Cns Tumors

CENTRAL NERVOUS SYSTEM PART 2: CNS TUMORS VOLTAIRE C. YABUT,M.D. DPSP

CNS TUMORS intracranial Intraspinal

10-17 : 100,000 population 1-2: 100,000 population

Primary ½-¾ Metastatic – remainder 20% of childhood tumors 

Posterior 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 Classes  Gliomas  Neuronal tumors  Poorly differentiated neoplasms  Meningiomas

GLIOMAS Astrocytomas Oligodendrogliomas Ependymomas

GLIOMAS Astrocytomas Categories: Fibrillary Glioblastoma Pilocytic Pleomorphic Xanthoastrocytoma

GLIOMAS Astrocytomas Categories: Fibrillary (Diffuse) Astrocytoma 80% of adult primary brain tumors Cerebral hemisphere Cerebellum, brainstem, spinal cord Age: 40 – 60 Symptoms: seizures, headaches, focal neuro deficits

GLIOMAS Astrocytomas Categories: Fibrillary (Diffuse) Astrocytoma Morphology: well differentiated less differentiated

GLIOMAS Astrocytomas Categories: Fibrillary (Diffuse) Astrocytoma Morphology: poorly defined gray infiltrative tumor expand and distort the brain few cm’s to displace entire hemispheres firm or gelatinous cystic degeneration Gliomatosis cerebri - multiple regions of the brain infiltrated by neoplastic astrocytes

GLIOMAS Astrocytomas Categories: Fibrillary (Diffuse) Astrocytoma Microscopic: mild to mod inc in number of glial cell nuclei variable nuclear pleomorphism GFAP (+) astrocytic cell processes Anaplastic densely cellular Mitotically active Gemistocytic Neoplastic astrocytes Brightly eosinophilic cell body, stout processes

ASTROCYTOMA

GEMISTOCYTIC ASTROCYTOMA

GLIOMAS Astrocytomas Categories: Glioblastoma (Glioblastoma Multiforme) variable gross appearance Firm white to soft and yellow Well demarcated with infiltration beyond outer margin Microscopic: Similar to Anaplastic Necrosis – “pseudopalisading” Vascular or endothelial proliferation – “glomeruloid body”

GLIOBLASTOMA

GLIOMAS Astrocytomas WHO Grading Grade I/IV

Pilocytic

Grade II/IV Grade III/IV Grade IV/IV

Well differentiated astrocytomas Anaplastic Glioblastoma

GLIOMAS Astrocytomas Molecular Genetics Inactivation 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 rate Well-differentiated remain static, progress slowly 

Mean survival 5 years

Anaplastic present with rapid deterioration, very poor prognosis Current treatment (resection, radiotx, chemotx) 8 – 10 mos surivival < 10% alive after 2 yrs

GLIOMAS Astrocytomas Categories: Pilocytic Children and young adults  Cerebellum, floor and wall of 3rd ventricles, optic nerves, cerebral hemispheres 

GLIOMAS Astrocytomas Categories: Pilocytic Morphology often cystic, with mural nodule in the cyst wall If solid, well circumscribed, less frequently infiltrative

GLIOMAS Astrocytomas Categories: Pilocytic Microscopic:

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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

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Narrow infiltrative border

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PILOCYTIC ASTROCYTOMA

GLIOMAS Astrocytomas Categories: Pilocytic Clinical Grow very slowly Cerebellar tumors treated with resection Rarely have p53 mutations or other changes found in diffuse fibrillary

GLIOMAS Astrocytomas Categories: Pleomorphic Xanthoastrocytoma Relatively superficial Temporal lobe Children and young adults Long history of seizures

GLIOMAS Astrocytomas Categories:  Pleomorphic Xanthoastrocytoma Microscopic: neoplastic occ bizarre astrocytes nuclear atypia can be extreme and may suggest high grade astrocytoma abundant reticulin deposits relative circumscription chronic inflammatory cell infiltrates absence of necrosis and mitotic activity

GLIOMAS Astrocytomas Categories:  Pleomorphic Xanthoastrocytoma WHO grade II/IV 80% survival rate at 5 years

GLIOMAS Oligodendrogliomas 5 - 15%  Age: 40 – 50  Seizures for several years  Predilection for white matter, cerebral hemispheres 

