cns tumors
TRANSCRIPT
CENTRAL NERVOUS SYSTEMPART 2: CNS TUMORS
VOLTAIRE C. YABUT,M.D. DPSP
CNS TUMORS
intracranial 10-17 : 100,000 populationIntraspinal 1-2: 100,000 population
Primary ½-¾Metastatic – remainder
20% of childhood tumorsPosterior fossa (70%)
Adults – cerebral hemispheres
CNS TUMORS
Distinction between benign and malignant less distinct
Limited ability to resect without compromise of neuro function
Anatomic site can have lethal consequences
Rarely metastasize outside CNS
subarachnoid space – brain and spinal cord seeding
CNS TUMORS
4 Major ClassesGliomasNeuronal tumorsPoorly differentiated neoplasmsMeningiomas
GLIOMAS
Astrocytomas
Oligodendrogliomas
Ependymomas
GLIOMAS
AstrocytomasCategories:
Fibrillary
Glioblastoma
Pilocytic
Pleomorphic Xanthoastrocytoma
GLIOMAS
AstrocytomasCategories:
Fibrillary (Diffuse) Astrocytoma80% of adult primary brain tumors
Cerebral hemisphere
Cerebellum, brainstem, spinal cord
Age: 40 – 60
Symptoms: seizures, headaches, focal neuro deficits
GLIOMAS
AstrocytomasCategories:
Fibrillary (Diffuse) AstrocytomaMorphology:
well differentiated
less differentiated
GLIOMAS
AstrocytomasCategories:
Fibrillary (Diffuse) AstrocytomaMorphology:
poorly definedgray infiltrative tumor expand and distort the
brainfew cm’s to displace entire hemispheresfirm or gelatinouscystic degeneration
Gliomatosis cerebri - multiple regions of the brain infiltrated by neoplastic astrocytes
GLIOMAS
AstrocytomasCategories:
Fibrillary (Diffuse) AstrocytomaMicroscopic:
mild to mod inc in number of glial cell nucleivariable nuclear pleomorphismGFAP (+) astrocytic cell processes
Anaplastic densely cellularMitotically active
GemistocyticNeoplastic astrocytesBrightly eosinophilic cell body, stout processes
ASTROCYTOMA
GEMISTOCYTIC ASTROCYTOMA
GLIOMAS
AstrocytomasCategories:
Glioblastoma (Glioblastoma Multiforme)variable gross appearanceFirm white to soft and yellowWell demarcated with infiltration beyond outer margin
Microscopic: Similar to AnaplasticNecrosis – “pseudopalisading”Vascular or endothelial proliferation – “glomeruloid body”
GLIOBLASTOMA
GLIOMAS
Astrocytomas
WHO Grading
Grade I/IV Pilocytic
Grade II/IV Well differentiated astrocytomas
Grade III/IV Anaplastic
Grade IV/IV Glioblastoma
GLIOMAS
Astrocytomas
Molecular GeneticsInactivation of p53
Overexpression of PDGF-A and its receptors
Transition to higher grade associated with additional disruption of tumor suppressor genes, the RB genes, p16/CDKNZA gene, putative tumor suppressor on chromosome 19q
GLIOMAS
Astrocytomas
Clinical Features:Presenting symptoms depend in part on location of tumor and growth rateWell-differentiated remain static, progress slowly
Mean survival 5 years
Anaplastic present with rapid deterioration, very poor prognosisCurrent treatment (resection, radiotx, chemotx)
8 – 10 mos surivival< 10% alive after 2 yrs
GLIOMAS
AstrocytomasCategories:
PilocyticChildren and young adults
Cerebellum, floor and wall of 3rd ventricles, optic nerves, cerebral hemispheres
GLIOMAS
AstrocytomasCategories:
Pilocytic
Morphologyoften cystic, with mural nodule in the cyst wall
If solid, well circumscribed, less frequently infiltrative
GLIOMAS
AstrocytomasCategories:
Pilocytic
Microscopic:Bipolar cells with long thin “hairlike” processes that are GFAP (+)
Rosenthal fibers
Eosinophilic granular bodies
Microcysts
Increase no. of blood vessels
Necrosis and mitosis uncommon
Narrow infiltrative border
PILOCYTIC ASTROCYTOMA
GLIOMAS
AstrocytomasCategories:
Pilocytic
ClinicalGrow very slowly
