(CNS) Tumors Lecture
Overview of Central Nervous System (CNS) Tumors
Central Nervous System (CNS) tumors encompass primary and secondary neoplasms located within the brain and spinal cord, occurring across both pediatric and adult populations.
Anatomical Distribution and Incidence:
of all CNS tumors involve the brain.
Of the brain tumors, are supratentorial (located above the tentorium / brainstem).
of all CNS tumors are located within the spine and spinal cord.
Mean age at diagnosis for brain tumors is approximately of age.
Five-year survival rates are significantly higher in younger patient cohorts than in older populations.
The overall male-to-female ratio across all CNS tumors is approximately equal ().
Etiology and Potential Risk Factors:
The definitive cause of primary CNS tumors remains largely unidentified compared to non-CNS malignancies.
Genetic / Familial Factors: Familial history of brain tumors is documented in of reported cases.
Environmental Exposures:
Electromagnetic fields (e.g., residential proximity to high-voltage power distribution lines).
Ionizing radiation exposure.
Industrial chemical exposure, including pesticides, formaldehyde, and vinyl chloride.
Biological Agents: Viral exposures are considered potential oncogenic contributors.
Cellular Telephones: The largest comprehensive studies investigating cellular phone usage have found no statistically significant correlation with an increased incidence of brain tumors.
Diagnostic Classifications & Terminology
Classification by Cell of Origin:
Tumors are categorized based on the specific cell line from which the neoplasm arises (e.g., neuronal vs. glial origin).
Primary vs. Metastatic (Secondary) Origin:
Primary Tumors: Originate directly from intrinsic parenchymal or supporting tissue cells within the CNS.
Metastatic / Secondary Tumors: Originate from a primary site outside the CNS (e.g., lung, breast) and disseminate to the brain or spine.
Histological & Clinical Nature (Benign vs. Malignant):
Histological distinction is based on cellular differentiation, replication rate, cellular atypia, and central necrosis.
Benign Tumors: Low replication rates and no central necrosis. However, due to the non-yielding intracranial vault, a benign tumor can cause severe mass effect, intracranial hypertension, recurrence, and death.
Malignant Tumors: High replication rates, invasive growth, central necrosis, and high mortality. However, certain well-demarcated malignant tumors can be surgically excised with favorable clinical outcomes.
Anatomical Relationship to Brain Parenchyma:
Intra-axial: Tumor resides directly within the functional brain tissue/parenchyma (e.g., astrocytoma, glioblastoma).
Extra-axial: Tumor resides within the cranium or spinal canal but outside the brain tissue itself (e.g., meningioma arising from meningeal layers).
Histopathological Tumor Grading System:
Grade I & Grade II: Classified as low-grade or benign tumors; exhibit minimal growth rates, low mitotic activity, and minimal disruption of the blood-brain barrier.
Grade III & Grade IV: Classified as high-grade or malignant tumors; characterized by rapid cell proliferation, extensive invasive borders, tissue necrosis, intratumoral hemorrhage, significant blood-brain barrier breakdown, and poor overall prognosis.
Cellular Framework of the Central Nervous System
Primary Cell Classes:
Neurons: Functional cells responsible for conducting electrochemical nerve impulses.
Glial Cells (Neuroglia): Supporting framework cells surrounding neurons, constituting the vast majority of total brain tissue volume.
Categories of Neuroglial Cells:
Astrocytes:
Abundant, star-shaped cells forming the majority of structural brain tissue.
Form cell bodies, the pioglial membrane, and the blood-brain barrier (BBB) that selectively restricts chemical and pharmaceutical transport into brain tissue.
Responsible for gliosis and scar tissue formation: Proliferate into dead space following localized infarction (stroke) or mechanical injury to fill parenchymal defects.
Give rise to Astrocytomas (a major subtype of glioma).
Oligodendrocytes:
Smaller than astrocytes; responsible for synthesizing and maintaining the myelin sheath around axons in CNS white matter, facilitating saltatory impulse conduction.
Execute myelin repair and remyelination following tissue injury or demyelinating disease processes (e.g., Multiple Sclerosis).
Give rise to Oligodendrogliomas.
