CNS PART 2: CNS TUMORS CNS PART 2: CNS TUMORS 16 February 2008 16 February 2008 CNS TUMORS CNS TUMORS CNS TUMORS CNS TUMORS • • •
• intracranialintracranialintracranialintracranial 10-17 : 100,000 population10-17 : 100,000 population10-17 : 100,000 population10-17 : 100,000 population •
•
•
• IntraspinalIntraspinalIntraspinalIntraspinal 1-2: 100,000 population1-2: 100,000 population1-2: 100,000 population1-2: 100,000 population •
•
•
• Primary ½-¾Primary ½-¾Primary ½-¾Primary ½-¾ •
•
•
• Metastatic – remainderMetastatic – remainderMetastatic – remainderMetastatic – remainder •
•
•
• 20% of childhood tumors20% of childhood tumors20% of childhood tumors20% of childhood tumors •
•
•
• Posterior fossa (70%)Posterior fossa (70%)Posterior fossa (70%)Posterior fossa (70%) •
•
•
• Adults – cerebral hemispheresAdults – cerebral hemispheresAdults – cerebral hemispheresAdults – cerebral hemispheres •
•
•
• Distinction between benign and malignant less distinctDistinction between benign and malignant less distinctDistinction between benign and malignant less distinctDistinction between benign and malignant less distinct •
•
•
• Limited ability to resect without compromise of neuroLimited ability to resect without compromise of neuroLimited ability to resect without compromise of neuroLimited ability to resect without compromise of neuro function function function function • • •
• Anatomic site can have lethal Anatomic site can have lethal consequencesAnatomic site can have lethal Anatomic site can have lethal consequencesconsequencesconsequences •
•
•
• Rarely metastasize outside CNSRarely metastasize outside CNSRarely metastasize outside CNSRarely metastasize outside CNS •
• subarachnoid spacesubarachnoid spacesubarachnoid spacesubarachnoid space– brain and spinal cord– brain and spinal cord– brain and spinal cord– brain and spinal cord seeding seeding seeding seeding 4 MAJOR CLASSES 4 MAJOR CLASSES 4 MAJOR CLASSES 4 MAJOR CLASSES
GliomasGliomasGliomasGliomas
Neuronal tumorsNeuronal tumorsNeuronal tumorsNeuronal tumors
Poorly differentiated neoplasmsPoorly differentiated neoplasmsPoorly differentiated neoplasmsPoorly differentiated neoplasms
MeningiomasMeningiomasMeningiomasMeningiomas GLIOMAS GLIOMAS GLIOMAS GLIOMAS • • AstrocytomasAstrocytomas • • OligodendrogliomasOligodendrogliomas • • EpendymomasEpendymomas A.
A. ASASTRTROCOCYTYTOMOMASAS Categories: Categories: • • FibrillaryFibrillary • • GlioblastomaGlioblastoma • • PilocyticPilocytic •
• Pleomorphic XanthoastrocytomaPleomorphic Xanthoastrocytoma 1.
1. FibFibrilrillarlary (Diy (Diffuffuse) Ase) Astrstrocyocytomtomaa •
• 80% of adult primary brain tumors80% of adult primary brain tumors •
• Cerebral hemisphereCerebral hemisphere •
• Cerebellum, brainstem, spinal cordCerebellum, brainstem, spinal cord •
• Age: 40 – 60Age: 40 – 60 •
• Symptoms: seizures, headaches, focal neuro deficitsSymptoms: seizures, headaches, focal neuro deficits Morphology:
Morphology: •
• well differentiatedwell differentiated •
• less differentiatedless differentiated •
• poorly definedpoorly defined •
• gray infiltrative tumor expand and distort thegray infiltrative tumor expand and distort the brain
brain •
• few cm’s to displace entire hemispheresfew cm’s to displace entire hemispheres •
• firm or gelatinousfirm or gelatinous •
• cystic degenerationcystic degeneration
Gliomat
Gliomatosis osis cerebrcerebri i - - mumultiltiplple e reregiogions ns of of ththe e brbraiainn
infiltrated by neoplastic astrocytes infiltrated by neoplastic astrocytes Microscopic:
Microscopic: •
• mild to mod inc in number of glial cell nucleimild to mod inc in number of glial cell nuclei
•
• variable nuclear pleomorphismvariable nuclear pleomorphism •
• GFAP (+) astrocytic cell processesGFAP (+) astrocytic cell processes Anaplastic
Anaplastic •
• densely cellulardensely cellular •
• Mitotically activeMitotically active Gemistocytic Gemistocytic •
• Neoplastic astrocytesNeoplastic astrocytes •
• Brightly eosinophilic cell body, stout processesBrightly eosinophilic cell body, stout processes ASTROCYTOMA
ASTROCYTOMA
GEMISTOCYTIC ASTROCYTOMA GEMISTOCYTIC ASTROCYTOMA 2.
