Neoplasms of the Nervous System - Clin Med

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Neoplasms Overview

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EpidemiologyNeoplasms Overview

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Etiology Neoplasms of the Brain

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Adult-pediatric neoplasms

What does this refer to

Malignant neoplasms of the brain

What does this refer to

• “Worst HA of my life”

• Progressive HA

• Onset > 50 yo

• Worse at night/early morning

• Marked exacerbation with straining

• Focal neurologic dysfunction

Clinical Features Of HA Suggestive Of Structural Brain Lesion

What does this refer to

• Nuchal rigidity

• Fever

• Papilledema

• Pathologic reflexes or reflex asymmetry

• Altered state of consciousness

Physical Exam Of HA Suggestive Of Structural Brain Lesion

What does this refer to

• Headache is common (Tension)

  • Dull/constant

  • Throbbing

• Followed by migrainous type

• MC bifrontal location

  • Worse on same side as tumor

• Sx severity worsens over time

Clinical historyNeoplasms Overview

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Clinical presentationNeoplasms Overview

What does this refer to

• Tumor-related seizures - repetitive and are stereotyped

• Ictal event may be preceded by an aura

  • Aura brief focal seizure

• Postictal sequelae

  • Period of fatigue and an urge to sleep

• Focal seizures, a postictal paresis (also known as a Todd’s paralysis) may be present

Malignant Brain NeoplasmSeizures

What does this refer to

• Muscle weakness

  • UMN lesion

  • Frequent response to glucocorticoids

• Sensory loss

  • Cortical sensory deficit

• Aphasia

  • Word finding/word substitution

  • Severe expressive-receptive aphasia

• Visual spatial dysfunction

  • Tumor related compression optic chiasm

    • Bitemporal hemianopsia

  • Central Scotoma (early)

    • Unilateral hemianopsia contralateral

• Cognitive dysfunction

  • Memory problems

  • Mood – personality change

• ↑ ICP

Physical exam findings Neoplasms

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WorkupNeoplasms

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Types of Brain Neoplasms

What does this refer to

• Brain Stem Glioma

• Craniopharyngioma

• Ependymoma

• Juvenile Pilocytic Astrocytoma (JPA)

• Medulloblastoma

• Optic Nerve Glioma

• Pineal Tumor

• Primitive Neuroectodermal Tumors (PNET)

• Rhabdoid Tumor

Types of brain tumors more common in children than adults

What does this refer to

• Neoplasm arising from the meninges

Benign Neoplasm

What does this refer to

• Risk factors

  • Age > 50

  • Family hx of brain tumors

  • Genetic condition that increases risks

• Previous radiation therapy

  • Especially head or neck

EpidemiologyBenign Neoplasm

What does this refer to

EtiologyBenign Neoplasm

What does this refer to

• Vision problems

• Hearing problems

• Balance problems

• Changes in mental abilities

• Change in sense of smell

• Nausea/vomiting

• Facial paralysis

• HA

• Numbness in extremities

Clinical historyBenign Neoplasm

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Differential diagnosisBenign Neoplasm

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WorkupBenign Neoplasm

What does this refer to

• 90% are benign

• Forms on membranes that cover the brain and spinal cord just inside the skull

• Forms on the three layers of membranes that are called meninges

• Slow-growing

Meningioma

What does this refer to

• Account for 20% of primary brain tumors

• MC African Americans

• F > M

• Incidence increases with age

  • Median age of dx 65yo

EpidemiologyMeningioma

What does this refer to

• Childhood exposure to diagnostic head CTs ↑ risk of brain tumor

• Genetic predisposition Neurofibromatosis type 2 (NF2)

• Atomic bomb exposure

• Estrogen therapy

• Obesity

• Breast CA

Etiology/Risk FactorsMeningioma

What does this refer to\

• Irritation → Seizures

• Compression → Headache

• Invading soft tissues

• Inducing vascular injury

Clinical historyMeningioma

What does this refer to

• Most often correlate with tumor location

• Seizures/muscle jerking (30% of cases)

• Obstructive hydrocephalus (tumor in posterior cranial fossa)

Physical examMeningioma

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Benign brain neoplasms

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Benign brain neoplasms

What does this refer to

• Brainstem glioma

• Glioblastoma multiforme

• Frontal lobe syndrome

• Neurofibromatosis Type 1/Type 2

Differential diagnosis Meningoma

What does this refer to

WorkupMeningioma

What does this refer to

• Referral to neurosurgery

• Medical

  • Radiation therapy for nonaccessible meningiomas

  • May be post-op tx

• Surgical resection

Clinical interventionMeningioma

What does this refer to

• Pre-op/post-op Corticosteroids

  • Dexamethasone (Decadron)

• Antiepileptic drugs

  • Started preoperatively in supratentorial surgery

  • Continued postoperatively for no less than 3 months

Clinical pharmacotherapeuticsMeningioma

What does this refer to

• 5-year survival usually range from 73-94%

• May produce severe morbidity before death due to the slow growing nature

• High post-op morbidity

  • Advanced age

  • Hx Diabetes or CAD

  • Preoperative neurologic status

  • Tumor characteristics – size/location/vascularity, etc

PrognosisMeningioma

What does this refer to

• Hemangioma – abnormal buildup of blood vessels in the skin or internal organs

• Hemangioblastoma – arises from the blood vessel lining

• Slow growing and well defined

• MC posterior fossa

Hemangioma/Hemangioblastoma

What does this refer to

• MC > 40 yo

• Hemangioblastoma

  • M > F

EpidemiologyHemangioma/Hemangioblastoma

What does this refer to

• Hemangioma – abnormal buildup of blood vessels in the skin or internal organs

• Hemangioblastoma – arises from the stromal cells of the blood vessel lining

• Retinal hemangioblastoma associated with von Hippel-Lindau syndrome

• Hemangiopericytoma – originates from cells surrounding blood vessels & meninges

EtiologyHemangioma/Hemangioblastoma

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Clinical historyHemangioblastoma

What does this refer to

• Loss of visual acuity

• Abnormal gait

• Poor coordination in extremities

Clinical presentationRetinal Hemangioblastoma

What does this refer to

• Ependymoma

• Subependymoma

• Cerebral neuroblastoma

• Astrocytoma

• Oligodendroglioma

• Meningioma

• Cranial Nerve-Choroid plexus papilloma

• AVM

Differential diagnosisHemangioma/Hemangioblastoma

What does this refer to

• Labs

  • Biopsy

• Imaging

  • CT scan or MRI w/ contrast

WorkupHemangioma/Hemangioblastoma

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DiagnosticsHemangioma/Hemangioblastoma

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WORKUP – IMAGINGHemangioma/Hemangioblastoma

What does this refer to

• Referral to neurosurgery

• Surgical resection

• Radiation tx —> tumor attached to brainstem

Clinical intervention Hemangioma/Hemangioblastoma

What does this refer to

• Very good prognosis if surgical extraction is successful

• Minimal neurologic deficit

• Poorer prognosis with retinal hemangioblastoma + VHL

PrognosisHemangioma/Hemangioblastoma

What does this refer to

• Specific type of astrocytoma

  • Grade 1 Astrocytoma

• Originates in glial cells

• Type of glioma

• Derived from astrocytes

• Slow growing

Pilocytic Astrocytoma

What does this refer to

• M > F (minimal prevalence)

• MC Caucasians than AA

• Glioma tumors account for 33% of all brain tumors

• MC glial tumor in children

EpidemiologyPilocytic Astrocytoma

What does this refer to

• Astrocytes

• Can appear in any part of the brain

• MC in cerebellum

EtiologyPilocytic Astrocytoma

What does this refer to

• Juvenile astrocytoma

• Typically localized

• Considered the most benign of all astrocytomas

• Includes cerebellar astrocytoma and desmoplastic infantile

EtiologyPilocytic Astrocytoma (Grade I)

What does this refer to

• Low grade

• Types

  • Fibrillary

  • Gemistocytic

  • Protoplasmic

• Tend to invade surrounding tissue

• Grows at relatively slow rate

EtiologyDiffuse astrocytoma (Grade II)

What does this refer to

• Rare, but very aggressive

Etiology Anaplastic Astrocytoma (Grade III)

What does this refer to

• MC primary CNS tumor in adults

Etiology Glioblastoma multiforme (Grade IV)

What does this refer to

• Ventricular tumors associated with tuberculous sclerosis

EtiologySubependymal Giant Cell Astrocytoma

What does this refer to

• Headache

• Nausea

• Vomiting

• Lethargy

Clinical history Pilocytic Astrocytoma

What does this refer to

Physical exam Pilocytic Astrocytoma

What does this refer to

• Other malignant brain neoplasms

• Brain abscess

• Brain metastasis

• Cardioembolic stroke

• Multiple sclerosis

Differential diagnosisPilocytic Astrocytoma

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Workup Pilocytic Astrocytoma

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DIAGNOSTICSBrain Biopsy – Pilocytic Astrocytoma

What does this refer to

• Contain microcysts and mucus-like fluid

• Grouped by appearance and behavior of the cells for which they are named

DIAGNOSTICSBrain Biopsy – Diffuse Astrocytoma

What does this refer to

• Tentacle-like projections grow into surrounding tissues

• Growth into surrounding tissues makes them difficult to remove during operative procedure

DIAGNOSTICSBrain Biopsy – Anaplastic Astrocytoma

What does this refer to

• May contain cystic material, calcium deposits, blood vessels and/or mixed grade of cells

DIAGNOSTICSBrain Biopsy – Astrocytoma Grade IV (Glioblastoma)

What does this refer to

• Pilocytic astrocytoma

  • Surgical excision

  • + radiation in older children and adults

• Diffuse astrocytoma

  • Surgical excision

  • +/- radiation tx

• Anaplastic astrocytoma

  • Surgical excision —> rad tx

  • +/- chemo

• Astrocytoma grade IB

  • Surgical excision —> rad tx

  • PLUS chemo

Clinical intervention for Astrocytoma

What does this refer to

• Degree of atypia (tumor grade) on histopathology is the best prognostic indicator

• Childhood survival Grade I and II

  • 5 yr survival 90%

• Low grade – average survival after surgery is 6-8 yrs

• > 40% live more than 10 yrs

• Grade IV Glioblastoma

  • Average survival 12-18 months

  • Only 25% survive > 1 yr

PrognosisAstrocytoma

What does this refer to

• A 63-year-old man is brought to the physician's office by his son due to progressively worsening headache and weakness.

• His headache began approximately 3 months prior to presentation and is described as diffuse but worse on the right-side of the head.

• The headache worsens with coughing and lifting heavy objects and is associated with nausea, multiple episodes of vomiting, and left-sided weakness.

• He previously worked for the synthetic rubber industry for over 30 years.

• Physical Exam: 3/5 strength in the left upper and lower extremities

Glioblastoma

What does this refer to

• Highly malignant (grade IV) Astrocytoma

• Most lethal & most common primary brain tumor

• Highly vascular/extensively irregular and infiltrative tumor

• MC in frontal lobes & cerebral hemispheres

• Primary and secondary origin

Glioblastoma

What does this refer to

Epidemiology of Giloblastoma

What does this refer to

• Arise from poorly differentiated neoplastic astrocytes

• Familial gliomas

Etiology Giloblastoma

What does this refer to

• Primary glioblastoma multiforme (MC)

  • 60% in adults older than 50 years

• Secondary glioblastoma multiforme

  • 40% in adults < 45 yo

• Variants

  • Classic – extra copies of epidermal growth factor receptor gene (EGFR)