Microglial Cells:
Smallest neuroglial cells functioning as resident CNS macrophages.
Migrate to areas of tissue degeneration, inflammation, or acute damage to clean debris via phagocytosis.
Important Exception: Microglial cells do not form neoplasms.
Ependymal (Epithelial) Cells:
Single layer of cuboidal cells lined with apical microvilli and cilia.
Line the cerebral ventricular system, central canal, and subarachnoid space.
Facilitate cerebrospinal fluid (CSF) circulation against gravity through coordinated ciliary movement (analogous to tracheal ciliary action).
Give rise to Ependymomas, which typically cause CSF flow obstruction and hydrocephalus.
Gliomas: Low-Grade and High-Grade Astrocytomas
General Pathological Features of Gliomas:
Arise from neuroglial progenitor cells and represent the most infiltrative class of primary brain tumors.
Diffuse, non-circumscribed growth pattern featuring finger-like parenchymal protrusions, rendering clear surgical margin identification and complete resection extremely difficult.
Low-grade gliomas maintain low cell proliferation and minimal blood-brain barrier breakdown; high-grade gliomas demonstrate marked necrosis, vascular proliferation, rapid expansion, and high mortality rates.
Astrocytomas (Grade I and Grade II):
Most common glial cell tumor, originating from astrocytes.
Can occur throughout the CNS (brain or spinal cord); most frequent location is the frontal lobe.
Peak Demographic: Adults aged of age, as well as pediatric populations.
Clinical Presentation:
Seizures or persistent headaches.
Headaches accompanied by progressive focal neurological deficits.
Insidious onset of frontal lobe syndromes: Personality changes, loss of behavioral inhibition, emotional lability, or subtle cognitive decline.
Prognosis & Treatment:
Surgical excision followed by adjuvant chemotherapy and/or radiation therapy results in a 5-year survival rate.
Omitting adjuvant radiation/chemotherapy drops 5-year survival to approximately .
Standard Protocol: Surgical resection/debulking followed by postoperative radiation and/or chemotherapy.
Natural History: Low-grade astrocytomas naturally progress and transform over time into high-grade malignant tumors.
Glioblastoma Multiforme (GBM / Grade IV Astrocytoma):
Represents the most advanced, malignant, highly invasive, and lethal stage of astrocytic tumors.
Demographics & Location: Predominantly affects the cerebral cortex (frontal and parietal lobes); capable of seeding the spinal cord via CSF pathways.
Clinical Presentation & Course:
Life expectancy is less than with aggressive multimodal therapy (surgical excision, radiation, chemotherapy); survival without adjuvant treatment can be measured in weeks.
Patients often present acutely with sudden headache onset, rapid neurological decline, focal deficits, or new-onset status epilepticus.
Neuroimaging Characteristics (CT/MRI):
Grade I/II Astrocytoma: Non-contrast enhancing or minimal enhancement without central necrosis.
Grade IV Glioblastoma: Demonstrates heterogeneous, irregular ring/rim enhancement following intravenous contrast administration, reflecting peripheral hypervascularity surrounding a necrotic, hazy core (distinguishable from the smooth, uniform ring of a brain abscess).
Intraoperative Surgical Challenges:
Low-grade astrocytomas closely resemble normal white matter tissue, making surgical differentiation difficult without intraoperative navigation or intraoperative MRI (iMRI).
Recurrence almost universally occurs as a Grade III or Grade IV malignant glioma due to residual microscopic infiltrating cells.
Additional Astrocytoma Subtypes:
Pilocytic Astrocytoma: Typically located within the cerebellum. Grade 1 tumor. Most common brain tumor in children
Subependymal Giant Cell Astrocytoma. Large grade 1 tumor in the ventricles
Brainstem Gliomas: Infiltrative astrocytomas located within the brainstem (e.g., pons).
Oligodendrogliomas
Pathological Characteristics & Location:
Arise from myelin-producing oligodendrocytes, predominantly within CNS white matter.
Anatomical Predilection: Cerebral cortex (frontal and parietal lobes) and periventricular white matter; rare in the cerebellum.
Biopsy Features: Pure oligodendrogliomas are extremely rare; the vast majority are mixed/combination tumors containing both oligodendrocytic and astrocytic cell lines.
