Brain tumours november 2014

CNS TumorsCNS Tumors

Brain Tumors Tumors

Prof. Nabil KhalilProf. Nabil Khalil


Core Learning Issues: Pathology +Major CLINICAL manifestations:

Raised ICP – Pathology & Clinical features. Pathology of common Primary and secondary Brain tumors in

different age groups. Clinical presentations.


CNS Tumors: General Features

10% of all tumors. Commonest solid cancers in children.(2nd to Leuk for

all malignancies) Age: double peak 1st & 6th decade Adults - 70% supratentorial Children - 70% infratentorial No/very rare extraneural

spread. Metastasis most common.

AdultsAdults

ChildrenChildren


Clinical features:

Raised Intracranial Pressure* Headache (morning), vomiting, slow pulse,

papilloedema. Local damage:

Lobes of the brain,Cerebellum,Nerve & tract deficits.Symptoms of Paralysis, seizures etc.


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.Cortex Brain Stem compress Frontal lobe Temporal lobe Motor area Cerebellum Optic tract, occipital.


CNS Anatomy - Clinical Features


Clinical symptoms

Some Clinical symptoms


7th nerve palsy: Cerebellopontine angle

tumours. Acoustic neuroma,epidermoid cysts, medulloblastomameningioma

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


Normal Fundus - Papilledema


Normal vs Glaucoma


CNS Tumors Classification:

Primary Tumors:Meninges – Meningioma

Glial cells: GliomaAstrocytoma & Glioblastoma. Oligodendroma, ependymoma.

Nerve sheath – Schwanoma, Neurofibroma.

Embryonal –PNET: Medulloblastoma, neuroblastoma, teratoma.

Blood vessels – angioma, angiosarcoma etc.

* Other Epithelial, Pituitary (craniopharyngioma) & Pineal gland tumors (pinloplastoma).

Secondary Tumors - Metastasis – common Melanoma, breast, lung, GIT.


Adults: Astrocytoma &

Glioblastoma. Meningioma Metastasis.

Children: Astrocytoma Medulloblastoma

Common:


CNS Tumors: Summary

Adults:Adults: Secondaries common fromSecondaries common from Lung, Skin melanomas, Lung, Skin melanomas,

breast..breast.. Primary - SupratentorialPrimary - Supratentorial

Astrocytoma / Astrocytoma / glioblastoma.glioblastoma.

MeningiomaMeningioma

Children:Children: 22ndnd common (leuk / lymph) common (leuk / lymph) InfratentorialInfratentorial

Astrocytoma (cystic Astrocytoma (cystic cerebellar)cerebellar)

MedulloblastomaMedulloblastoma Hydrocephalus.Hydrocephalus. Meningeal spread.Meningeal spread.


Meningioma:

Arise from arachnoid granulations of venous sinuses. Attached to dura.

Common sites: parasagittal (falx), sphenoidridge, olfactory groove, cerebellopontine angle. specific clinical features.

Females common (2:1) Slow growth, well differentiated &

demarcated. Does not invade brain (Benign). Reactive skull Hyperostosis over the tumor. Microscopy: spindle cells in whorls and

psammoma bodies(microcalcification).

Meningioma—bilateral parasagittal-falx


Meningioma


Meningioma-ant. Falx+post


Meningioma ant .parasagittal


Meningioma-cortical


Meningioma-basal subfrontal

•Well demarcated•Capsulated


Meningioma – whorls of clear cells.

NormalArachnoidGranulation


Meningioma NodulesNodules

Psammoma Body

Psammoma bodies


Glioma:

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

children Benign * to Aggressively malignant.

Astrocytoma (anaplastic & G.B.M) Ependymoma - Rare, 4th ventricle. Oligodendroglioma - Benign, adults,

rare


Astrocytomas

Adults:Commonest 80%, Supratentorial.Solid – Fibrillary – low grade*. Varigated, Hemorrhagic - Malignant,

glioblastoma multiforme.Children:

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


Astrocytoma-Lowgrade fibrillary


Astrocytoma


Astrocytoma: * Lat. Vent. *petechial hem.


Glioma Brain Stem – note diffuse tumor


Glioma Cerebrum cystic degeneration


Glioma:fronto-pareital


Astrocytoma (Glioma)cerebellar


Glioma Brain Normal


Astrocytoma


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.


Genetic abnormalities in Glioma:Low grade Anaplastic GBM


Glioma: high grade


Glioma:Enhancement with peritumoral edema.


Glioblastoma:


GBM:+ glioma Enhancement with peritumoral edema.