2. GliGliobloblastastoma (Glioma (Glioboblaslastomtoma a MuMultiltiforformeme)) •
• variable gross appearancevariable gross appearance •
• Firm white to soft and yellowFirm white to soft and yellow •
• Well demarcated with infiltration beyond outer Well demarcated with infiltration beyond outer marginmargin Microscopic:
Microscopic: •
• Similar to AnaplasticSimilar to Anaplastic •
• Necrosis – “pseudopalisading” Necrosis – “pseudopalisading” •
• VascuVascular or lar or endothelial proliferation –endothelial proliferation – “glomeruloid body”
“glomeruloid body”
brim, leu, virns
GLIOBLASTOMA GLIOBLASTOMA WHO Grading
WHO Grading G
Grraadde Ie I//IIVV PPiillooccyyttiicc G
Grarade de IIII/I/IVV WWelell dil difffefererentntiaiateted ad aststrorocycytotommasas G
Grraadde e IIIIII//IIVV AAnnaappllaassttiicc G
Grraadde e IIVV//IIVV GlliioG obbllaassttoommaa Molecular Genetics Molecular Genetics
•
• Inactivation of p53Inactivation of p53 •
• Overexpression of PDGF-A and its receptorsOverexpression of PDGF-A and its receptors •
• TTransition to higher ransition to higher grade associated withgrade associated with additional disruption of tumor suppressor genes, additional disruption of tumor suppressor genes, the RB genes, p16/CDKNZA gene, putative tumor the RB genes, p16/CDKNZA gene, putative tumor suppressor on chromosome 19q
suppressor on chromosome 19q Clinical Features:
Clinical Features: •
• Presenting symptoms depend in part on locationPresenting symptoms depend in part on location of tumor and growth rate
of tumor and growth rate •
• Well-differentiated remain static, progress slowlyWell-differentiated remain static, progress slowly •
• Mean survival 5 yearsMean survival 5 years •
• Anaplastic present with rapid deterioration, veryAnaplastic present with rapid deterioration, very poor prognosis
poor prognosis •
• Current treatment (resection, radiotx, Current treatment (resection, radiotx, chemotx)chemotx) •
• 8 – 10 mos surivival8 – 10 mos surivival •
• < 10% alive after 2 yrs< 10% alive after 2 yrs 3
3.. PPiillooccyyttiicc •
• Children and young adultsChildren and young adults •
• CerCerebeebellullum, m, flofloor or and and wawall ll of of 3rd 3rd venventritriclescles, , optiopticc nerves, cerebral hemispheres
nerves, cerebral hemispheres Morphology
Morphology •
• often cystic, with mural nodule in the cyst walloften cystic, with mural nodule in the cyst wall •
• If solid, well circumscribed, less frequentlyIf solid, well circumscribed, less frequently infiltrative
infiltrative Microscopic: Microscopic:
•
• Bipolar cells with long thin “hairlike” processesBipolar cells with long thin “hairlike” processes that are GFAP (+)
that are GFAP (+) •
• Rosenthal fibersRosenthal fibers •
• Eosinophilic granular bodiesEosinophilic granular bodies •
• MicrocystsMicrocysts •
• Increase no. of blood vesselsIncrease no. of blood vessels •
• Necrosis and mitosis uncommonNecrosis and mitosis uncommon •
• Narrow infiltrative borderNarrow infiltrative border
PILOCYTIC ASTROCYTOMA PILOCYTIC ASTROCYTOMA Clinical
Clinical •
• Grow very slowlyGrow very slowly •
• Cerebellar tumors treated with resectionCerebellar tumors treated with resection •
• RaRarely rely hahave ve p53 p53 mumutattationions s or or othother er chachangengess found in diffuse fibrillary
found in diffuse fibrillary 4.
4. PlePleomoomorphrphic Xaic Xanthnthoasoastrotrocytcytomaoma •
• Relatively superficialRelatively superficial •
• Temporal lobeTemporal lobe •
• Children and young adultsChildren and young adults •
• Long history of seizuresLong history of seizures Microscopic:
Microscopic: •
• neoplastic occ bizarre astrocytesneoplastic occ bizarre astrocytes •
• nuclear atypia can be extreme and may suggestnuclear atypia can be extreme and may suggest high grade astrocytoma
high grade astrocytoma •
• abundant reticulin depositsabundant reticulin deposits •
• relative circumscriptionrelative circumscription •
• chronic inflammatory cell infiltrateschronic inflammatory cell infiltrates •
• absence of necrosis and mitotic activityabsence of necrosis and mitotic activity •
• WHO grade II/IVWHO grade II/IV •
• 80% survival rate at 5 years80% survival rate at 5 years B.
