Cns tumors


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Cns tumors

  1. 1. CNS
  2. 2. Pattern of CNS Diseases Congenital Malformation &Perinatal Brain Injury Trauma Cerebrovascular diseases Infections Tumors Degenerative Diseases
  3. 3. CNS Tumors Learning objectives To discuss Benign and malignant tumours of the CNS and Familial tumour syndromes in terms of genetics, clinical features, associated lesions, and complications, clinical course Learning outcomes At the end of the lecture the student will be able to  Classify the tumours of the brain  Discuss types, age and sex predominance, incidence, clinical presentation, morphology and clinical course-prognosis of common brain tumours  Discuss the common familial tumour syndromes associated with brain tumours
  4. 4. CNS Tumors  Tumors of the CNS are a larger proportion of cancers of childhood  CNS tumors in childhood differ from those in adults both in histologic subtype and location  In childhood tumors are likely to arise in the posterior fossa  In adults - supratentorial
  5. 5. CNS Normal Neurons Glia Astrocytes, Oligodendrocytes, Ependymal Cells, Microglia
  6. 6. CNS Tumors Tumors of the nervous system may arise from Cells of the coverings Cells intrinsic to the brain Other cell populations within the skull Metastases (spread from elsewhere in the body )
  8. 8. CLASSIFICATION TUMOURS OF THE GLIAL TISSUE – (GLIOMAS) Astrocytoma Oligodendroglioma Ependymoma TUMOURS OF NEURONS Gangliocytoma Neuroblastoma Ganglioneurocytoma Gliomatosis cerebri Cerebral neuroblastoma Central neurocytoma MIXED TUMOURS WITH TUMOURS OF GLIAL & NEURONAL THE COMPONENTS MENINGES Ganglioglioma Meningioma Dysembryoplastic Neuroepithelial tumour PERIPHERAL NERVE (DNT) SHEATH POORLY DIFFERENTIATED AND TUMOURS EMBRYONAL Schwannoma TUMOURS Neurofibroma Medulloblastoma Malignant Atypical nerve sheath teratoid/rhabdoid tumourtumour MPNST Medulloepithelioma (Malignant Dysplastic Schwannoma Gangliocytoma of the ) cerebellum (Lhermitte – Duclos disease) Polar spongioblastoma Miscellaneous TUMOURS Hemangioblastoma Craniopharyngiom a Pituitary tumours Mesenchymal tumours METASTATIC TUMOURS PRIMARY CNS LYMPHOMA
  9. 9. Tumors of the nervous system have unique characteristics Histologic distinction between benign and malignant lesions The pattern of growth The anatomic site of the neoplasm The pattern of spread
  10. 10. CNS-Tumours • Incidence of CNS tumors ranges from 10 to 17 per 100,000 • Half to three-quarters are primary tumors, rest are metastatic • 70% of childhood CNS tumors arise in the posterior fossa • In adults tumours arise within the cerebral hemispheres above the tentorium. • Distinction between benign & malignant lesions is less evident
  11. 11. CNS-Tumours • Ability to surgically resect infiltrating glial neoplasms without compromising neurologic function is limited • Anatomic site of the neoplasm can have lethal consequences irrespective of histologic classification
  12. 12. CNS-Tumours • Pattern of spread of primary CNS neoplasms differs -Even the most highly malignant Gliomas rarely metastasize outside the CNS • The subarachnoid space provides a pathway for spread - occur in highly anaplastic as well as in well-differentiated neoplasms that extend into the CSF pathways.
  13. 13. The criteria used to determine malignancy 1. Even highly malignant intracranial neoplasms generally do not metastasize 2. Destructive infiltration of the brain is the major criterion of malignancy for intracranial neoplasms. Neurologic deficits resulting from destructive invasion by malignant neoplasms are irreversible. Benign neoplasms, on the other hand, cause neurologic deficits due to compression; these often reverse when the neoplasm is removed
  14. 14. The criteria used to determine malignancy 3. The rate of growth of neoplasms also correlates well with malignant behavior . 4. Recurrence after treatment is almost invariable with malignant intracranial neoplasms. 5. The term benign for any intracranial neoplasm is probably implies rather that they are slow growing and do not infiltrate the brain substance.
