Tumors originating from the neuroepithelium are collectively known as gliomas, which account for 40-50% of cranial tumors and are the most common intracranial malignant tumors. The annual incidence rate is about 3-8 per 100,000 population.
Classification
1. According to the morphology of tumor cells
Glioma is mainly classified according to the degree of similarity between tumor cell morphology and normal glial cells (not necessarily their true cellular origin) as follows.
(1) astrocytoma – astrocytes
(2) Oligodendrocytoma – oligodendrocytes
(3) Ventricular meningioma – ventricular meningeal cells
(4) Mixed gliomas, such as oligodendroglioma-astrocyte tumors, which contain mixed types of glial cells
2.According to the malignancy of tumor cells
Gliomas can be further classified according to the pathological malignancy of tumor cells.
(1) Low-grade gliomas (WHO grade 1-2), which are well-differentiated gliomas; although these tumors are not biologically benign, the prognosis of patients is relatively good.
(2) High-grade gliomas (WHO grade 3-4), which are poorly differentiated gliomas; these tumors are malignant and patients have a poor prognosis for survival.
Although there are many grading systems for gliomas, the most commonly used is the grading system developed by the World Health Organization (WHO). According to this grading system, gliomas are classified as grade 1 (least malignant and best prognosis) to grade 4 (most malignant and worst prognosis). Among them, the so-called mesenchymal glioma of traditional cytopathology corresponds to WHO grade 3; glioblastoma corresponds to WHO grade 4.
3. Classification according to the location of the tumor
Glioma can be classified according to its location in the brain. The cerebellar curtain divides the brain tissue into supratentorial and infratentorial regions. Accordingly, glioma is also classified as supratentorial glioma and subcortical glioma.
(1) Supratentorial glioma: located on the cerebellar curtain, mainly in the cerebral hemispheres, it is the most common glioma in adults (70%).
(2) Subcapsular glioma: located in the subcapsular cerebellum, mainly in the cerebellar hemispheres, and is the most common glioma in children (70%).
(3) Pontine glioma: located in the brainstem. The brain stem includes three parts: mesencephalon, pontine brain and medulla oblongata, of which the pontine brain controls important functions including respiration. Surgery in the pontine brain carries a high degree of risk.
Etiology
Like other tumors, gliomas result from the interaction of congenital genetic risk factors and environmental carcinogenic factors. Some known genetic disorders, such as neurofibromatosis (type I) and tuberous sclerosis, are genetic susceptibility factors for glioma. Patients with these diseases have a much higher chance of developing glioma than the general population. In addition, some environmental carcinogenic factors may also be associated with the development of glioma. Some studies have suggested that electromagnetic radiation, such as cell phone use, may be associated with the development of gliomas. However, there is no evidence that there is a necessary causal relationship. Although most patients with glioblastoma have had a macrophage virus infection, and evidence of macrophage virus infection is found in the vast majority of glioblastoma pathology specimens, it is not entirely clear whether there is a causal relationship between the two.
Signs and Symptoms
The signs and symptoms caused by gliomas depend on their occupational effects and the function of the brain regions affected. Gliomas can cause headaches, nausea and vomiting, seizures, and blurred vision due to their “occupying” effect in space. In addition, they can also cause other symptoms due to their impact on local brain tissue function. For example, glioma of the optic nerve can cause loss of vision; glioma of the spinal cord can cause pain, numbness, and weakness of the limbs; glioma of the central region can cause motor and sensory impairment; and glioma of the speech area can cause difficulty in speech expression and understanding. The rate of symptoms varies depending on the degree of malignancy of the glioma. For example, patients with low-grade gliomas often have a history of several months or even years, while patients with high-grade gliomas often have a history of a few weeks to a few months. Based on the patient’s history, symptoms, and signs, an initial inference can be made about the location of the lesion and its malignancy.
