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Pathology of Brain tumors (CNS tumors) for undergraduate medical students.
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Pathology of CNS Tumors CPC-4.3.7 – Jenna 27y teacher. <ul><li>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 ’. </li></ul><ul><li>Brought to ED by paramedics, accompanied by teaching colleague. Collapsed approx 30 mins ago. </li></ul><ul><li>(Aim: The aim of this CPC is to get students to initially look at a broad range of differential diagnoses for a witnessed, generalized tonic- clonic seizure . Then get them to focus on idiopathic epilepsy , convulsion secondary to infection ( meningitis ), and convulsion secondary to brain tumour . get them to discuss ‘what if’ questions; outlined below are a variety of scenarios for you to draw from. </li></ul><ul><li>please remind students re. importance of accurate collateral history in seizure description </li></ul>
CPC-4.3.7 – Differential Diag. <ul><li>Epileptic seizure </li></ul><ul><ul><li>Idiopathic - epilepsy </li></ul></ul><ul><ul><li>Secondary: </li></ul></ul><ul><ul><ul><li>Stroke - Cerebrovascular accident n.b. sub- arachnoid haemorrhage in this scenario. </li></ul></ul></ul><ul><ul><ul><li>Infection ( meningitis,encephalitis ) </li></ul></ul></ul><ul><ul><ul><li>Tumour : primary or secondary </li></ul></ul></ul><ul><ul><ul><li>Drugs : drug or alcohol withdrawal; drug overdose cocaine; amphetamines; tricyclics, buproprion (Zyban) </li></ul></ul></ul><ul><ul><ul><li>Genetic : neurofibromatosis;tuberous sclerosis.. </li></ul></ul></ul><ul><ul><ul><li>Autoimmune : SLE; Hashimoto’s, encephalitis </li></ul></ul></ul><ul><ul><ul><li>Head Injury : Trauma . </li></ul></ul></ul><ul><ul><ul><li>Metabolic disorders: uraemia; hypoglycaemia; hypo-+ hypercalcaemia; hypo-+hypernatraemia </li></ul></ul></ul><ul><ul><ul><li>Neurodegenerative diseases e.g. Alzheimer’s </li></ul></ul></ul><ul><li>Non epileptic events : consider syncope ; cardiac arrythmias ; pseudoseizures; TIA…etc </li></ul> CPC-4.3.7 – Differential Diag. <ul><li>Epileptic seizure </li></ul><ul><ul><li>Idiopathic - epilepsy </li></ul></ul><ul><ul><li>Secondary: </li></ul></ul><ul><ul><ul><li>Stroke - Cerebrovascular accident n.b. sub- arachnoid haemorrhage in this scenario. </li></ul></ul></ul><ul><ul><ul><li>Infection ( meningitis,encephalitis ) </li></ul></ul></ul><ul><ul><ul><li>Tumour : primary or secondary </li></ul></ul></ul><ul><ul><ul><li>Drugs : drug or alcohol withdrawal; drug overdose cocaine; amphetamines; tricyclics, buproprion (Zyban) </li></ul></ul></ul><ul><ul><ul><li>Genetic : neurofibromatosis;tuberous sclerosis.. </li></ul></ul></ul><ul><ul><ul><li>Autoimmune : SLE; Hashimoto’s, encephalitis </li></ul></ul></ul><ul><ul><ul><li>Head Injury : Trauma . </li></ul></ul></ul><ul><ul><ul><li>Metabolic disorders: uraemia; hypoglycaemia; hypo-+ hypercalcaemia; hypo-+hypernatraemia </li></ul></ul></ul><ul><ul><ul><li>Neurodegenerative diseases e.g. Alzheimer’s </li></ul></ul></ul><ul><li>Non epileptic events : consider syncope ; cardiac arrythmias ; pseudoseizures; TIA…etc </li></ul>
Scenario: Epilepsy: <ul><li>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. </li></ul><ul><li>GCS E2V3M4 </li></ul><ul><li>Detailed check no neck stiffness , no skin lesions/rash </li></ul><ul><li>Tongue has been bitten; pupils equal and reactive to light; fundoscopy normal </li></ul><ul><li>Decreased tone R upper limb, ?normal tone other limbs </li></ul><ul><li>Reflexes increased on R upper + lower limb; decreased on L upper +lower; </li></ul><ul><li>Plantar reflexes upgoing </li></ul><ul><li>Evidence of urinary incontinence </li></ul><ul><li>All other systems : nil abnormal </li></ul><ul><li>Ix - BSL : 5.1; toxicology screen : negative </li></ul> Scenario: Epilepsy: <ul><li>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. </li></ul><ul><li>GCS E2V3M4 </li></ul><ul><li>Detailed check no neck stiffness , no skin lesions/rash </li></ul><ul><li>Tongue has been bitten; pupils equal and reactive to light; fundoscopy normal </li></ul><ul><li>Decreased tone R upper limb, ?normal tone other limbs </li></ul><ul><li>Reflexes increased on R upper + lower limb; decreased on L upper +lower; </li></ul><ul><li>Plantar reflexes upgoing </li></ul><ul><li>Evidence of urinary incontinence </li></ul><ul><li>All other systems : nil abnormal </li></ul><ul><li>Ix - BSL : 5.1; toxicology screen : negative </li></ul>
Scenario: Meningitis <ul><li>ABC breathing spontaneously rr 18/min 4l O2 via mask, sats 90%; pulse 110 bpm reg small volume; BP 90/60 mmHg T39.6C </li></ul><ul><li>GCS - E2V3M4 </li></ul><ul><li>Detailed check - petechiae non blanching rash trunk, buttocks, Neck stiffness </li></ul><ul><li>Small contusion L temperoparietal area </li></ul><ul><li>Capillary refill time > 3 secs, peripheral cyanosis+ </li></ul><ul><li>Brudzinski sign positive </li></ul><ul><li>Ix skin scraping from lesion : gram negative diplococci ; CSF gram negative diplococci; FBC wcc 18 (polymorhic leucocytosis ) </li></ul>Brudzinski sign, Kernig sign, CSF findings Scenario: Meningitis <ul><li>ABC breathing spontaneously rr 18/min 4l O2 via mask, sats 90%; pulse 110 bpm reg small volume; BP 90/60 mmHg T39.6C </li></ul><ul><li>GCS - E2V3M4 </li></ul><ul><li>Detailed check - petechiae non blanching rash trunk, buttocks, Neck stiffness </li></ul><ul><li>Small contusion L temperoparietal area </li></ul><ul><li>Capillary refill time > 3 secs, peripheral cyanosis+ </li></ul><ul><li>Brudzinski sign positive </li></ul><ul><li>Ix skin scraping from lesion : gram negative diplococci ; CSF gram negative diplococci; FBC wcc 18 (polymorhic leucocytosis ) </li></ul>Brudzinski sign, Kernig sign, CSF findings
Core Learning Issues: <ul><li>Pathology Major CLI: </li></ul><ul><ul><li>Raised ICP – Pathology & Clinical features. </li></ul></ul><ul><ul><li>Pathology of common Primary and secondary CNS tumors in different age groups. </li></ul></ul><ul><ul><li>Astrocytoma – grades, clinical types, presentation & complications. </li></ul></ul><ul><ul><li>Pathology & Microbiology of Meningitis – common types *Bacterial, viral, fungal & others. </li></ul></ul><ul><li>Pathology Minor CLI: </li></ul><ul><ul><li>Pathology of Epilepsy (note this is major clinical learning issue) </li></ul></ul><ul><ul><li>Meningioma, Acoustic neuroma, Craniopharyngioma / pituitary tumors. Medulloblastoma. </li></ul></ul><ul><ul><li>Overview of Pathogenesis of Epilepsy (include theories for idiopathic epilepsy). </li></ul></ul><ul><ul><li>CJD-Creutzfeldt jakob's disease. (Mad cow disease). </li></ul></ul> Core Learning Issues: <ul><li>Pathology Major CLI: </li></ul><ul><ul><li>Raised ICP – Pathology & Clinical features. </li></ul></ul><ul><ul><li>Pathology of common Primary and secondary CNS tumors in different age groups. </li></ul></ul><ul><ul><li>Astrocytoma – grades, clinical types, presentation & complications. </li></ul></ul><ul><ul><li>Pathology & Microbiology of Meningitis – common types *Bacterial, viral, fungal & others. </li></ul></ul><ul><li>Pathology Minor CLI: </li></ul><ul><ul><li>Pathology of Epilepsy (note this is major clinical learning issue) </li></ul></ul><ul><ul><li>Meningioma, Acoustic neuroma, Craniopharyngioma / pituitary tumors. Medulloblastoma. </li></ul></ul><ul><ul><li>Overview of Pathogenesis of Epilepsy (include theories for idiopathic epilepsy). </li></ul></ul><ul><ul><li>CJD-Creutzfeldt jakob's disease. (Mad cow disease). </li></ul></ul>
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 some good qualities…!” 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 some good qualities…!”
Pathology of CNS Tumors Dr. Venkatesh M. Shashidhar, MD Associate Professor & Head of Pathology Pathology of CNS Tumors Dr. Venkatesh M. Shashidhar, MD Associate Professor & Head of Pathology
CNS Tumors: General Features <ul><li>10% of all tumors. </li></ul><ul><li>Commonest solid cancers in children.(2 nd to Leuk for all malignancies) </li></ul><ul><li>Age: double peak 1 st & 6 th decade </li></ul><ul><li>Adults - 70% supratentorial </li></ul><ul><li>Children - 70% infratentorial </li></ul><ul><li>No/very rare extraneural spread. </li></ul><ul><li>Metastasis most common. </li></ul>Adults Children CNS Tumors: General Features <ul><li>10% of all tumors. </li></ul><ul><li>Commonest solid cancers in children.(2 nd to Leuk for all malignancies) </li></ul><ul><li>Age: double peak 1 st & 6 th decade </li></ul><ul><li>Adults - 70% supratentorial </li></ul><ul><li>Children - 70% infratentorial </li></ul><ul><li>No/very rare extraneural spread. </li></ul><ul><li>Metastasis most common. </li></ul>Adults Children
Clinical features: <ul><li>Raised Intracranial Pressure * </li></ul><ul><ul><li>Headache (morning) , vomiting, slow pulse, papilloedema. </li></ul></ul><ul><li>Local damage: </li></ul><ul><ul><li>Nerve & tract deficits, Paralysis, seizures etc. </li></ul></ul> Clinical features: <ul><li>Raised Intracranial Pressure * </li></ul><ul><ul><li>Headache (morning) , vomiting, slow pulse, papilloedema. </li></ul></ul><ul><li>Local damage: </li></ul><ul><ul><li>Nerve & tract deficits, Paralysis, seizures etc. </li></ul></ul>
. CNS Tum: Clinical Features-Pathogenesis <ul><li>Headaches (morning) </li></ul><ul><li>Papilloedema </li></ul><ul><li>Nausea or vomiting </li></ul><ul><li>Bradycardia </li></ul><ul><li>Seizures (convulsions). </li></ul><ul><li>Drowsiness, Obtundation </li></ul><ul><li>Personality or memory </li></ul><ul><li>Changes in speech </li></ul><ul><li>Limb weakness </li></ul><ul><li>Balance/Stumbling </li></ul><ul><li>eye movements or vision </li></ul><ul><li>Increased ICP </li></ul><ul><li>Increased ICP </li></ul><ul><li>ICP – Medulla ob. </li></ul><ul><li>ICP – Parasymp. </li></ul><ul><li>Irritation. </li></ul><ul><li>Brain Stem compress </li></ul><ul><li>Frontal lobe </li></ul><ul><li>Temporal lobe </li></ul><ul><li>Motor area </li></ul><ul><li>Cerebellum </li></ul><ul><li>Optic tract, occipital. </li></ul>
. CNS Tumors Classification: <ul><li>Primary Tumors: </li></ul><ul><li>Meninges – Meningioma </li></ul><ul><li>Glial cells: Glioma </li></ul><ul><ul><li>Astrocytoma & Glioblastoma. Oligodendroma, ependymoma. </li></ul></ul><ul><ul><li>Nerve sheath – Schwanoma, Neurofibroma. </li></ul></ul><ul><li>Embryonal – Medulloblastoma , neuroblastoma, teratoma. </li></ul><ul><li>Blood vessels – angioma, angiosarcoma etc. </li></ul><ul><li>* Other Epithelial, Pituitary & Pineal gland tumors. </li></ul><ul><li>Secondary Tumors - Metastasis – common Melanoma, breast, lung, GIT. </li></ul>
. <ul><li>Adults: </li></ul><ul><ul><li>Astrocytoma & Glioblastoma. </li></ul></ul><ul><ul><li>Meningioma </li></ul></ul><ul><ul><li>Metastasis. </li></ul></ul><ul><li>Children: </li></ul><ul><ul><li>Astrocytoma </li></ul></ul><ul><ul><li>Medulloblastoma </li></ul></ul>Common:
. Meningioma: <ul><li>Arise from arachnoid granulations of venous sinuses. Attached to dura. </li></ul><ul><li>Common sites: parasagittal (falx), sphenoid ridge, olfactory groove, cerebellopontine angle. specific clinical features. </li></ul><ul><li>Females common (2:1) </li></ul><ul><li>Slow growth, well differentiated & demarcated. Does not invade brain (Benign). </li></ul><ul><li>Reactive skull Hyperostosis over the tumor. </li></ul><ul><li>Microscopy: spindle cells in whorls and psammoma bodies(microcalcification). </li></ul>
. Meningioma <ul><li>Well demarcated </li></ul><ul><li>Capsulated </li></ul>
. Meningioma – whorls of clear cells. Normal Arachnoid Granulation
. Glioma: <ul><li>Gliomas are neoplasms of glial cells. </li></ul><ul><li>Commonest both in adults and children </li></ul><ul><li>Benign * to Aggressively malignant. </li></ul><ul><ul><li>Astrocytoma ( anaplastic & G.B.M ) </li></ul></ul><ul><ul><li>Ependymoma - Rare, 4th ventricle. </li></ul></ul><ul><ul><li>Oligodendroglioma - Benign, adults, rare </li></ul></ul>
. Astrocytomas <ul><li>Adults : </li></ul><ul><ul><li>Commonest 80%, Supratentorial. </li></ul></ul><ul><ul><li>Solid – Fibrillary – low grade*. </li></ul></ul><ul><ul><li>Varigated, Hemorrhagic - Malignant, glioblastoma multiforme. </li></ul></ul><ul><li>Children: </li></ul><ul><ul><li>Infratentorial (Cerebellum), </li></ul></ul><ul><ul><li>Cystic, Low grade*, Pilocytic </li></ul></ul>
. Astrocytomas <ul><li>Adults : </li></ul><ul><ul><li>Commonest 80%, Supratentorial. </li></ul></ul><ul><ul><li>Solid – Fibrillary – low grade*. </li></ul></ul><ul><ul><li>Varigated, Hemorrhagic - Malignant, glioblastoma multiforme. </li></ul></ul><ul><li>Children: </li></ul><ul><ul><li>Infratentorial (Cerebellum), </li></ul></ul><ul><ul><li>Cystic, Low grade*, Pilocytic </li></ul></ul>
. Glioblastoma Multiforme (GBM): <ul><li>High grade Astrocytoma - Grade IV </li></ul><ul><li>Commonest & malignant brain tumor in adults – mean survival <1y – cerebral supratentorial . </li></ul><ul><li>Loss of heterozygosity on Chromosome 10 (80%) </li></ul><ul><li>Most GBMs have lost one entire copy of C – 10 </li></ul><ul><li>2 types: Primary (worst) or Secondary from low grade astrocytomas (better prog). </li></ul><ul><li>Variants: giant cell GBM, gliosarcoma </li></ul><ul><li>Microscopy: </li></ul><ul><li>Necrosis , palisading , hypercellularity, nuclear atypia & vascular proliferation & mitoses. </li></ul>
. Genetic abnormalities in Glioma: Low grade Anaplastic GBM
. GBM: + glioma Enhancement with peritumoral edema.
. Glioblastoma Multiforme (high grade Astrocytoma)