  15. 15. neurological deficit hydrocephalous Obstruction to CSF flow seizures compression irritation Intracranial neoplasm space occupying Raised ICP Patho- physiological affects of intracranial neoplasms destruction oedema neurological deficit Raised ICP
  16. 16. TUMOURS OF THE GLIAL TISSUE – (GLIOMAS)  Astrocytoma  Oligodendroglioma  Ependymoma Astrocytoma  Fibrillary astrocytoma  Glioblastoma  Pilocytic astrocytoma, and  Pleomorphic xanthoastrocytoma
  17. 17. WHO Grading system for astrocytomas Variables such as nuclear atypia/mitosis/ endothelial proliferation & necrosis are scored as Grade 1 if none = pilocystic astrocytoma Grade 2 if any one = diffuse astrocytoma Grade 3 if any two= anaplastic astrocytoma Grade 4 if three or all = glioblastoma multiforme
  18. 18. Fibrillary (Diffuse) Astrocytomas (grade II/IV) • Most common adult CNS tumour • 80% of adult primary brain tumors • Location: cerebral hemispheres, also occur in the cerebellum, brainstem, or spinal cord • Fourth through sixth decades • most common presenting signs and symptoms are seizures, headaches, and focal neurologic deficits related to the anatomic site of involvement
  19. 19. Fibrillary (Diffuse) Astrocytomas (grade II/IV) Gross Poorly defined gray infiltrative tumor that expands and distorts the brain C/S of the tumor - firm or soft and gelatinous; cystic degeneration few centimeters - enormous lesions
  20. 20. Low-grade astrocytoma is seen as expanded white matter of the left cerebral hemisphere thickened corpus callosum and fornices
  21. 21. Fibrillary (Diffuse) Astrocytomas (grade II/IV) MICRO Mild to moderate increase in the number of glial cell nuclei Tumor cells - stellate, spindle-shaped with fiber like processes Intervening feltwork of fine, GFAP-positive astrocytic cell processes that give the background a fibrillary appearance
  22. 22. Other types • Anaplastic astrocytomas (Grade III/IV) • Gemistocytic astrocytoma :predominant neoplastic astrocyte shows a brightly eosinophilic cell body from which emanate abundant, stout processes
  23. 23. Glioblastoma (grade IV/IV) • Older age group Morphology • show variation in the gross appearance : Some areas are firm and white, others are soft and yellow (the result of tissue necrosis), and yet others show regions of cystic degeneration and hemorrhage • well demarcated from the surrounding brain tissue, but infiltration beyond the outer margins is always present • Gliomatosis cerebri- multiple regions of the brain are infiltrated by neoplastic astrocytes
  24. 24. Glioblastoma multiforme GROSS appearing as a necrotic, hemorrhagic, infiltrating mass variation in the gross appearance of the tumor from region to region is Characteristic Some areas are firm and white,others are soft and yellow (the result of tissue necrosis), and still others show regions of cystic degeneration and hemorrhage
  25. 25. Glioblastoma- morphology MICRO: •Densely cellular with nuclear pleomorphism •Necrosis in a serpentine pattern •Tumour cells crowded along the edges of necrosis referred to as pseudopalisading • When vascular cell proliferation is extreme, the tuft forms a ball-like structure, the glomeruloid body
  26. 26. Nuclearpalisading Serpentine necrosis
  27. 27. Glioblastoma multiforme
  28. 28. Pilocytic Astrocytoma (Grade 1) • Have relatively benign behavior • They typically occur in children and young adults • Located in the cerebellum but may also appear in the floor and walls of the third ventricle, the optic nerves, and occasionally the cerebral hemispheres
  29. 29. Pilocytic Astrocytoma (Grade 1) Grossly well circumscribed cystic, with a mural nodule in the wall of the cyst cystic astrocytoma of the cerebellum in a child
  30. 30. Pilocytic Astrocytoma (Grade 1) The tumor is composed of bipolar cells with long, thin “hairlike”processes that are GFAP-positive Rosenthal fibers,eosinophilic granular bodies, and microcysts are often present; necrosis and mitoses are rare
