A low-grade glioma (LGG) is a type of primary brain tumor that originates from the glial cells, the supportive tissues of the central nervous system (CNS). These tumors are considered “low grade” because their cells look closer to normal cells and are characterized by a slow growth rate compared to their high-grade counterparts. LGGs affect the brain and spinal cord, and their slow-growing nature means they can exist for years before causing noticeable symptoms. The modern understanding and classification of these tumors rely heavily on both how the cells appear and their specific genetic makeup.
Understanding Tumor Grade and Growth Rate
The World Health Organization (WHO) uses a standardized grading system from I to IV to classify CNS tumors based on how aggressive they appear under a microscope. Low-grade gliomas fall into the WHO Grade I and Grade II categories. Grade I tumors, such as pilocytic astrocytomas, are typically well-defined, localized, and rarely spread.
Grade II gliomas are also slow-growing but are generally diffuse, meaning they tend to infiltrate nearby healthy brain tissue. This infiltrative nature makes them more challenging to remove completely than Grade I tumors. Although Grade II tumors grow slowly, they carry the potential to transform into higher, more aggressive grades over time, a process known as malignant transformation. This potential for progression requires careful, long-term monitoring.
Identifying Specific Low Grade Glioma Subtypes
The classification of low-grade gliomas now incorporates specific molecular markers, which provide a more accurate prediction of tumor behavior and treatment response. Two major subtypes are Astrocytoma and Oligodendroglioma, which are defined by their genetic alterations. This molecular approach has become the standard for defining specific diagnoses.
A primary molecular alteration is the status of the IDH (Isocitrate Dehydrogenase) gene mutation. Gliomas with an IDH mutation generally have a better long-term outlook than those that are IDH-wildtype, which often behave more aggressively. The IDH mutation status is used to categorize diffuse gliomas into IDH-mutant and IDH-wildtype groups.
Astrocytomas are typically characterized as IDH-mutant but lack the 1p/19q codeletion. These tumors often also show mutations in the TP53 gene and loss of the ATRX gene. Oligodendrogliomas are defined by having both the IDH mutation and the 1p/19q codeletion (a combined loss of genetic material from chromosomes 1 and 19). This specific dual molecular signature is associated with a more favorable prognosis and greater sensitivity to chemotherapy.
Recognizing Symptoms and Initial Diagnostic Steps
Symptoms caused by a low-grade glioma are highly variable and depend primarily on the tumor’s size and its precise location within the brain or spinal cord. Because of their slow growth, LGGs can often reach a considerable size before any symptoms appear. The most common initial presentation for many patients is a new-onset seizure.
Persistent headaches are also a frequent symptom, often caused by increased pressure within the skull as the tumor grows. These headaches may be worse in the morning or accompanied by nausea and vomiting. Depending on the tumor’s location, patients may experience neurological deficits, such as weakness, numbness, vision changes, or difficulty with walking and balance. Changes in personality, memory, or cognitive function can also occur gradually.
The first step in diagnosis is typically imaging, with Magnetic Resonance Imaging (MRI) being the preferred method to visualize the tumor’s size and extent. MRI provides detailed images that can suggest the presence of a low-grade glioma, which often appears as a non-enhancing lesion. However, a definitive diagnosis, including molecular classification, requires obtaining tissue through either a biopsy or surgical resection. This tissue is then examined by a pathologist to determine the WHO grade and specific molecular markers, which informs subsequent treatment decisions.
Overview of Treatment and Long-Term Management
The management of a low-grade glioma is determined by the tumor’s molecular markers, size, location, and the patient’s overall health and age. For small, asymptomatic tumors discovered incidentally in non-critical areas of the brain, active surveillance, or “watch-and-wait,” may be recommended. This involves regular MRI scans to monitor for any signs of growth or malignant change before treatment begins.
Surgical resection is generally the primary goal of treatment, aiming for “maximal safe resection.” Removing as much of the tumor as possible without causing new neurological deficits is associated with improved outcomes. Advanced techniques like intraoperative brain mapping are often used during surgery to identify and protect areas that control speech, movement, and other functions.
Following surgery, or for tumors that cannot be fully removed, adjuvant therapies may be necessary. Radiation therapy can be used to control tumor growth, although the timing is often debated to preserve quality of life. Chemotherapy, often using the combination regimen of Procarbazine, Lomustine, and Vincristine (PCV) or Temozolomide, is frequently used. These agents are particularly effective for IDH-mutant and 1p/19q codeleted tumors due to their sensitivity. Because LGGs tend to recur or progress to higher grades, long-term management requires lifelong monitoring with regular imaging and follow-up visits.