cns tumors

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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