  31. 31. Oligodendrogliomas (Grade II/IV) • Constitute 5% to 15% of gliomas ,Fourth and fifth decades. • Cerebral hemispheres, with a predilection for white matter. Morphology • Grossly they are well-circumscribed, gelatinous, gray masses, often with cysts, focal hemorrhage, and calcification • Microscopically the tumors are composed of sheets of regular cells with spherical nuclei containing finely granular chromatin surrounded by a clear halo of cytoplasm (fried egg appearance) • The tumor typically contains a delicate network of anatomizing capillaries(chickenwire) • Calcification seen in 90% of cases
  32. 32. Oligodendrogliomas (Grade II/IV) fried egg appearance chickenwire
  33. 33. Oligodendrogliomas (Grade II/IV) Calcification fried egg appearance chickenwire
  34. 34. Ependymomas- (Grade II/IV) •Arise next to the ependyma - lined ventricular system •First two decades of life - - they typically occur near the fourth ventricle •In adults, the spinal cord is their most common location; tumors in this site are frequent in the setting of neurofibromatosis type 2 Gross: • Solid/papillary masses extending from the floor of the ventricle • Variant :Myxopapillary ependymomas occurs in the filum terminale of the spinal cord
  35. 35. ependymoma arising from the ependymal lining of the fourth ventricle above the brainstem and bulging toward the cerebellum CT scan horizontal section of the brain reveals a large ependymoma of the fourth ventricle
  36. 36. Ependymomas- (Grade II/IV) Cells with regular, round to oval nuclei with abundant granular chromatin in a dense fibrillary background Tumor cells may form gland-like round or elongated structures (rosettes, canals) that resemble the embryologic ependymal canal
  37. 37. • Subependymomas are solid, sometimes calcified, slow-growing nodules attached to the ventricular lining and protruding into the ventricle • Choroid plexus papillomas can occur anywhere along the choroid plexus and are most common in children (lateral ventricles). In adults, they are found in the fourth ventricle. • There are rare cases of choroid plexus carcinoma
  38. 38. NEURONAL TUMORS TUMOURS OF NEURONS       Gangliocytoma Neuroblastoma Ganglioneurocytoma Gliomatosis cerebri Cerebral neuroblastoma Central neurocytoma
  39. 39. NEURONAL TUMORS • Central neurocytoma: low-grade neoplasm found within and adjacent to the ventricular system characterized by evenly spaced, round, uniform nuclei and often islands of neuropil • Gangliogliomas are tumors with a mixture of glial elements, usually a low-grade astrocytoma, and matureappearing neurons • Dysembryoplastic neuroepithelial tumor is a distinctive, low-grade childhood tumor
  40. 40. Embryonal (Primitive) Neoplasms Medulloblastoma •neuroectodermal origin, retain cellular features of primitive, undifferentiated cells. •accounts for 20% of the brain tumors in children •Location :exclusively in the cerebellum. Morphology •Grossly : well circumscribed, gray, and friable •Microscopically : highly cellular and are composed of diffuse masses of small, undifferentiated oval or round cells, like a lymphoma Rosette formation- are groups of tumor cells arranged in a circle around a fibrillary center
  41. 41. Embryonal (Primitive) Neoplasms Medulloblastoma Medulloblastoma Sagittal section of brain showing medulloblastoma destroying the superior midline cerebellum Medulloblastoma small round blue cells with Rosette formation
  42. 42. Medulloblastoma cerebellum fourth ventricle posterior fossa mass brainstem small round blue cells with Rosette formation
  43. 43. MENINGIOMAS (mostly Grade I/IV) • predominantly benign tumors of adults, usually attached to the dura • That arise from the meningothelial cell of the arachnoid. Common sites of involvement • Parasagittal aspect of the brain convexity • Dura over the lateral convexity • Wing of the sphenoid • Olfactory groove, sella turcica • Foramen magnum • Ectopic meningiomas