Gross Morphological & Surgical Features:
Fleshy, reddish-gray appearance, relatively solid consistency, and discrete tumor margins.
Less infiltrative and invasive than astrocytomas, allowing for higher rates of gross total surgical resection.
Clinical Demographics & Prognosis:
Overall median survival range: .
Peak Incidence: Adults aged of age.
Gender Distribution: Predominantly affects males.
Metastasis: Can disseminate through CSF pathways to the spinal canal (rarely metastasizes outside the CNS).
Neuroimaging Findings:
Frequently demonstrate focal tumor calcifications visible on non-contrast computed tomography (CT) scans.
Ependymomas
Cellular Origin & Histology:
Arise from ependymal cells lining the ventricular system and subarachnoid space of the brain and spinal cord.
Histologically benign (graded Grade I through Grade IV), but clinical morbidity and mortality depend on anatomical location.
Age-Specific Anatomical Distribution:
Pediatric Population: Predominantly infratentorial, occurring in the fourth ventricle, brainstem, and cerebellar regions, resulting in high morbidity and mortality rates.
Adult Population: Predominantly supratentorial, involving the lateral and third ventricles.
Clinical Manifestations:
Ventricular mass lesion leads to non-communicating (obstructive) hydrocephalus.
Signs of Hydrocephalus: Nausea, projectile vomiting, severe headache, diplopia, dizziness, ataxia, and visual disturbances.
CSF Dissemination: High propensity to seed throughout the CSF pathway to the spinal cord.
Spinal Ependymomas (Primary or Metastatic):
Direct spinal involvement presents with localized back pain, lower extremity sensory disturbances, bilateral lower extremity weakness/paraparesis, and bowel/bladder dysfunction secondary to spinal cord compression.
Treatment & Management:
Complete Surgical Resection: Primary treatment modality. Ependymomas form well-circumscribed, plastic-like masses that allow high rates of complete surgical removal and favorable long-term prognosis.
Radiation Therapy: Utilized for incompletely resected tumors or delicate brainstem/fourth ventricle locations to avoid high-risk surgical brainstem manipulation.
Meningiomas
Classification & Demographics:
Histologically benign, extra-axial neoplasms arising from the arachnoid/meningeal layers lining the inner skull and spinal canal.
Peak Age: of age.
Gender Distribution: Significantly higher incidence in females compared to males.
Anatomical & Neuroimaging Characteristics:
Extra-axial: Situated entirely outside the functional brain parenchyma, located within the cranium.
Dural Attachment: Neuroimaging (CT/MRI) demonstrates persistent tumor attachment to the cranial bone across all anatomical cross-sections.
Hyperostosis and Erosion: Chronic pressure against bone can induce focal skull erosion, presenting as a palpable subgaleal mass beneath the scalp.
Common Sites: Skull convexity, falx cerebri, or basilar skull (sphenoid ridge). Basilar skull locations present increased surgical complexity and operative morbidity.
Surgical Considerations & Complications:
Highly vascular tumors, presenting a high risk for intraoperative hemorrhage.
Well-encapsulated with clear anatomical borders, allowing complete surgical resection.
Mass Effect Resolution: Meningiomas produce symptoms via parenchymal displacement and focal brain compression. Surgical decompression typically leads to complete resolution of preoperative neurological deficits.
Incomplete resection predisposes the patient to tumor recurrence, often returning with higher growth rates and aggressive/malignant characteristics.
Basilar Skull Precautions: Surgical resection near the base of the skull carries risks of CSF leaks and CNS infections (meningitis). Nasogastric or nasotracheal tubes are strictly contraindicated due to the risk of intracranial entry.
Neuronal Sheath Tumors (Neuromas & Schwannomas)
Definitions:
Neuroma: Tumor originating directly from neuronal structures.
Schwannoma: A neuroma arising from the Schwann cell sheath of a cranial nerve.
Neurolemmoma: Term used for bilateral cranial nerve schwannomas.
Acoustic Neuroma (Acoustic Schwannoma):
Primary Anatomical Origin: Vestibular branch of Cranial Nerve VIII (Vestibulocochlear nerve).
