The annual incidence of primary central nervous system (CNS) tumors is 16.5 per 100,000, with nearly half being malignant tumors. These account for approximately 1.5% of all malignant tumors, with gliomas being the most common, representing around 40% of CNS tumors.
Etiology
Known causes include certain genetic syndromes and prior radiation therapy. Potential risk factors include electromagnetic radiation, neurocarcinogens, allergic diseases, and viral infections. Residual cells or tissues from embryonic development can also grow into tumors, such as craniopharyngiomas, chordomas, and teratomas.
Pathological Classification
The fifth edition of the World Health Organization Classification of CNS Tumors (WHO CNS 5, 2021) adopts a model of "integrated diagnosis" combining histopathological diagnosis and genetic characteristics. This edition further emphasizes the importance of molecular diagnosis and introduces new tumor types and related subtypes.
Clinical Manifestations
The clinical features vary depending on the tumor's biological characteristics and primary location, with increased intracranial pressure and neurological localization symptoms being common features.
Increased Intracranial Pressure
Reasons include tumor-related mass effect, peritumoral brain edema, and obstructed cerebrospinal fluid circulation leading to hydrocephalus.
Neurological Localization Symptoms
Neurological dysfunction results from the tumor's direct stimulation, compression, or destruction of cranial nerves.
Destructive Symptoms
These arise from the tumor invading brain tissue. Tumors in the central precentral or postcentral gyrus can cause contralateral motor and sensory deficits. Frontal lobe tumors often lead to psychiatric disturbances. Occipital lobe tumors may result in visual field defects. Tumors in the inferior parietal lobe, including the angular and supramarginal gyri, can lead to acalculia, alexia, apraxia, and anomic aphasia. Damage to the motor speech center may cause motor aphasia. Tumors affecting the hypothalamus manifest as endocrine disorders, while those in the tectal plate lead to upward gaze palsy. Tumors in the vermis of the cerebellum can cause hypotonia and truncal or lower limb ataxia, while those in the cerebellar hemispheres result in ipsilateral limb ataxia. Brainstem tumors can present as alternating hemiplegia.
Compression Symptoms
Tumors in the sellar region can cause visual and visual field impairments. Tumors in the cavernous sinus may compress the 3rd, 4th, 5th, and 6th cranial nerves, resulting in symptoms of cavernous sinus syndrome, such as ptosis, impaired eye movement, and reduced facial sensation. Early cranial nerve symptoms provide valuable clues for localization.
Epilepsy
The incidence of epilepsy associated with brain tumors ranges from 30% to 50%. Slowly growing brain tumors, such as dysembryoplastic neuroepithelial tumors (DNETs) and low-grade gliomas, have a substantially higher incidence of epilepsy compared to rapidly growing malignant tumors like glioblastoma or metastatic lesions. The occurrence and type of tumor-associated epilepsy are related to the tumor's location. For instance, epileptic seizures occur in up to 90% of cases involving gliomas in the motor area, typically presenting as focal seizures. Frontal lobe tumors are more commonly associated with generalized seizures. Tumors in the central region and parietal lobe are often linked to partial seizures, while temporal lobe tumors may lead to complex partial seizures with symptoms such as olfactory hallucinations. Long-term video-electroencephalographic monitoring during seizure episodes can detect diagnostic features such as sharp waves and spike waves.
Characteristics of Intracranial Tumors in the Elderly and Children
In elderly individuals, brain atrophy causes relatively increased intracranial space, resulting in less pronounced signs of increased intracranial pressure during tumor development, leading to a higher likelihood of misdiagnosis. Supratentorial meningiomas and metastatic tumors are more common among the elderly. In children, midline tumors are more frequent, with medulloblastomas and ependymomas commonly observed in the infratentorial region, and craniopharyngiomas being predominant in the supratentorial region. Hydrocephalus symptoms often overshadow localization signs, increasing the risk of misdiagnosis as gastrointestinal diseases.
Diagnosis
Diagnosis involves both localization diagnosis (identifying the tumor's position and its relationship with surrounding structures) and qualitative diagnosis (determining the tumor's nature and biological characteristics). Differential diagnosis is required to distinguish tumors from brain inflammatory conditions, degenerative diseases, or cerebrovascular disorders.
Head CT and MRI
Abnormal density on CT images, signal changes on MRI images, compression of brain ventricles, displacement of brain tissue, and the extent of peritumoral brain edema can assist in determining the tumor's location, size, number, blood supply, and anatomical relationship with surrounding structures. Secondary changes in the tumor tissue, such as necrosis, hemorrhage, cystic degeneration, and calcification, also aid in qualitative diagnosis for most tumors. Functional MRI (fMRI) has seen increasing clinical applications, revealing the relationship between tumors, cortical functional areas, and subcortical fiber tracts. However, caution is needed when the tumor is adjacent to critical areas, as fMRI-based localization may become unreliable when the tumor is less than 4 mm from nearby motor regions.
Positron Emission Tomography (PET)
PET utilizes positron-emitting radionuclides to measure metabolic activity, protein synthesis rates, and receptor density and distribution, reflecting overall metabolism and function in the body. It can detect tumors at an early stage, assess the malignancy of brain tumors, and is particularly useful in diagnosing brain metastases and identifying the primary site. PET is also valuable in distinguishing primary central nervous system lymphoma from systemic lymphoma that has metastasized to the brain.
Biopsy
Biopsy, using stereotactic or neuronavigation techniques to obtain specimens for histological examination, confirms tumor pathology and determines the treatment approach.
Treatment
Medical Treatment
Lowering intracranial pressure is a primary measure.
For patients with a history of epilepsy before surgery, postoperative antiepileptic drugs are typically administered for three months. If there are no epileptic episodes and follow-up electroencephalography (EEG) results are negative, the medication can be gradually reduced and discontinued. In patients without a preoperative history of epilepsy, those with supratentorial tumors do not require prophylactic antiepileptic drugs before surgery. Postoperatively, antiepileptic drugs are generally given for two weeks, and if no seizures occur, the medication can be tapered and discontinued. For patients with high-risk factors associated with epilepsy, the duration of postoperative antiepileptic therapy should be appropriately extended.
Surgical Treatment
Surgical resection of the tumor within the maximum safe range helps to reduce intracranial pressure and relieve compression on cranial nerves.
Radiation Therapy
Radiation therapy is used as an adjuvant treatment following the surgical resection of most malignant tumors or as the primary treatment for select tumor types. Germ cell tumors and lymphomas are highly sensitive to radiation, while pituitary adenomas, craniopharyngiomas, chordomas, and astrocytomas show low sensitivity. For tumors prone to spreading by seeding, such as medulloblastomas, germ cell tumors, and embryonal tumors, whole-brain and whole-spine irradiation is often required.
Chemotherapy
Temozolomide is the first-line chemotherapeutic agent for treating malignant gliomas. Concurrent radiation therapy with temozolomide followed by six cycles of maintenance chemotherapy is the standard post-surgical treatment for glioblastoma. Second-line chemotherapeutic agents for malignant gliomas often include carmustine (BCNU), lomustine (CCNU), etoposide (VP16), teniposide (VM26), and platinum-based drugs.