  44. 44. MENINGIOMAS (mostly Grade I/IV) Macro: • usually rounded masses, bosselated or polypoid appearance • Extension into the overlying bone may be present • The surface of the mass is usually encapsulated • Usually, they displace brain tissue without invading it • Some meningiomas grow flat on the surface of the brain – en plaque variant
  45. 45. Morphology-Micro - types • Syncytial appropriately named for the whorled clusters of cells that sit in tight groups without visible cell membranes • Fibroblastic with elongated cells and abundant collagen deposition between them • Psammomatous with numerous psammoma bodies, apparently forming from calcification of the syncytial nests of meningothelial cells • Secretory with PAS-positive intracytoplasmic droplets and intracellular lumens by electron microscopy • Transitional which share features of the syncytial and fibroblastic types • Microcystic with a loose, spongy appearance • Atypical, Anaplastic ,Papillary and Rhabdoid
  46. 46. Morphology whorled nests of meningothelial cells
  47. 47. Morphology numerous psammoma bodies whorled nests of meningothelial cells
  48. 48. METASTATIC TUMORS • Metastatic lesions, mostly carcinomas, account for approximately a quarter to half of intracranial tumors • The five most common primary sites are lung, breast, skin (melanoma), kidney, and gastrointestinal tract, accounting for about 80% of all metastases. • The Meninges are also a frequent site of involvement by metastatic disease. • Intraparenchymal metastases form sharply demarcated masses, often at the gray matterwhite matter junction • The boundary between tumor and brain parenchyma is well defined microscopically as well; melanoma is one tumor that does not always follow this rule
  49. 49. METASTATIC TUMORS Metastatic melanoma multicentricity and well-demarcated margins The dark pigment in the tumor nodules in this case is characteristic of most malignant melanomas Carcinomas that metastasize to the brain parenchyma reach the brain via arterial channels most commonly encountered in the territory of the middle cerebral artery, often implant at graywhite junctions, typically well circumscribed
  50. 50. PERIPHERAL NERVE SHEATH TUMORS arise from cells of the peripheral nerve, including  Schwann cells  perineurial cells  fibroblasts Many express Schwann cell characteristics, including the presence of S-100 antigen MPNST -Malignant Peripheral Nerve Sheath Tumor (MPNST, Malignant Schwannoma) :Are highly malignant sarcomas that are locally invasive
  51. 51. Schwannoma • These benign tumors arise from the neural crestderived Schwann cell and are associated with neurofibromatosis type 2. • common location - cerebellopontine angle usually attached to vestibular branch of the eighth nerve • Elsewhere within the dura, sensory nerves are preferentially involved, including branches of the trigeminal nerve and dorsal roots • When extradural, most commonly found in association with large nerve trunks, where motor and sensory modalities are intermixed
  52. 52. Site: in the acoustic (eighth cranial) nerve at the cerebellopontine angle Patients may present with hearing loss Schwannomas extra-axial, circumscribed and encapsulated and range from small and solid to large, irregular, cystic, and hemorrhagic tumors
  53. 53. Micro : Two growth patterns Antoni A pattern elongated cells with cytoplasmic processes arranged in fascicles Regions of nuclear palisading The "nuclear-free zones" are termed Verocay bodies Antoni B Pattern The tumor is less densely cellular With a loose meshwork of cells- looser, myxoid regions