Cerebellar tumors treated with resection
Rarely have p53 mutations or other changes found in diffuse fibrillary
GLIOMAS
AstrocytomasCategories:
Pleomorphic XanthoastrocytomaRelatively superficial
Temporal lobe
Children and young adults
Long history of seizures
GLIOMAS
AstrocytomasCategories: Pleomorphic XanthoastrocytomaMicroscopic:
neoplastic occ bizarre astrocytesnuclear atypia can be extreme and may suggest high grade astrocytomaabundant reticulin depositsrelative circumscriptionchronic inflammatory cell infiltratesabsence of necrosis and mitotic activity
GLIOMAS
AstrocytomasCategories: Pleomorphic Xanthoastrocytoma
WHO grade II/IV
80% survival rate at 5 years
GLIOMAS
Oligodendrogliomas5 - 15%
Age: 40 – 50
Seizures for several years
Predilection for white matter, cerebral hemispheres
GLIOMAS
OligodendrogliomasMorphology:
well-circumscribed, gelatinous, gray massesoften with cysts, focal hemorrhage and calcification
Microscopic:Sheets of regular cells with spherical nuclei containing finely granular chromatin surrounded by clear halo of cytoplasmDelicate network of anastomosing capillariesCalcifications in 90%Low mitotic activityWHO grade II/IVAnaplastic oligodendrogliomas – increased cell density, nuclear anaplasia, inc mitotic activity, necrosis
OLIGODENDROGLIOMA
GLIOMAS
Oligodendrogliomas
Molecular genetics:loss of heterozygosity for chromosomes 1p and 19q
If without other alterations consistent and long lasting response to chemotherapy and radiation
Clinical Features:
Better prognosis than astrocytomas
Ave 5 – 10 years survival
GLIOMAS
EpendymomasArise next to ependyma-lined ventricular system
First 2 decades – 4th ventricle 5 – 10% of primary brain tumors
Adults – most common in spinal cord
GLIOMAS
Ependymomas
Morphology:In 4th ventricle, solid or papillary massesIntraspinal, sharply demarcated
Microscopic:Cells with regular, round to oval nuclei with abundant granular chromatinDense fibrillary backgroundRosettes, canalsPerivascular pseudorosettesGFAP (+)
EPENDYMOMA
GLIOMAS
Ependymomas
Morphology:Well-differentiated – WHO Grade II/IVAnaplastic ependymomas – WHO Grade III/IV
Myxopapillary ependymomas – occur in filum terminale of spinal cord
Papillary elements in myxoid background
GLIOMAS
Ependymomas
Molecular genetics: Spinal ependymomas associated with Neurofibromatosis 2
and NF2 gene on chromosome 22
Clinical features: Posterior fossa ependymomas manifest with hydrocephalus
sec to obstruction of 4th ventricle Prognosis is poor CSF dissemination is common
GLIOMAS
Ependymomas
Other tumors associated with other cell type that forms the venticular system:
Subependymomas Choroid plexus papillomas Colloid cyst of the third ventricle
NEURONAL TUMORS
Ganglion cell tumorsContain ganglion cells
Gangliocytoma – entire population of lesion
Ganglioglioma – admixture with glial neoplasm
Slow growing
Glial components occ become anaplastic and progress rapidly
Present with seizure disorder
WHO grade I-II/IV
NEURONAL TUMORS
OTHER TUMORS WITH GLIAL AND NEURONAL COMPONENTS
Dysembryoplastic neuroepithelial tumor (DNT)Low grade tumor of childhood
Seizure disorder
Slow growth
Good prognosis
NEURONAL TUMORS
TUMORS WITH ONLY NEURONAL ELEMENTS
Cerebral neuroblastomaRare, occur in children, highly aggressive
Resemble peripheral neuroblastomas
Homer Wright rosettes
Central neurocytomaLow grade neuronal tumors
Lateral and third ventricles
Resemble oligodendroglioma
POORLY DIFFERENTIATED NEOPLASMS
Medulloblastoma
Atypical Teratoid/Rhabdoid Tumor (AT/RT)