Neighboring Structures: Anatomically adjacent to Cranial Nerve V (Trigeminal) and Cranial Nerve VII (Facial).
Histology & Location: Benign, slow-growing, typically unilateral tumor located precisely at the cerebellopontine angle.
Pathophysiology & Structural Effects:
Initial involvement affects the vestibular division greater than the cochlear division.
As the lesion expands at the cerebellopontine angle, it can compress the pons (impairing motor tracts), distort the fourth ventricle (inducing obstructive hydrocephalus), and erode adjacent basilar skull bones.
Clinical Manifestations:
CN VIII Signs: Tinnitus, dizziness, vertigo, unsteadiness, gait ataxia, and progressive unilateral sensorineural hearing loss.
CN V Signs: Loss of facial sensation, facial numbness, altered corneal reflex, altered tear production, and headaches.
CN VII Signs: Facial muscular weakness, facial droop, asymmetry, and impaired eyelid closure.
Advanced Symptoms: Nystagmus, status epilepticus, severe hydrocephalus, and bulbar brainstem symptoms.
Management & Postoperative Complications:
Treated via complete surgical resection or stereotactic radiation therapy.
Postoperative Complications: CSF leaks, CNS infection/meningitis, localized hemorrhage, persistent hydrocephalus, cerebral edema, elevated intracranial pressure (ICP), permanent CN V and CN VII palsies, and permanent CN VIII sensorineural hearing loss.
Pineal Region Tumors (Pinealomas)
Pathological Features & Demographics:
Extremely rare neoplasms arising from primitive germ cells within the pineal gland region.
Gross Morphology: Soft, friable, highly vascular tissue with a grayish-granular appearance.
Demographics: Highest incidence in young males aged of age.
Anatomical Compression & Clinical Presentation:
Located adjacent to the cerebral aqueduct and third ventricle; expansion leads to CSF flow obstruction and hydrocephalus.
Optic Chiasm Compression: Superior expansion compresses the overlying optic chiasm, producing bitemporal hemianopsia (loss of bilateral peripheral/lateral visual fields).
Endocrine Disruption: Pineal melatonin dysregulation causes sleep-wake cycle disturbances and potential precocious or inhibited sexual development in pediatric patients.
Treatment:
Surgical resection and radiation; high propensity for local recurrence and CSF seeding if complete removal is not achieved.
Pituitary Tumors (Pituitary Adenomas)
Overview & Characteristics:
Typically benign primary anterior pituitary gland tumors.
Gender Distribution: Significantly higher incidence in females.
Functional Classifications: Secretory (hypersecreting specific hormones) vs. Non-secretory adenomas.
Mechanical Mass Effects:
Direct superior extension compresses the optic chiasm located immediately above the sella turcica.
Classical Finding: Bitemporal hemianopsia (bilateral loss of peripheral visual fields).
Subtypes based on Hormone Secretion:
Prolactinoma:
Secretes high levels of serum prolactin.
Medical Management (First-line): Does not typically require primary surgical resection. Pharmacologically treated with dopamine agonist therapy (e.g., bromocriptine, cabergoline). Dopamine inhibits prolactin secretion, leading to tumor shrinkage.
Growth Hormone (GH) Secreting Adenoma:
Secretes excess growth hormone.
Pre-pubertal Onset: Results in Gigantism.
Post-pubertal Onset: Results in Acromegaly (pathological enlargement of hands, feet, jaw, and soft tissues).
Treatment: Transsphenoidal surgical resection; adjuvant octreotide (Sandostatin) or dopamine agonists to reduce GH hypersecretion.
ACTH Secreting Adenoma:
Secretes excessive Adrenocorticotropic Hormone (ACTH), stimulating adrenal gland cortisol release, producing Cushing's Disease.
Treatment: Transsphenoidal surgical resection, radiation therapy, and antifungal medications (e.g., ketoconazole) to inhibit adrenal steroid synthesis.
Non-Secreting Adenoma:
Non-functional mass causing local visual compression or hypopituitarism.
Transsphenoidal Surgical Approach & Postoperative Management:
Operative Route: Surgical entry through the nasal cavity and sphenoid sinus into the sella turcica in an upright position.
Postoperative Complications:
CSF rhinorrhea/leak and CNS infections (meningitis).
Transient or permanent Diabetes Insipidus (DI) due to posterior pituitary/stalk manipulation.
Mandatory Nursing Care: Continuous hourly monitoring of urine output, urine osmolality, and serum osmolality.
Secondary (Metastatic) Brain Tumors
Pathological Nature & Common Sources:
Secondary brain tumors result from hematogenous spread of systemic primary cancers.
Histological evaluation reveals non-neural cells (e.g., oat cell/small cell carcinoma from primary lung neoplasms).
Common Primary Sources: Lung cancer (most common, especially oat cell carcinoma), breast cancer, melanoma/skin cancer, renal cell carcinoma (kidney), and gastrointestinal tract carcinomas.
Neuroimaging Characteristics:
Non-contrast/Contrast CT and MRI reveal multiple, spherical, highly contrast-enhancing lesions located at the gray-white matter junction, surrounded by vasogenic edema.
Less commonly present as a single solitary lesion.
Can induce focal cranial bone erosion.
Clinical Manifestations:
Classic Diagnostic Triad: Progressive headache, vomiting, and papilledema.
Acute Presentation: New-onset seizures, sudden loss of consciousness, or rapidly progressive focal neurological deficits.
Unrecognized Malignancy: Discovery of multiple contrast-enhancing lesions in a patient without a prior cancer diagnosis mandates comprehensive whole-body staging CT scans.
Treatment Modalities:
Guided by systemic disease extent, functional performance status, and total intracranial lesion count.
Options include surgical resection, whole-brain radiation therapy (WBRT), stereotactic radiosurgery (Gamma Knife), chemotherapy, or transition to palliative care for widespread end-stage metastasis.
Focal Neurological Signs by Anatomical Location
Frontal Lobe:
Progressive personality changes, emotional lability, loss of social inhibition, irritability, executive dysfunction, cognitive decline, and contralateral motor weakness.
Temporal Lobe:
Psychomotor seizures, auditory hallucinations, visual field cuts, and memory impairments.
Parietal Lobe:
Sensory neglect syndromes, astereognosis (inability to recognize objects by touch), spatial disorientation, and sensory loss.
Occipital Lobe:
Visual disturbances, cortical blindness, and visual agnosia.
Cerebellum:
Severe gait ataxia, dysmetria, intention tremor, dizziness, and unsteadiness resembling acute alcohol intoxication.
Brainstem:
Multiple cranial nerve palsies, bulbar symptoms (dysphagia, dysarthria), motor/sensory tract deficits, and vital sign instability.
Diagnostic Procedures & Surgical Innovations
Neuroimaging Diagnostics:
Computed Tomography (CT) & Magnetic Resonance Imaging (MRI): Essential for lesion localization, mass effect evaluation, and contrast dynamics.
Magnetic Resonance Angiography (MRA): Differentiates neoplasms from vascular malformations, such as Arteriovenous Malformations (AVMs).
Functional MRI (fMRI): Maps eloquent brain regions (e.g., Broca’s and Wernicke’s speech centers, primary motor cortex) relative to tumor margins prior to resection.
Positron Emission Tomography (PET): Evaluates metabolic activity and differentiates tumor recurrence from radiation necrosis.
Intraoperative Surgical Guidance & Technologies:
Framed and Frameless Stereotactic Navigation: Maintains spatial accuracy despite brain shift following fluid release and tumor debulking.
Intraoperative MRI (iMRI): Real-time intraoperative scanning allowing real-time assessment of resection margins without leaving the operating suite.
Awake Craniotomy: Performed during tumor resection in eloquent cortex regions. Brain parenchyma lacks nociceptors, enabling intraoperative cortical mapping and continuous motor/speech testing in an awake patient.
Adjuvant Delivery Modalities:
Radiation Therapy: External beam radiation therapy or targeted stereotactic radiosurgery (Gamma Knife).
Biodegradable Chemotherapy Wafers: Implanted directly into the surgical cavity following tumor resection; slowly dissolve over to deliver high local concentrations of chemotherapeutic agents directly to residual surgical margins.