1. Tumours of Central Nervous System

2. Objective: The objective of lecture is to discuss the benign and malignant tumours of CNS and familial tumour syndomes in terms of genetics, clinical features,associated lesions& complications-clinical course
Learning Outcomes:At the end of lecture the student should be able to:
Classify the tumours of brain.
Discuss the types, incidence ,age & sex predominance,clinical presentation, morphology, clinical course & prognosis of common brain tumours.
Discuss the common familial tumour syndromes associated with brain tumours,

3. CELLS OF CNS
CNS consist of neurons and glial cells;50% each by volume. Four types of glial cells
Astrocytes:-star shaped; provide support and nutrition to neurons
Oligodendrocyte:- provide support and produce myelin sheath which insulates axons.
Microglial cells;- smallest of glial cells.some act as phagocytic and cleaning up of CNS; most serve as representative of immune system in brain.
Ependymal cells:- line ventricles

5. Classification of Tumours Of CNS
TUMORS OF NEURO-GLIA(GLIOMAS)
Astrocytoma
Oligodendroglima
Ependymoma
Choroid plexus papilloma
TUMORS OF NEURONS
Neuroblastoma
Ganglio neuroblastoma
Ganglio neuroma

6. NEURONS& NEUROGLIA
Ganglioglioma
POORLY DIFF. TUMORS(embryonal)
Medulloblastoma
PNET
MENINGES
Meningioma
Meningial sarcoma
NERVE SHEATH TUMORS
Schwannoma
Neurofibroma
M P N S T

7. OTHERS
Haemangioblastoma
PRIMARY CNS LYMPHOMA
Germ cell tumours
Malignant Melanoma
Craniopharyngioma
Pineal cell tumors
Pituitary tumors
METASTATIC TUMORS

8. GRADING OF CNS TUMOURS CRITERIA
a) Nuclear Atypia b) Mitosis c) Endothelial Proliferation-'piled-up' endothelial cells. NOT Hypervascularity
d) Necrosis.

9. WHO Grading CNS Tumours
Grade I tumors are slow-growing, nonmalignant, and associated with long-term survival.
Do not meet any criteria
Grade II tumors are relatively slow-growing but sometimes recur as higher grade tumors. They can be nonmalignant or malignant.
Show nuclear atypia
Grade III tumors are malignant and often recur as higher grade tumors.
Show nuclear atypia and mitosis
Grade IV tumors reproduce rapidly and are very aggressive malignant tumors.
Meet 3 or 4 of criteria

10. Meningioma

11. Meningioma
Circumscribed reddish-yellow firm neoplasm beneath the dura next to the falx

12. Brain, meningioma – Gross, coronal section

13. Resected meningioma

14. MENINGIOMA Age- 20-60 YEARS Sex- Slight female preponderance
Cell of oigin- Arise from menigothelial cells of arachnoid
Incidence-30% of all brain tumours.
COMMON SITES:
Lateral cerebral convexities along falx cerebri & olfactory groove& sphenoid ridge.
Usually benign.(Grade I)
Genetics-NF II gene on long arm of chromosome 22
GROSS:
Usually Solitary
Multiple when associated with Type ll NF
Solid, well circumscribed,firm tumour1-10 cm(dia)
C\S –firm, foci of calcification

15. TYPES
Based on microscopic features. MENINGIOTHELIOMATOUS(Syncytial) Whorled cluster of polygonal cells with round to oval central nuclei. FIBROBLASTIC Spindle shaped tumor cells form parallel or interlacing collagen bundles. TRANSITIONAL Syncytial & fibroblastic appearance. Psammomatous-plenty of psamoma bodies

16. Atypical-high rate of recurrence.More aggressive
ANGIOBLASTIC
Hemangioblastic or hemangiopericytic pattern seen.
Atypical-high rate of recurrence.More aggressive
ANAPLASTIC
malignant variant.Resembles high grade sarcoma
features of anaplasia seen.
invades brain & spinal cord.

17. Meningioma beneath the dura
PSAMMOMA BODIES
WHORLING OF CELLS

18. Meningioma -Whorling

19. Brain, meningioma – High power
neoplastic proliferations of meningothelial cells

20. Meningioma along falx cerebri
Miro:-multiple psammoma bodies(arrow)
(Psammomatous)

21. Meningioma with a whorled pattern of cell growth and psammoma bodies.

22. Clinical features ,course and prognosis
Usually benigns Slow-growing lesions (Grade-I )that present either with vague nonlocalizing symptoms or with focal findings referable to compression of underlying brain.
92% benign ,5 yr survival rate %
Meningiomas often express progesterone receptors and may grow more rapidly during pregnancy.
Atypical and anaplastic meningioma(II-IV)

23. ASTROCYTOMA

24. Astrocytoma Cerebral Hemisphere

25. A large brainstem glioma ( astrocytoma)

26. Astrocytoma Commonest type of gliomas.
Arises from star shaped glial cells (astrocytes)
Peak age in 60’s
Predominantly in cerebral hemispheres
Tendency to progress from low grade to high grade( Grade I to Grade IV)

27. Types &Grading of astrocytoma
Pilocytic astrocytoma I Low Grade
Diffuse astrocytoma II
Anaplastic astrocytoma- III High Grade
Glioblastoma IV

28. Low Grade-localised and grow slowly over a long time.
Most astrcytoma(80%) in children are low grade.
Common site cerebellum and brain stem
High Grade- much more aggressive,require intensive therapy.
Most astrocytoma in adults.
Most common site cerebral hemisphere

29. Pilocytic Astrocytoma
Relatively benign-WHO Grade-1. usually non infiltrating
Age- Children and young adults
Site :cerebellum ,3rd ventricle ,optic nerve
Gross
Often cystic with mural nodules in cyst wall
Microscopic
Predominantly composed of pilocytic astrocytes (bipolar cells with long thin hair like processes)
Rosenthal fibres,
Hyaline granular bodies

30. Cystic astrocytoma of cerebellum

31. Pilocytic astrocytoma

32. Fibrillary astrcytoma
Grade –II.Also called diffuse astrocytoma. Usually infiltrating tumour.does not have well defined border.
Occurs in adults 20-40yrs.
Common site cerebral hemisphere.
Gross – Poorly defined gray white,infiltraing normal brain tissue beyond visible margin.
Microscopic – Well differentiated astrocytes separated by variable amount of fibrillary background of astrocytic processes

33. Glioma arising in the cerebral hemisphere

34. Diffuse astrocytoma

35. Glioblastoma Multiforme

36. Glioblastoma –haemorrhage and necrosis

37. Glioblastoma Multiforme
Grade IV ,most aggressive. 25% of all brain tumors
Age-Adults 50-80yrs.
Gross:– Variegated appearance because of haemorrhage and necrosis.Surrounding brain tissue shows infiltration
Micro :-
Highly anaplastic cells, frequent mitosis and Giant cells
Tumour necrosis and haemorrhage
Pseudopalisading
Microvascular endothelium proliferation ( formation of glomeruloid bodies )
Prog- Survival m0nths

38. GBM Showing necrosis,pallisading and vas cular proliferation

39. GBM-ENDOTHELIAL PROLIFERATION

40. OLIGODENDROGLIOMA

41. OLIGODENDROGLIOMA

42. Oligodendroglioma Age:-4th-5th decades
Site – cerebral hemisphere-white matter
Prog:-WHO=GR II and III
Slow growing,better prognosis. Average survival=5-10 yrs. Anaplastic variant worst prognosis
Gross – Well circumscribed gray white gelatinous area with cystic spaces,focal hemorrhages and calcification

43. Micro –
Uniform cells surrounded by clear halo =Fried egg appearance.
Foci of calcification
Chicken wire capillary system

44. Oligodendrglioma -Showing characteristic branching small chicken wire like blood vessels and fried egg like cells

45. ASTROCYTOMA NECROSIS PALISADING OF CELLS GLIOBLASTOMA MULTIFORME
OLIGODENDROGLIOMA
FRIED EGG APPEARANCE OF CELLS

46. EPENDYMOMA

47. Ependymoma arising from the ependymal lining of the fourth ventricle
above the brainstem bulging toward the cerebellum

48. Ependymoma Arises from ependymal lining of ventricles and spinal cord.
Age:-Child hood (< 20 years).30% of all brain tumours in children
Commonest sites in children – 4th ventricle (obstructive hydrocephalus)
In adults spinal cord is most common site.
Prog:- Most are Gr I.Others Gr II and Gr III(anaplastic)
Slow growing tumour.
Clinical outcome of supratentorial and spinal is always better than post fossa tumour.
Prognosi in children is better (5 yr survival-70%)as against adult of 14%

49. Gross –
Solid or papillary extending in the floor of ventricles
Micro –
Ependymal cells form pseudo rosettes and canals (embryonal).
Rosettes-- Tumour cells are arranged around vessels.

50. Ependymoma

51. Variants
Myxopapillary Ependymoma Region of cauda equine Myxoid areas and papillary structures Slow growing tumour(WHO-GR I)

52. Myxopapillary Ependymoma

53. Medulloblastoma

54. Medulloblastoma
irregular posterior fossa mass
near the midline of the cerebellum and extending into the fourth ventricle 
above the brainstem 

55. Medulloblastoma Age:- most common in children
Site :- midline of cerebellum
Occlude flow of CSF --Hydrocephalus
Micro:-Highly cellular,cells are small, hyperchromatic,scant cytoplasm,abundant mitosis.Rosettes formation(Homer- Wright)

56. Microscopic appearance of a medulloblastoma with small round blue cells

57. SCHWANNOMA

58. Schwannoma
The mass lesion here is arising in the acoustic (eighth cranial) nerve at the cerebellopontine angle.
This is a schwannoma. Patients may present with hearing loss.
These benign neoplasms can be removed.

59. SCHWANNOMA Solitary, C-P angle,extradural,tumour of 8th Nerve Benign.
Firm, encapsulated
Mico:-Compact-ANTONI A areas
Loose-ANTONI B areas.
VEROCAY bodies

61. A B
Tumor showing cellular areas (Antoni A), including Verocay bodies (far right)
as well as looser, myxoid regions (Antoni B, center).

62. METASTATIC TUMOURS

63. Metastatic melanoma. Metastatic lesions are distinguished grossly from most primary CNS tumors by their multicentricity and well-demarcated margins. The dark pigment in the tumor nodules in this case is characteristic of most malignant melanomas

64. Brain, metastatic carcinoma – Gross, coronal section
Metastases most often appear at the border of the grey and white matter
in the distribution of the middle cerebral artery

65. Metastatic tumours Form 1/4th to half of all intracranial tumours.
Five common primary sites are:-
Lung-Bronchogenic Carcinoma-most common
Breast
Skin(melanoma)
Kidney
GIT

66. Clinical Features of CNS Tumours
CNS is locked inside bony cage,therefore any new growth (primary or secondary)can only grow at the expense of structures already inside the skull.
General non localising sign and symptoms. ( due to I C T)
Persistent Headache not responding to medication
Nausea ,Protracted or projectile vomiting
A change in mental status and behaviour drowsiness,cognitive impairement
papilloedema.
Focal sign and symptoms( Effect of tumour on specific structure)
Weakness ,paresis,ataxia, change in gait
Deficit in speech or vision
Late onset focal seizure(jacksonian Epilepsy)

67. Clinical course & Prognosis
Course and prognosis of brain tumours depends upon
Type
Grade
Rate of growth
Size and extent at diagnosis
Site
Age at diagnosis
Response to different treatment

68. Anatomical site can have lethal consequences
Anatomical site can have lethal consequences. Benign meningioma in post fossa by compressing medulla can cause cardiorespiratory arrest.
Tumours located in post fossa have worse outcome compared to supratentorial tumour of similar grade because of limited space and dificulty in its complete removal.
Survivors of brain tumours after removal often suffer lifelong side effect of treatment such as surgery,radiation and chemotherapy.

69. Brain tumours in children
CNS tumours are more common in children.
20% 0f all childhood tumours
> 60% brain tumours in children located in Post. Fossa.
Non malignant tumours can kill if their location prevents removal or other curative treatment
Brain stem glioma is deadliest--<20% survival rate

70. Common Tumours in children Medulloblastoma. Pilocytic astrocytoma
Brain stem glioma.
Ependymoma 4th ventricle
Other tumours in children
Pineoblastoma
Germ cell tumour
Craniopharyngioma
Post. fossa

71. Post. Fossa Tumours Common post fossa tumours Medulloblastoma,PNET
Pilocytic Astrocytoma of cerebellum,
Brain stem glioma
Mixed glioma unique in children
Dermoid tumours
Ependymoma 4th ventrcle
Post. Fossa tumours are considered critical lesions because of limited space and potential involvement of vital brain stem nuclei.
50-70% of all childhood tumours originate in post fossa as against15-20 % of adults.

72. Common familial tumour syndromes associated with brain tumours,
Neurofibromatosis1-(Von Recklinghausen disease)
Neurofibromatosis2(CentralNeurofibromatosis)
Von Hippel-Lindau disease
Tuberous Sclerosis
Li-Fraumeni syndrome

73. Plexiform neurofibroma, MPNST, optic and other gliomas
SYNDROME
GENE/LOCUS
CNS TUMORS
OTHER TUMORS
NF1
NF1/17q
Plexiform neurofibroma, MPNST, optic and other gliomas
Pheochromocytoma, GIST
NF2
NF2/22q
Vestibular and PN shwannoma, meningioma, other brain tumors NA TS
TSC1/9q,TSC2/16p
SEGA(Sub-ependymal giant cell astrocytoma)
Renal AMLs, lung LAM, cardiac rhabdomyoma
VHL
VHL/3p
Hemangioblastoma
Renal cell carcinoma, Pheochromocytoma
Li-Fraumeni
TP53/17p
Astrocytoma
Breast carcinoma, bone and soft tissue sarcoma
Turcot
FAP/5q
Medulloblastoma, GBM
GI polyps, colorectal cancer
Gorlin
PTCH/9q
Desmoplastic medulloblastoma
Nevoid basal cell carcinoma, Odontogenic keratocysts
AML: Angiomyolipoma; GIST: Gastrointestinal stromal tumor; LAM: Lymphangioleiomyomatosis; MPNST: Malignant peripheral nerve sheath tumor