POORLY DIFFERENTIATED NEOPLASMS
MedulloblastomaPredominantly in children
Exclusively in the cerebellum
Largely undifferentiated
MorphologyMidline of cerebellum
Lateral in adults
Well circumscribed, gray and friable
POORLY DIFFERENTIATED NEOPLASMS
MedulloblastomaMicroscopic:
Extremely cellular, sheets of anaplastic cellsLittle cytoplasmHyperchromatic nuclei, elongated or crescent shapedMitosis abundant(+) Ki-67 markersExpress neuronal (neurosecretory granules, Homer Wright rosettes) and glial (GFAP) phenotypes
MEDULLOBLASTOMA
POORLY DIFFERENTIATED NEOPLASMS
MedulloblastomaMolecular Genetics:
Loss of short arm of chromosome 17
Clinical features: Highly malignant Prognosis dismal in untreated patients radiosensitive Better survival following complete resection 75% 5-year survival rate for total excision and radiation
POORLY DIFFERENTIATED NEOPLASMS
Atypical Teratoid/Rhabdoid Tumor (AT/RT)Highly malignant tumor of young children
Posterior fossa and supratentorial compartments
“rhabdoid cells” resembling those of a rhabdomyosarcoma
90% - Loss of genetic material from chromosome 22
Very young patients – before age 5
Live less than a year after diagnosis
OTHER PARENCHYMAL TUMORS
Primary CNS LymphomaGerm cell tumorsPineal Parenchymal Tumors
OTHER PARENCHYMAL TUMORS
Primary CNS Lymphoma2% of extranodal lymphomas
1% of intracranial tumors
Most common CNS neoplasm in immunosuppressed (AIDS)
Occur in multiple sites WITHIN the brain parenchyma
Majority B-cell origin
Poor response to chemotherapy
OTHER PARENCHYMAL TUMORS
Germ cell tumorsMidline
Most common in pineal and suprasellar regions
0.2% to 1% of brain tumors among Europeans
10% of brain tumors in Japanese
90% occur during first two decades
More common are teratomas
OTHER PARENCHYMAL TUMORS
Pineal Parenchymal TumorsArise from pineocytes
Pineocytomas – well-differentiated
Pineoblastomas – high grade tumors
MENINGIOMAS
Benign tumors of adults
Attached to dura
Arise from meningothelial cell of arachnoid
External surface of brain as within the ventricular system
MENINGIOMAS
Morphology:Rounded, bosselated, polypoid masses
Well-defined dural base that compress underlying brain but easily separated from it
May extend to overlying bone
Encapsulated with thin fibrous tissue
“en plaque” variant – spreads in sheetlike fashion along the surface of dura
Most are WHO grade I/IV
MENINGIOMAS
TYPESSyncytial
Fibroblastic
Transitional
Psammomatous
Secretory
Microcystic
Atypical meningiomas – mitotic index of 4 or more mitosis/10 hpf, 3 or more atypical features (inc cellularity, small cells with high N:C ratio, prominent nucleoli, patternless growth, necrosis)
Anaplastic (malignant)Meningioma
WHO grade III/IV
Mitosis >20/10 hpf
MENINGIOMA
MENINGIOMAS
Clinical Features:
Slow growing
Vague nonlocalizing symptoms or focal findings referable to compression of underlying brain
Common sites: parasagittal aspect of brain convexity, dura over latera convexity, wing of sphenoid, olfactory groove, sella turcica, foramen magnum
Usually solitary
Multiple tumors assoc with acoustic neuroma or glial tumors suggest neurofibromatosis type 2
METASTATIC TUMORS
Mostly carcinomas
Common primary sites (80%): lung, breast, skin (melanoma), kidney, GIT
Meninges are frequently involved
Present clinically as mass lesions, may occasionally be the first manifestation of cancer
Grossly form sharply demarcated masses, at gray matter-white matter junction, surrounded by zone of edema
BRAIN METASTASES
PARANEOPLASTIC SYNDROMES
