Neoplastic Lesions of the CNS

Introduction

Neoplastic diseases disrupt the brain's structure.
Meningiomas: low-malignancy tumors growing from meninges, expanding but not infiltrating the brain.
Glioblastomas: aggressive, infiltrating cancers causing yellowish-brown color due to necrosis.
Blood-brain barrier: prevents cancer spread but also protects the body.

Metastasis

Metastases: irregularly shaped areas with specific limits, often multiple.
Lung cancer metastasis can act as a cancer embolus.
Brain neoplastic diseases include metastasis within the brain.

Epidemiology

Incidence: 10-17 cases per 100,000 people in the US.
Location: mostly in the brain; spine is rare (50-70% primitive).
Detection: CT scans/MRIs can indicate primary lesions or metastasis.
Children: one-fifth of cancers are brain cancers, often aggressive.
Adults: 70% of cancers are above the tentorium; children: below the tentorium.
Skull base cancers: hard to reach and operate on.
Brain edema or increased intracranial pressure can compress vital structures.

Surgical Intervention

Neurosurgical interventions: balance between surgical damage and cancer growth.
Benefits of surgery must outweigh damage.
Interventional radiology: less damaging alternatives.
Brain tumors typically do not spread outside the brain due to the blood-brain barrier; metastasis is mostly within the brain and spine.

Epidemiology of CNS Tumors

Data from Cancer Research UK; rates are growing.
Older age increases cancer risk due to reduced cell repair.

SEER Program

Surveillance Epidemiology and End Results (SEER) Program: US statistics on brain neoplastic disease.
US has the largest national registry.
Estimated new cases in the US in 2024: 25,400 (1% of all cancer patients).
High death rate: two-thirds of cases resulting in death.
3% of all cancer deaths from brain cancer suggest it is very aggressive.

Trends in Death Rate

Data lags about two years.
Death rate is slowly declining, indicating effective interventions.

Affected Populations

Males are more frequently and severely affected than females.
Hispanic people are more affected than non-Hispanic.
Black people are less affected than non-Hispanic people.
White men in the United States are the most affected (8.6 cases per 100,000).

Age and Diagnosis

Median age at diagnosis: 60 (spike in <20 due to pediatric tumors).
7th and 8th decades are most affected (70-80s).
Percentage of new cases drops in the 80s-90s.
Highest death rate: 7th decade of life.
Median death age: 67. 30% of deaths occur around ages 65-70.

Importance of Brain Cancer

Brain cancers rank 16th epidemiologically.
Breast cancer: high incidence but low death rate.
Prostate cancer: hormone-related; most men over 70 affected, low death rate.
Lung cancer: 50% death rate.
Pancreatic cancer: almost as many deaths as cases.
5-year survival rate for CNS cancers: 33.4%.

Trends in Cases and Deaths

Slight decrease in both cases and deaths from 1975 to 2022.
5-year relative survival improved to about 35% until 2010. Post-2010 decline may be due to more difficult cases.

Origin of CNS Cancers

CNS cancers can originate from various CNS components.
"Tumor" refers to a mass bulging from the CNS component.
Germ cell tumors along the midline can be very aggressive.
Tumor classification ranges from A to G.

Classification of Neuroepithelial Tumors

Astrocytic tumors
Oligodendroglia tumors
Mixed gliomas
Ependymal tumors
Choroid plexuses tumors
Uncertain origin glial tumors
Neuronal and neuronal-glial mixed tumors
Neuroplastic tumors
Pineal tumors
Embryonal tumors

Peripheral Nerve Tumors

Schwannoma
Neurofibroma
Perineurioma
Malignant peripheral nerve sheet tumors (MPNST)
Can be found anywhere in the body, not limited to the CNS

Meningeal Tumors

Meningothelial tumors
Non-meningothelial mesenchymal tumors
Primary melanocytic tumors (lower grade, not called melanoma)
Uncertain histogenesis tumors

General Features of CNS Neoplastic Diseases

Not very frequent, accounting for only 10% of all tumors
Divided into primitive and metastatic groups
Gliomas are the largest fraction within the primitive group (60%), followed by meningiomas and schwannomas (10% each)
Two-thirds of cases in children occur below the tentorium, while 75% of adult cases are above the tentorium
Symptoms unrelated to tumor location result from high intracranial pressure or edema
Specific symptoms depend on cancer location (e.g., Broca’s area: speech problems)
Irritative stimuli can cause seizures, even in non-epileptic patients
Metastases often come from the lung and melanomas, although other cancers can also spread to the brain

Broader Classification: Neuroepithelial Astrocytic Tumors

Bad cancer = Bad prognosis.
Nuclear atypia, mitosis, and cellularity are key features to look for.
Necrosis indicates rapid tumor proliferation and inadequate vessel formation.

