Astrocytoma

Overview

Definition

Astrocytomas are neuroepithelial tumors in the CNS arising from astrocytes Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system – the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from ‘star’ cells) are irregularly shaped with many long processes, including those with ‘end feet’ which form the glial (limiting) membrane and directly and indirectly contribute to the blood-brain barrier. They regulate the extracellular ionic and chemical environment, and ‘reactive astrocytes’ (along with microglia) respond to injury. Nervous System: Histology, a type of star-shaped glial cell.

• Glial cells Glial Cells The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain barrier and blood-retinal barrier, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. Nervous System: Histology are supportive tissues within the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification.
• Neuroepithelial tumors are those involving the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification parenchyma.
• Astrocytomas are graded, but not staged.

Classification of nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification tumors

Classification of astrocytomas

There are several classification systems for astrocytomas, but the most widely used is the WHO grading Grading Methods which attempt to express in replicable terms the level of cell differentiation in neoplasms as increasing anaplasia correlates with the aggressiveness of the neoplasm. Grading, Staging, and Metastasis system, which divides astrocytomas into 4 grades according to the extent of nuclear atypia Atypia Fibrocystic Change, mitotic activity, cellularity, vascular proliferation, and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage.

• Grade I: noninvasive tumors that typically occur in children
  • Pilocytic astrocytoma:
    • Well-circumscribed, slow-growing, cystic Cystic Fibrocystic Change tumors 
    • Usually arise in the cerebellum Cerebellum The cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Cerebellum: Anatomy → may lead to compression Compression Blunt Chest Trauma of the 4th ventricle and/or ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
  • Pleomorphic Pleomorphic Bacteroides xanthoastrocytoma:
    • Originates in temporal lobe Temporal lobe Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the occipital lobe. Cerebral Cortex: Anatomy
    • Commonly associated with seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Subependymal giant cell astrocytoma (SEGA):
    • Periventricular tumors → may obstruct CSF outflow → hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage
    • Associated with tuberous sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor
• Grade II: low-grade diffuse astrocytomas
  • Also known as fibrillary astrocytomas
  • Invasive tumors with no clear separation from surrounding brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
  • Show nuclear atypia Atypia Fibrocystic Change alone
  • May progress to glioblastoma
• Grade III: anaplastic astrocytomas
  • Show nuclear atypia Atypia Fibrocystic Change and ↑ mitotic activity and cellularity
  • Lack necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage and microvascular proliferation
  • Progression to glioblastoma, typically within 2 years
• Grade IV: glioblastoma multiforme Glioblastoma multiforme Glioblastoma multiforme is a high-grade astrocytoma, an aggressive brain tumor arising from astrocytes, with an unknown cause and a poorly understood link to risk factors. There are two main types: primary, a more aggressive form seen more commonly in older patients, and secondary, developing from lower-grade astrocytomas and seen more commonly in younger patients. Glioblastoma Multiforme (GBM)
  • Most malignant and aggressive type of astrocytoma
  • Characterized by areas of necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage or microvascular proliferation
  • May progress from a lower-grade astrocytoma (10%) or originate directly as a GBM (90%)
  • Dismal prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

Epidemiology

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency:
  • Age-standardized incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 4.7 per 100,000 person-years
  • In the United States, 15,000 new astrocytomas are diagnosed per year.
• Race/ethnicity: no significant differences
• Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria predominance:
  • No sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria predominance in pilocytic astrocytoma.
  • Slight male predominance in low-grade diffuse astrocytoma
  • Male:female predominance of approximately 2:1 in anaplastic astrocytoma
• Grade IV astrocytomas:
  • Most common malignant primary brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumor Tumor Inflammation: accounts for 23% of all primary brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumors
  • 60% of all astrocytomas are grade IV at diagnosis.

Etiology

The cause of most astrocytomas is unknown. Ultimately, genetic mutations Genetic Mutations Carcinogenesis lead to uncontrolled cell growth and tumor Tumor Inflammation proliferation.