B. OLOLIGIGODODENENDRDROGOGLILIOMOMASAS •
• 5 - 15%5 - 15% •
• Age: 40 – 50Age: 40 – 50 •
• Seizures for several yearsSeizures for several years •
• Predilection for white matterPredilection for white matter, cerebral hemispheres, cerebral hemispheres Morphology:
Morphology: •
• well-circumscribed, gelatinous, gray masseswell-circumscribed, gelatinous, gray masses •
• ofofteten n wwitith h cycyststs, s, fofoccal al hehemmororrhrhaage ge anandd calcification
calcification Microscopic:
Microscopic: •
• ShSheeeets ts of of reregugulalar r cecells lls wiwith th spsphehericrical al nunuclcleiei containing finely granular chromatin surrounded containing finely granular chromatin surrounded by clear halo of cytoplasm
by clear halo of cytoplasm •
• Delicate network of anastomosing capillariesDelicate network of anastomosing capillaries •
• Calcifications in 90%Calcifications in 90% •
• Low mitotic activityLow mitotic activity •
• WHO grade II/IVWHO grade II/IV •
• AnapAnaplastilastic c oligodoligodendroendrogliomgliomas as – – increaincreased sed cellcell dens
densityity, , nuclnuclear ear anapanaplasia, lasia, inc inc mitotmitotic ic activactivityity,, necrosis
necrosis Molecular genetics: Molecular genetics:
•
• loss of heterozygosity for chromosomes 1p andloss of heterozygosity for chromosomes 1p and 19q
19q •
• If without other alterations consistent and longIf without other alterations consistent and long lasting response to chemotherapy and radiation lasting response to chemotherapy and radiation Clinical Features:
•
• Better prognosis than astrocytomasBetter prognosis than astrocytomas •
• Ave 5 – 10 years survivalAve 5 – 10 years survival
OLIGODENDROGLIOMA OLIGODENDROGLIOMA C C.. EEPPENENDDYYMMOOMMAASS • • •
• Arise next to ependyma-lined ventricular systemArise next to ependyma-lined ventricular systemArise next to ependyma-lined ventricular systemArise next to ependyma-lined ventricular system •
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•
• First 2 decades – 4th ventricleFirst 2 decades – 4th ventricleFirst 2 decades – 4th ventricleFirst 2 decades – 4th ventricle •
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•
• 5 – 10% of primary brain tumors5 – 10% of primary brain tumors5 – 10% of primary brain tumors5 – 10% of primary brain tumors •
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•
• Adults – most common in spinal cordAdults – most common in spinal cordAdults – most common in spinal cordAdults – most common in spinal cord Morphology: Morphology: Morphology: Morphology: • • •
• In 4th ventricle, solid or In 4th ventricle, solid or papillary massesIn 4th ventricle, solid or In 4th ventricle, solid or papillary massespapillary massespapillary masses •
•
•
• Intraspinal, sharply demarcatedIntraspinal, sharply demarcatedIntraspinal, sharply demarcatedIntraspinal, sharply demarcated Microscopic: Microscopic: Microscopic: Microscopic: • • •
• Cells CelCelCells witls ls with witwith regh h regularegregularr, ulaularr, , rou, rourouround nd to nd nd to ovto to oval ovoval nucal al nuclei nucnuclei lei lei witwithwitwithhh abundant granular chromatin
abundant granular chromatin abundant granular chromatin abundant granular chromatin •
•
•
• Dense fibrillary backgroundDense fibrillary backgroundDense fibrillary backgroundDense fibrillary background •
•
•
• Rosettes, canalsRosettes, canalsRosettes, canalsRosettes, canals •
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•
• Perivascular pseudorosettesPerivascular pseudorosettesPerivascular pseudorosettesPerivascular pseudorosettes •
•
•
• GFAP (+)GFAP (+)GFAP (+)GFAP (+)
EPENDYMOMA EPENDYMOMA EPENDYMOMA EPENDYMOMA Morphology: Morphology: Morphology: Morphology: • • •
• Well-differentiated – WHO Grade II/IVWell-differentiated – WHO Grade II/IVWell-differentiated – WHO Grade II/IVWell-differentiated – WHO Grade II/IV •
•
•
• Anaplastic ependymomas – WHO Grade III/IVAnaplastic ependymomas – WHO Grade III/IVAnaplastic ependymomas – WHO Grade III/IVAnaplastic ependymomas – WHO Grade III/IV •
• Myxopapillary Myxopapillary ependymoMyxopapillary Myxopapillary ependymomasependymoependymomasmasmas – occur in filum– occur in filum– occur in filum– occur in filum terminale of spinal cord
terminale of spinal cord terminale of spinal cord terminale of spinal cord •
•
•
• Papillary elements in myxoid backgroundPapillary elements in myxoid backgroundPapillary elements in myxoid backgroundPapillary elements in myxoid background Molecular genetics: Molecular genetics: Molecular genetics: Molecular genetics: • • •
• SpSSSpppininaininal aal l l eepeeppepeneennnddyddymyymommomoomammas aas s s aassssoaassssocioociaciciatteaatted eed d d wwiitthwwitithhh Ne
Neuurroofifibbrroommaattoosisis s 2 2 aannd d NNFF2 2 ggeenne e oonn Ne
Neuurroofifibbrroommaattoosisis s 2 2 anand d NNFF2 2 ggeenne e oonn chromosome 22 chromosome 22 chromosome 22 chromosome 22 Clinical features: Clinical features: Clinical features: Clinical features: • • •
• PoPoPostePosterior stesterior fosrior rior fossa fosfossa sa epesa ependyepeependyndyndymommomas mommomas manas as manifemanmanifest ifeifest witst st withwitwithhh hydrocephalus sec to obstruction of 4th ventricle hydrocephalus sec to obstruction of 4th ventricle hydrocephalus sec to obstruction of 4th ventricle hydrocephalus sec to obstruction of 4th ventricle •
•
•
• Prognosis is poorPrognosis is poorPrognosis is poorPrognosis is poor •
•
•
• CSF dissemination is commonCSF dissemination is commonCSF dissemination is commonCSF dissemination is common
OTH
OTHER ER TUMOTUMORS RS ASSOCASSOCIATEIATED D WITWITH H OTHOTHER ER CELL CELL TYPTYPEE OTH
OTHER ER TUMOTUMORS RS ASSOCASSOCIATEIATED D WITH OTHER WITH OTHER CELL CELL TYPTYPEE THAT FORMS THE VENTICULAR SYSTEM:
THAT FORMS THE VENTICULAR SYSTEM: THAT FORMS THE VENTICULAR SYSTEM: THAT FORMS THE VENTICULAR SYSTEM:
•
•
•
• SubependymomasSubependymomasSubependymomasSubependymomas •
•
•
• Choroid plexus papillomasChoroid plexus papillomasChoroid plexus papillomasChoroid plexus papillomas •
•
•
• Colloid cyst of the third ventricleColloid cyst of the third ventricleColloid cyst of the third ventricleColloid cyst of the third ventricle
NEURONAL TUMORS NEURONAL TUMORS NEURONAL TUMORS NEURONAL TUMORS A.
A. GAGANGNGLILION ON CECELL TLL TUMUMORORSS •
• Contain ganglion cellsContain ganglion cells •
• Gangliocytoma – entire population of lesionGangliocytoma – entire population of lesion •
• Ganglioglioma – admixture with glial neoplasmGanglioglioma – admixture with glial neoplasm •
• Slow growingSlow growing •
• Glial components occ become anaplastic andGlial components occ become anaplastic and progress rapidly
progress rapidly •
• Present with seizure disorderPresent with seizure disorder •
• WHO grade I-II/IVWHO grade I-II/IV B.
B. OOTTHHEER R TTUMUMOORRS S WIWITTH H GLGLIIAL AL ANAND D NNEEURUROONNALAL COMPONENTS
COMPONENTS i.
i. DyseDysembrymbryoplaoplastic stic NeuNeuroeproepitheithelial lial TumoTumorr (DNT)
(DNT)
Low grade tumor of childhood Low grade tumor of childhood Seizure disorder Seizure disorder Slow growth Slow growth Good prognosis Good prognosis C.
C. TUMOTUMORS RS WITWITH OH ONLY NLY NEURNEURONAL ONAL ELEMELEMENTENTSS i.
i. Cerebral NeuroblastomaCerebral Neuroblastoma
Rare, occur in children, highly aggressive Rare, occur in children, highly aggressive Resemble peripheral neuroblastomas Resemble peripheral neuroblastomas Homer Wright rosettes
Homer Wright rosettes ii.
ii. Central NeurocytomaCentral Neurocytoma
Low grade neuronal tumors Low grade neuronal tumors Lateral and third ventricles Lateral and third ventricles Resemble oligodendroglioma Resemble oligodendroglioma
POORLY DIFFERENTIATED NEOPLASMS POORLY DIFFERENTIATED NEOPLASMS POORLY DIFFERENTIATED NEOPLASMS POORLY DIFFERENTIATED NEOPLASMS
•
• MedulloblastomaMedulloblastoma •
• Atypical Teratoid/Rhabdoid Tumor (AT/RT)Atypical Teratoid/Rhabdoid Tumor (AT/RT) A.
A. MEMEDUDULLLLOBOBLALASTSTOMOMAA •
• Predominantly in childrenPredominantly in children •
• Exclusively in the cerebellumExclusively in the cerebellum •
• Largely undifferentiatedLargely undifferentiated Morphology
Morphology •
• Midline of cerebellumMidline of cerebellum •
• Lateral in adultsLateral in adults •
• Well circumscribed, gray and friableWell circumscribed, gray and friable Microscopic:
Microscopic: •
• Extremely cellularExtremely cellular, sheets of , sheets of anaplastic cellsanaplastic cells •
• Little cytoplasmLittle cytoplasm •
• HypHypercerchrohromamatic tic nunucleclei, i, eloelongangated ted or or crecrescescentnt shaped
shaped •
• Mitosis abundantMitosis abundant •
•
• ExpExpresress s neuneuronronal al (ne(neurourosecsecretoretory ry gragranulnules,es, Ho
Homemer r WWririghght t rorosesetttteses) ) anand d glgliaial l (G(GFFAPAP)) phenotypes
phenotypes Molecular Genetics: Molecular Genetics:
•
• Loss of short arm of Loss of short arm of chromosome 17chromosome 17
MEDULLOBLASTOMA MEDULLOBLASTOMA Clinical features:
Clinical features: •
• Highly malignantHighly malignant •
• Prognosis dismal in untreated patientsPrognosis dismal in untreated patients •
• radiosensitiveradiosensitive •
• Better survival following complete resectionBetter survival following complete resection •
• 75% 5-year survival rate for total excision and75% 5-year survival rate for total excision and radiation
radiation B.
B. ATYPATYPICAL ICAL TERATERATOITOID/RHD/RHABDOABDOID TID TUMOR UMOR (AT/(AT/RT)RT) •
• Highly malignant tumor of young childrenHighly malignant tumor of young children •
• Posterior fossa and supratentorial compartmentsPosterior fossa and supratentorial compartments •
• ““rrhhaabbddooiid d cceellllss” ” rreesseemmbblliinng g tthhoosse e oof f aa rhabdomyosarcoma
rhabdomyosarcoma •
• 90% - Loss of genetic material from 90% - Loss of genetic material from chromosome 22chromosome 22 •
• Very young patients – before age 5Very young patients – before age 5 •
• Live less than a year after Live less than a year after diagnosisdiagnosis
OTHER PARENCHYMAL TUMORS OTHER PARENCHYMAL TUMORS OTHER PARENCHYMAL TUMORS OTHER PARENCHYMAL TUMORS
•
• Primary CNS LymphomaPrimary CNS Lymphoma •
• Germ cell tumorsGerm cell tumors •
• Pineal Parenchymal TumorsPineal Parenchymal Tumors A.
