The concept of malignant glioma includes many different types of tumors. They are anaplastic astrocytoma AA, glioblastoma multiforme GBM, gliosarcoma and malignant oligdendroglioma MO. . Whether these tumors represent a histological spectrum of common cellular origin remains controversial. In the treatment of malignant gliomas, accurate histopathological diagnosis is more important than differential analysis of biological behavior because of the different prognosis and treatment outcomes of these tumor types.
Epidemiology
Malignant astrocytomas are the most common type of primary intracranial tumors in adults. Although these tumors account for only 2% of all tumors in adults and have an incidence of only 5/100,000? years, they are still the 4th leading cause of death from tumors. Among malignant gliomas, AA and GBM account for 50% and 20%, respectively. Among patients in the age group >75 years, the incidence of GBM has increased exponentially in the last decade. Although the widespread use of CT and MRA has improved patient detection rates, the trend of increasing incidence remains difficult to interpret.
Family history and molecular genetics
The majority of patients with malignant glioma do not have a family genetic background, but some families can exhibit a familial tumor syndrome characterized by autosomal dominant inheritance, and these families show a high incidence of tumors in breast cancer, leukemia, soft tissue tumors, and malignant glioma. In particular, astrocytomas and medulloblastomas. Patients with tuberous sclerosis and neurofibromatosis type II may present with a spectrum of CNS malignancies, including gliomas, and Li-Fraumeni syndrome is a classic autosomal familial disorder in which patients often present with tumors of the brain, breast, soft tissue, bone, blood, and adrenal cortex. Scholars are studying genetic defects to define low-grade gliomas, AA and even glioblastomas. The genetic defects include: a heterozygous deletion on the short arm of chromosome 17 and the long arm of chromosome 19 (TP53 gene) associated with AA; GBM also involves a heterozygous deletion on chromosome 10 and a mutation and amplification of the receptor gene for endothelial growth factor; this mutation in the receptor for endothelial growth factor has been confirmed in at least one third of GBM patients. This rapid and irregular cell division often leads to a surge in the number of mutated genes, which further leads to a deregulation of the cell growth cycle.
Histopathology and grading
It has long been recognized that the aggressive growth of malignant gliomas limits the effectiveness of surgical and local treatment. The invasive growth is not limited to the distribution of the internal carotid artery or vertebral artery on one side, but often spreads along the cerebrospinal fluid pathway; in addition, biopsies taken from areas outside of all MR abnormalities can reveal tumor cells after in vitro cell culture of specimens from this area, despite normal histopathology. As far as the current technical means are concerned, imaging and histological examinations still do not allow a clear assessment of the actual borders of the tumor.
A group of neuropathologists was organized to reclassify gliomas, and the WHO classification was published in 1979 and has been revised several times in recent years, and is the most widely used one. The WHO four-grade scheme for astrocytic tumors includes hairy cell astrocytoma (grade 1), low-grade basal cell tumor (grade 2), mesenchymal astrocytoma (grade 3) and GBM (grade 4). grade 2 tumors may have nuclear anisotropy; grade 3 tumors may have nuclear anisotropy and nuclear schwannomatous phase; and grade 4 tumors have nuclear anisotropy, nuclear schwannomatous phase and endothelial proliferation or necrosis. Gliosarcoma has long been considered a subtype of GBM. The mesenchymal component of gliosarcoma exhibits marked malignancy, and it remains unclear whether GBM induces malignancy in the surrounding connective tissue or whether it is due to hypofractionation of precursor cells containing glial and mesenchymal components that leads to malignancy. Gliosarcoma is a rare tumor with a similar clinicobiological behavior to GBM, except for a slightly higher metastasis rate outside the central nervous system. The disease is not responsive to radiotherapy and chemotherapy. The exact incidence of malignant oligodendroglial cell tumors (MO) is difficult to estimate. Oligodendroglioma accounts for less than 10% of intracranial tumors, and tumors often contain abnormal astroglial components, but it is not certain that these mesenchymal cells represent the mesenchymal component of the tumor. cell differentiation in MO is low, and its publication and biological behavior are similar to GBM. Recurrent oligodendrogliomas have a 50-75% chance of showing mesenchymal changes and a 15% chance of evolving into GBM.52 MO has the highest sensitivity to chemotherapy and radiation compared to AA, GBM, and gliosarcoma.
Diagnosis
The common clinical manifestations of glioma are headache, focal neurological deficits and seizures. Signs vary depending on the location of the tumor. However, invasion of important functional cortical areas by tumor cells does not necessarily result in loss of function or diminished function. Gliomas can be very large and asymptomatic, but they can also be small and present with neurological deficits. Adults with persistent headaches, first seizures or neurological dysfunction need imaging, especially MRI.
Cranial plain films, angiography and CT were the main modalities of neuroimaging in the past, but now MRI has become the preferred method. fMRI (functional MRI) can be used to determine the location of the central sulcus and visual cortex, in addition to having a higher resolution to detect smaller lesions. Magnetic resonance spectroscopy (MRS) can also be used to help identify tumors, strokes, old trauma, radiation necrosis, infections, and multiple sclerosis. In the diagnosis of cranial tumors, MRI, like other imaging techniques, has some limitations. However, currently, MRI is the best method for diagnosis and preoperative evaluation.
In addition to MRI, other imaging studies may be useful in some cases; FDG-PET can detect the high metabolic rate of malignant gliomas; this feature can be used to differentiate tumors, tumor recurrence, and radiation necrosis; CT can differentiate intra-tumor calcifications and acute intracranial hematomas.
Treatment
Surgery
The aim of surgery for malignant glioma is threefold: to obtain a pathological diagnosis, to reduce the occupying effect and to reduce the harm of the tumor. Since imaging cannot accurately determine the type and grade of the tumor, obtaining a sample of the tumor is necessary before determining treatment options and estimating prognosis. After surgical removal of the tumor, reduction of the local occupancy effect may improve neurological symptoms, reduce hormone dependence, and even prevent early death. The importance of reducing tumor occupancy is well established. Of course there is still controversy regarding the impact of surgery on survival.
Many technological applications and developments have improved the safety of resected lesions. The development of functional mapping techniques has allowed surgeons to maximize the extent of lesion resection without damaging the functional cortex. Functional mapping techniques are important for identifying functional cortical areas such as speech, motor, sensory, and other functional areas during surgery. The application of intraoperative navigation techniques allows the operator to determine the boundaries and anatomical landmarks of the tumor intraoperatively, greatly improving the neurosurgeon’s ability to resect deep lesions. Currently, the application of new technologies such as intraoperative CT or MRI can help neurosurgical hospitals to more effectively and completely resect imaging abnormal tissues.
Biopsies alone may be performed when the lesion is located in an area that is difficult to remove surgically, when craniotomy is extremely risky or when the patient’s survival is predicted to be short based on the morbidity. Surgeons can obtain a histologic diagnosis through accurate stereotactic puncture without general anesthesia at low cost and with minimal surgical risk.
Radiation therapy
The three most important factors affecting the prognosis of malignant glioma are the presence or absence of radiation therapy, the patient’s age, and the patient’s clinical performance status. Of the three, radiation therapy is the only factor that can be modulated by the clinician. By analyzing the total dose of radiation therapy, tumor grade, type and size of radiation particles, duration of radiation therapy, and whether it is combined with chemotherapy, high voltage therapy, cryotherapy, and intra-stromal brachytherapy, one would expect the outcome of radiation therapy to improve patient prognosis. Many medical centers treat AA, MO, GBM, and gliosarcoma in a more similar fashion. Most patients undergo surgical treatment with biopsy followed by resection, followed by radiation therapy, which may lead to synchronization of the cell division cycle after radiotherapy for AA and MO, thus making subsequent chemotherapy more sensitive.
Chemotherapy
Chemotherapy also has an impact on the progression of malignant glioma and patient survival. Chemotherapy is currently used as a treatment option of limited effectiveness for recurrent patients who are not suitable for further radiation therapy, but also as a radical combination therapy for young patients who are still in good health.
Alkylating agents are currently the main agents of chemotherapy. Experiments have shown that alkylating agents are effective in the treatment of different types of tumors. The effectiveness of treatment is determined by the change in tumor size on imaging. The effectiveness of carazolamide is about 40%. These early studies have been used as the gold standard to judge the effectiveness of the application of new chemotherapy regimens. The mechanisms regarding tumor resistance to chemotherapeutic agents are multifactorial. How drugs enter the central nervous system has been a major clinical challenge. The blood-brain barrier seems to be an insurmountable barrier. It is the smaller, highly lipid-soluble and structurally unaltered molecules that are able to cross the blood-brain barrier.
New therapeutic options for malignant gliomas are being investigated. How quickly new treatment options can be translated from the laboratory research phase to clinical application becomes critical. The lack of randomized controlled prospective clinical trials to evaluate the efficacy of treatments has slowed the introduction of these new treatment options. Patients with this disease should be enrolled in larger comprehensive care facilities so that new treatment options can be tested quickly and effectively in the clinic and thus be used in a wider range of settings.