GLIOMAS Oligodendrogliomas Morphology: well-circumscribed, gelatinous, gray masses often with cysts, focal hemorrhage and calcification Microscopic: Sheets of regular cells with spherical nuclei containing finely granular chromatin surrounded by clear halo of cytoplasm Delicate network of anastomosing capillaries Calcifications in 90% Low mitotic activity WHO grade II/IV Anaplastic 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 Ependymomas Arise next to ependyma-lined ventricular system  First 2 decades – 4th ventricle 

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5 – 10% of primary brain tumors

Adults – most common in spinal cord

GLIOMAS Ependymomas Morphology: In 4th ventricle, solid or papillary masses  Intraspinal, sharply demarcated Microscopic:  Cells with regular, round to oval nuclei with abundant granular chromatin  Dense fibrillary background  Rosettes, canals  Perivascular pseudorosettes  GFAP (+) 

EPENDYMOMA

GLIOMAS Ependymomas Morphology: Well-differentiated – WHO Grade II/IV Anaplastic 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 tumors Contain 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 neuroblastoma   

Rare, occur in children, highly aggressive Resemble peripheral neuroblastomas Homer Wright rosettes

Central neurocytoma   

Low grade neuronal tumors Lateral and third ventricles Resemble oligodendroglioma

POORLY DIFFERENTIATED NEOPLASMS Medulloblastoma Atypical Teratoid/Rhabdoid Tumor (AT/RT)

POORLY DIFFERENTIATED NEOPLASMS Medulloblastoma Predominantly in children Exclusively in the cerebellum Largely undifferentiated

Morphology Midline of cerebellum  Lateral in adults  Well circumscribed, gray and friable 

POORLY DIFFERENTIATED NEOPLASMS Medulloblastoma Microscopic:  Extremely cellular, sheets of anaplastic cells  Little cytoplasm  Hyperchromatic nuclei, elongated or crescent shaped  Mitosis abundant  (+) Ki-67 markers  Express neuronal (neurosecretory granules, Homer Wright rosettes) and glial (GFAP) phenotypes

MEDULLOBLASTOMA

POORLY DIFFERENTIATED NEOPLASMS Medulloblastoma Molecular 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 Lymphoma  Germ cell tumors  Pineal Parenchymal Tumors

OTHER PARENCHYMAL TUMORS Primary CNS Lymphoma      

2% 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 tumors Midline  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 Tumors Arise 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 TYPES Syncytial 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 Examples Paraneoplastic 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  Schwannoma  Neurofibroma  Malignant

Peripheral Nerve Sheath Tumor (MPNST, Malignant Schwannoma)

PERIPHERAL NERVE SHEATH TUMORS Schwannoma Neural 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 Schwannoma Microscopic: Mixture of two growth patterns Antoni A – pattern of growth of elongated cells with cytoplasmic processes arranged in fascicles in areas of moderate to high cellularity with little stromal matrix Antoni B – pattern of growth,less densely cellular with loose meshwork of cells along with microcysts and myxoid changes

SCHWANNOMA

PERIPHERAL NERVE SHEATH TUMORS Schwannoma Clinical 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 Neurofibroma Two types: Cutaneous neurofibroma (skin) or Solitary neurofibroma (peripheral nerve)  Dermis and subcutaneous fat  Well-delineated, unencapsulated  Spindle cells  Stroma highly collagenized Plexiform neurofibroma – occur only in NF1  Involve major nerve trunks, potential for malignant transformation  Frequently multiple  Loose myxoid background, low cellularity  Schwann cells, multipolar fibroblastic cells, inflammatory cells

PERIPHERAL NERVE SHEATH TUMORS Malignant Peripheral Nerve Sheath Tumor (MPNST, Malignant Schwannoma)  

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 

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 sclerosis  Von 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 disorder Bilateral VIII nerve schwannomas Multiple meningiomas Ependymomas of spinal cord Schwannosis Meningioangiomatosis Glial hamartia

FAMILIAL TUMOR SYNDROMES Tuberous sclerosis Autosomal-dominant Hamartomas  

Cortical tubers Subependymal hamartomas

Benign neoplasms involving the brain and other tissues Renal angiomyolipomas Retinal glial hamartomas Pulmonary lesions Cardiac rhabdomyomas Cysts in liver, kidneys, pancreas Cutaneous lesions e.g. Angiofibromas,Shagreen patches, ash-leaf patches, subungal fibromas

FAMILIAL TUMOR SYNDROMES Von Hippel Lindau Disease  

  

Autosomal-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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