A. PRPRIMIMARARY CNY CNS LYS LYMPMPHOHOMAMA •
• 2% of extranodal lymphomas2% of extranodal lymphomas •
• 1% of intracranial tumors1% of intracranial tumors •
• Most Most commcommon on CNS CNS neopneoplasm lasm in in immuimmunosunosuppressppresseded (AIDS)
(AIDS) •
• Occur in multiple sites WITHIN the brain parenchymaOccur in multiple sites WITHIN the brain parenchyma •
• Majority B-cell originMajority B-cell origin •
• Poor response to chemotherapyPoor response to chemotherapy B.
B. GEGERM RM CECELL LL TUTUMOMORSRS •
• MidlineMidline •
• Most common in pineal and suprasellar regionsMost common in pineal and suprasellar regions •
• 0.2% to 1% of 0.2% to 1% of brain tumors among Europeansbrain tumors among Europeans •
• 10% of brain tumors in 10% of brain tumors in JapaneseJapanese •
• 90% occur during first two decades90% occur during first two decades •
• More common are teratomasMore common are teratomas C.
C. PIPINENEAL AL PARPARENENCHYCHYMAMAL TL TUMOUMORSRS •
• Arise from pineocytesArise from pineocytes
•
• Pineocytomas – well-differentiatedPineocytomas – well-differentiated •
• Pineoblastomas – high grade tumorsPineoblastomas – high grade tumors MENINGIOMAS
MENINGIOMAS
•
• Benign tumors of adultsBenign tumors of adults •
• Attached to duraAttached to dura •
• Arise from meningothelial cell of arachnoidArise from meningothelial cell of arachnoid •
• ExtExternernal al sursurfacface e of of brabrain in as as witwithin hin the the venventrictriculaularr system
system Morphology: Morphology:
•
• Rounded, bosselated, polypoid massesRounded, bosselated, polypoid masses •
• Well-defined dural base that compress underlyingWell-defined dural base that compress underlying brain but easily separated from it
brain but easily separated from it •
• May extend to overlying boneMay extend to overlying bone •
• Encapsulated with thin fibrous tissueEncapsulated with thin fibrous tissue •
• “en plaque” variant – spreads in sheetlike fashion “en plaque” variant – spreads in sheetlike fashion along the surface of dura
along the surface of dura •
• Most are WHO grade I/IVMost are WHO grade I/IV TYPES TYPES • • SyncytialSyncytial • • FibroblasticFibroblastic • • TransitionalTransitional • • PsammomatousPsammomatous • • SecretorySecretory • • MicrocysticMicrocystic •
• AtyAtypicapical l menmeningingiomiomas as – – mitmitotic index of otic index of 4 4 oror more mitosis/10 hpf, 3 or more atypical features more mitosis/10 hpf, 3 or more atypical features (inc cellulari
(inc cellularityty, , small cells small cells with high with high N:C ratio,N:C ratio, prominent nucleoli, patternless growth, necrosis) prominent nucleoli, patternless growth, necrosis) •
• Anaplastic Anaplastic (malignant)Menin(malignant)Meningiomagioma •
• WHO grade III/IVWHO grade III/IV • • Mitosis >20/10 hpf Mitosis >20/10 hpf MENINGIOMA MENINGIOMA Clinical Features: Clinical Features: •
• Slow growingSlow growing •
• VaVague gue nonlnonlocalizocalizing ing sympsymptoms toms or or focal findingsfocal findings referable to compression of underlying brain referable to compression of underlying brain •
• CoCommmmon on sisitetes: s: papararasasagigittattal l asaspepect ct of of brbraiainn conv
convexityexity, , dura over dura over laterlatera a convconvexityexity, , wing of wing of sphenoid, olfactory groove, sella turcica, foramen sphenoid, olfactory groove, sella turcica, foramen magnum
•
• Usually solitaryUsually solitary •
• Multiple tumors assoc with acoustic neuroma orMultiple tumors assoc with acoustic neuroma or glial tumors suggest neurofibromatosis type 2 glial tumors suggest neurofibromatosis type 2 METASTATIC TUMORS
METASTATIC TUMORS
•
• Mostly carcinomasMostly carcinomas •
• ComCommon mon priprimarmary y sitsites es (80(80%): %): lunlung, g, brebreastast, , skiskinn (melanoma), kidney, GIT
(melanoma), kidney, GIT •
• Meninges are frequently involvedMeninges are frequently involved •
• Present clinically as mass lPresent clinically as mass l esions, may occasionally beesions, may occasionally be the first manifestation of cancer
the first manifestation of cancer •
• GroGrossly ssly forform m shasharply rply demdemarcarcateated d masmassesses, , at at gragrayy matter-white matter junction, surrounded by zone of matter-white matter junction, surrounded by zone of edema edema BRAIN METASTASES BRAIN METASTASES PARANEOPLASTIC SYNDROMES PARANEOPLASTIC SYNDROMES •
• Involve the peripheral and central nervous Involve the peripheral and central nervous systemssystems •
• Most common in small cell carcinoma of the lungMost common in small cell carcinoma of the lung •
• ExamplesExamples •
• Paraneoplastic cerebellar Paraneoplastic cerebellar degenerationdegeneration •
• Limbic encephalitisLimbic encephalitis •
• Subacute sensory neuropathySubacute sensory neuropathy •
• Eye movement disorders, opsoclonusEye movement disorders, opsoclonus •
• Retinal degenerationRetinal degeneration •
• Stiff-man syndromeStiff-man syndrome •
• Lambert-Eaton myasthenic syndromeLambert-Eaton myasthenic syndrome PERIPHERAL NERVE SHEATH TUMORS
PERIPHERAL NERVE SHEATH TUMORS
Arise from Schwann cells, perineurial cells, Arise from Schwann cells, perineurial cells, fibroblastsfibroblasts
Express S-100 antigen, melanocytic differentiationExpress S-100 antigen, melanocytic differentiation
•
• SchwannomaSchwannoma •
• NeurofibromaNeurofibroma •
• MaligMalignant nant PeriPeripherapheral l Nerve Nerve SheaSheath th TTumor umor (MPNS(MPNSTT,, Malignant Schwannoma)
Malignant Schwannoma) A
A.. SCSCHHWAWANNNNOOMMAA •
• Neural crest-derived Schwann cellNeural crest-derived Schwann cell •
• Assoc with Neurofibromatosis type 2Assoc with Neurofibromatosis type 2 •
• Well circumscribed, encapsulated masses attached toWell circumscribed, encapsulated masses attached to nerve but can be separated from it
nerve but can be separated from it •
• Firm, gray massesFirm, gray masses •
• Cystic Cystic and xaand xanthomatous nthomatous changechange Microscopic:
Microscopic: •
• Mixture of two growth patternsMixture of two growth patterns •
• AnAntotoni ni AA – – papatttterern n oof f grgrowowth th of of el
elonongagateted d cecelllls s wiwith th ccytytopoplalasmsmicic processes arranged in fascicles in areas processes arranged in fascicles in areas
of moderate to high cellularity with little of moderate to high cellularity with little stromal matrix
stromal matrix •
• AnAntotoni ni BB – – papatttterern n of of grgrowowthth,l,lesesss densely cellular with loose meshwork of densely cellular with loose meshwork of cells along with microcysts and myxoid cells along with microcysts and myxoid changes
changes Clinical Features: Clinical Features:
•
• Most common in cerebellopontine angle, attachedMost common in cerebellopontine angle, attached to vestibular branch of 8th cranial nerve
to vestibular branch of 8th cranial nerve •
• Tinnitus and hearing lossTinnitus and hearing loss •
• “Acoustic neuroma” (vestibular “Acoustic neuroma” (vestibular schwannschwannoma)oma)
SCHWANNOMA SCHWANNOMA B.
B. NENEURUROFOFIBIBROROMAMA Two types: Two types:
•
• Cutaneous Cutaneous NeurofibNeurofibromaroma (sk(skin) in) oror SolitarySolitary Neurofibroma
Neurofibroma (peripheral nerve)(peripheral nerve) •
• Dermis and subcutaneous fatDermis and subcutaneous fat •
• Well-delineated, unencapsulatedWell-delineated, unencapsulated •
• Spindle cellsSpindle cells •
• Stroma highly collagenizedStroma highly collagenized •
• Plexiform NeurofibromaPlexiform Neurofibroma– occur only in NF1– occur only in NF1 •
• Involve major nerve trunks, potential forInvolve major nerve trunks, potential for malignant transformation
malignant transformation •
• Frequently multipleFrequently multiple •
• Loose myxoid background, low cellularityLoose myxoid background, low cellularity •
• SchSchwawann nn celcells, ls, mulmultiptipolaolar r fibfibrobroblaslastictic cells, inflammatory cells
cells, inflammatory cells C.
C. MAMALILIGNGNANANT T PEPERIRIPHPHERERAL AL NENERVRVE E SHSHEAEATH TH TUTUMOMOR R (MPNST, MALIGNANT SCHWANNOMA)
(MPNST, MALIGNANT SCHWANNOMA) •
• Highly malignant sarcomaHighly malignant sarcoma •
• LoLocacally lly ininvavasisiveve, , frfreqequeuentlntly y leleadadining g to to mumultltipiplele recurrences and metastasis
recurrences and metastasis •
• AriArise se de de novnovo o or or frofrom m tratransfnsformormatiation on of of pleplexifxiformorm neurofibroma
neurofibroma •
• Assoc with NF type 1Assoc with NF type 1 •
• “T “Triton tumor” riton tumor” – with – with rhabdomyoblastic differentiationrhabdomyoblastic differentiation
FAMILIAL TUMOR SYNDROMES FAMILIAL TUMOR SYNDROMES
•
• Neurofibromatosis TypNeurofibromatosis Type 1 e 1 (NF1)(NF1) •
• Neurofibromatosis TypNeurofibromatosis Type 2 e 2 (NF2)(NF2) •
• TTuberous sclerosuberous scleros isis •
• Von Hippel Lindau DiseaseVon Hippel Lindau Disease A.
A. NENEUROUROFIFIBROBROMATMATOSIOSIS TYPS TYPE 1 (NF1E 1 (NF1)) •
•
• Neurofibromas (plexiform and solitary)Neurofibromas (plexiform and solitary) •
• Gliomas of optic nerveGliomas of optic nerve •
• Lisch nodulesLisch nodules •
• Café au lait spotsCafé au lait spots •
• Propensity to undergo malignant degenerationPropensity to undergo malignant degeneration B.