• Astrocytomas occur more frequently in the following genetic disorders:
  • Li–Fraumeni syndrome (p53 germline mutations)
  • Turcot syndrome Turcot syndrome Familial Adenomatous Polyposis (mutations in several tumor Tumor Inflammation suppressor genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure, including APC APC A polyposis syndrome due to an autosomal dominant mutation of the apc genes on chromosome 5. The syndrome is characterized by the development of hundreds of adenomatous polyps in the colon and rectum of affected individuals by early adulthood. Familial Adenomatous Polyposis and MMR MMR A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome)
  • Neurofibromatosis type 1 Type 1 Spinal Muscular Atrophy ( NF1 NF1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1)
  • Tuberous sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor
• Ionizing radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma is an established risk factor:
  • Pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types adenoma radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy: 16× increased risk of astrocytoma
  • Children who receive radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma for acute lymphocytic leukemia (ALL): 22× increased risk of developing a CNS malignancy Malignancy Hemothorax in 5–10 years (including grade II, III, and IV astrocytomas)

Pathophysiology

Pathogenesis

Several genetic mutations Genetic Mutations Carcinogenesis are associated with astrocytomas.

• Mutations in isocitrate dehydrogenase 1 Isocitrate Dehydrogenase 1 Oligodendroglioma (IDH1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics):
  • IDH1:
    • Catalyzes the reversible oxidative decarboxylation Decarboxylation The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. Catabolism of Amino Acids of isocitrate → α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA) cycle 
    • Primary producer of nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes ( NADPH NADPH Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5′-phosphate (nmn) coupled by pyrophosphate linkage to the 5′-phosphate adenosine 2. Pentose Phosphate Pathway) in most tissues, especially the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
    • Also involved in mitigating oxidative damage
  • Mutations lead to production and buildup of a 2-hydroxyglutarate (2-HG):
    • 2-HG inhibits enzymatic function of α-ketoglutarate (KG)-dependent dioxygenases, which are involved in DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure demethylation.
    • ↑ 2-HG causes epigenetic dysregulation → can lead to tumor Tumor Inflammation development
• Methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids (i.e., silencing) of the methylguanine methyltransferase (MGMT) promoter:
  • MGMT is an enzyme involved in DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure repair (including DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure repair after chemotherapy Chemotherapy Osteosarcoma with an alkylating agent Alkylating Agent Alkylating agents are cell cycle-independent antineoplastic drugs that work primarily by binding alkyl groups to various parts of DNA. The overall action produces cross-linking of DNA, leading to inhibition of DNA replication and DNA damage. Alkylating Agents and Platinum).
  • MGMT methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids at the promoter region:
    • Silences expression of the gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
    • May occur during tumor Tumor Inflammation development → prevents repair of DNA damage DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a mutation or a block of DNA replication. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (pyrimidine dimers) or interstrand crosslinking. Damage can often be repaired (DNA repair). If the damage is extensive, it can induce apoptosis. DNA Repair Mechanisms
    • Improves chemotherapy Chemotherapy Osteosarcoma responsiveness and overall survival (independent of other risk factors) 
• Inactivating p53 mutations (present in ⅔ of low-grade astrocytomas)
• Overexpression of platelet-derived growth factor Platelet-derived growth factor Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. Hypertrophic and Keloid Scars alpha (PDGF-A) 
• Certain human leukocyte antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (HLA) types are associated with either decreased or increased risk.

Pathophysiology

• Astrocytomas usually arise in the cerebral hemispheres (i.e., parenchyma).
• Regional effects on brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification parenchyma include:
  • Compression Compression Blunt Chest Trauma
  • Invasion
  • Destruction
• ↑ Intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension ( ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP)) may be due to:
  • Direct mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast effect
  • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema in surrounding brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tissue
  • ↑ Blood volume
  • ↑ CSF volume/ hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage
• Disruption of normal parenchymal functions are due to:
  • Hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage
  • Competition for nutrients
  • Release of metabolic end products:
    • Free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage
    • Altered electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
    • Neurotransmitters
  • Release and recruitment Recruitment Skeletal Muscle Contraction of cellular mediators (e.g., cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response)

Clinical Presentation

Neurologic signs and symptoms related to astrocytomas result from perturbations in CNS function.

