genetic level, this transformation involves additional mutations that disrupt the machinery controlling how genes are read and expressed. Research on IDH1-mutated gliomas that progressed to higher grades found new alterations in genes involved in RNA processing, gene regulation, and the maintenance of stem-cell-like properties in cancer cells.¹⁰ In rare cases, even clearly benign low-grade tumors driven by the MAPK pathway have been reported to transform through dramatic chromosomal changes.¹¹

This risk of transformation is a core reason why even “benign-looking” gliomas demand long-term monitoring. A patient who hears “low-grade” and assumes the tumor is static may not appreciate why their doctor insists on regular scans for years or even decades.

Pediatric Versus Adult Gliomas

Age reshapes the entire glioma landscape. About two-thirds of childhood gliomas are classified as low-grade, compared with only around 20% in adults.¹² The differences go far beyond incidence. Pediatric low-grade gliomas are driven by different genetic alterations, tend to arise in different brain regions, and rarely transform into high-grade tumors, a pattern that sets them apart sharply from adult low-grade gliomas.¹³

For families hearing that their child has a low-grade glioma, this is genuinely good news. Most pediatric low-grade gliomas behave in a way that justifies the word “benign” in practice, even if they sometimes require treatment for symptoms related to their location. In adults, the same histological label carries a heavier weight, because adult diffuse low-grade gliomas are more likely to eventually progress. Understanding which population the statistics come from matters enormously when interpreting a prognosis.

The Challenge of Getting the Diagnosis Right

Grading a glioma accurately is harder than it might seem. On MRI, low-grade gliomas typically appear as small lesions without the bright contrast enhancement seen in high-grade tumors, which tend to look irregular with surrounding swelling and internal dead tissue.¹⁴ Advanced MRI techniques, such as diffusion-weighted imaging, can help distinguish low-grade from high-grade tumors by measuring how freely water molecules move through the tissue.¹⁵ But imaging alone is imperfect: roughly a third of gliomas that lack contrast enhancement and look low-grade on conventional MRI turn out to be high-grade when tissue is examined.¹⁶

Biopsy is the gold standard for diagnosis, but it has its own limitations. Because gliomas are often heterogeneous, meaning different parts of the same tumor may have different grades, a needle biopsy can sample a low-grade region and miss a high-grade pocket nearby. One study comparing stereotactic biopsy results with findings from subsequent surgical resection found complete diagnostic agreement in only about a third of cases, with undergrading of grade 3 tumors occurring in roughly 28% of biopsies.¹⁷ Differentiating between non-enhancing grade 2 and grade 3 gliomas with advanced MRI metrics remains difficult as well, achieving only moderate accuracy in research settings.¹⁸

These diagnostic uncertainties have real consequences. A patient told they have a grade 2 glioma may actually harbor a higher-grade tumor. This is why the molecular markers discussed earlier have become so important: they add an independent layer of information that does not depend on which piece of tumor the surgeon happened to sample.

How Surgery Shapes Outcomes

For low-grade gliomas, surgery serves two purposes: obtaining tissue for accurate diagnosis and removing as much tumor as possible. The extent of resection is one of the strongest predictors of long-term survival. A meta-analysis of published studies found that complete (gross total) resection was associated with dramatically better five-year and ten-year survival compared with partial resection or biopsy alone.¹⁹

Even for gliomas discovered incidentally, before they cause any symptoms, there is evidence that earlier surgery with greater removal is linked to longer survival, and this benefit held regardless of the tumor’s molecular subclass.²⁰ The catch is that more aggressive surgery in the brain carries its own risks. The tumor may sit in areas controlling speech, movement, or memory, and the surgeon has to balance maximum removal against preserving function. This trade-off is part of why low-grade glioma management is so individualized.

A New Generation of Targeted Drugs

For decades, the treatment options after surgery for low-grade gliomas were limited to watching and waiting, or turning to radiation and traditional chemotherapy, both of which carry significant side effects. A breakthrough arrived with vorasidenib, a drug designed to block the mutant IDH enzyme that drives many grade 2 gliomas. In a large phase 3 trial, patients with non-enhancing grade 2 IDH-mutant gliomas who took vorasidenib after surgery had a median time before their tumor progressed of about 27.7 months, compared with 11.1 months for those taking a placebo. The drug also more than tripled the time before patients needed their next treatment.²¹

This is one of the first times a pill targeting the specific genetic mutation in a low-grade glioma has shown clear benefit in a rigorous trial. Earlier phase 1 work showed that both vorasidenib and a related drug, ivosidenib, could shrink tumors after surgery, with response rates in the range of 35 to 43% at higher doses.²² The significance extends beyond the numbers: vorasidenib represents a shift toward precision medicine in a space where treatment has historically been blunt.²³

When Patients Hear “Benign” or “Low-Grade”

The way glioma diagnoses are communicated to patients deserves its own discussion. Research observing neuro-oncology consultations has found that when patients first learn about a brain tumor, the language is often deliberately vague, with clinicians using phrases like “a finding in your brain” while uncertainty remains. Patients themselves tend to avoid the word “cancer,” preferring terms like “my condition” or “the lump.”²⁴ This ambiguity has benefits and costs. It can reduce initial distress, but it can also leave patients without a clear understanding of what they are facing.

For someone with a grade 1 pilocytic astrocytoma, calling the tumor “benign” is accurate and appropriate. For someone with a diffuse grade 2 glioma, the same word could create a false sense of security about a tumor that may need treatment and surveillance for years. Patients benefit from understanding not just the grade but what it means for their particular tumor’s molecular profile and expected behavior. The grade alone is no longer the whole story.

Liquid Biopsies and Monitoring Without Surgery

One of the more promising developments in glioma monitoring is the idea of tracking tumor DNA circulating in the blood, sometimes called a liquid biopsy. Traditional monitoring depends on MRI, but imaging can be ambiguous. A tumor that appears to grow on a scan may actually be swelling from treatment effects rather than true progression, a phenomenon called pseudoprogression. Research on a different type of brain tumor, diffuse midline glioma, has shown that tracking tumor-specific DNA fragments in the blood can sometimes distinguish genuine tumor growth from treatment-related swelling more accurately than MRI alone. In one reported case, a child’s blood-based DNA levels dropped even as MRI showed apparent tumor growth, correctly predicting that the patient was actually responding to treatment.²⁵ This technology is still early in development for most glioma types, but it points toward a future where patients might need fewer invasive procedures and get faster, clearer answers about whether their tumor is changing.

Dogs, Gliomas, and What They Teach Us

An unexpected window into glioma biology has come from veterinary medicine. Dogs develop spontaneous gliomas that share striking molecular similarities with human tumors. A large comparative study analyzing 83 canine gliomas found that the genetic changes driving these tumors overlapped substantially with those in human gliomas, including mutations in receptor signaling pathways, cell-cycle regulators, and even the IDH1 gene. The canine tumors showed particularly strong resemblance to human pediatric gliomas in their patterns of chromosomal changes, mutation rates, and DNA methylation.²⁶ Efforts are underway to establish standardized diagnostic classifications for canine gliomas to further strengthen their value as a model for testing treatments that might eventually benefit human patients.²⁷ Because dogs share our living environments and develop these tumors naturally rather than through laboratory induction, they offer a model that clinical trials in mice simply cannot replicate.