B. NENEUROUROFIBFIBROMROMATATOSIOSIS TYPS TYPE 2 (NFE 2 (NF2)2) •
• Autosomal-dominAutosomal-dominant ant disorderdisorder •
• Bilateral VIII nerve Bilateral VIII nerve schwannomschwannomasas •
• Multiple meningiomasMultiple meningiomas •
• Ependymomas of spinal cordEpendymomas of spinal cord •
• SchwannosisSchwannosis •
• MeningioangiomatosisMeningioangiomatosis •
• Glial hamartiaGlial hamartia
C.
C. TUTUBEBEROROUS US SCSCLELEROROSISISS •
• Autosomal-dominantAutosomal-dominant •
• HamartomasHamartomas •
• Cortical tubersCortical tubers •
• Subependymal hamartomasSubependymal hamartomas •
• BenBenign ign neoneoplasplasms ms invinvolvolving ing the the brbrain ain and and othotherer tissues
tissues •
• Renal Renal angiomyolipomaangiomyolipomass •
• Retinal glial hamartomasRetinal glial hamartomas •
• Pulmonary lesionsPulmonary lesions •
• Cardiac rhabdomyomaCardiac rhabdomyomass •
• Cysts in liver, kidneys, pancreasCysts in liver, kidneys, pancreas •
• Cutaneous lesions e.g.Cutaneous lesions e.g. Angiofibromas,Sh
Angiofibromas,Shagreen patches, agreen patches, ash-leaf ash-leaf patches, subungal fibromas
patches, subungal fibromas D.
D. VOVON HIN HIPPPPEL LEL LININDAU DAU DIDISEASEASESE •
• Autosomal-dominantAutosomal-dominant •
• CapilCapillary lary hemahemangiobngioblastolastomas mas within the within the cerebcerebellarellar hemispheres, retina, less commonly in
hemispheres, retina, less commonly in brain stem andbrain stem and spinal cord
spinal cord •
• Cysts in pancreas, liver, kidneysCysts in pancreas, liver, kidneys •
• Renal cell carcinomaRenal cell carcinoma •
• AAssssoocciiaatteed d wwiitth h ppoollyyccyytthheemmiia a iin n 1100% % oof f hemangioblastomas
hemangioblastomas
FIVE (5) lessons to make you
FIVE (5) lessons to make you think about the way we treat people.think about the way we treat people.
1 - First Important Lesson - Cleaning Lady.
1 - First Important Lesson - Cleaning Lady.
During my second month of college, our professor gave us a pop quiz. I
During my second month of college, our professor gave us a pop quiz. I
was a conscientious student and had breezed through the questions until
was a conscientious student and had breezed through the questions until
I read the last one:
I read the last one:
"What is the first name of
"What is the first name of the woman who cleans the school? " Surely the woman who cleans the school? " Surely
this was some kind of
this was some kind of joke. I had seen the cleaning joke. I had seen the cleaning woman several times.woman several times.
She was tall, dark-haired and in her 50s, but how would I know her
She was tall, dark-haired and in her 50s, but how would I know her
name?
name?
I handed in my
I handed in my paper, leaving the last question blank. Just before paper, leaving the last question blank. Just before classclass
ended, one student asked if the last question
ended, one student asked if the last question would count toward ourwould count toward our
quiz grade.
quiz grade.
"Absolutely," said the professor. " In your
"Absolutely," said the professor. " In your careers, you will meet many careers, you will meet many
people. All are significant. They deserve your
people. All are significant. They deserve your attention and care, even if attention and care, even if
all you do is smile and say " hello".
all you do is smile and say " hello".
I've never forgotten that lesson. I also learned her
I've never forgotten that lesson. I also learned her name was Dorothy.name was Dorothy.
2. - Second Important Lesson - Pickup in the Rain
2. - Second Important Lesson - Pickup in the Rain
One night, at 11:30 p.m., an older
One night, at 11:30 p.m., an older African American woman wasAfrican American woman was
standing on the side of an Alabama highway trying to endure a lashing
standing on the side of an Alabama highway trying to endure a lashing
rainstorm. Her car had broken down
rainstorm. Her car had broken down and she desperately needed a ride.and she desperately needed a ride.
Soaking wet, she decided to flag down the next car. A young white man
Soaking wet, she decided to flag down the next car. A young white man
stopped to help her, generally unheard of
stopped to help her, generally unheard of in the conflict-filled 1960s. Thein the conflict-filled 1960s. The
man took her to safety, helped her
man took her to safety, helped her get assistance and put her into get assistance and put her into aa
taxicab.
taxicab.
She seemed to be in a big hurry, but wrote down his address and
She seemed to be in a big hurry, but wrote down his address and
thanked him.
thanked him.
Seven days went by and a knock came on the man's door. To his
Seven days went by and a knock came on the man's door. To his
surprise, a
surprise, a
giant console color TV was
giant console color TV was delivered to his home. A special note wasdelivered to his home. A special note was
attached.
attached.
It read:
It read: "Thank you so much for assisting me on the highway the other"Thank you so much for assisting me on the highway the other
night.
night. The rain drenched not only mThe rain drenched not only my clothes, but also my spirity clothes, but also my spirits. Thens. Then
you came along. Because of you, I was able to make it to my dying
you came along. Because of you, I was able to make it to my dying
husband's bedside just before he passed away... God
husband's bedside just before he passed away... God bless you forbless you for
helping me and unselfishly serving others."
helping me and unselfishly serving others."
Sincerely, Mrs. Nat King Cole.