Types and Grading

Classified into diffuse, anaplastic (fully differentiated), and glioblastoma forms
Grading measures morphology to determine aggressiveness (grades 1-4)
Genetic information includes P53, PDGF-Ra overexpression, EGFR, PTEN, and PDGF-Ra overexpression

Neoplastic Diseases of Glial Cells

Two main groups based on transcription profiles: neural, classical, mesenchymal, and proneural.
IDH-wildtype glioblastoma develops with clinical history and mutations.
IDH1-2 mutation leads to diffuse astrocytoma and oligodendroglioma, further developing into anaplastic astrocytoma and glioblastoma.
IDH (isocitrate dehydrogenase 1) mutation causes loss of function of DNA demethylase
Glioblastoma can be caused by mutated IDH or IDH-wildtype.

IDH as a Marker

IDH is a marker indicating cancer development (mutated or wildtype)
IDH-wildtype: Genetic damages are more severe, and tumors are less responsive to alkylating agents
IDH-mutated: Tumors respond better to treatment with alkylating agents
Primary (IDH wildtype) and secondary (IDH mutated) glioblastoma are important categories
Secondary GBM has better survival; 50% of patients with mutated IDH live longer

GBM Types

Curve is reversed; there is an increase in the curve.
Grade 4 tumor by WHO classification: cells may be relatively normal in some parts, but very bad looking in others.

Astrocytomas

Astrocytomas arise from transformed astrocytes, representing a diverse group of cancers.

Subtypes:

Fibrillary Astrocytoma: slow-growing, infiltrative with thread-like astrocytic cells
Fibrillary Glioblastoma: aggressive, high-grade with dense cellularity, necrosis, and microvascular proliferation
Pilocytic Astrocytoma: benign, cystic with bipolar cells and Rosenthal fibers, common in children and young adults
Pleomorphic Xanthoastrocytoma (PXA): rare, low-grade with pleomorphic, lipid-laden astrocytes, predilection for the temporal lobe

Histological subtypes offer some insight but do not always provide reliable prognostic info.
Grading correlates more directly with tumor aggressiveness and prognosis.
Grades range from 1 to 4, with grade 4 (glioblastoma) being the most aggressive.

Grades:

Low grades (slower-growing, less aggressive)
- Grade 1: pilocytic astrocytoma
- Grade 2: diffuse astrocytoma (Pleomorphic Xanthoastrocytoma and Fibrillary Astrocytoma)
High grade (more aggressive, fast-growing tumors)
- Grade 3: anaplastic astrocytoma
- Grade 4: glioblastoma (most malignant, poorest prognosis)

Naming and Features of Astrocytomas

Named by neuropathologists based on distinct features.
Can vary in structure and location, usually in cerebral hemispheres, but sometimes in the brainstem or medulla.
Most commonly develop between 40 and 60, incidence increases with age, peaking around the seventh decade.

Symptoms:

Seizures
Headaches
Other neurological signs
Symptoms alone don’t reveal the tumor type or grade.
Clinical progression depends on biological and genetic characteristics.
Pilocytic astrocytomas (grade 1) are generally low-grade and have well-defined margins, often cystic.
Diffuse astrocytomas have less defined margins, challenging to distinguish from surrounding tissue, even though low-grade

Appearance of Astrocytomas

Appearance varies significantly depending on tissue characteristics and growth rate.
Tumor tissue with necrosis is friable and fragile.
Pilocytic astrocytomas are usually compact, with a jelly-like or soft consistency.
Necrosis or hemorrhage affects color and consistency.
Glioblastoma multiforme: varied appearance under the microscope.
Glioblastomas have distinct areas with different cell density and aggressiveness.
Typical features: necrosis (dead tissue).
Imaging (CT scans/MRI) helps neuroradiologists make informed guesses about the histological type.
Scans reveal patterns of blood flow and contrast uptake, providing information about aggressiveness and structural complexity.
Autopsy images show a tumor originating in one hemisphere extending to the opposite side likely via cerebrospinal fluid circulation through ventricles.

Tissue Analysis

Affected areas lose normal brain tissue structure, with a more homogenous phase.
Central area of the tumor shows a reddish color, suggesting significant necrosis and hemorrhage.
Smaller metastatic lesions display similar characteristics on the opposite hemisphere.
In more affected hemisphere, there’s complete replacement of normal brain tissue.
Multiple cavities are visible, representing morphological changes that disrupt the brain’s normal structure.
Tumor infiltrates both gray and white matter, with hemorrhage indicating active tissue damage.

Challenges in Distinguishing Tissue

Difficult to distinguish between cancerous and non-cancerous areas in the brain.
Neurosurgeons must remove seemingly normal tissue around the tumor.
Need to discuss potential impact on brain function with patients because removing extra tissue can lead to neurological damage.
Gliomas exhibit eosinophilic characteristics (pinkish hue when stained).
Cancer cells (astrocytes, oligodendrocytes) appear larger and more irregular.
Increased cellular density indicates tumor aggressiveness.
Normal and cancerous tissue may appear deceptively similar.
Glioblastoma: increased cell density