Onset of symptoms

• Grades I and II: Onset is usually subtle and tumors develop slowly because of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification’s ability to temporarily adapt to the presence of a slow-growing tumor Tumor Inflammation.
• Grades III and IV: Onset is more often sudden and/or debilitating.

Symptoms

Symptoms are primarily dependent on the location of the tumor Tumor Inflammation in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification The symptoms are divided into 2 categories:

• General symptoms: symptoms that can occur with tumors in any location
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess (usually in the morning)
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia 
  • Cognitive difficulties:
    • Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment problems
    • Mood or personality changes
  • Gait Gait Manner or style of walking. Neurological Examination disorders 
  • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
  • Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension
• Focal symptoms: symptoms that occur because of tumors in specific locations
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures:
    • Most common symptom of astrocytomas 
    • Low-grade tumors are more likely to cause seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures than high-grade tumors.
  • Aphasia Aphasia A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. Ischemic Stroke 
  • Visual field Visual Field The Visual Pathway and Related Disorders deficits
  • Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology weakness 
  • Hemiparesis Hemiparesis The term hemiparesis refers to mild to moderate weakness involving one side of the body. Epidural Hemorrhage
  • Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology abnormalities

Diagnosis

Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant is the only test necessary to diagnose an astrocytoma. The gold standard is MRI, though CT is also sometimes used.

MRI

• Gold standard imaging study
• Preferably ordered with and without gadolinium Gadolinium An element of the rare earth family of metals. It has the atomic symbol gd, atomic number 64, and atomic weight 157. 25. Its oxide is used in the control rods of some nuclear reactors. Magnetic Resonance Imaging (MRI) enhancement
• Higher-grade astrocytomas show:
  • T1 isointensity and T2 hyperintensity
  • Enhancement with paramagnetic contrast agents Contrast agents Substances used to allow enhanced visualization of tissues. Computed Tomography (CT) 
• Low-grade astrocytomas typically do not enhance with contrast.

CT scan

• Indications:
  • Contraindication to MRI 
  • Acute settings (e.g., where hemorrhage and/or stroke needs to be ruled out)
  • CT of the chest/abdomen/ pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy may be warranted to look for alternative primary lesions if metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis is suspected.
• Findings show a poorly defined parenchymal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast.
• Low-grade lesions typically do not enhance with contrast.

Other tests

• EEG EEG Seizures: may be used to evaluate and monitor seizure activity
• CSF studies: may assist in ruling out other diagnoses (e.g., CNS lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum, metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis)

Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

A biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is indicated for grading Grading Methods which attempt to express in replicable terms the level of cell differentiation in neoplasms as increasing anaplasia correlates with the aggressiveness of the neoplasm. Grading, Staging, and Metastasis, and/or confirming the diagnosis after the tumor Tumor Inflammation is identified on neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant.

• Pilocytic astrocytoma:  Rosenthal fibers Rosenthal Fibers Hemangioblastoma: eosinophilic cytoplasmic inclusions, appearing as corkscrew-like fibers
• Low-grade diffuse astrocytoma:
  • Mild to moderate increase in number of glial cell nuclei
  • Nuclear pleomorphism
  • Nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles:cytoplasm ratio quite high
  • Intervening feltwork of fine, glial fibrillary acidic protein (GFAP) astrocytic cell processes 
  • Grossly: poorly defined tumors that are gray in color
• Anaplastic astrocytoma:
  • Increased cellularity and nuclear pleomorphism
  • Marked mitotic activity and nuclear atypia Atypia Fibrocystic Change
  • High proliferative rate based on Ki67 staining
• Glioblastoma multiforme Glioblastoma multiforme Glioblastoma multiforme is a high-grade astrocytoma, an aggressive brain tumor arising from astrocytes, with an unknown cause and a poorly understood link to risk factors. There are two main types: primary, a more aggressive form seen more commonly in older patients, and secondary, developing from lower-grade astrocytomas and seen more commonly in younger patients. Glioblastoma Multiforme:
  • Increased mitotic figures, cellularity, and nuclear pleomorphism
  • Vascular and/or endothelial cell proliferation
  • Areas of necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage (grossly appear firm and white or soft and yellow)
  • Tumor Tumor Inflammation cells are “pseudopalisading.”