Glioblastoma – high grade Astrocytoma


Glioblastoma – high grade Astrocytoma


Glioblastoma Multiforme (high grade Astrocytoma)


Glioblastoma Cerebrum-intraventricular


Glioblastoma Cerebrum-intraventricular


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


Glioblastoma Multiforme

PalisadingPalisading

NecrosisNecrosis



NecrosisNecrosisPalisadingPalisading



Palisading

B.V

Necrosis



PalisadingNecrosis




Astrocytomas---Pilocytic:

Adults:Commonest 80%, Supratentorial.Solid – Fibrillary – low grade*. Varigated, Hemorrhagic - Malignant,

glioblastoma multiforme.Children:

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


Pilocytic astrocytoma

Common in childhood Most slow growing of the gliomas Sites: cerebellum, around 3rd Ventricle. optic

nerve. Grossly cystic with mural nodule Microscopic

elongated hair-like (pilocytic) elongated cells & Rosenthal fibers.


Pilocytic Astrocytoma - children


Pilocytic Astrocytoma - children


Pilocytic astrocytomaMural nodule


Pilocytic Astrocytoma: Microscopy

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

CNS TumorsCNS TumorsOLIGODENDROGLIOMA


Glioma:

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

children Benign * to Aggressively malignant.

Astrocytoma (anaplastic & G.B.M) Ependymoma - Rare, 4th ventricle. Oligodendroglioma - Benign, adults,

rare


Ependymoma


Ependymoma 4th Ventricle


Ependymoma 4th Ventricle


Ependymoma-hemorrhage


Ependymoma


Primitive Neuroectodermal Tumors-PNET

Origin from primitive blast cells. Rosettes - attempted nerve formation.

CNS

1. Medulloblastoma – Cerebellum

2. Pineal tumors(pinloplastoma)

Non CNS

1. Retinoblastoma – Retina(eye)

2. Neuroblastoma – Adrenal glands

3. Ganglioneuroma - Mediastinum

Other CNS tumors


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

common. Rosettes & neuronal or glial differentiation

rarely seen.


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

Origin

Spread


Medulloblastoma


Medulloblastoma


Medulloblastoma


Epithelial tumours



Craniopharyngioma


pituitary tumors Pituitary adenomas:Tumors from anterior

pituitary component.Secreting or nonSecreting chromopobe adenomas.

Posterior pituitary (neuro-hypophysis):tumors that decrease secreting Anti diuretic hormone (ADH). Polyuria


Nerve Sheath 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


Schwannoma / Neurofibroma


Schwannoma 8th Nerve:


Bilateral 8th nerve schwannomas.


Schwannoma:


Schwannoma


Neurofibromatosis:


Neurofibromatosis:

Café-au-lait spot


Schwannoma


Schwannoma


32y Female with Fleshy pappules:


Neurofibromatosis: Autosomal dominant, NF1- Peripheral/Von Recklinghausen’s NF2- known as central NF. However, NF1 may cause central characteristics. About 50% familial, 50% sporadic gene mutation. NF1/ von Recklinghausen disease, gene mutation

on chromosome 17, 1 in every 3000-4000 births. Diagnosis of NF1 if > 2 of 6 or more café au lait spots (irregularly shaped, evenly

pigmented, brown macules), 2 or more neurofibromas, axillary or inguinal freckling, Lisch nodules on the iris or optic glioma, various types of osseous lesions, a first-degree relative with the condition.


Neurofibromatosis: NF2 – Gene mutation chromosome 22. 1 in every 33,000-40,000 births Typically present with acoustic neuromas or vestibular

schwannomas. Tinnitus, balance disorders, and progressive hearing loss May also have meningiomas and juvenile cataracts. First-degree relative and on any 2 of the conditions listed for NF1. Patients with NF1 are at increased risk of malignancy. Annual ocular examinations are recommended. Genetic testing is

also advocated in patients with NF who wish to have children. Surgery has been a successful treatment for the lesions

themselves; however, recurrence often occurs, and nerve damage is a risk when tumors are located along neural pathways

(National Institute of Neurologic Disorders and Stroke, 2006).


METASTASEScommon brain tumours in adults especially in

the elderly


Metastatic Melanoma: multiple


Brain Metastases: Surrounding edema.


Most common CNS Tumors:

Glioblastoma MF


Summary: Children – 70% INFRAtentorial Adults – 70% SUPRAtentorial Common Malignant - adults, metastatic tumors (Lungs) Common - adults – glioblastoma multiforme

Intracerebral Common Benign - children – cerebellar astrocytoma. Common Malig - children – cerebellar

medulloblastoma Very rare in children– meninges and schwann cells

tumours(meningiomas and schwannomas) – usually found in adults


Pathology of Pathology of

Increased Intracranial PressureIncreased Intracranial Pressure


Pathogenesis: Increased intracranial pressure (ICP): - if >

40 mm Hg cerebral hypoxia, cerebral ischemia, cerebral edema, hydrocephalus, and brain herniation.

