CNS Tumors

CPC-44: 22y Sam G, Seizure. Mr. SG, 22y, previously healthy male. On bus, became agitated, combative, had a

seizure and became unresponsive. From Boston, USA, on holidays, 3 days. No H/O neck stiffness, no skin lesions/rash Pupils minimally reactive and 6mm bilaterally;

fundoscopy normal.

CNS Tumors

CPC-4.3.7 – Jenna 27y teacher. Jenna is a 27 year old teacher in Ingham who

collapsed in her classroom today. She was seen by her pupils to ‘shake all over’.

Brought to ED by paramedics, accompanied by teaching colleague. Collapsed approx 30 mins ago.

Tutors: ..look at a broad range of differential diagnoses for a witnessed, generalized tonic- clonic seizure. Focus… on epilepsy, infection (meningitis), and brain tumour.

..discuss ‘what if’ questions..

CNS Tumors

CPC-44: 22y Sam G, Seizure. Epileptic seizure

CVA, CNS Injury, infection, tumour & Epilepsy*Drugs: drug withdrawal/ overdose Idiopathic (epilepsy), Genetic, Autoimmune,

endocrine..Metabolic: uraemia, Hypoglycaemia, Neurodegenerative diseases e.g. Alzheimer’s

Non epileptic: Syncope* - vasovagalArrhythmias, Pseudoseizures (psychogenic),Concussion, TIA

CNS Tumors

Scenario: Brain Tumor

Chronic Crescendo Morning - Head ache* Pulse 62 bpm reg small volume; BP 140/90 mmHg

T37.4C. GCS - variable. Localising signs – seizures, aphasia, anosmia,

vision defects, paralysis (unilateral), dementia. Cushing’s reflex – Bradycardia+hypertension (ICP) Papilloedema * raised ICP Lesion on imaging. Peritumoral edema – rapidly growing/inflammed.

Cresc. Chron. Morn. headache*, Seizures, localizing signs

CNS Tumors

Scenario: Meningitis ABC breathing spontaneously rr 18/min 4l O2 via

mask, sats 90%; pulse 110 bpm reg small volume; BP 90/60 mmHg T39.6C

GCS - E2V3M4 Detailed check - petechiae non blanching rash

trunk, buttocks, Neck stiffness Small contusion L temperoparietal area Capillary refill time > 3 secs, peripheral cyanosis+ Brudzinski sign positive Ix skin scraping from lesion : gram negative

diplococci; CSF gram negative diplococci; FBC wcc 18 (polymorhic leucocytosis)

Brudzinski sign, Kernig sign, CSF findings

CNS Tumors

Scenario: Epilepsy: ABC breathing spontaneously rr 14/min; 4l O2 via

mask , sats (O2 Sat study) 96% ; pulse 100 bpm regular good volume T 36.1 C BP 148/94.

GCS E2V3M4 Detailed check no neck stiffness, no skin lesions/rash Tongue has been bitten; pupils equal and reactive to

light; fundoscopy normal Decreased tone R upper limb, ?normal tone other limbs Reflexes increased on R upper + lower limb; decreased

on L upper +lower; Plantar reflexes upgoing Evidence of urinary incontinence All other systems : nil abnormal Ix - BSL : 5.1; toxicology screen : negative

Negative signs, family / past history

CNS Tumors

Core Learning Issues: Pathology Major CLI:

Raised ICP – Pathology & Clinical features. Pathology of common CNS tumors in different age

groups. Astrocytoma – grades, clinical types, presentation &

complications. – “glioblastoma multiforme” Meningitis – common types *Bacterial – Micro-Lec*.

Pathology Minor CLI: Pathology of Epilepsy (note this is major clinical

learning issue) Meningioma, Acoustic neuroma, Craniopharyngioma /

pituitary tumors. Medulloblastoma. CJD-Creutzfeldt jakob's disease. (Mad cow disease).

In every person who comes near you look for what is good and strong;

honor that; try to learn it, and your faults will drop off like dead leaves

when their time comes.

--John Ruskin

Look for good in others “No one is without faults and everyone has good qualities…!”

