1. Central Nervous System 9. Tumors

2. Clinical Presentation of brain tumors
Headaches
Seizures
Nausea & vomiting
Loss of consciousness
Cognitive dysfunction
Neurological dysfx- weakness, sensory loss, aphasia, visual spatial dysfunction

3. Types of Brain Tumors Meninges: meningioma, hemangiopericytoma
Glia: astrocytoma, oligodendroglioma, ependymoma, choroid plexus papilloma..
Vascular: hemangioblastoma.
Primitive cells: neuroblastoma, germinoma, medulloblastoma, pineoblastoma, retinoblastoma
Neuronal: ganglioglioma, gangliocytoma
Pituitary: adenoma, craniopharyngioma
Nerves: schwannoma, neurofibroma, MPNST

4. INTRACRANIAL TUMORS (ICTS)
Primary or Metastatic
Occur with equal frequency in adults, but in children primary tumors are far more common.
Primary ICTs account for
~2% of cancers in adults
20% of all cancers in children.
In children 70% of ICTs arise in  Posterior fossa (infra-tentorial). as
In adults 70% of ICTs arise in  Supra-tentorial.
Because of its location, a benign ICT may have fatal “malignant” effects.
Malignant ICTs spread by:
Direct infiltration of adjacent tissues
May disseminate within the CNS via CSF.
Gliomas account for 60% of primary ICTs
Meningiomas for 20% & all others 20%.
All CNS tumors behave as malignant clinically . Limited space
Less than 5 years small round cell tumors eg wills, neuroblastoma leukemia's ets between 5 to 14 lymphomas and CNS tumors

5. Normal Anatomy of Brain (MRI)
Supratentorial compartment:
Cerebral hemispheres
Basal ganglia
Thalamic nuclei
Lateral ventricles
Hypothalamus
Corpus callosum
Infratentorial compartment:
Cerebellum
Brain stem (MB/P/MO)
4th ventricle
Sagittal
Axial
INTP - PPO, PHO, IAP.
P2 – 6/27

6. The unique features of CNS tumors – “ICP”
1. CNS tumors- < 2% of all malignant tumors. They grow in a unique environment: the intracranial space.
2. The intracranial contents - incompressible Brain and blood contained within a rigid unyielding bony structure.
3. Intracranial pathologies (tumors, abscess, hematoma, infarction, edema, etc.) eventually produce life threatening increase of the intracranial-pressure: ICP.

7. Cytologic origin of CNS tumors
Neuro-ectodermal – most important are the Gliomas;
Mesenchymal – most frequent ones are the Meningiomas;
Ectopic tissues – from tissues „displaced” during embryogenesis: Ex., Dermoid cyst;
Retained embryonal structures: various cysts – Paraphyseal cyst;
Metastases: Lung, Breast, Melanoma, etc. in 50% of cases

8. Neuro – ecto - dermal tumors
Glial cells:
astrocytes (A) - Astrocytoma
Oligodendroglial cells - Oligodendroglioma
Ependymal cells – Ependymoma
Neurons - Gangliocytoma

9. WHO Grading System (evolves)
Low-grade
WHO Grade I i.e., Juvenile Pilocytic Astrocytoma
WHO Grade II i.e., Diffuse Astrocytoma
High-grade
WHO Grade III i.e., Anaplastic Astrocytoma
WHO Grade IV i.e., Glioblastoma Multiforme

10. ASTROCYTOMAS Account for ~ 80% of primary ICTS in adults
MC in the cerebral hemispheres
MC Symptoms: headaches, seizures, focal neurologic deficits ( usually in the anterior or middle)
Low-grade Astrocytomas:
Gross:
Poorly defined gray-white infiltrative tumors.
Histology:
Hypercellularity; astrocytic nuclei of mild degree of atypia & astrocytic processes  fibrillary background = fingers of astrocytes

11. Low-grade Astrocytomas
Pilocytic Astrocytomas:
MC in the cerebellum of children & young adults; and less commonly in the optic nerve, hypothalamic region or cerebral hemispheres
Morphology:
Cystic, with a tumor nodule in the wall of the cyst.
Composed of bipolar astrocytes, with long hair-like processes, Rosenthal fibers & Micro-cysts+ calcification = good prognosis
Grow very slowly (some patients have survived for >40 yrs after incomplete resection) & have an Excellent prognosis
DD ;- not to confuse with low grade Fibrillary Astrocytoma

12. Grade I. tumor: pilocytic astro~

13. Pilocytic Astrocytoma
NB fibrially back ground

14. Pilocytic Astrocytoma

15. Rosenthal fibers

16. Gr. II. Astrocytoma
Hypercellularity + nuclear atypia

17. Low-Grade Astrocytoma (Grade II)
Characteristics
Slow growing
Rarely spreads to other parts of the CNS
Borders not well defined
Common among men and women in their 20s-50s
Treatment
Treatment depends on the size and location of the tumor. The doctor will most likely perform a biopsy or surgery to remove the tumor. Partial resections or inoperable tumors may be treated with radiation. Recurring tumors may require additional surgery, radiation and/or chemotherapy.