Sincerely, Mrs. Nat King Cole.
3 - Third Important
3 - Third Important Lesson - Lesson - Always remember thosAlways remember those whoe who
serve.
serve.
In the days when an
In the days when an ice cream sundae cost much less, a 10-year-old boy ice cream sundae cost much less, a 10-year-old boy
entered a hotel coffee shop and sat at a table. A waitress put a glass of
entered a hotel coffee shop and sat at a table. A waitress put a glass of
water in front of him.
water in front of him.
"How much is an ice
"How much is an ice cream sundae?" he asked.cream sundae?" he asked.
"Fifty cents," replied the
"Fifty cents," replied the waitress.waitress.
The little boy pulled is hand out of his pocket and studied the coins in it.
The little boy pulled is hand out of his pocket and studied the coins in it.
"Well, how much is a plain dish of ice cream?" he inquired.
"Well, how much is a plain dish of ice cream?" he inquired.
By now more people were waiting
By now more people were waiting for a table for a table and the waitress wasand the waitress was
growing impatient.
growing impatient.
"Thirty-five cent
"Thirty-five cents," she s," she brusquely repliedbrusquely replied
The little boy again counted his
The little boy again counted his coins.coins.
"I'll have the plain ice cream," he said.
"I'll have the plain ice cream," he said.
The waitress brought the ice cream, put the bill
The waitress brought the ice cream, put the bill on the table and walkedon the table and walked
away. The boy finished the i
away. The boy finished the ice cream, paid the cashier and ce cream, paid the cashier and left. When theleft. When the
waitress came back, she began to cry
waitress came back, she began to cry as she wiped down the table. There,as she wiped down the table. There,
placed neatly beside the empty dish, were two nickels
placed neatly beside the empty dish, were two nickels and five pennies.and five pennies.
You see, he couldn't have the sundae, because he had
You see, he couldn't have the sundae, because he had to have enough leftto have enough left
to leave her a tip.
to leave her a tip.
4 - Fourth Important Lesson - The obstacle in Our Path.
4 - Fourth Important Lesson - The obstacle in Our Path.
In ancient times, a King had a boulde
In ancient times, a King had a boulder placed on a roadway. r placed on a roadway. Then he hidThen he hid
himself and watched to see if
himself and watched to see if anyone would remove the huge rock. Someanyone would remove the huge rock. Some
of the king's wealthiest merchants and courtiers came by and
of the king's wealthiest merchants and courtiers came by and simply simply
walked around it. Many loudly blamed the King for not keeping the
walked around it. Many loudly blamed the King for not keeping the
roads clear, but none did anything about getting the stone out of the
roads clear, but none did anything about getting the stone out of the
way.
way.
Then a peasant came along carrying
Then a peasant came along carrying a load of a load of vegetables. Uponvegetables. Upon
approaching the boulder, the peasant laid down his
approaching the boulder, the peasant laid down his burden and tried toburden and tried to
move the stone to the side of
move the stone to the side of the road. After much pushing andthe road. After much pushing and
straining, he finally succeeded. After the peasant picked up
straining, he finally succeeded. After the peasant picked up his load of his load of
vegetables, he noticed a purse lying
vegetables, he noticed a purse lying in the road where the boulder hadin the road where the boulder had
been. The purse contained many gold coins and a note from the King
been. The purse contained many gold coins and a note from the King
indicating that the gold was for
indicating that the gold was for the person who removed the boulderthe person who removed the boulder
from the roadway. The peasant learned what many of
from the roadway. The peasant learned what many of us neverus never
understand!
understand!
Every obstacle presents an opportunity to improve our condition.
5 - Fifth Important Lesson - Giving When it Counts...
5 - Fifth Important Lesson - Giving When it Counts...
Many years ago, when I worked as a volunteer at a hospital, I got to
Many years ago, when I worked as a volunteer at a hospital, I got to
know a little girl named Liz who was suffering from a rare & serious
know a little girl named Liz who was suffering from a rare & serious
disease. Her only chance of recovery
disease. Her only chance of recovery appeared to be a blood appeared to be a blood transfusiontransfusion
from her 5-year old
from her 5-year old brother, who had miraculously survived the samebrother, who had miraculously survived the same
disease and had developed the antibodies needed to combat the illness.
disease and had developed the antibodies needed to combat the illness.
The doctor explained the situation to her little brother, and
The doctor explained the situation to her little brother, and asked theasked the
little boy if he would be willing to give his blood to
little boy if he would be willing to give his blood to his sister.his sister.
I saw him hesitate for only
I saw him hesitate for only a moment before taking a deep breath a moment before taking a deep breath andand
saying, "Yes I'll do it if it will save her." As the transfusion progressed, he
saying, "Yes I'll do it if it will save her." As the transfusion progressed, he
lay in bed next to his sister and smiled, as we all did, seeing the color
lay in bed next to his sister and smiled, as we all did, seeing the color
returning to her cheek. Then his face
returning to her cheek. Then his face grew pale and his grew pale and his smile faded.smile faded.
He looked up at the doctor and
He looked up at the doctor and asked with a trembling voice, "Will Iasked with a trembling voice, "Will I
start to die right away."
start to die right away."
Being young, the little boy
Being young, the little boy had misunderstood the doctor; he thought hehad misunderstood the doctor; he thought he
was going to have to give his sister all of his blood in order
was going to have to give his sister all of his blood in order to save her.to save her.
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