Central Nervous System 9. Tumors

1. Central Nervous System9. 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. • Primitivecells: 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 adults70% 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

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 http://www.suck.uk.com/photos/FireBucket1.jpg

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

14. Pilocytic Astrocytoma

15. Rosenthal fibers

16. Gr. II. Astrocytoma

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

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

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

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. 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

45. Meningioma

46. Meningothelial whorls

47. Meningioma Syncytial Psammomatous Epithelial Membrane Antigen

48. NERVE SHEATH TUMORS 1. Schwannomas: • 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