Management and Prognosis

Management by grade

Management depends on the grade, location of the tumor Tumor Inflammation (i.e., how much can be safely resected), and symptoms. Management typically involves a combination of surgery, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, and chemotherapy Chemotherapy Osteosarcoma.

• Grade I astrocytoma:
  • Best management is controversial due to:
    • Lack of strong data
    • Relatively indolent nature of tumor Tumor Inflammation
    • Morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status associated with the treatments
    • Relatively young age of the typical patient
  • Consider maximal safe surgical resection if tumor Tumor Inflammation is accessible.
  • Partial surgical removal when the tumor Tumor Inflammation involves crucial parts of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
  • Consider radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy when the tumor Tumor Inflammation is not fully resectable.
• Grade II astrocytoma:
  • Surgical resection is recommended for accessible tumors:
    • Not curative
    • Additional therapies (i.e., radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy and chemotherapy Chemotherapy Osteosarcoma) are ultimately required in all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma plus adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination chemotherapy Chemotherapy Osteosarcoma (typically temozolomide Temozolomide A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of malignant glioma and malignant melanoma. Alkylating Agents and Platinum) 
  • Follow-up to check for recurrence/progression
• Grade III and IV astrocytomas:
  • Standard therapy is surgery, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, and chemotherapy Chemotherapy Osteosarcoma (typically with temozolomide Temozolomide A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of malignant glioma and malignant melanoma. Alkylating Agents and Platinum).
  • Surgery may include:
    • Resection 
    • Symptom-relieving procedures (e.g., shunt placement to relieve hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage)
  • If surgery is not possible, then radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma and chemotherapy Chemotherapy Osteosarcoma are used.
• Other therapy to consider:
  • DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis prophylaxis Prophylaxis Cephalosporins in nonambulatory and hospitalized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Anticonvulsant Anticonvulsant Anticonvulsant drugs are pharmacological agents used to achieve seizure control and/or prevent seizure episodes. Anticonvulsants encompass various drugs with different mechanisms of action including ion-channel (Na+ and Ca+2) blocking and GABA reuptake inhibition. First-Generation Anticonvulsant Drugs therapy in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a history of seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures (prophylactic anticonvulsant Anticonvulsant Anticonvulsant drugs are pharmacological agents used to achieve seizure control and/or prevent seizure episodes. Anticonvulsants encompass various drugs with different mechanisms of action including ion-channel (Na+ and Ca+2) blocking and GABA reuptake inhibition. First-Generation Anticonvulsant Drugs therapy remains controversial)
  • Corticosteroids Corticosteroids Chorioretinitis (e.g., dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics) may be used for their antiinflammatory properties to reduce tumor Tumor Inflammation mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast effect.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

Factors that affect prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas include:

• Tumor Tumor Inflammation grade:
  • Grade I: 96% 5-year survival rate
  • Grade II: Median survival is 8 years.
  • Grade III: Median survival is 2–5 years.
  • Grade IV: Median survival is 15 months.
• Extent of surgical resection
• Use of adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy and/or chemotherapy Chemotherapy Osteosarcoma
  • Age: younger age at diagnosis associated with longer survival.
• Functional status (e.g., minimal symptoms and/or normal neurologic function) associated with longer survival

Differential Diagnosis

When a patient presents with neurologic symptoms on exam, the differential diagnosis may include vascular processes (e.g., hemorrhage, infarct Infarct Area of necrotic cells in an organ, arising mainly from hypoxia and ischemia Ischemic Cell Damage), infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (e.g., abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease, viral encephalitis Viral encephalitis Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of togaviridae infections; herpesviridae infections; adenoviridae infections; flaviviridae infections; bunyaviridae infections; picornaviridae infections; paramyxoviridae infections; orthomyxoviridae infections; retroviridae infections; and arenaviridae infections. Encephalitis), and inflammatory processes (e.g., multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor) in addition to primary brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumors. Imaging is typically able to narrow the differential to a brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumor Tumor Inflammation.

• Oligodendroglioma Oligodendroglioma Oligodendrogliomas are malignant CNS tumors arising from neural glial cell precursors. Oligodendrogliomas often arise in the frontal lobes of the brain and have a generally favorable prognosis when compared to other gliomas. Oligodendrogliomas are the 3rd most common CNS tumor. The most frequent presenting symptom is a seizure. Oligodendroglioma: CNS tumor Tumor Inflammation arising from oligodendrocytes. Oligodendroglioma Oligodendroglioma Oligodendrogliomas are malignant CNS tumors arising from neural glial cell precursors. Oligodendrogliomas often arise in the frontal lobes of the brain and have a generally favorable prognosis when compared to other gliomas. Oligodendrogliomas are the 3rd most common CNS tumor. The most frequent presenting symptom is a seizure. Oligodendroglioma most commonly develops in the cerebral hemisphere, usually in the frontal lobe Frontal lobe The part of the cerebral hemisphere anterior to the central sulcus, and anterior and superior to the lateral sulcus. Cerebral Cortex: Anatomy. Oligodendrogliomas can present with focal neurologic deficits Neurologic Deficits High-Risk Headaches, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, and personality changes depending on its exact location. Diagnosis is made by MRI and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management involves surgical resection, possibly accompanied by radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma and/or chemotherapy Chemotherapy Osteosarcoma.
• Medulloblastoma Medulloblastoma Medulloblastomas are malignant primitive neuroectodermal tumors that arise in the posterior fossa in children. Medulloblastomas are the most common malignant brain tumors in children. Patients with medulloblastoma present with symptoms of increased intracranial pressure and cerebellar signs, which both evolve and worsen over weeks to a few months. Medulloblastoma: tumor Tumor Inflammation that arises in the posterior fossa. Medulloblastoma Medulloblastoma Medulloblastomas are malignant primitive neuroectodermal tumors that arise in the posterior fossa in children. Medulloblastomas are the most common malignant brain tumors in children. Patients with medulloblastoma present with symptoms of increased intracranial pressure and cerebellar signs, which both evolve and worsen over weeks to a few months. Medulloblastoma is the most common malignant brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumor Tumor Inflammation in children. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with symptoms of increased ICP Increased ICP Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage as well as cerebellar signs that generally worsen over time. Diagnosis is suspected based on MRI findings, but histopathologic analysis at the time of surgical resection is required for diagnosis. Treatment is with a combination of surgery, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy, and chemotherapy Chemotherapy Osteosarcoma. 
• Ependymoma Ependymoma Ependymomas are glial cell tumors arising from CSF-producing ependymal cells lining the ventricular system. Ependymomas most commonly occur within the posterior fossa in contact with the 4th ventricle, or within the intramedullary spinal cord. Ependymoma: subset of glial tumors that often arise in or adjacent to the ependymal lining of the ventricular system Ventricular System The ventricular system is an extension of the subarachnoid space into the brain consisting of a series of interconnecting spaces and channels. Four chambers are filled with cerebrospinal fluid (CSF): the paired lateral ventricles, the unpaired 3rd ventricle, and the unpaired 4th ventricle. Ventricular System: Anatomy, most commonly within the posterior fossa, in contact with the 4th ventricle, or within the intramedullary spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy. The clinical presentation varies depending on the location of the tumor Tumor Inflammation. MRI is the standard imaging technique, but histologic confirmation is required for diagnosis. Treatment involves surgical resection and adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma or chemotherapy Chemotherapy Osteosarcoma (based on age). 
• Metastatic tumor Tumor Inflammation: neoplastic cells that have spread to the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification from primary tumors elsewhere in the body. Metastatic neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors are the most common neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification. Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant often shows multiple foci of the carcinoma, suggesting nonbrain origin. Clinical presentation depends on the primary tumor Tumor Inflammation and location and extent of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis. Treatment is directed at the underlying neoplasm and may involve surgical resection, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy, and chemotherapy Chemotherapy Osteosarcoma.