Involve the peripheral and central nervous systems
Most common in small cell carcinoma of the lung
ExamplesParaneoplastic cerebellar degeneration
Limbic encephalitis
Subacute sensory neuropathy
Eye movement disorders, opsoclonus
Retinal degeneration
Stiff-man syndrome
Lambert-Eaton myasthenic syndrome
PERIPHERAL NERVE SHEATH TUMORS
Arise from Schwann cells, perineurial cells, fibroblasts
Express S-100 antigen, melanocytic differentiation
PERIPHERAL NERVE SHEATH TUMORS
SchwannomaNeurofibromaMalignant Peripheral Nerve Sheath Tumor
(MPNST, Malignant Schwannoma)
PERIPHERAL NERVE SHEATH TUMORS
SchwannomaNeural crest-derived Schwann cell
Assoc with Neurofibromatosis type 2
Well circumscribed, encapsulated masses attached to nerve but can be separated from it
Firm, gray masses
Cystic and xanthomatous change
PERIPHERAL NERVE SHEATH TUMORS
SchwannomaMicroscopic:
Mixture of two growth patternsAntoni A – pattern of growth of elongated cells with cytoplasmic processes arranged in fascicles in areas of moderate to high cellularity with little stromal matrixAntoni B – pattern of growth,less densely cellular with loose meshwork of cells along with microcysts and myxoid changes
SCHWANNOMA
PERIPHERAL NERVE SHEATH TUMORS
SchwannomaClinical Features:
Most common in cerebellopontine angle, attached to vestibular branch of 8th cranial nerve
Tinnitus and hearing loss
“Acoustic neuroma” (vestibular schwannoma)
PERIPHERAL NERVE SHEATH TUMORS
NeurofibromaTwo types:
Cutaneous neurofibroma (skin) or Solitary neurofibroma (peripheral nerve)
Dermis and subcutaneous fatWell-delineated, unencapsulatedSpindle cellsStroma highly collagenized
Plexiform neurofibroma – occur only in NF1Involve major nerve trunks, potential for malignant transformationFrequently multipleLoose myxoid background, low cellularitySchwann cells, multipolar fibroblastic cells, inflammatory cells
PERIPHERAL NERVE SHEATH TUMORS
Malignant Peripheral Nerve Sheath Tumor (MPNST, Malignant Schwannoma)
Highly malignant sarcoma
Locally invasive, frequently leading to multiple recurrences and metastasis
Arise de novo or from transformation of plexiform neurofibroma
Assoc with NF type 1
“Triton tumor” – with rhabdomyoblastic differentiation
FAMILIAL TUMOR SYNDROMES
Neurofibromatosis Type 1 (NF1)Neurofibromatosis Type 2 (NF2)Tuberous sclerosisVon Hippel Lindau Disease
FAMILIAL TUMOR SYNDROMES
Neurofibromatosis Type 1 (NF1)Autosomal-dominant disorder
Neurofibromas (plexiform and solitary)
Gliomas of optic nerve
Lisch nodules
Café au lait spots
Propensity to undergo malignant degeneration
FAMILIAL TUMOR SYNDROMES
Neurofibromatosis Type 2 (NF2)Autosomal-dominant disorderBilateral VIII nerve schwannomasMultiple meningiomasEpendymomas of spinal cordSchwannosisMeningioangiomatosisGlial hamartia
FAMILIAL TUMOR SYNDROMES
Tuberous sclerosisAutosomal-dominantHamartomas
Cortical tubersSubependymal hamartomas
Benign neoplasms involving the brain and other tissuesRenal angiomyolipomasRetinal glial hamartomasPulmonary lesionsCardiac rhabdomyomasCysts in liver, kidneys, pancreasCutaneous lesions e.g. Angiofibromas,Shagreen patches, ash-leaf patches, subungal fibromas
FAMILIAL TUMOR SYNDROMES
Von Hippel Lindau DiseaseAutosomal-dominant
Capillary hemangioblastomas within the cerebellar hemispheres, retina, less commonly in brain stem and spinal cord
Cysts in pancreas, liver, kidneys
Renal cell carcinoma
Associated with polycythemia in 10% of hemangioblastomas
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