Diagnosis
The diagnosis of glioma is a comprehensive consideration and judgment based on the patient’s history, symptoms, signs, ancillary tests, and postoperative pathology. After a patient has clinical manifestations, the most common tests performed at the time of consultation include cranial CT and MRI. cranial CT can initially determine whether there is an intracranial occupancy. On CT, gliomas often appear as intracerebral, low-signal lesions; low-grade gliomas are usually without peritumoral edema, while high-grade gliomas are often accompanied by peritumoral edema. In addition, CT is superior to MRI in detecting the presence of tumor hemorrhage as well as calcification. Hemorrhage occurring in tumor strokes, which appear as high signal on CT, suggests a high degree of malignancy of the tumor. The occurrence of tumor with calcification suggests a high probability that the pathological type of the tumor is oligodendritic. Magnetic resonance is superior to CT examination in showing the location and nature of the tumor. Low-grade gliomas often appear as intracerebral lesions with low T1 signal and high T2 signal on MRI, mainly located in the white matter, and often have clear borders with the surrounding brain tissue on the image. High-grade gliomas generally have heterogeneous signal, with low signal in T1 and high signal in T2; however, if hemorrhage is present, there is sometimes high signal in T1; tumors often have obvious heterogeneous enhancement; tumors are poorly defined with surrounding brain tissue; and peritumoral edema is more severe. Sometimes, gliomas are not easily distinguished from other lesions, such as inflammation and ischemia. Therefore, it may be necessary to do other tests, including PET and MRS, to further understand the glucose metabolism and other molecular metabolism of the lesion, so that the differential diagnosis can be distinguished. In addition, sometimes a so-called functional magnetic resonance examination (fMRI) is performed to clarify the relationship between the lesion and the function of the surrounding brain tissue. With these examinations, it is usually possible to make a preliminary clinical judgment about the site of the glioma and the grade of malignancy before surgery. However, the final diagnosis depends on the pathological diagnosis after surgery.
Treatment
1.Surgery
Surgery is often the first step in the treatment of glioma. Surgery not only provides the final pathological diagnosis, but also can quickly remove most of the tumor cells, relieve the patient’s symptoms, and facilitate the next step of other treatments. For some low-grade gliomas, such as hairy cell astrocytomas, complete surgical excision is possible to provide radical cure as well as long-term survival of the patient. Current glioma surgery has entered an era of minimally invasive procedures that are safer, less invasive, and more completely resected tumors than before. The application of microscopy for glioma resection allows for clearer identification of the boundary between the tumor and the brain tissue, as well as the surrounding important neurovascular and other structures, thus enabling the removal of the glioma in a safe and maximized manner. The application of neuronavigation has taken surgical resection of gliomas to a new level. Similar to car navigation, neuronavigation allows surgeons to be more precise and refined before surgery, from the design of incisions, to the identification of functional brain areas during surgery, and the selection of surgical resection methods. Intraoperative magnetic resonance, which has emerged in recent years, can further improve the integrity of complete surgical resection and reduce complications such as postoperative functional deficits in patients. The application of intraoperative cortical stimulation electrodes can improve the intraoperative recognition of motor and speech areas, thus helping surgeons to better protect the important functions of the brain.
2. Radiotherapy
After surgical treatment, further radiotherapy is often required for patients with high-grade gliomas. For patients with low-grade glioma, radiotherapy should also be considered if there are high-risk factors (e.g. tumor size over 6 cm, incomplete surgical resection, etc.). Radiotherapy includes local radiotherapy and stereotactic radiotherapy. Stereotactic radiotherapy is generally not used for gliomas that are first detected. Depending on the technique used, local radiotherapy can be divided into conformal intensity modulated radiotherapy and 3D shaping radiotherapy. For patients with recurrent glioma, especially in the functional area, sometimes stereotactic radiotherapy can be considered.
3.Chemotherapy
Chemotherapy and targeted therapy are gradually playing an important role in the treatment of glioma. For high-grade glioma, the application of temozolomide can significantly prolong the survival prognosis of patients. Currently, temozolomide is the only chemotherapeutic agent with clear efficacy in the treatment of glioma. In patients with primary high-grade glioma, temozolomide should be continued for a period of time (6-12 cycles) alone after its concomitant application with radiotherapy (concurrent radiotherapy phase). Other chemotherapeutic agents (e.g., nimostatin) may be effective in the treatment of recurrent gliomas. The newly emerged vascular-targeting drug, Avastin, has clear efficacy for recurrent high-grade gliomas and can significantly prolong patient survival.
Prognosis
After comprehensive treatment, median survival ranges from 8-10 years for patients with low-grade gliomas (WHO grade 1-2), 3-4 years for patients with mesenchymal gliomas (WHO grade 3), and 14.6-17 months for patients with glioblastomas (WHO grade 4). Notably, for patients with glioblastoma, the emerging regimen of radiation therapy with temozolomide chemotherapy can result in survival to more than 5 years in nearly 10% of patients; prior to the advent of temozolomide, less than 1% of patients could exist for 5 years with radiation therapy alone.
Gliomas are difficult to eradicate and often recur. After tumor recurrence, depending on the patient’s functional status, treatment such as re-surgery, radiotherapy, and chemotherapy may be considered.