  • Mesenchymal – TP53 mutation and mutation/alteration of gene encoding for neurofibromatosis

Etiology – GlioblastomaPrimary and Secondary Tumor

What does this refer to

Clinical HistoryGlioblastoma

What does this refer to

• Headache (50-60%)

• New onset seizures (20-50%)

• Focal neurologic symptoms (10-40%)

PresentationHigh Grade Glioblastoma (GBM)

What does this refer to

• Focal neurologic deficit (dependent on tumor location) is MC

• Papilledema on fundoscopic exam

• Hemiparesis

• Dysphasia

• Dyspraxia

• CN Palsies

• Visual field deficits

• AMS

Physical Exam Glioblastoma

What does this refer to

• Occurs when the Optic nerve is swollen due to pressure in or around the brain

• Symptoms

  • Visual disturbances

  • Headaches & nausea

Fundoscopic Exam- PapilledemaGlioblastoma

What does this refer to

• Anaplastic Astrocytoma

• Cerebral Abscess

• Demyelination disease

• Encephalitis

• ICH

• Metastasis

Differential Diagnosis Giloblastoma

What does this refer to

Workup Glioblastoma

What does this refer to

• Confirms dx

• Malignant astrocytes +necrotizing hemorrhagic center surrounded by pseudopalisading (tumor cells lining necrotic cells)

Diagnostics - Histopathology Glioblastoma

What does this refer to

DIAGNOSTICS – MRI Glioblastoma

What does this refer to

• Butterfly gliomas

  • High grade astrocytoma

    • Usually a glioblastoma

      • Crosses the midline via the corpus callosum.

  • May involve other white matter commissures

  • The term butterfly refers to the symmetric wing-like extensions across the midline.

WORKUP – MRIButterfly Glioma

What does this refer to **PICTURE WILL BE ON EXAM

Butterfly Glioma

What does this refer to

• Maximal surgical resection

• Adjuvant radiation – not curative (after surgery)

• Concurrent and adjuvant chemotherapy

• Antineoplastic – Temozolomide (Temodar) [PO or IV]

Clinical InterventionGlioblastoma

What does this refer to

• Most of the medications used to treat Sx 2° to GBM

• Seizures

  • Levetiracetam (Keppra) 1st line tx

  • Phenytoin (Dilantin)

  • Carbamazepine (Tegretol)

• Vasogenic Cerebral Edema

  • Dexamethasone (Decadron) + Famotidine

• Antineoplastics with radiation tx – POST-OP

  • Temozolomide (Temodar) 1st line tx

  • Carmustine (BiCNU)

Clinical Pharmacotherapeutics Glioblastoma

What does this refer to

• There is no cure

• Significant overall survival improvement in patients treated with temozolomide and radiation compared with radiotherapy alone

• Without tx – die within 3 months

• Optimal combination tx – 12 month survival

• 2 year survival – less than 25%

• 5 year survival – less than 10%

• Survivors may have cognitive deficits/focal neuro deficits/personality changes

PrognosisGlioblastoma

What does this refer to

• Type of embryonal tumor

  • Starts in fetal brain cells

  • Occurs in cerebellum

• Specific etiology is unknown

• Wingless/Integrated (WNT) signaling pathway

• Sonic Hedge Hog (SHH) protein

Meduloblastoma

What does this refer to

• MC malignant pediatric brain tumor

• Accounts for 64% of embryonal tumors in patients 0-19 yo

• M > F and most common in boys 1 – 10 yo

• Peak age of dx is 5-9yo

• MC Caucasian and Asian/Pacific Islander race

Medulloblastoma

What does this refer to

• 4 molecular subgroups

  • WNT

  • Sonic hedgehog (SHH) protein

  • Group 3

  • Group 4

Etiology Medulloblastoma

What does this refer to

• Sx of ↑ ICP & cerebellar dysfunction

  • Nocturnal or morning headaches

  • Nausea/vomiting

  • Altered mental status

• Tumors in midline

  • Gait ataxia

  • Truncal instability

• Tumors in lateral cerebellar hemispheres

  • Limb clumsiness/incoordination

Clinical History Medulloblastoma

What does this refer to

Physical Exam Medulloblastoma

What does this refer to

• Pilocytic astrocytoma

• Ependymoma

• Atypical teratoid/rhabdoid tumors (ATRT)

Differential diagnosisMedulloblastoma

What does this refer to

WorkupMedulloblastoma

What does this refer to

Diagnostic Imaging Medulloblastoma

What does this refer to

• Consult/referral pediatric neurosurgery, pediatric oncology/neuro-oncology

• Surgical resection, radiation and chemotherapy

• Placement of CSF shunt for ICP ↑

• Minimal neurologic signs and no hydrocephalus – preop workup can be done outpatient

• Impending hydrocephalus

  • Decreased mental status 1st sign

• Initiated within 28 days of dx

  • Macroscopic complete tumor resection THEN

  • Craniospinal irradiation

• Post-op MRI

Clinical Intervention for Medulloblastoma

What does this refer to

Clinical pharmacotherapeuticsMedulloblastoma

What does this refer to

• Hydrocephalus

• Cerebellar dysfunction

  • Brainstem invasion of the tumor was the only risk factor identified as having a positive correlation with the development of cerebellar mutism

MorbidityMedulloblastoma

What does this refer to

• Prognosis correlates with age of dx, post procedure residual deficit, bio-molecular marker

• Survival rates in children depend on the patient's age and how much the tumor spreads

• 5 yr survival rate child < 3yo is 40-50%

• Has not spread to spinal cord

  • Survival rate into adulthood are ~75%

• Spread to the spinal cord

  • Survival rate ~60%

• Within 1.5 yrs after tx

  • GH deficiency noted (94%)

  • TSH deficiency noted (10%)

Prognosis Medulloblastoma

What does this refer to

• Rare malignant tumor of the retina that affects young children

• A 2-year-old boy presents to his pediatrician for strabismus. Family history is notable for osteosarcoma in his father. Physical examination is notable for strabismus and bilateral leukocoria. He is referred to a pediatric ophthalmologist for further evaluation.

Retinoblastoma

What does this refer to

• MC primary ocular cancer of childhood

• Accounts for 13% of cancer in the first year of life

  • Median age dx 18-20 months

• Unilateral and bilateral 40%

• Heritable and non-heritable

EpidemiologyRetinoblastoma

What does this refer to

• Arises from the retina

• Heritable

  • Germline mutations in the RB1 gene

  • Usually leads to bilateral disease

• Non-heritable

  • Somatic mutations in the RB1 gene

  • Typically leads to unilateral disease

• Mutation in the long arm of chromosome 13

  • Normal gene suppresses Retinoblastoma

EtiologyRetinoblastoma

What does this refer to

Clinical History/Physical Exam Retinoblastoma

What does this refer to

• Leukocoria

• Strabismus

• Red, painful eye with glaucoma

• Nystagmus

• Orbital cellulitis

Physical ExamRetinoblastoma

What does this refer to

Screening Retinoblastoma

What does this refer to

• Congenital cataract

• Exudative Retinal Detachment

• Retinopathy of Prematurity

• Anterior Uveitis of Childhood

Differential Diagnosis Retinoblastoma

What does this refer to

• Histology

  • Classic histologic finding (ocular tissue)

    • Flexner-Wintersteiner rosettes

    • Spoke and wheel shaped cell formation

Workup Retinoblastoma

What does this refer to

• Immediate consult with Pediatric Oncologic Ophthalmologist

  • Exam with dilation

• Control of tumor size/vision preservation

• Radioactive Isotope plaques

• Chemotherapy

Clinical Intervention Retinoblastoma