Meningiomas are tumors that originate in the meninges, the protective layers of tissue surrounding the brain and spinal cord. They are usually slow-growing and often not cancerous. Because their behavior is highly variable, ranging from indolent growth to aggressive recurrence, a standardized classification system is necessary to predict their course. The World Health Organization (WHO) provides this standardized system, which is universally used to grade meningiomas and guide management decisions.
Understanding the WHO Grading System
The WHO classification system for central nervous system tumors categorizes meningiomas into three distinct grades: Grade 1, Grade 2, and Grade 3. This grading predicts the tumor’s biological behavior, particularly its likelihood of recurrence after treatment. The grades represent a spectrum of aggressiveness, with Grade 1 being the least aggressive and Grade 3 the most aggressive. This systematic approach allows physicians to communicate the expected clinical course and tailor treatments effectively.
The current standard is defined in the 5th Edition of the WHO Classification of CNS Tumours, published in 2021. The numerical grades serve as a prognostic indicator for patients, with higher numbers signifying a greater risk of the tumor returning. Grade 1 tumors demonstrate a low risk of recurrence, Grade 2 indicates an intermediate risk, and Grade 3 is associated with a high likelihood of recurrence and aggressive behavior.
Detailed Characteristics of Grades 1, 2, and 3
Grade 1 Meningiomas
Grade 1 meningiomas represent the majority of diagnoses, accounting for approximately 80% of all cases. These tumors are considered benign and are characterized by slow growth rates and well-defined borders. Patients with Grade 1 tumors have a favorable long-term outlook, with a five-year survival rate near 95.7%. Surgical removal is often curative due to the low risk of recurrence, and these tumors rarely invade surrounding brain tissue.
Grade 2 Meningiomas
Grade 2 meningiomas are classified as atypical, falling between benign and malignant behavior. These tumors have a higher risk of recurrence compared to Grade 1 tumors, necessitating closer post-treatment monitoring. Their growth rate is often faster than Grade 1 lesions, and they may show an increased tendency to spread into adjacent tissues. The five-year survival rate for patients with Grade 2 meningiomas is estimated to be around 81.8%.
Grade 3 Meningiomas
Grade 3 meningiomas are classified as malignant and are the least common, representing 1.5% to 2% of diagnoses. These tumors exhibit aggressive behavior, including rapid cell division and a very high risk of recurrence and progression. The prognosis is less favorable, with reported five-year survival rates dropping to approximately 46.7%. Grade 3 tumors often require the most intensive and multimodal treatment strategies.
Key Pathological Features Determining Grade
The WHO grade is assigned based on a pathologist’s examination of the tumor tissue under a microscope. Pathological features indicating a higher grade relate to the tumor cells’ appearance and their rate of division. A primary criterion for grading is the mitotic count, which measures the number of dividing cells observed within a specific field of view.
Criteria for Grade 2
A meningioma is classified as Grade 2 if it displays four or more mitotic figures per ten high-power fields (HPFs) of microscopic view, or if it shows brain invasion. Brain invasion, where the tumor penetrates the surrounding brain tissue, automatically qualifies the tumor as Grade 2. Other secondary features, such as increased cellularity, small cell formation, or spontaneous necrosis, can also contribute to a Grade 2 designation when at least three are present.
Criteria for Grade 3
A Grade 3 classification is assigned when the tumor exhibits twenty or more mitotic figures per ten HPFs, or shows frank anaplasia, which is a highly abnormal, malignant cell appearance. The 2021 WHO classification also introduced specific molecular features as definitive criteria for Grade 3, even without meeting all histological requirements. The presence of a TERT promoter mutation or a homozygous deletion of the CDKN2A/B gene is sufficient to classify a meningioma as Grade 3.
Treatment Decisions Based on WHO Grade
The assigned WHO grade dictates the clinical management plan, ranging from observation for low-grade lesions to aggressive multimodal therapy for high-grade tumors.
Grade 1 Treatment
For most asymptomatic Grade 1 meningiomas, initial observation with serial magnetic resonance imaging (MRI) may be the recommended approach. When intervention is necessary, surgical resection is the primary and often curative treatment.
Grade 2 Treatment
Management of Grade 2 meningiomas is more proactive due to the increased risk of recurrence. The standard approach involves aggressive surgical removal, followed by consideration of adjuvant radiation therapy. Postoperative radiation is frequently utilized for Grade 2 tumors, particularly if the entire tumor could not be safely removed or if the tumor shows a high proliferative index. This additional treatment aims to reduce the likelihood of the tumor returning.
Grade 3 Treatment
Grade 3 meningiomas necessitate an aggressive, multimodal treatment strategy from the outset. This generally includes maximal safe surgical removal, immediately followed by postoperative radiation therapy to the tumor bed. Given the poor outcome associated with this grade, physicians may also consider systemic therapies or enrollment in clinical trials testing new targeted or immunotherapeutic drugs. The combination of surgery and radiation is intended to manage the high proliferative capacity and aggressive nature of the malignant tumor cells.