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Pathology of CNS Tumors


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Pathology of Brain tumors (CNS tumors) for undergraduate medical students.

Pathology of CNS Tumors

  1. 1. 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>
  2. 2. 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>
  3. 3. 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>
  4. 4. 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
  5. 5. 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>
  6. 6. 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…!”
  7. 7. Pathology of CNS Tumors Dr. Venkatesh M. Shashidhar, MD Associate Professor & Head of Pathology
  8. 8. 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
  9. 9. 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>
  10. 10. 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>
  11. 11. CNS Anatomy - Clinical Features
  12. 12. 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>
  13. 13. <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:
  14. 14. 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>
  15. 15. Meningioma
  16. 16. Meningioma
  17. 17. Meningioma
  18. 18. Meningioma
  19. 19. Meningioma
  20. 20. Meningioma
  21. 21. Meningioma <ul><li>Well demarcated </li></ul><ul><li>Capsulated </li></ul>
  22. 22. Meningioma – whorls of clear cells. Normal Arachnoid Granulation
  23. 23. Meningioma Nodules Psammoma Body
  24. 24. Psammoma bodies
  25. 25. 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>
  26. 26. 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>
  27. 27. Astrocytoma-Lowgrade fibrillary
  28. 28. Astrocytoma
  29. 29. Astrocytoma: * Lat. Vent. *petechial hem.
  30. 30. Glioma Brain Stem – note diffuse tumor
  31. 31. Glioma Cerebrum cystic degeneration
  32. 32. Glioma:
  33. 33. Astrocytoma (Glioma)
  34. 34. Glioma Brain Normal
  35. 35. Astrocytoma
  36. 36. 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>
  37. 37. 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>
  38. 38. Genetic abnormalities in Glioma: Low grade  Anaplastic  GBM
  39. 39. Glioma: high grade
  40. 40. Glioma: Enhancement with peritumoral edema.
  41. 41. Glioblastoma:
  42. 42. GBM: + glioma Enhancement with peritumoral edema.
  43. 43. Glioblastoma – high grade Astrocytoma
  44. 44. Glioblastoma – high grade Astrocytoma
  45. 45. Glioblastoma Multiforme (high grade Astrocytoma)
  46. 46. Glioblastoma Cerebrum
  47. 47. Glioblastoma Cerebrum
  48. 48. Glioblastoma Multiforme Palisading Necrosis
  49. 49. Glioblastoma Multiforme Necrosis Palisading
  50. 50. Glioblastoma Multiforme Palisading B.V Necrosis
  51. 51. Glioblastoma Multiforme Palisading Necrosis
  52. 52. Glioblastoma Multiforme
  53. 53. A Astrocytoma Low grade B Glioblastoma Multiforme(GBM) C Necrosis with pseudopalisading in GBM.
  54. 54. 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>
  55. 55. Pilocytic astrocytoma <ul><li>Common in childhood </li></ul><ul><li>Most slow growing of the gliomas </li></ul><ul><li>Sites: cerebellum, around 3 rd Ventricle. optic nerve. </li></ul><ul><li>Grossly cystic with mural nodule </li></ul><ul><li>Microscopic </li></ul><ul><ul><li>elongated hair-like (pilocytic) elongated cells & Rosenthal fibers. </li></ul></ul>
  56. 56. Pilocytic Astrocytoma - children
  57. 57. Pilocytic Astrocytoma - children
  58. 58. Pilocytic astrocytoma Mural nodule
  59. 59. Pilocytic Astrocytoma: Microscopy Palisading pilocytic astrocytes – note plenty of Rosenthal fibres between cells.
  60. 60. Medulloblastoma: <ul><li>Children. </li></ul><ul><li>Cerebellum – vermis. </li></ul><ul><li>Primitive neuroectodermal tum. </li></ul><ul><li>Blast cells – round scanty cytoplasm. </li></ul><ul><li>4 th ventricle Obstruction – hydrocephalus. </li></ul><ul><li>CSF seeding and Meningeal infiltration is common. </li></ul><ul><li>Rosettes & neuronal or glial differentiation rarely seen. </li></ul>
  61. 61. Medulloblastoma: Primitive neuroectodermal tumor: Children, vermis of cerebellum. Origin Spread
  62. 62. Medulloblastoma
  63. 63. Medulloblastoma
  64. 64. Youtube Videos: <ul><li>Glioblastoma Multiforme: </li></ul><ul><ul><li>http:// =idSos1XOi7A </li></ul></ul><ul><ul><li> </li></ul></ul><ul><li>Meningioma: </li></ul><ul><ul><li> </li></ul></ul><ul><li>Pyogenic Meningitis: </li></ul><ul><ul><li> </li></ul></ul>
  65. 65. Most common CNS Tumors: Glioblastoma MF
  66. 66. CNS Tumors: Summary <ul><li>Adults: </li></ul><ul><li>Secondary common </li></ul><ul><li>Lung, Skin, breast.. </li></ul><ul><li>Primary - Supratentorial </li></ul><ul><ul><li>Astrocytoma / glioblastoma. </li></ul></ul><ul><ul><li>Meningioma </li></ul></ul><ul><li>Children: </li></ul><ul><li>2 nd common (leuk / lymph) </li></ul><ul><li>Infratentorial </li></ul><ul><ul><li>Astrocytoma (cystic cerebellar) </li></ul></ul><ul><ul><li>Medulloblastoma </li></ul></ul><ul><ul><li>Hydrocephalus. </li></ul></ul><ul><ul><li>Meningeal spread. </li></ul></ul>
  67. 67. Learning Medicine...! <ul><li>Learning medicine should be a JOY , not an ordeal. </li></ul><ul><li>Everybody learns according to their own best style. </li></ul><ul><li>The Hippocratic oath issues of patient privacy, compassion, and FREE sharing of knowledge have to be honored. </li></ul><ul><li>Exam and grade anxieties are the CANCERS of medical education. </li></ul><ul><li>If your school admitted students which they feel need to be whipped, the SCHOOL has failed, not YOU! </li></ul><ul><li>If you claim you NEED to be pushed, I do not want you as my doctor. </li></ul><ul><li>John R. Minarcik, MD ( http:// ) </li></ul>
  68. 68. Pathology of Increased Intracranial Pressure
  69. 69. Pathogenesis: <ul><li>Increased intracranial pressure (ICP): - if > 40 mm Hg  cerebral hypoxia, cerebral ischemia, cerebral edema, hydrocephalus, and brain herniation. </li></ul><ul><li>Cerebral edema: Edema - Disruption of the blood brain barrier – vasodilatation – swelling. </li></ul><ul><li>Hydrocephalus  communicating type common in Total Body Irradiation. </li></ul>
  70. 70. Pathogenesis: <ul><li>Brain herniation : Supratentorial herniation common. 3 sub types </li></ul><ul><ul><li>Subfalcine herniation: The cingulate gyrus of the frontal lobe (commonest) </li></ul></ul><ul><ul><li>Central transtentorial herniation: displacement of the basal nuclei and cerebral hemispheres downward </li></ul></ul><ul><ul><li>Uncal herniation: Medial edge of the uncus and the hippocampal gyrus </li></ul></ul><ul><li>Cerebellar herniation : infratentorial herniation - tonsil of the cerebellum is pushed through the foramen magnum and compresses the medulla, leading to bradycardia and respiratory arrest. </li></ul>
  71. 71. Common CNS Herniations: <ul><li>Subfalcine: </li></ul>
  72. 72. Subfalcine Herniation: in brain trauma. <ul><li>Contusion of the inferior temporal lobe (blue arrow) has resulted in diffuse edema. (compressed and flattened gyri on the right). </li></ul><ul><li>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). </li></ul>
  73. 73. Uncal Herniation: <ul><li>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. </li></ul>
  74. 74. Uncal Herniation:
  75. 75. acute brain swelling + Uncal Herniation <ul><li>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. </li></ul>
  76. 76. Cerebellar Tonsil - Herniation <ul><li>Note the cone shape of the herniated tonsils around the medulla in this cerebellum specimen. </li></ul><ul><li>Results in compression and Duret hemorrhages in the pons. </li></ul>
  77. 77. Transtentorial herniation: <ul><li>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. </li></ul>
  78. 78. Cerebral Herniation: Pathogenesis Decerebrate posture Cardiorespiratory failure Death Acute obstruction of CSF pathway   Decerebrate posture Cardiorespiratory failure Death Brainstem compression and haemorrhage Foramen magnum Decerebrate posture Cardiorespiratory failure Death Brainstem compression and haemorrhage   Upper motor neurone signs Cerebral peduncle compression   Occipital infarction Cortical blindness Posterior cerebral artery compression   Horizontal diplopia, convergent squint Ipsilateral 6th cranial nerve compression   Ipsilateral fixed dilated pupil Ipsilateral 3rd cranial nerve compression Transtentorial Clinical consequence Effect Site of herniation
  79. 79. Decorticate posturing, with elbows, wrists and fingers flexed, and legs extended and rotated inward.
  80. 80. Look for good in others… no one is without faults and everyone has some good qualities! BK.
  81. 81. 52y, F, CNS tumor: ? diagnosis <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Metastases </li></ul><ul><li>Medulloblastoma </li></ul><ul><li>Meningioma </li></ul>
  82. 82. 52y, F, CNS tumor: ? diagnosis <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>
  83. 83. 52y, F, CNS tumor: ? diagnosis <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>
  84. 84. 52y, F, parasagittal tum attached to falx: ? diagnosis <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>
  85. 85. Commonest primary CNS tumor in Adults ? <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>
  86. 86. 52y, F, CNS tumor: ? Arrow Feature <ul><li>Necrosis. </li></ul><ul><li>Psammoma body </li></ul><ul><li>Calcification </li></ul><ul><li>Blood vessel </li></ul><ul><li>Epithelial pearl </li></ul>
  87. 87. 60y smoker, chronic bronchitis complains of difficulty walking. PE: stiff, expressionless face. A tremor of his fingers is apparent but ceases when he tries to reach for something. Image shows brain stem . Diagnosis? <ul><li>Alzheimers disease </li></ul><ul><li>Lacunar infarcts </li></ul><ul><li>Picks disease </li></ul><ul><li>Parkinsons disease </li></ul><ul><li>Durett hemorrhages </li></ul>
  88. 88. Commonest primary CNS tumor in Children ? <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>
  89. 89. Commonest Location of CNS tumor in Children ? <ul><li>Supratentorial </li></ul><ul><li>Cerebellum </li></ul><ul><li>Infratentorial </li></ul><ul><li>Cerebrum. </li></ul><ul><li>Brain stem </li></ul>
  90. 90. 7y, F, CNS tumor: ? diagnosis <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>
  91. 91. 55y Female. Died following car crash. Coroners autopsy Image shows Brain stem- What is the likely cause of death? <ul><li>Herniation of cerebral tonsil </li></ul><ul><li>Intracerebral hemorrhage. </li></ul><ul><li>Subdural hemotoma </li></ul><ul><li>Subarachnoid hemorrhage. </li></ul><ul><li>Glioblastoma multiforme. </li></ul>
  92. 92. 56y, F Rapidly growing parietal lobe tumor: ? diagnosis <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>
  93. 93. 49y, M, CNS tumor: ? diagnosis <ul><li>Metastases </li></ul><ul><li>Astrocytoma sy. </li></ul><ul><li>Meningiomatosis </li></ul><ul><li>Neurofibromatosis </li></ul><ul><li>Lipomatosis </li></ul>
  94. 94. 54y woman dies 48 hours after suffering severe head injuries in an automobile accident. Just before her death, her left pupil becomes fixed and dilated. An inferior view of the patient's brain at autopsy is shown. Most likely cause of death? <ul><li>Diffuse axonal shearing </li></ul><ul><li>Laminar necrosis </li></ul><ul><li>Thrombosis of sagittal sinus </li></ul><ul><li>Transtentorial herniation </li></ul><ul><li>Watershed infarct </li></ul>
  95. 95. 48y male, Frontal lobe tum, What is the most likely diagnosis? <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>
  96. 96. SAQ / KFP <ul><li>Should seizure patients have imaging done immediately? </li></ul><ul><li>Personality changes indicate which location? </li></ul><ul><li>Differentials for young adult with insidious symptoms, seizures and decreased signal on T1 and increased signal on T2 weighted MRI? </li></ul><ul><li>What is the treatment and prognosis for someone with a low-grade astrocytoma? </li></ul><ul><li>How should the symptoms be treated? </li></ul><ul><li>What tests could have been done in the absence of neuroimaging? </li></ul><ul><li>Yes, 10-20% tumors. </li></ul><ul><li>Frontal lobe </li></ul><ul><li>Other gliomas </li></ul><ul><li>Conservative – Poor </li></ul><ul><li>Steroids, anti epileptic, symptomatic. </li></ul><ul><li>EEG </li></ul>
  97. 97. SAQ / KFP <ul><li>Why was the child hitting his head? </li></ul><ul><li>Why did the child have a headache? </li></ul><ul><li>If the child does have hydrocephalus, at what level is the ventricular system being obstructed at? </li></ul><ul><li>Should a lumbar puncture be performed? </li></ul><ul><li>Where in the cerebellum is the lesion located? </li></ul><ul><li>What is the radiolucent area visible along the antero-superior aspect of the radiograph? </li></ul><ul><li>Indicating headache. </li></ul><ul><li>Increased ICP, tum. </li></ul><ul><li>4 th ventricle. </li></ul><ul><li>No – coning…* </li></ul><ul><li>Central – vermis </li></ul><ul><li>Separation/malfusion of anterior frontoparietal suture due to hydrocephalus. </li></ul>
  98. 98. 50y Female smoker - Headache. <ul><li>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. </li></ul><ul><li>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. </li></ul>
  99. 99. 50y Female smoker - Headache.
  100. 100. 50y Female smoker - Headache.
  101. 101. <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>What is the most likely diagnosis?
  102. 102. SAQ / KFP <ul><li>Name the location of tumor? </li></ul><ul><li>What cranial nerves are involved? </li></ul><ul><li>List differential diagnosis </li></ul><ul><li>Explain pathogenesis of headache and papilledema? </li></ul><ul><li>What does the histological pattern represent in slide 1? slide 2? </li></ul><ul><li>Cerebellopontine angle </li></ul><ul><li>Cranial Nerves 5,7 & 8 </li></ul><ul><li>Teratoma, meningioma, acoustic neuroma. </li></ul><ul><li>Increased intracranial tension. </li></ul><ul><li>Tumor attempting to form Arachnoid grannulations. Origin of tumor. </li></ul>
  103. 103. 35y Male, depression <ul><li>2-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. </li></ul><ul><li>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. </li></ul>
  104. 104. 35y Male, depression Axial T1 weighted MRI Axial T2 weighted MRI
  105. 105. 35y Male, depression Coronal T1 weighted MRI Coronal T2 weighted MRI
  106. 106. 3y Male, constant cry…. <ul><li>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. </li></ul><ul><li>Physical: Bilateral papilledema and gait ataxia was noted on the physical exam. </li></ul>
  107. 107. 3y Male, constant cry…. Axial T1 weighted MRI Axial T2 weighted MRI
  108. 108. 3y Male, constant cry…. Coronal T1 weighted MRI
  109. 109. <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>What is the most likely diagnosis?
  110. 110. 65y Fem morning headache. <ul><li>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. </li></ul><ul><li>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.  </li></ul>
  111. 111. 65y Fem morning headache.
  112. 112. Brain Metastasis: <ul><li>Lung, Breast, Skin, Kidney, GIT. </li></ul><ul><li>Prostate – never..! </li></ul><ul><li>Well demarcated, usually multiple with surrounding rim of inflammation. </li></ul><ul><li>Carcinomatosis: Meningeal CSF spread of malignant cells. </li></ul>
  113. 113. Metastatic Melanoma: multiple
  114. 114. Brain Metastases: Surrounding edema.
  115. 115. <ul><li>Glioblastoma m. </li></ul><ul><li>Astrocytoma </li></ul><ul><li>Meningioma </li></ul><ul><li>Ependymoma </li></ul><ul><li>Medulloblastoma </li></ul>What is the most likely diagnosis?
  116. 116. SAQ / KFP <ul><li>Are there clinical signs of nerve compression? </li></ul><ul><li>What is the most likely cause of the homonymous hemianopia? </li></ul><ul><li>Why does the patient have progressive right upper limb weakness, and paroxysmal left upper and lower limb weakness? </li></ul><ul><li>Should a lumbar puncture be performed? </li></ul><ul><li>Why was the patient obtunded? </li></ul><ul><li>Why was an-x-ray taken? </li></ul><ul><li>Yes, ptosis, pupils 3 rd </li></ul><ul><li>Optic pathway -occipital. </li></ul><ul><li>Motor cortex compression – tum. </li></ul><ul><li>Risky. </li></ul><ul><li>Brainstem compression. </li></ul><ul><li>Meningioma hyperostosis. </li></ul>
  117. 117. CPC-3.7– KFP Questions: <ul><li>Meningitis Types, classification & comparison. </li></ul><ul><li>Septic, Viral & TB meningitis. </li></ul><ul><li>Morphology, complications. </li></ul><ul><li>Laboratory diagnosis, CSF findings. </li></ul><ul><li>CNS tumours: common features. </li></ul><ul><li>Adult and childhood CNS tumors. </li></ul><ul><li>Common Types & features. </li></ul><ul><li>Increased intracranial pressure – Pathologic basis of clinical features. </li></ul>
  118. 118. It has been my philosophy of life that difficulties vanish when faced boldly . --Isaac Asimov
  119. 119. Other CNS tumors
  120. 120. Neuroectodermal Tumors <ul><li>Origin from primitive blast cells. </li></ul><ul><li>Rosettes - attempted nerve formation. </li></ul><ul><li>Medulloblastoma – Cerebellum </li></ul><ul><li>Retinoblastoma - Retina </li></ul><ul><li>Neuroblastoma – Adrenal glands </li></ul><ul><li>Ganglioneuroma - Mediastinum </li></ul>
  121. 121. Medulloblastoma
  122. 122. Ependymoma-hemorrhage
  123. 123. Ependymoma 4 th Ventricle
  124. 124. Ependymoma 4 th Ventricle
  125. 125. Ependymoma
  126. 126. Nerve Sheath Tumors: <ul><li>Neurofibroma: </li></ul><ul><ul><li>Epi & endoneurial fibroblasts. </li></ul></ul><ul><ul><li>Form whorls of fibroblasts with nerves </li></ul></ul><ul><ul><li>Well differentiated, benign, capsulated. </li></ul></ul><ul><li>Schwannoma: </li></ul><ul><ul><li>Schwann cells, elongated form whorls </li></ul></ul><ul><ul><li>Nuclear palisading </li></ul></ul>
  127. 127. Schwannoma / Neurofibroma
  128. 128. Schwannoma 8 th Nerve:
  129. 129. Bilateral 8 th nerve schwannomas.
  130. 130. Schwannoma:
  131. 131. Schwannoma
  132. 132. Neurofibromatosis:
  133. 133. Neurofibromatosis: Café-au-lait spot
  134. 134. Schwannoma
  135. 135. Schwannoma
  136. 136. Summary: <ul><li>Children – 70% INFRAtentorial </li></ul><ul><li>Adults – 70% SUPRAtentorial </li></ul><ul><li>Common Malignant - adults, metastatic tumors (Lungs) </li></ul><ul><li>Common - adults – glioblastoma multiforme Intracerebral </li></ul><ul><li>Common Benign - children – cerebellar astrocytoma. </li></ul><ul><li>Common Mal - children – cerebellar medulloblastoma </li></ul><ul><li>Very rare – meninges and schwann cells (meningiomas and schwannomas) – usu. found in adults </li></ul>
  137. 137. A 26-year old female <ul><li>Headache,vomiting, an epileptic attack, weakness of legs. Now drowsy. Two weeks before admission she gave her second birth. </li></ul><ul><li>CT and NMR revealed a huge parasagittal tumor (80x67x65 mm), enhanced by contrast, compressed corpus callosum and ventricles. </li></ul>
  138. 138. Histopathology: <ul><li>Bifrontal parasagittal tumor, craniectomy and tumor was totally removed. </li></ul><ul><li>Well demarcated, firm white lobular. </li></ul>
  139. 139. Fibrous – spindle cells.
  140. 140. 37 yr Female <ul><li>Serious automobile accident and sustained a close head injury,she does not immediately seek medical attention, but is brought to the emergency room two hours later by her brother,on physical examination there is mydriasis and loss of pupillary light reflex,several hours later she is unable to follow a flash light with her eyes,which of the following herniation is most likely occuring in this patient???? A)cerebellar tonsils into the forman magnum B)cerebellum upward past the tentorium C)singulate gyrus under the falx D)medulla into the foramen magnum E)temporal lobe under the tentorium </li></ul>
  141. 141. 32y Female Fleshy pappules: <ul><li>Several fleshy papules on face, trunk, and upper extremities. </li></ul><ul><li>Since 10y of age. Increased & Irritation over the past 5 y. </li></ul><ul><li>Previous excision have recurred. </li></ul><ul><li>No other significant history. </li></ul>
  142. 142. Neurofibromatosis: <ul><li>Autosomal dominant, </li></ul><ul><li>NF1- Peripheral/Von Recklinghausen’s </li></ul><ul><li>NF2- known as central NF. </li></ul><ul><li>However, NF1 may cause central characteristics. </li></ul><ul><li>About 50% familial, 50% sporadic gene mutation. </li></ul><ul><li>NF1/ von Recklinghausen disease, gene mutation on chromosome 17, 1 in every 3000-4000 births. Diagnosis of NF1 if > 2 of </li></ul><ul><ul><li>6 or more café au lait spots (irregularly shaped, evenly pigmented, brown macules), </li></ul></ul><ul><ul><li>2 or more neurofibromas, </li></ul></ul><ul><ul><li>axillary or inguinal freckling, </li></ul></ul><ul><ul><li>Lisch nodules on the iris or optic glioma, </li></ul></ul><ul><ul><li>various types of osseous lesions, </li></ul></ul><ul><ul><li>a first-degree relative with the condition. </li></ul></ul>
  143. 143. Neurofibromatosis: <ul><li>NF2 – Gene mutation chromosome 22. </li></ul><ul><li>1 in every 33,000-40,000 births </li></ul><ul><li>Typically present with acoustic neuromas or vestibular schwannomas. </li></ul><ul><li>Tinnitus, balance disorders, and progressive hearing loss </li></ul><ul><li>May also have meningiomas and juvenile cataracts. </li></ul><ul><li>First-degree relative and on any 2 of the conditions listed for NF1. </li></ul><ul><li>Patients with NF1 are at increased risk of malignancy. </li></ul><ul><li>Annual ocular examinations are recommended. Genetic testing is also advocated in patients with NF who wish to have children. </li></ul><ul><li>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 </li></ul><ul><li>(National Institute of Neurologic Disorders and Stroke, 2006). </li></ul>
  144. 144. 7 th nerve palsy: <ul><li>Cerebellopontine angle tumours. </li></ul><ul><ul><li>Acoustic neuroma, </li></ul></ul><ul><ul><li>epidermoid cysts, </li></ul></ul><ul><ul><li>medulloblastoma </li></ul></ul><ul><ul><li>meningioma </li></ul></ul><ul><li>Affected cranial nerves: </li></ul><ul><ul><li>5 trigeminal - masticatio </li></ul></ul><ul><ul><li>7 facial –face muscles </li></ul></ul><ul><ul><li>8 auditory – hearing </li></ul></ul>
  145. 145. Brudzinski Sign of Meningitis:
  146. 146. Scenario: Brain Tumor <ul><li>ABC as for scenario 1 </li></ul><ul><li>GCS E3V4M5 </li></ul><ul><li>Detailed check no neck stiffness, no rash </li></ul><ul><li>Tongue has been bitten; small contusion L temperoparietal area </li></ul><ul><li>PEARL fundoscopy normal L sided weakness arm > leg with increased tone and reflexes L plantar reflex equivocal; R plantar reflex downgoing </li></ul><ul><li>Evidence urinary incontinence </li></ul><ul><li>All other systems : no abnormalities </li></ul><ul><li>Ix - as per scenario 1; MRI scan </li></ul><ul><li>?gliobalstoma multiforme R fronto-parietal region </li></ul>
  147. 147. GBM: Glomeruloid bodies:
  148. 148. Normal Fundus - Papilledema
  149. 149. Normal vs Glaucoma