18. Gr. II. astrocytoma

19. Gr. III. astrocytoma

20. Gr. III. astrocytoma

21. Gr. III. Astrocytoma
Increased cellularity + nuclear atypia+ mitotic figures

22. Anaplastic Astrocytoma (Grade III)
Characteristics  
Grows faster and more aggressively than grade II astrocytomas
Tumor cells are not uniform in appearance
Invades neighboring tissue
Common among men and women in their 30s-50s
More common in men than women
Accounts for four percent of all brain tumors
Treatment
Treatment depends on the location of the tumor and how far it has progressed. Surgery and radiation therapy, with chemotherapy during or following radiation, are the standard treatments. If surgery is not an option, then the doctor may recommend radiation and/or chemotherapy. Many clinical trials (experimental treatments) using radiation, chemotherapy, or a combination are available for initial and recurrent anaplastic astrocytomas

23. Gr. IV. astro ~ = GBM
Grade + giant cells

24. Glioblastoma Multiforme (GBM ) (Grade IV )
Characteristics  
Most invasive type of glial tumor
Commonly spreads to nearby tissue
Grows rapidly
May be composed of several different kinds of cells (i.e., astrocytes, oligodendrocytes)
May have evolved from a low-grade astrocytoma or an oligodendroglioma (see below)
Common among men and women in their 50s-70s
More common in men than women
Accounts for 23 percent of all primary brain tumors

25. Treatment
Standard treatment is surgery followed by radiation therapy. If surgery is not an option, the doctor may administer radiation therapy. Chemotherapy is sometimes given during or after radiation therapy or if the tumor recurs. Many clinical trials (experimental treatments) using radiation, chemotherapy, or a combination are available for initial and recurrent GBM.

26. glioblastoma multiforme

27. Gr. IV. astro ~ = GBM

28. Gr. IV. astro ~ = GBM

29. GBM: necrosis/pseudo-palisade
Pseudo pallisding central necrosis with perpendicular cells

30. GBM: pleomorphic cytology

31. Gr. IV. Astro ~ = GBM
Die directly

32. OLIGODENDROGLIOMA Comprise ~ 5 -15% of Gliomas
Arise in the cerebral white matter
MC in the 4th & 5th decades
Gross:
Well circumscribed, gelatinous, gray masses, with foci of hemorrhage & calcification.
Histology:
Sheets of cells with rounded nuclei surrounded by a halo of clear cytoplasm (fried egg appearance).
There is often a delicate network of capillaries & scattered foci of calcification (psammoma bodies)( seen in thyroid, CNS, kidneys etc).
Grows slowly, presents commonly with seizures, prognosis is better than Astrocytoma, average survival is 5-10 yrs (with modern therapeutic approaches

33. Oligodendroglioma

34. Oligodendroglioma

35. Oligodendroglioma

36. Oligo-Astrocytoma

37. EPENDYMOMA
Arise from the Ependymal lining of the ventricles or the central canal of the spinal cord
Arise in the
Fourth ventricle in children & young adults
Spinal cord in the middle aged.
Morphology:
Highly cellular, tumor cells have regular nuclei
May exhibit epithelial features with formation of “rosettes” (Flexner…) or “canals”, also perivascular pseudo-rosettes (homer …)
Most tumors are well differentiated
4th ventricle tumors:
May cause hydrocephalus, usually can’t be completely removed
CSF dissemination may occur
Average survival is ~ 4 yrs

38. Myxo-papillary Ependymomas
Arise in the filum terminale of the spinal cord
Prognosis depends on completeness of surgical excision

39. Ependymoma
“Rosettes” & perivascular Pseudo-rosettes

40. MEDULLOBLASTOMAS Second MC ICT of childhood (after Astrocytomas).
Occurs exclusively in the cerebellum.
Derived from fetal external granular layer of cerebellum.
Grows rapidly & occludes CSF flow  hydrocephalus.
Seeds through CSF  implants around the spinal cord & cauda equina (need irradiation of the whole Neuraxis).
Histology:
Extremely cellular, anaplastic, small round or carrot-shaped cells with hyperchromatic nuclei,  N/C, may form Homer-Wright pseudo-rosettes
Highly malignant, yet radiosensitive & 5-yr survival 75%.

