Download - Pathology of CNS Tumours - Lecture
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
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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
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Most common CNS Tumors:
children
Adults
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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.
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Meningioma:
Note location in the venus sinus & adherent to dura.
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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)
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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
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Astrocytoma
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Glioma Brain Stem – note diffuse tumor
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Glioma Cerebrum cystic degeneration
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Glioma:
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Astrocytoma: * Lat. Vent. *petechial hem.
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Astrocytoma (Glioma) – brain stem
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Glioma Brain Normal
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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.
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Glioma: high grade
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GBM: MRIEnhancement with peritumoral edema.
CNS Tumors
Glioblastoma – high grade Astrocytoma
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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
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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
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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
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Medulloblastoma
CNS Tumors
Medulloblastoma
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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.
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Herniation: Central Pontine / Duret Hem.
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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
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35y Male, depression
Coronal T1 weighted MRI
Coronal T2 weighted MRI
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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.
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Axial T1 weighted MRI Axial T2 weighted MRI
3y Male, constant cry….
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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
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Schwannoma 8th Nerve:
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Bilateral 8th nerve schwannomas.
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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: