Pathology of CNS Tumours - Lecture


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pathology lecture on CNS tumours to 4th year pre-clinical medical students.

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Pathology of CNS Tumours - Lecture

  1. 1. 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.
  2. 2. 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..
  3. 3. 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* - vasovagal  Arrhythmias, Pseudoseizures (psychogenic),  Concussion, TIA
  4. 4. 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
  5. 5. 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
  6. 6. 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
  7. 7. 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 jakobs disease. (Mad cow disease).
  8. 8. 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 RuskinLook for good in others “No one is without faults and everyone has good qualities…!”
  9. 9. Pathology ofCNS TumorsDr. Venkatesh M. Shashidhar, MD Associate Professor & Head of Pathology
  10. 10. 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.
  11. 11. CNS Tumors Most common CNS Tumors: Adults children
  12. 12. 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.
  13. 13. 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.
  14. 14. CNS Tumors CNS Tum: Clinical Features-Pathogenesis  Headaches (morning)  Increased ICP  Papilloedema  Increased ICP  Nausea or vomiting  ICP – Medulla ob.  Bradycardia  ICP – Parasymp.  Seizures (convulsions).  Irritation.  Drowsiness, Obtundation  Brain Stem compress  Personality or memory  Frontal lobe  Changes in speech  Temporal lobe  Limb weakness  Motor area  Balance/Stumbling  Cerebellum  eye movements or vision  Optic tract, occipital.
  15. 15. CNS Tumors CNS functional anatomy – localizing signs
  16. 16. CNS Tumors Common:  Adults:  Astrocytoma & (Metastases) Glioblastoma.  Meningioma  Metastasis.  Children:  Astrocytoma  Medulloblastoma
  17. 17. 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.
  18. 18. CNS Tumors Meningioma: Note location in the venus sinus & adherent to dura.
  19. 19. CNS Tumors Meningioma: multiple
  20. 20. CNS Tumors Meningioma Tumor MCAQ Pituitary
  21. 21. CNS Tumors Meningioma
  22. 22. CNS Tumors Meningioma high grade: (rare)
  23. 23. CNS Tumors Meningioma Nodules Capsulated, spindle cells in whorls and psammoma bodies (common type).
  24. 24. Psammoma bodies(calcification)
  25. 25. 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
  26. 26. CNS Tumors Astrocytomas - Glioma  Adults:  Commonest 80%, Cerebral.  Low Gr: Solid, Fibrillary glioma  High Gr: glioblastoma multiforme Varigated, Hemorrhagic - Malignant,.  Children:  Cystic, Low grade*, Pilocytic  Infratentorial (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.
  27. 27. CNS Tumors Astrocytoma-Lowgrade fibrillary
  28. 28. CNS Tumors Astrocytoma
  29. 29. CNS Tumors Glioma Brain Stem – note diffuse tumor
  30. 30. CNS Tumors Glioma Cerebrum cystic degeneration
  31. 31. CNS Tumors Glioma:
  32. 32. CNS Tumors Astrocytoma: * Lat. Vent. *petechial hem.
  33. 33. CNS Tumors Astrocytoma (Glioma) – brain stem
  34. 34. CNS Tumors Glioma Brain Normal
  35. 35. CNS Tumors Astrocytomas  Adults:  Commonest 80%, Cerebral.  Low Gr: Solid, Fibrillary.  High Gr: glioblastoma multiforme Varigated, Hemorrhagic - Malignant,.  Children:  Cystic, Low grade*, Pilocytic  Infratentorial (Cerebellum),
  36. 36. 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.
  37. 37. 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.
  38. 38. CNS Tumors Glioma: high grade
  39. 39. CNS Tumors GBM: MRI Enhancement with peritumoral edema.
  40. 40. CNS Tumors Glioblastoma – high grade Astrocytoma
  41. 41. CNS Tumors Glioblastoma – high grade Astrocytoma Note: Looks like abscess, but it is necrosis..!
  42. 42. CNS Tumors Glioblastoma Multiforme (high grade Astrocytoma)
  43. 43. CNS Tumors Glioblastoma Cerebrum
  44. 44. CNS Tumors High Gr.: Glioblastoma multiforme (high grade- Hypercellularity, necrosis, hemorrhage & palisading) Hyper cel. Hem Necro
  45. 45. CNS Tumors Glioblastoma Multiforme Necrosis Palisading
  46. 46. CNS Tumors Glioblastoma Multiforme
  47. 47. A Astrocytoma Low gradeB Glioblastoma Multiforme(GBM)C Necrosis with pseudopalisading in GBM.
  48. 48. CNS Tumors Astrocytomas  Adults:  Commonest 80%, Cerebral.  Low Gr: Solid, Fibrillary.  High Gr: glioblastoma multiforme Varigated, Hemorrhagic - Malignant,.  Children:  Cystic, Low grade*, Pilocytic Astrocytoma  Infratentorial (Cerebellum),
  49. 49. 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.
  50. 50. CNS Tumors Pilocytic Astrocytoma - children
  51. 51. CNS Tumors Pilocytic Astrocytoma: solid, brightly contrast-enhancing mural component and associated cyst.
  52. 52. CNS Tumors Pilocytic Astrocytoma: Microscopy Palisading pilocytic astrocytes – note plenty of Rosenthal fibres between cells.
  53. 53. 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.
  54. 54. CNS Tumors Medulloblastoma: Primitive neuroectodermal tumor: Children, vermis of cerebellum. Spread Origin
  55. 55. CNS Tumors Medulloblastoma
  56. 56. CNS Tumors Medulloblastoma
  57. 57. CNS Tumors Youtube Videos:  Glioblastoma Multiforme:    Meningioma:   Pyogenic Meningitis: 
  58. 58. 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
  59. 59. 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.
  60. 60. CNS Tumors AV Malformation:
  61. 61. Pathology ofIncreased IntracranialPressure.
  62. 62. 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)
  63. 63. 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.
  64. 64. CNS Tumors Common CNS Herniations:  Subfalcine: common, Headache contralateral leg weakness.  Transtentorial: occulomotor (CN III) paresis (ipsilateral dilated pupil, abnormal EOMs), contralateral hemiparesion.  Tonsillar: Obtundation.
  65. 65. 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).
  66. 66. 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.
  67. 67. CNS Tumors Herniation: Central Pontine / Duret Hem.
  68. 68. 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.
  69. 69. CNS Tumors Cerebral Herniation: Pathogenesis Site of herniation Effect Clinical consequence Transtentorial Ipsilateral 3rd cranial nerve Ipsilateral fixed dilated pupil compression Ipsilateral 6th cranial nerve Horizontal diplopia, convergent compression squint Posterior cerebral artery Occipital infarction Cortical blindness compression Cerebral peduncle Upper motor neurone signs compression Brainstem compression and Decerebrate posture haemorrhage Cardiorespiratory failure Death Foramen Brainstem compression and Decerebrate posture magnum haemorrhage Cardiorespiratory failure Death Acute obstruction of CSF Decerebrate posture elbows, Decorticate posturing: The pathway Cardiorespiratory failure wrists and fingers flexed, legs Death and rotated inward. extended
  70. 70. CNS Tumors Why pupils dilate? “Sympathetic system shows sympathy to your pants”
  71. 71. 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.
  72. 72. 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 (
  73. 73. It has been my philosophy of life that difficulties vanish when faced boldly. --Isaac Asimov
  74. 74. CNS Tumors SAQ / KFP  Should seizure patients have imaging done immediately?  Yes, 10-20% tumors.  Personality changes indicate  Frontal lobe which location?  Differentials for young adult  Other gliomas with insidious symptoms, seizures and decreased signal on T1 and increased signal on  Conservative – Poor T2 weighted MRI?  Steroids, anti  What is the treatment and prognosis for someone with a epileptic, low-grade astrocytoma?  How should the symptoms be symptomatic. treated?  What tests could have been  EEG done in the absence of neuroimaging?