41. Medulloblastoma

42. Medulloblastoma
Homer-Wright pseudo-rosettes
carrot-shaped cells

43. Usually Benign slow-growing tumors of adults, F/M 3:2
MENINGIOMAS
Usually Benign slow-growing tumors of adults, F/M 3:2
Originate from meningothelial cells of the arachnoid.
Usually solitary ( multiple meningiomas  NF2 )
Morphology:
Firm rounded masses, adherent to the dura and compressing the underlying brain (no infiltration).
Histologic variants include:
Syncytial, fibroblastic, transitional, Psammomatous & papillary ( propensity to recur).
Malignant Meningioma is very rare
Infiltrates the underlying brain, shows marked nuclear atypia,  mitoses, & foci of necrosis.
Other rare sarcomas of meninges include:
Hemangiopericytoma, malignant fibrous histiocytoma & Fibrosarcoma.

44. Meningioma
Easily removed with little neurological complication rarely

45. Meningioma

46. Meningothelial whorls

47. Meningioma
Syncytial
Psammomatous
Epithelial Membrane Antigen

48. NERVE SHEATH TUMORS 1. Schwannomas: Consist of
Benign tumors of Schwann cells
MC in the vestibular branch of the VIII CN at the cerebello-pontine angle (acoustic neuroma)  tinnitus & hearing loss
Also involve branches of the trigeminal nerve & dorsal nerve roots
Tumors are encapsulated, attached to one side of the nerve; axons do not pass through the tumor
Consist of
Antoni -A areas of high cellularity
Nuclei form palisades “Verocay bodies”
Antoni -B myxoid areas

49. Schwannoma/Acoustic neuroma

50. Antony A Antony B

51. Schwannoma
Antoni – A hyprecellular
Antoni –B Sparsely cellular

52. 2. Neurofibromas:
Benign tumors composed predominately of Schwann cells, but also containing fibroblasts & perineural cells
May involve single or multiple dorsal spinal nerve roots (multiple in patients with von Ricklinghausen's disease - NF1)
CN involvement is extremely rare
May present as
Localized fusiform enlargement of a nerve or
Extensively infiltrate along the nerve  “ropy enlargement” of the nerve & it’s branches (plexiform Neurofibroma)
Plexiform neurofibromas are usually part of NF1, excision is very difficult
Histology:
Wavy spindle shaped cells, myxoid collagenous stroma with interspersed nerve fibers

53. Neurofibromatosis - Von Recklinghausen
Dominant inheritance
Multiple neurofibromas
Central - CNS
peripheral nerves
Increased incidence of:
meningioma
glioma
schwannoma - bilateral VIII N.
Cafe-au-lait (melanosis) in skin
Elephantiasis: increased connective tissue

54. Von Recklinghausen’s Disease
Café-au-lait spots
Multiple neurofibromas

55. „Acoustic Neurinoma” (Schwannoma)
USAULLY bilaterally

56. METASTATIC ICTS 50% of ICTs. Common Primaries: Sites of metastases:
Broncho-genic small cell undifferentiated (oat cell) ca., Breast ca., Malignant melanoma, RCC. & Colon ca.
Sites of metastases:
Cerebral cortex 80%;
Rest are in the cerebellum & brain stem.
50% are multiple; at the junction between the gray & white matter.
Vertebral column is a common site for metastases of
Breast & Prostatic carcinomas
Thoracic spine 60%, Cervical 20% & Lumbar 20%
Treatment : Radiotherapy

57. Metastasis
Tumor material different from brain tissue

58. Brain Metastasis - (lung)

59. CHOROID PLEXUS PAPILLOMA
MC in children  Arising from the lateral ventricles
In adults they are found MC in the 4th ventricle
Present with Hydrocephalus
Due to either over-production of CSF or to obstruction of the ventricular system.
Consist of papillae with fibrovascular stalks covered with a cuboidal or columnar ciliated epithelium, recapitulating the structure of the normal choroid plexus.

60. COLLOID CYST OF THE THIRD VENTRICLE A non-neoplastic cystic lesion
Morphology:
Having a thin fibrous capsule, a lining of Cuboidal to columnar epithelium & containing gelatinous Proteinaceous material.
Attached to the roof of the third ventricle at the foramina of Munroe & may cause sudden obstruction of the CSF flow  acute non-communicating hydrocephalus  brain herniation & death
Symptoms: headaches (often positional), “drop attacks”, incontinence
Goblet cells are confirmatory

61. MISCELLANEOUS (MIDLINE) TUMORS
Pinealomas:
True pineocytomas are extremely rare, may also have pineoblastomas
Germinomas:
MC in the pineal & suprasellar regions in adolescents & young adults
Closely resemble testicular Seminomas & ovarian Dysgerminomas
Other GCTs (Teratomas & Choriocarcinomas) also occur
Not clear how GCTs arise within the CNS
Craniopharyngiomas:
Benign cystic tumors of children & adolescents
Develop in the suprasellar region  Hypopituitarism
Originate from remnants of Rathke’s pouch & contain squamous & columnar epithelium, calcifications are common.