Cerebral edema: Edema - Disruption of the blood brain barrier – vasodilatation – swelling.

Hydrocephalus communicating OR NON communicating type according to tumor site.


Pathogenesis: Brain 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.


Common CNS Herniations: Subfalcine:


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).


Uncal Herniation:

Inferior view, The herniated uncus is bulging over the position of the tentorium (black arrows) and compressing the midbrain. The two mammillary bodies (blue arrows) have been shifted to the patients right due to the pressure.


Uncal Herniation:


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.


Cerebellar Tonsil - Herniation Note the cone shape of the

herniated tonsils around the medulla in this cerebellum specimen.

Results in compression and hemorrhages in the pons.


Transtentorial herniation: Transtentorial herniation

at the base of the brain. A prominent groove surrounds the displaced parahippocampal gyrus (arrow). The adjacent 3rd nerve (N) is compressed and distorted and the ipsilateral cerebral peduncle (P) is distorted with small areas of haemorrhage.


Cerebral Herniation: PathogenesisSite of Site of herniationherniation EffectEffect Clinical consequenceClinical 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

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

Look for good in others… no one is without faults and everyone has some good qualities!


cases


52y, F, CNS tumor: ? diagnosis

1 2 3 4 5

0%

10%

90%

0%0%

1.1. Glioblastoma m.Glioblastoma m.

2.2. AstrocytomaAstrocytoma

3.3. MetastasesMetastases

4.4. Medulloblastoma Medulloblastoma

5.5. MeningiomaMeningioma



1 2 3 4 5

4%

90%

6%0%0%

A.A. Glioblastoma m.Glioblastoma m.

B.B. AstrocytomaAstrocytoma

C.C. MeningiomaMeningioma

D.D. EpendymomaEpendymoma

E.E. MedulloblastomaMedulloblastoma



1 2 3 4 5

95%

2% 2%0%0%







52y, F, parasagittal tum attached to falx: ? diagnosis

1 2 3 4 5

6% 8% 10%4%

71%




4.4. EpendymomaEpendymoma



Q:Commonest primary CNS tumor in Adults ?

1 2 3 4 5

15%

73%

0%0%

12%







52y, F, CNS tumor: ? Arrow Feature

1 2 3 4 5

0%

98%

0%2%0%

1.1. Necrosis.Necrosis.

2.2. Psammoma bodyPsammoma body

3.3. CalcificationCalcification

4.4. Blood vesselBlood vessel

5.5. Epithelial pearlEpithelial pearl

60y smoker, chronic bronchitis complains of difficulty walking. , stiff, expressionless face. A tremor of his fingers is apparent but ceases when he tries to reach for something. Image shows

basal ganglia atrophy. Diagnosis?

1 2 3 4 5

0%4% 2%

92%

2%

1.1. Alzheimers diseaseAlzheimers disease2.2. Lacunar infarctsLacunar infarcts3.3. Picks diseasePicks disease4.4. Parkinsons diseaseParkinsons disease5.5. haemorhagehaemorhage


Commonest primary CNS tumor in Children?

1 2 3 4 5

0%

67%

28%

4%0%







Commonest Location of CNS tumor in Children?

1 2 3 4 5

4%

37%

4%2%

53%

A.A. SupratentorialSupratentorial

B.B. Cerebellum Cerebellum

C.C. InfratentorialInfratentorial

D.D. Cerebrum.Cerebrum.

E.E. Brain stemBrain stem









astrocytoma


56y, F Rapidly growing parietal lobe tumor:? diagnosis

1 2 3 4 5

88%

0%6%6%

0%







49y, M, CNS tumor: ? diagnosis

1 2 3 4 5

0% 0%

20%

80%

0%

A.A. MetastasesMetastases

B.B. Astrocytoma sy.Astrocytoma sy.

C.C. MeningiomatosisMeningiomatosis

D.D. NeurofibromatosisNeurofibromatosis

E.E. LipomatosisLipomatosis


SAQ / KFP Should seizure patients have

imaging done immediately? Personality changes indicate

which location? Differential diagnosis 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?

Yes, 10-20% tumors. Frontal lobe Gliomas

Conservative – Poor Steroids, anti

epileptic, symptomatic.


SAQ / KFP Indication of a 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?

Indicating headache. Increased ICP, tum.

4th ventricle.

No – coning…* Central – vermis


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.


35y Male, depression

Axial T1 weighted MRI

Axial T2 weighted MRI


35y Male, depression

Coronal T1 weighted MRI



ASTROCYTOMA


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.


Axial T1 weighted MRI Axial T2 weighted MRI

3y Male, constant cry….



3y Male, constant cry….





4.4. EpendymomaEpendymoma


What is the most likely diagnosis?


THANK YOU

Health & Medicine

Brain tumours november 2014