  54. 54. Neurofibromas Two forms cutaneous neurofibroma • The most common form occurs in the skin (cutaneous neurofibroma) or in peripheral nerve (solitary neurofibroma). • These arise sporadically or in association with neurofibromatosis type 1 • The risk of malignant transformation from these tumors is extremely small, and cosmetic concerns are their major morbidity
  55. 55. Neurofibromas Plexiform neurofibroma •occur only in patients with neurofibromatosis type 1 •frequently multiple and the nerve is irregularly expanded •difficulty in surgical removal of these plexiform tumors when they involve major nerve trunks •have a significant potential for malignant transformation
  56. 56. Morphology Gross: • Present in the dermis and subcutaneous fat or arise anywhere along a nerve • not encapsulated On microscopic examination - a loose, myxoid background with a low cellularity A number of cell phenotypes are present - Schwann cells, Inflammatory cells, Larger multipolar fibroblastic cells - areas of collagen bundles, which have a “shredded carrot" appearance
  57. 57. OTHER TUMORS • Atypical Teratoid / Rhabdoid Tumor - highly malignant tumor of young child • Primary CNS lymphoma (PCNSL) It is the most common CNS neoplasm in immunosuppressed ,are high grade Non-Hodgkin's B-cell ,Poor prognosis • Hemangioblastoma :Arises in the cerebellum Important component of VHL • Germ Cell Tumors :Occur along the midline, most commonly in the pineal and the suprasellar regions. Teratomas are common Pineal Parenchymal Tumors – well-differentiated lesions (pineocytomas) high-grade tumors (pineoblastomas)
  58. 58. FAMILIAL TUMOR SYNDROMES • These are a group of inherited diseases characterized by the development of hamartomas and neoplasms throughout the body with particular involvement of the nervous system • Many of the disorders are inherited in an autosomal-dominant pattern and have been linked to tumor-suppressor genes
  59. 59. FAMILIAL TUMOR SYNDROMES 1)Neurofibromatosis Type 1 (NF1) Autosomal-dominant characterized by Neurofibromas Gliomas of the optic nerve Pigmented nodules of the iris (Lisch nodules) Cutaneous hyperpigmented macules (café au lait spots) 2)Neurofibromatosis Type 2 (NF2) Autosomal-dominant disorder Commonly bilateral VIII nerve schwannomas and multiple meningiomas & Gliomas
  60. 60. Neurofibromatosis an inherited disorder Affected individual develop multiple benign neurofibromas that arise within or are attached to the nerve trunks in the skin On the right side of the neck and shoulder of this patient, extensive subcutaneous neurofibromas have formed pendulous masses called plexiform neurofibromas an increased risk of developing neurofibrosarcomas This condition arises from mutations in the NF1 tumor suppressor gene
  61. 61. . This patient shows another typical feature of neurofibromatosis: cafe' au lait spots. These spots on the skin (macules) have light brown pigmentation. Neurofibromas are not seen well in this picture.
  62. 62. FAMILIAL TUMOR SYNDROMES 3)Tuberous Sclerosis • Autosomal-dominant syndrome • Characterized by hamartomas and benign neoplasms involving the brain and other tissues. • other lesions include renal angiomyolipomas, retinal glial hamartomas, and cardiac rhabdomyomas • Cysts found in the liver, kidneys, and pancreas • Cutaneous lesions include angiofibromas, leathery thickenings in localized patches (shagreen patches), hypopigmented areas (ashleaf patches), and subungual fibromas
  63. 63. 4) Von Hippel-Lindau Disease • Autosomal-dominant disease • Individuals develop capillary hemangioblastomas within the cerebellum ,retina, & the brainstem and spinal cord. • cysts involving the pancreas, liver, and kidneys are present • may develop renal cell carcinoma of the kidney . 5) Others • Turcot syndrome (APC)– Medulloblastoma • Gorlin’s syndrome (PTCH)- Medulloblastoma • MEN syndrome – Schwannomas • Retinoblastoma (RB1) – Retinoblastoma,pineoblastoma • Li FRAUMENI –(P53) Malignant glioma