62. CNS LYMPHOMA Primary CNS lymphomas Secondary CNS lymphomas
Account for ~1% of ICTs
MC CNS neoplasm in AIDS & other immunosuppressed patients often arise deep within the cerebral hemispheres & are commonly bilateral
Lymphoma cells exhibit an angiocentric distribution
Usually are B-cell lymphomas & many appear to be EBV-related.
Secondary CNS lymphomas
Lymphomas arising outside of the CNS rarely involve the brain parenchyma
May involve the meninges, intradural spinal nerve roots & epidural space

63. Phakomatosis (Neurocut. dysplasia)
Neurologic abnormalities + defects of skin or retina (ectodermal).
Neurofibromatosis (von Recklinghausen)
Tuberous Sclerosis
Sturge-Weber Sy (Encephalofacial Angiomatosis)
von Hippel-Lindau Disease
Neurocutaneous Melanosis

64. PHAKOMATOSES NEUROCUTANEOUS SYNDROMES (PHAKOMATOSES) AD
Hamartomas & Neoplasms
Esp. involving the nervous system & skin
Mutations in tumor suppressor genes
1. Neurofibromatosis Type 1 (NF1):
Neurofibromas, Neurofibro-sarcomas
Optic nerve Gliomas
Pigmented cutaneous macules (café au lait spots)
Pigmented nodules of iris (Lisch nodules)
2. Neurofibromatosis Type 2 (NF2):
Bilateral Schwannomas of CN VIII
Multiple meningiomas
Spinal cord Ependymomas

65. Seizures & mental retardation Extra CNS findings:
3. Tuberous Sclerosis
Hamartomas (“tubers”) in the cerebral cortex, Sub-Ependymal hamartomas (“candle drippings”)  Sub-Ependymal giant cell Astrocytomas
Seizures & mental retardation
Extra CNS findings:
Kidney (Angiomyolipoma), Heart (Rhabdomyoma MCC in kids, adult = mixomas ), skin (Angiofibroma)

66. 4. von Hippel-Lindau disease
Hemangioblastomas of the cerebellum, retina, brain stem & spinal cord
Cysts of liver, kidney & pancreas
 incidence of RCC, may be bilateral
~ 10% of Hemangioblastomas  polycythemia

67. Peripheral nerve tumors
Schwannoma
Schwann cells
Compress the nerve trunk
Encapsulated
Easily resectable without nerve damage
Microscopic:
Antony A and B fibers
Verocay bodies
Neurofibroma
Schwann cells, neurites, fibroblasts
Fusiform and involves nerve trunk
Not encapsulated
Not resectable without sacrificing nerve
Micro- Intermingled cells with wavy nuclei

68. Embryonal tumors (Primitive neuroectodermal tumors)
Neuroblastoma - cerebral hemispheres Neuroblastic (neuronal) differentiation
Medulloblastoma - cerebellum Neuronal and glial differentiation
Ependymoblastoma – ventricles Ependymal differentiation
Pineoblastoma- pineal region Retinoblastic differentiation
All commonly known as Primitive neuroectodermal tumor (PNET)

69. Histologic patterns: definitions
Whorls: onion-skinning pattern of tumor cells
Psammoma bodies: laminated calcium
Pseudopalisading: lining up of the tumor cells around a central necrotic area
Palisade: lining up of tumor cells around their own cytoplasmic processes. No necrosis.
Pseudorosette: tumor cells around blood vessels, cells equidistant from vessel walls.
Rosettes: tumor cells around central lumen or fibrillary area of cellular processes

70. Tumors of Nerve Roots and Peripheral Nerves
1. Schwannoma viii Cranial nerve (Acoustic sch.) Spinal roots, posterior Peripheral nerves
2. Neurofibroma Spinal Roots, rare Peripheral nerves
3. Malignant variants Malignant peripheral nerve sheath tumor (MPNT) Rare

71. Metastatic brain tumors
Most common brain tumor in adults.
Common primary sites: melanoma, lung, breast, GI tract, kidney.
Most are in cerebrum (MCA territory).
In gray-white junctions due to rich capillarity
Discrete, globoid, sharply demarcated tumors. Amenable to surgical resection.
Single or multiple.
Brain edema frequent.