Pathology of CNS Tumors

Dr. Venkatesh M. Shashidhar, MDAssociate Professor & Head of Pathology

CNS Tumors

CNS Tumors: General Features

10% of all tumors. (10 to 17 per 100,000) Commonest solid cancers in children.(2nd to Leuk) Age: double peak 1st & 6th decade Adults - 70% supratentorial Children - 70% infratentorial Metastatic tumors are

the most common (50-70%) Primary - glial origin. Very rare extraneural

spread. Location & not nature determines

prognosis.

Adults

Children

CNS Tumors

Most common CNS Tumors:

children

Adults

CNS Tumors

CNS Tumors Classification:

Secondary Tumors - Metastasis – commonest >50%* breast, lung, GIT, Melanoma.

Primary Tumors: (not from neurons…!)Glial cells: Glioma * commonest

Astrocytoma (& Glioblastoma). Oligodendroma, ependymoma.

Nerve sheath – Schwanoma, Neurofibroma.

Meninges: Meningioma

Germ cell: Medulloblastoma, neuroblastoma, teratoma, neuroma, neuroganglioma.

Lymphocytes: CNS Lymphoma

* Other BV: (angioma)Epithelial, Pituitary & Pineal gland tumors.

CNS Tumors

Clinical features:

Slow, Progressive..*Crescendo, Chronic, Morning head ache.

Local damage:Nerve & tract deficits, unilateral*

Paralysis, vision defects, anosmia, seizures.. etc.

Raised Intracranial Pressure* Headache, vomiting, slow pulse,

papilloedema.

CNS Tumors

CNS Tum: Clinical Features-Pathogenesis Headaches (morning) Papilloedema Nausea or vomiting Bradycardia Seizures (convulsions). Drowsiness, Obtundation Personality or memory Changes in speech Limb weakness Balance/Stumbling eye movements or vision

Increased ICP Increased ICP ICP – Medulla ob. ICP – Parasymp. Irritation. Brain Stem compress Frontal lobe Temporal lobe Motor area Cerebellum Optic tract, occipital.

CNS Tumors

CNS functional anatomy – localizing signs

CNS Tumors

Adults:Astrocytoma &

Glioblastoma.MeningiomaMetastasis.

Children:AstrocytomaMedulloblastom

a

Common:

(Metastases)

CNS Tumors

Meningioma:

Arachnoid granulation fibroblasts venous sinuses (Attached to dura).

Females(2:1), progesterone, cyclical/preg*

Common site: parasagittal (falx), Slow growth, well differentiated &

demarcated. Does not invade brain (Benign).

Reactive skull Hyperostosis over the tumor.

CNS Tumors

Meningioma:

Note location in the venus sinus & adherent to dura.

CNS Tumors

Meningioma: multiple

CNS Tumors

Meningioma

Pituitary

MCAQ

Tumor

CNS Tumors

Meningioma

CNS Tumors

Meningioma high grade: (rare)

CNS Tumors

Meningioma Nodules

Capsulated,spindle cells in whorls and psammoma bodies (common type).

Psammoma bodies(calcification)

CNS Tumors

Glioma:

Gliomas are neoplasms of glial cells. Commonest both in adults and

children. Benign * to Aggressively malignant.

Astrocytoma (low & high grade) Ependymoma - Rare, 4th ventricle. Oligodendroglioma - Benign, adults,

rare

CNS Tumors

Astrocytomas - Glioma

Adults:Commonest 80%, Cerebral.Low Gr: Solid, Fibrillary glioma High Gr: glioblastoma multiforme Varigated,

Hemorrhagic - Malignant,. Children:

Cystic, Low grade*, PilocyticInfratentorial (Cerebellum),

mutations of the metabolic enzyme Isocitrate DeHydrogenase (IDH1 and IDH2) are common in lower-grade astrocytomas. As a result, immunostaining for the mutated form of IDH1 has become an important diagnostic tool for low grade gliomas.

CNS Tumors

Astrocytoma-Lowgrade fibrillary

CNS Tumors

Astrocytoma

CNS Tumors

Glioma Brain Stem – note diffuse tumor

CNS Tumors

Glioma Cerebrum cystic degeneration

CNS Tumors

Glioma:

CNS Tumors

Astrocytoma: * Lat. Vent. *petechial hem.

CNS Tumors

Astrocytoma (Glioma) – brain stem

CNS Tumors

Glioma Brain Normal

CNS Tumors

Astrocytomas

Adults:Commonest 80%, Cerebral.Low Gr: Solid, Fibrillary. High Gr: glioblastoma multiforme

Varigated, Hemorrhagic - Malignant,.Children:

Cystic, Low grade*, PilocyticInfratentorial (Cerebellum),

CNS Tumors

Glioblastoma Multiforme (GBM): High grade Astrocytoma - Grade IV Commonest & malignant brain tumor in adults –

mean survival <1y – cerebral supratentorial. Loss of heterozygosity on Chromosome 10 (80%) Most GBMs have lost one entire copy of C – 10 2 types: Primary (worst) or Secondary from low grade

astrocytomas (better prog). Variants: giant cell GBM, gliosarcoma Microscopy: Necrosis, palisading, hypercellularity, nuclear atypia

& vascular proliferation & mitoses.

CNS Tumors

Genetic abnormalities in Glioma:Low grade Anaplastic GBM

* GBM can occur alone without prior glioma

In glioblastoma, loss-of-function mutations in the p53 and Rb tumor suppressor pathways and gain-of-function mutations in the oncogenic PI3K pathways have central roles in tumorigenesis.

CNS Tumors

Glioma: high grade

CNS Tumors

GBM: MRIEnhancement with peritumoral edema.

CNS Tumors

Glioblastoma – high grade Astrocytoma

CNS Tumors

Glioblastoma – high grade Astrocytoma

Note: Looks like abscess, but it is necrosis..!

CNS Tumors

Glioblastoma Multiforme (high grade Astrocytoma)

CNS Tumors

Glioblastoma Cerebrum

CNS Tumors

High Gr.: Glioblastoma multiforme(high grade- Hypercellularity, necrosis, hemorrhage & palisading)

Hem

Necro

Hyper cel. Palis.

CNS Tumors

Glioblastoma Multiforme

Palisading

B.V

Necrosis

CNS Tumors

Glioblastoma Multiforme

A Astrocytoma Low gradeB Glioblastoma Multiforme(GBM)C Necrosis with pseudopalisading in GBM.

CNS Tumors

Astrocytomas

Adults:Commonest 80%, Cerebral.Low Gr: Solid, Fibrillary. High Gr: glioblastoma multiforme

Varigated, Hemorrhagic - Malignant,.Children:

Cystic, Low grade*, Pilocytic AstrocytomaInfratentorial (Cerebellum),

CNS Tumors

Pilocytic astrocytoma Children, slowest

growth, Cerebellum, Cystic with mural

nodule Micro: elongated

hair-like (pilocytic) cells

Mutations in IDH1 and IDH2 (common in low-grade diffuse astrocytomas) are not found in pilocytic tumors. These genetic distinctions support the division of these astrocytomas into two diagnostic categories.

CNS Tumors

Pilocytic Astrocytoma - children

CNS Tumors

Pilocytic Astrocytoma: solid, brightly contrast-enhancing mural component and associated cyst.

CNS Tumors

Pilocytic Astrocytoma: Microscopy

Palisading pilocytic astrocytes – note plenty of Rosenthal fibres between cells.

CNS Tumors

Medulloblastoma: Children. Cerebellum – vermis. Primitive neuroectodermal tum. Blast cells – round scanty cytoplasm. 4th ventricle Obstruction – hydrocephalus. CSF seeding and Meningeal infiltration is

common. Rosettes & neuronal or glial differentiation

rarely seen.

CNS Tumors

Medulloblastoma: Primitive neuroectodermal tumor:Children, vermis of cerebellum.

Origin

Spread

CNS Tumors

Medulloblastoma

CNS Tumors

Medulloblastoma

CNS Tumors

Youtube Videos: Glioblastoma Multiforme:

http://www.youtube.com/watch?v=idSos1XOi7A http://www.youtube.com/watch?v=bGawC2RJ-Sc

Meningioma: http://www.youtube.com/watch?v=ddEB5ITx2fw

Pyogenic Meningitis: http://www.youtube.com/watch?v=L9jpjxTSLws

CNS Tumors

CNS Lymphoma: Rare, 1%, most common

CNS neoplasm in immunosuppressed (transplant recipients, AIDS), caused by Epstein-Barr Virus.

High grade, large B-cell lymphomas. Poor response to chemotherapy

CNS Tumors: Summary

Adults: Secondary common Lung, Skin, breast.. Primary - Supratentorial

Astrocytoma / glioblastoma.

Meningioma

Children: 2nd common (leuk / lymph) Infratentorial

Astrocytoma (cystic cerebellar)

Medulloblastoma Hydrocephalus. Meningeal spread.

CNS Tumors

AV Malformation:

Pathology of Increased Intracranial Pressure.

CNS Tumors

Increased ICP: Pathogenesis & Clinical.

Increased intracranial pressure (ICP): Ischemia, Hematoma, Infection, tumor, >40 mm Hg cerebral hypoxia, ischemia, edema Cerebral edema: Vasogenic – inflammation/tumors or Cytotoxic

hypoxic, toxins. Clinical Features:

Headache + impaired consciousness, Vomiting, bradycardia, arterial hypertension Papilloedema.

False localizing signs: Ipsilateral pupillary dilatation & Hemiparesis. 6th nerve lesion uni or bilateral. Bilateral extensor plantar response (+ve Babinski)

CNS Tumors

Pathogenesis of complications: Cerebral herniation: Supratentorial herniation

common. 3 sub types Subfalcine herniation: The cingulate gyrus of the frontal

lobe (commonest) Central transtentorial herniation: displacement of the

basal nuclei and cerebral hemispheres downward Uncal herniation: Medial edge of the uncus and the

hippocampal gyrus Cerebellar herniation: infratentorial herniation

Tonsil of the cerebellum is pushed through the foramen magnum and compresses the medulla, leading to bradycardia and respiratory arrest.

CNS Tumors

Common CNS Herniations: Subfalcine: common,

Headache contralateral leg weakness.

Transtentorial: occulomotor (CN III) paresis (ipsilateral dilated pupil, abnormal EOM's), contralateral hemiparesion.

Tonsillar: Obtundation.

CNS Tumors

Subfalcine Herniation: in brain trauma.

Contusion of the inferior temporal lobe (blue arrow) has resulted in diffuse edema. (compressed and flattened gyri on the right).

This has resulted in subfalcine herniation of the cingulate gyrus (red arrow), with a secondary hemorrhagic infarction above that (black arrow). A midline shift from right to left is also present, as is uncal herniation (yellow arrow).

CNS Tumors

acute brain swelling + Uncal Herniation

Swelling of the left cerebral hemisphere has produced a shift with herniation of the uncus of the hippocampus through the tentorium, leading to the groove seen at the white arrow.

CNS Tumors

Herniation: Central Pontine / Duret Hem.

CNS Tumors

Cerebellar Tonsil - Herniation Note the cone shape of the

herniated tonsils around the medulla in this cerebellum specimen.

Results in compression and Duret hemorrhages in the pons.

CNS Tumors

Cerebral Herniation: PathogenesisSite of herniation Effect Clinical consequenceTranstentorial Ipsilateral 3rd cranial nerve

compressionIpsilateral fixed dilated pupil

  Ipsilateral 6th cranial nerve compression

Horizontal diplopia, convergent squint

  Posterior cerebral artery compression

Occipital infarction Cortical blindness

  Cerebral peduncle compression

Upper motor neurone signs

  Brainstem compression and haemorrhage

Decerebrate posture Cardiorespiratory failureDeath

Foramen magnum

Brainstem compression and haemorrhage

Decerebrate posture Cardiorespiratory failure Death

  Acute obstruction of CSF pathway

Decerebrate posture Cardiorespiratory failureDeath

Decorticate posturing: The elbows, wrists and fingers flexed, legs extended and rotated inward.

CNS Tumors

Why pupils dilate?

“Sympathetic system shows sympathy to your pants”

CNS Tumors

CPC-3.7– KFP Questions: Meningitis Types, classification & comparison. Septic, Viral & TB meningitis - CSF findings. Increased intracranial pressure – Pathologic

basis of clinical features. CNS tumours: common features. Adult and childhood CNS tumors. Meningioma, astrocytoma & Glioblastoma. Children astrocytoma & medulloblastoma. Epilepsy – clinical.

CNS Tumors

Learning Medicine...! Learning medicine should be a JOY, not an ordeal. Everyone learns according to their own best style. The Hippocratic oath issues of patient privacy,

compassion, and FREE sharing of knowledge have to be honored.

Exam and grade anxieties are the CANCERS of medical education.

If your school admitted students which they feel need to be whipped, the SCHOOL has failed, not YOU!

If you claim you NEED to be pushed, I do not want you as my doctor.

John R. Minarcik, MD (http://www.medicalschoolpathology.com)

It has been my philosophy of life that difficulties vanish

when faced boldly.

--Isaac Asimov

CNS Tumors

SAQ / KFP Should seizure patients have

imaging done immediately? Personality changes indicate

which location? Differentials for young adult

with insidious symptoms, seizures and decreased signal on T1 and increased signal on T2 weighted MRI?

What is the treatment and prognosis for someone with a low-grade astrocytoma?

How should the symptoms be treated?

What tests could have been done in the absence of neuroimaging?

Yes, 10-20% tumors. Frontal lobe Other gliomas Conservative – Poor Steroids, anti

epileptic, symptomatic.

EEG

CNS Tumors

SAQ / KFP Why was the child hitting his

head? Why did the child have a

headache? If the child does have

hydrocephalus, at what level is the ventricular system being obstructed at?

Should a lumbar puncture be performed?

Where in the cerebellum is the lesion located?

What is the radiolucent area visible along the antero-superior aspect of the radiograph?

Indicating headache. Increased ICP, tum. 4th ventricle. No – coning…* Central – vermis Separation/malfusion of

anterior frontoparietal suture due to hydrocephalus.

CNS Tumors

SAQ / KFP Name the location of

tumor? What cranial nerves

are involved? List differential

diagnosis Explain pathogenesis

of headache and papilledema?

What does the histological pattern represent in slide 1? slide 2?

Cerebellopontine angle Cranial Nerves 5,7 & 8 Teratoma, meningioma,

acoustic neuroma. Increased intracranial

tension. Tumor attempting to form

Arachnoid grannulations. Origin of tumor.

CNS Tumors

50y Female smoker - Headache.This 50 year-old female smoker known for hypertension and diabetes mellitus type 2 was in her usual state of health until 2 years ago, when she began to have morning headaches that would usually go away by themselves. Year later began to have hearing problem on her left side. Recently, she noticed intermittent loss of sensation of the left side of her face. She is taking a thiazide diuretic, captopril, glyburide, and metformin. She has no known allergies.

Physical exam: Slight drooping in the left mouth and lower eyelid. Incomplete closure of the left eyelid with corneal touch. Reduced pain and light touch on the left side. Fundoscopic exam revealed bilateral papilledema.

CNS Tumors

35y Male, depression2-year history of loss of initiative, depression. He had slowly lost his drive to win all the big deals he always done so well at work. 3 months ago he began to experience headache, which did not respond to acetaminophen or aspirin. His wife noticed that his lethargic state had increased in the past few months. 3 days ago his right arm began to convulse uncontrollably for 1 minute. 1 day ago the patient began again violently shaking his right arm, and the right side of face began to twitch at the dinner table. No fever.

Physical exam: Bilateral papilledema, increased deep tendon reflexes of the right bicep, tricep, +ve babinski sign on the right foot, reduced leg strength on the right.

CNS Tumors

35y Male, depression

Axial T1 weighted MRI

Axial T2 weighted MRI

CNS Tumors

35y Male, depression

Coronal T1 weighted MRI

Coronal T2 weighted MRI

CNS Tumors

3y Male, constant cry….Constant crying and not interacting with other children at daycare since 1m. Mother noticed that he was pointing to his head often. Family physician who stated that he was developing normally, and that the “ terrible two’s” are difficult period for parents. Recently started vomiting on a daily basis and started wobbling even though he learned to walk 6 months ago.

Physical: Bilateral papilledema and gait ataxia was noted on the physical exam.

CNS Tumors

Axial T1 weighted MRI Axial T2 weighted MRI

3y Male, constant cry….

CNS Tumors

Coronal T1 weighted MRI

3y Male, constant cry….

CNS Tumors

1. Glioblastoma m.

2. Astrocytoma

3. Meningioma

4. Ependymoma

5. Medulloblastoma

What is the most likely diagnosis?

CNS Tumors

65y Fem morning headache.Morning headache 2y, Progressive right upper limb weakness. She woke up this morning obtunded, and did not initially respond to her husband’s cries. She screamed to her husband that she could not see anything to her right, and that she that her left arm and leg were very weak. At this point her husband rushed her to the nearest hospital.Physical Exam: left lid ptosis, left-pupillary dilation, and failure of her left eye to constrict to light directly or consenually. Patient had bilateral lower limb weakness, with increased deep tendon reflexes on the left side, and a +ve babinski on the left side. Bilateral Papilledema. Homonymous hemianopia of the right side. Visual acuity was corrected to 20/20 with glasses. 

CNS Tumors

65y Fem morning headache.

CNS Tumors

Brain Metastasis: Lung, Breast, Skin,

Kidney, GIT. Prostate – never..! Well demarcated,

usually multiple with surrounding rim of inflammation.

Carcinomatosis: Meningeal CSF spread of malignant cells.

CNS Tumors

Metastatic Melanoma: multiple

CNS Tumors

Brain Metastases: Surrounding edema.

CNS Tumors

1. Glioblastoma m.

2. Astrocytoma

3. Meningioma

4. Ependymoma

5. Medulloblastoma

What is the most likely diagnosis?

CNS Tumors

SAQ / KFP Are there clinical signs of

nerve compression? What is the most likely cause

of the homonymous hemianopia?

Why does the patient have progressive right upper limb weakness, and paroxysmal left upper and lower limb weakness?

Should a lumbar puncture be performed?

Why was the patient obtunded?

Why was an-x-ray taken?

Yes, ptosis, pupils 3rd Optic pathway -

occipital. Motor cortex

compression – tum. Risky. Brainstem

compression. Meningioma

hyperostosis.

Other CNS tumors

CNS Tumors

Nerve Sheath Tumors:

Neurofibroma: Epi & endoneurial fibroblasts. Form whorls of fibroblasts with nerves Well differentiated, benign, capsulated.

Schwannoma: Schwann cells, elongated form whorls Nuclear palisading

CNS Tumors

Schwannoma / Neurofibroma

CNS Tumors

Schwannoma 8th Nerve:

CNS Tumors

Bilateral 8th nerve schwannomas.

CNS Tumors

Schwannoma:

Neurofibromatosis:

Café-au-lait spot

Neurofibromatosis:

CNS Tumors

Schwannoma

CNS Tumors

A 26-year old femaleHeadache,vomiting, an epileptic attack, weakness of legs. Now drowsy. Two weeks before admission she gave her second birth.

CT and NMR revealed a huge parasagittal tumor (80x67x65 mm), enhanced by contrast, compressed corpus callosum and ventricles.

CNS Tumors

7th nerve palsy: Cerebellopontine angle

tumours. Acoustic neuroma,epidermoid cysts, medulloblastomameningioma

Affected cranial nerves:5 trigeminal - masticatio7 facial –face muscles8 auditory – hearing

CNS Tumors

Brudzinski Sign of Meningitis: