Pathology of CNS Tumors

1. Pathology of CNS Tumors CPC-44: 22y Sam G, Seizure. <br />Sam Gully, 22y, previously healthy male.<br />On bus, became agitated, combative, had a seizure and became unresponsive. <br />From Boston, USA, on holidays, 3 days.<br />No neck stiffness, no skin lesions/rash<br />Pupils minimally reactive and 6mm bilaterally; fundoscopy normal.<br />

2. CPC-44: 22y Sam G, Seizure. <br />Epileptic seizure <br />CVA, CNS infection, Brain tumour<br />Drugs: drug withdrawal/ overdose<br />Idiopathic (epilepsy), Genetic, Autoimmune, endocrine..<br />Head Injury <br />Metabolic: uraemia, Hypoglycaemia, <br />Neurodegenerative diseases e.g. Alzheimer’s <br />Non epileptic: <br />Syncope, arrythmias, <br />Pseudoseizures, TIA, <br /> CPC-44: 22y Sam G, Seizure. <br />Epileptic seizure <br />CVA, CNS infection, Brain tumour<br />Drugs: drug withdrawal/ overdose<br />Idiopathic (epilepsy), Genetic, Autoimmune, endocrine..<br />Head Injury <br />Metabolic: uraemia, Hypoglycaemia, <br />Neurodegenerative diseases e.g. Alzheimer’s <br />Non epileptic: <br />Syncope, arrythmias, <br />Pseudoseizures, TIA, <br />

3. CPC-4.3.7 – Jenna 27y teacher.<br />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’.<br />Brought to ED by paramedics, accompanied by teaching colleague. Collapsed approx 30 mins ago.<br />Tutors: (Aim: ..look at a broad range of differential diagnoses for a witnessed, generalized tonic- clonicseizure. Focus… on epilepsy, infection (meningitis), and braintumour. <br />..discuss ‘what if’ questions..<br /> CPC-4.3.7 – Jenna 27y teacher.<br />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’.<br />Brought to ED by paramedics, accompanied by teaching colleague. Collapsed approx 30 mins ago.<br />Tutors: (Aim: ..look at a broad range of differential diagnoses for a witnessed, generalized tonic- clonicseizure. Focus… on epilepsy, infection (meningitis), and braintumour. <br />..discuss ‘what if’ questions..<br />

4. Scenario: Brain Tumor<br />Chronic Crescendo Morning - Head ache*<br />Pulse 62 bpm reg small volume; BP 140/90 mmHg T37.4C. GCS - variable.<br />Localising signs – seizures, aphasia, anosmia, vision defects, paralysis (unilateral), dementia.<br />Cushing’s reflex – Bradycardia hypertension (ICP)<br />Papilloedema * raised ICP<br />Lesion on imaging. <br />Peritumoral edema – rapidly growing/inflammed.<br />Cesc. Chron. Morn. headache*, Seizures, localizing signs<br /> Scenario: Brain Tumor<br />Chronic Crescendo Morning - Head ache*<br />Pulse 62 bpm reg small volume; BP 140/90 mmHg T37.4C. GCS - variable.<br />Localising signs – seizures, aphasia, anosmia, vision defects, paralysis (unilateral), dementia.<br />Cushing’s reflex – Bradycardia hypertension (ICP)<br />Papilloedema * raised ICP<br />Lesion on imaging. <br />Peritumoral edema – rapidly growing/inflammed.<br />Cesc. Chron. Morn. headache*, Seizures, localizing signs<br />

5. Scenario: Meningitis<br />ABC breathing spontaneously rr 18/min 4l O2 via mask, sats 90%; pulse 110 bpm reg small volume; BP 90/60 mmHg T39.6C<br />GCS - E2V3M4<br />Detailed check - petechiae non blanching rash trunk, buttocks, Neck stiffness<br />Small contusion L temperoparietal area<br />Capillary refill time > 3 secs, peripheral cyanosis+<br />Brudzinski sign positive<br />Ix skin scraping from lesion : gram negative diplococci; CSF gram negative diplococci; FBC wcc 18 (polymorhic leucocytosis)<br />Brudzinski sign, Kernig sign, CSF findings <br /> Scenario: Meningitis<br />ABC breathing spontaneously rr 18/min 4l O2 via mask, sats 90%; pulse 110 bpm reg small volume; BP 90/60 mmHg T39.6C<br />GCS - E2V3M4<br />Detailed check - petechiae non blanching rash trunk, buttocks, Neck stiffness<br />Small contusion L temperoparietal area<br />Capillary refill time > 3 secs, peripheral cyanosis+<br />Brudzinski sign positive<br />Ix skin scraping from lesion : gram negative diplococci; CSF gram negative diplococci; FBC wcc 18 (polymorhic leucocytosis)<br />Brudzinski sign, Kernig sign, CSF findings <br />

6. Scenario: Epilepsy:<br />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.<br />GCS E2V3M4<br />Detailed check no neck stiffness, no skin lesions/rash<br />Tongue has been bitten; pupils equal and reactive to light; fundoscopy normal<br />Decreased tone R upper limb, ?normal tone other limbs<br />Reflexes increased on R upper + lower limb; decreased on L upper +lower;<br />Plantar reflexes upgoing<br />Evidence of urinary incontinence<br />All other systems : nil abnormal<br />Ix - BSL : 5.1; toxicology screen : negative<br /> Scenario: Epilepsy:<br />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.<br />GCS E2V3M4<br />Detailed check no neck stiffness, no skin lesions/rash<br />Tongue has been bitten; pupils equal and reactive to light; fundoscopy normal<br />Decreased tone R upper limb, ?normal tone other limbs<br />Reflexes increased on R upper + lower limb; decreased on L upper +lower;<br />Plantar reflexes upgoing<br />Evidence of urinary incontinence<br />All other systems : nil abnormal<br />Ix - BSL : 5.1; toxicology screen : negative<br />

7. Core Learning Issues:<br />Pathology Major CLI:<br />Raised ICP – Pathology & Clinical features.<br />Pathology of common CNStumors in different age groups.<br />Astrocytoma – grades, clinical types, presentation & complications.<br />Meningitis – common types *Bacterial, viral, fungal. <br />Pathology Minor CLI:<br />Pathology of Epilepsy (note this is major clinical learning issue) <br />Meningioma, Acoustic neuroma, Craniopharyngioma / pituitary tumors. Medulloblastoma.<br />CJD-Creutzfeldt jakob's disease. (Mad cow disease).<br /> Core Learning Issues:<br />Pathology Major CLI:<br />Raised ICP – Pathology & Clinical features.<br />Pathology of common CNStumors in different age groups.<br />Astrocytoma – grades, clinical types, presentation & complications.<br />Meningitis – common types *Bacterial, viral, fungal. <br />Pathology Minor CLI:<br />Pathology of Epilepsy (note this is major clinical learning issue) <br />Meningioma, Acoustic neuroma, Craniopharyngioma / pituitary tumors. Medulloblastoma.<br />CJD-Creutzfeldt jakob's disease. (Mad cow disease).<br />

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…!”<br /> 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…!”<br />

9. Pathology ofCNS Tumors<br />Dr. Venkatesh M. Shashidhar, MD<br />Associate Professor & Head of Pathology<br /> Pathology ofCNS Tumors<br />Dr. Venkatesh M. Shashidhar, MD<br />Associate Professor & Head of Pathology<br />

10. . CNS Tumors: General Features<br />10% of all tumors.<br />Commonest solid cancers in children.(2nd to Leuk for all malignancies)<br />Age: double peak 1st& 6th decade<br />Adults - 70% supratentorial<br />Children - 70% infratentorial<br />No/very rare extraneural spread.<br />Metastasis most common.<br />Adults<br />Children<br />

11. . Most common CNS Tumors:<br />Glioblastoma MF<br />

12. . Clinical features:<br />Slow, Progressive..*<br />Crescendo, Chronic, Morning head ache.<br />Local damage:<br />Nerve & tract deficits, unilateral* Paralysis, vision defects, anosmia, seizures.. etc.<br />Raised Intracranial Pressure* <br />Headache, vomiting, slow pulse, papilloedema.<br />

13. . CNS Anatomy - Clinical Features<br />

14. . CNS Tum: Clinical Features-Pathogenesis<br />Headaches (morning) <br />Papilloedema <br />Nausea or vomiting <br />Bradycardia <br />Seizures (convulsions).<br />Drowsiness, Obtundation<br />Personality or memory <br />Changes in speech<br />Limb weakness <br />Balance/Stumbling<br />eye movements or vision<br />Increased ICP<br />Increased ICP<br />ICP – Medulla ob.<br />ICP – Parasymp.<br />Irritation.<br />Brain Stem compress<br />Frontal lobe<br />Temporal lobe<br />Motor area<br />Cerebellum<br />Optic tract, occipital.<br />

15. . CNS Tumors Classification:<br />Secondary Tumors- Metastasis – commonest* breast, lung, GIT, Melanoma.<br />Primary Tumors: (not from neurons…!)<br />Glial cells:Glioma * commonest<br />Astrocytoma (& Glioblastoma).Oligodendroma, ependymoma.<br />Nerve sheath – Schwanoma, Neurofibroma.<br />Meninges: Meningioma<br />Germ cell: Medulloblastoma, neuroblastoma, teratoma, neuroma, neuroganglioma.<br />Lymphocytes: CNS Lymphoma<br />* Other BV: (angioma)Epithelial, Pituitary & Pineal gland tumors.<br />

16. . Adults:<br />Astrocytoma & Glioblastoma.<br />Meningioma<br />Metastasis.<br />Children:<br />Astrocytoma<br />Medulloblastoma<br />(Metastases)<br />Common:<br />

17. . Meningioma:<br />Arachnoid granulation fibroblastsvenous sinuses (Attached to dura).<br />Females(2:1), progesterone, cyclical/preg*<br />Common site: parasagittal (falx), <br />Slow growth, well differentiated & demarcated. Does not invade brain (Benign). <br />Reactive skull Hyperostosis over the tumor.<br />

18. . Meningioma:<br />Note location in the venus sinus & adherent to dura.<br />

19. . Meningioma: multiple<br />

20. . Meningioma<br />

21. . Meningioma<br />

22. . Meningioma high grade: (rare)<br />

23. . Meningioma<br />Nodules<br />Capsulated,<br />spindle cells in whorls and psammoma bodies (common type).<br />

24. . Psammoma bodies<br />(calcification)<br />

25. . Glioma:<br />Gliomas are neoplasms of glial cells.<br />Commonest both in adults and children.<br />Benign * to Aggressively malignant.<br />Astrocytoma(low & high grade)<br />Ependymoma - Rare, 4th ventricle.<br />Oligodendroglioma - Benign, adults, rare<br />

26. . Astrocytomas<br />Adults:<br />Commonest 80%, Cerebral.<br />Low Gr: Solid, Fibrillary. <br />High Gr: glioblastomamultiformeVarigated, Hemorrhagic - Malignant,.<br />Children:<br />Cystic, Low grade*, Pilocytic<br />Infratentorial(Cerebellum), <br />

27. . Astrocytoma-Lowgrade fibrillary<br />

28. . Astrocytoma<br />

29. . Glioma Brain Stem – note diffuse tumor<br />

30. . Glioma Cerebrum cystic degeneration<br />

31. . Glioma:<br />

32. . Astrocytoma: * Lat. Vent. *petechial hem. <br />

33. . Astrocytoma (Glioma) – brain stem<br />

34. . Glioma Brain Normal<br />

35. . Astrocytomas<br />Adults:<br />Commonest 80%, Cerebral.<br />Low Gr: Solid, Fibrillary. <br />High Gr: glioblastomamultiformeVarigated, Hemorrhagic - Malignant,.<br />Children:<br />Cystic, Low grade*, Pilocytic<br />Infratentorial(Cerebellum), <br />

36. . Glioblastoma Multiforme (GBM):<br />High grade Astrocytoma - Grade IV<br />Commonest & malignant brain tumor in adults – mean survival <1y – cerebral supratentorial.<br />Loss of heterozygosity on Chromosome 10 (80%)<br />Most GBMs have lost one entire copy of C – 10<br />2 types: Primary (worst) or Secondary from low grade astrocytomas (better prog).<br />Variants: giant cell GBM, gliosarcoma<br />Microscopy: <br />Necrosis, palisading, hypercellularity, nuclear atypia & vascular proliferation & mitoses.<br />

37. . Genetic abnormalities in Glioma:Low grade  AnaplasticGBM<br />Note: GBM can occur alone without prior glioma<br />

38. . Glioma: high grade<br />

39. . GBM: MRIEnhancement with peritumoral edema.<br />

40. . Glioblastoma – high grade Astrocytoma<br />

41. . Glioblastoma – high grade Astrocytoma<br />Note: Looks like abscess, but it is necrosis..!<br />

42. . Glioblastoma Multiforme (high grade Astrocytoma)<br />

43. . Glioblastoma Cerebrum<br />

44. . High Gr.: Glioblastomamultiforme(high grade- Hypercellularity, necrosis, hemorrhage & palisading) <br />Hem<br />Hyper cel.<br />Palis.<br />Necro<br />

45. . Glioblastoma Multiforme<br />B.V<br />Necrosis<br />Palisading<br />

46. . Glioblastoma Multiforme<br />

47. . A Astrocytoma Low gradeB Glioblastoma Multiforme(GBM)C Necrosis with pseudopalisading in GBM.<br />

48. . Astrocytomas<br />Adults:<br />Commonest 80%, Cerebral.<br />Low Gr: Solid, Fibrillary. <br />High Gr: glioblastomamultiformeVarigated, Hemorrhagic - Malignant,.<br />Children:<br />Cystic, Low grade*, Pilocytic Astrocytoma<br />Infratentorial(Cerebellum), <br />

49. . Pilocytic astrocytoma<br />Children, slowest growth, <br />Cerebellum, <br />Cystic with mural nodule<br />Micro: elongated hair-like (pilocytic) cells<br />

50. . Pilocytic Astrocytoma - children<br />