  75. 75. CNS Tumors SAQ / KFP  Why was the child hitting his  Indicating headache. head?  Why did the child have a  Increased ICP, tum. headache?  4th ventricle.  If the child does have hydrocephalus, at what level  No – coning…* is the ventricular system being obstructed at?  Central – vermis  Should a lumbar puncture be  Separation/malfusion of performed?  Where in the cerebellum is anterior frontoparietal the lesion located? suture due to  What is the radiolucent area hydrocephalus. visible along the antero- superior aspect of the radiograph?
  76. 76. CNS Tumors SAQ / KFP  Name the location of  Cerebellopontine angle tumor?  Cranial Nerves 5,7 & 8  What cranial nerves  Teratoma, meningioma, are involved? acoustic neuroma.  List differential  Increased intracranial diagnosis tension.  Explain pathogenesis  Tumor attempting to form of headache and Arachnoid grannulations. papilledema? Origin of tumor.  What does the histological pattern represent in slide 1? slide 2?
  77. 77. 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.
  78. 78. CNS Tumors 35y Male, depression 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. 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.
  79. 79. CNS Tumors 35y Male, depression Axial T2 weighted MRI Axial T1 weighted MRI
  80. 80. CNS Tumors 35y Male, depression Coronal T2 weighted MRI Coronal T1 weighted MRI
  81. 81. 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.
  82. 82. CNS Tumors 3y Male, constant cry…. Axial T1 weighted MRI Axial T2 weighted MRI
  83. 83. CNS Tumors 3y Male, constant cry…. Coronal T1 weighted MRI
  84. 84. CNS Tumors What is the most likely diagnosis? 1. Glioblastoma m. 2. Astrocytoma 3. Meningioma 4. Ependymoma 5. Medulloblastoma
  85. 85. 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.
  86. 86. CNS Tumors 65y Fem morning headache.
  87. 87. 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.
  88. 88. CNS Tumors Metastatic Melanoma: multiple
  89. 89. CNS Tumors Brain Metastases: Surrounding edema.
  90. 90. CNS Tumors What is the most likely diagnosis? 1. Glioblastoma m. 2. Astrocytoma 3. Meningioma 4. Ependymoma 5. Medulloblastoma
  91. 91. CNS Tumors SAQ / KFP  Are there clinical signs of  Yes, ptosis, pupils 3rd nerve compression?  What is the most likely cause  Optic pathway - of the homonymous occipital. hemianopia?  Why does the patient have  Motor cortex progressive right upper limb compression – tum. weakness, and paroxysmal left upper and lower limb  Risky. weakness?  Should a lumbar puncture be  Brainstem performed? compression.  Why was the patient obtunded?  Meningioma  Why was an-x-ray taken? hyperostosis.
  92. 92. Other CNStumors
  93. 93. 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
  94. 94. CNS Tumors Schwannoma / Neurofibroma
  95. 95. CNS Tumors Schwannoma 8th Nerve:
  96. 96. CNS Tumors Bilateral 8th nerve schwannomas.
  97. 97. CNS Tumors Schwannoma:
  98. 98. Neurofibromatosis: Café-au-lait spot
  99. 99. Neurofibromatosis:
  100. 100. CNS Tumors Schwannoma
  101. 101. CNS Tumors A 26-year old female Headache,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.
  102. 102. CNS Tumors 7th nerve palsy:  Cerebellopontine angle tumours.  Acoustic neuroma,  epidermoid cysts,  medulloblastoma  meningioma  Affected cranial nerves:  5 trigeminal - masticatio  7 facial –face muscles  8 auditory – hearing
  103. 103. CNS Tumors Brudzinski Sign of Meningitis: