Tumors of the Central Nervous System- ICRO1 - pdfMachine …aroi.org/ICRO_PDF/1st ICRO TMH...
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Pathology of tumors of the
central nervous system
Preetha NairPreetha NairAsst PathologistAsst Pathologist
ACTREC & Tata memorial hospitalACTREC & Tata memorial hospital
id2986734 pdfMachine by Broadgun Software - a great PDF writer! - a great PDF creator! - http://www.pdfmachine.com http://www.broadgun.com
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P Nair
Plan of Discussion�
WHO classification WHO classification --
Diagnostic tools Diagnostic tools --
Glioma Glioma -- gradinggrading AstrocytomaAstrocytoma
OligodendrogliomaOligodendroglioma
EpendymomaEpendymoma
EmbryonalEmbryonal-- MedulloblastomaMedulloblastoma
MeningiomaMeningioma
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P Nair
General Considerations�General Considerations�
PrognosisPrognosis-- Tumor factorsTumor factors
Histologic type & gradeHistologic type & grade IHCIHC-- proliferation markers & molecular proliferation markers & molecular
parametersparameters Patient factorsPatient factors
Age/ statusAge/ status Tumor siteTumor site-- Limited space, Vital structuresLimited space, Vital structures
Rare: extra neural metastasisRare: extra neural metastasis
PrimaryPrimary �� children children
50% infiltrative50% infiltrativeMetastaticMetastatic �� Adults Adults
wellwell--demarcateddemarcated
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P Nair
Types of Brain Tumors Meninges:Meninges: meningioma, hemangiopericytomameningioma, hemangiopericytoma
Glia:Glia: astrocytoma, oligodendroglioma, astrocytoma, oligodendroglioma, ependymoma, choroid plexus tumorsependymoma, choroid plexus tumors
Primitive cells:Primitive cells: neuroblastoma, germinoma, neuroblastoma, germinoma, medulloblastoma, pineoblastoma, medulloblastoma, pineoblastoma, retinoblastomaretinoblastoma
Neuronal:Neuronal: gangliogliomaganglioglioma, gangliocytoma, gangliocytoma
Pituitary:Pituitary: adenoma, craniopharyngiomaadenoma, craniopharyngioma
Nerves:Nerves: schwannomaschwannoma, neurofibroma, MPNST, neurofibroma, MPNST
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P Nair
WHO classification [2000]
I]I] NEUROEPITHELIALNEUROEPITHELIAL AstrocyticAstrocytic
DiffuseDiffuse-- Fibrillary/ Protoplasmic/ Fibrillary/ Protoplasmic/ Gemistocytic [II]Gemistocytic [II]
Anaplastic Astrocytoma [III]Anaplastic Astrocytoma [III] GBM [IV]GBM [IV] PA [I] / SEGA [I] / PXA [II] PA [I] / SEGA [I] / PXA [II]
OligodendroglialOligodendroglial: : Oligodendroglioma Oligodendroglioma [II] / anapl. [III][II] / anapl. [III]
Mixed Mixed gliomaglioma-- OA [II] / anaplastic OA OA [II] / anaplastic OA [III][III]
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P Nair
WHO classification [2000]
I] I] NEUROEPITHELIAL NEUROEPITHELIAL contd/contd/--
EpendymalEpendymal Ependymoma & variants [II] / Ependymoma & variants [II] /
anaplasticanaplastic [III][III] MyxopapillaryMyxopapillary E [II] / E [II] / SubependymomaSubependymoma [I][I]
Glial tumors of uncertain originGlial tumors of uncertain origin-- A� A� blastoma, Gl. cerebri, chordoid glioma of III blastoma, Gl. cerebri, chordoid glioma of III ventricleventricle
Neuronal & mixed glial neuronalNeuronal & mixed glial neuronal Ganglioglioma/ G. cytoma/ DIGG/ DIA/ Ganglioglioma/ G. cytoma/ DIGG/ DIA/
DNET/ CNDNET/ CN
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P Nair
WHO classification [2000]
I] I] NEUROEPITHELIALNEUROEPITHELIAL contd/contd/--
NeuroblasticNeuroblastic-- OlfOlf NbNb/ / N.epitheliomaN.epithelioma
Pineal parenchymal tumorsPineal parenchymal tumors P.cytomaP.cytoma/ / P.blastomaP.blastoma/ PPTI/ PPTI
EmbryonalEmbryonal tumorstumors MedulloepitheliomaMedulloepithelioma/ / EpendymoblastomaEpendymoblastoma
Medulloblastoma/ STMedulloblastoma/ ST-- PNET/ ATRTPNET/ ATRT
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P Nair
WHO classification [2000]
II]II] TUMORS OF MENINGESTUMORS OF MENINGES
MeningothelialMeningothelial-- MeningiomasMeningiomas
Non Non �� meningothelial meningothelial -- MesenchymalMesenchymal
III]III] LYMPHOMA/ HEMOPOEITIC TUMORSLYMPHOMA/ HEMOPOEITIC TUMORS
Lymphoma/ Plasmacytoma/ Granulocytic Lymphoma/ Plasmacytoma/ Granulocytic sarcoma / HDsarcoma / HD
IV]IV] GERM CELL TUMORSGERM CELL TUMORS-- germinoma/ EC/ germinoma/ EC/ YSTYST
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WHO classification [2000]
V]V] TUMORS OF SELLAR REGIONTUMORS OF SELLAR REGION--
Craniopharyngioma/ Granular cell tumorCraniopharyngioma/ Granular cell tumor
VI]VI] TUMORS OF PERIPHERAL NERVESTUMORS OF PERIPHERAL NERVES Schwannoma/ NF/ Perineurioma/ Schwannoma/ NF/ Perineurioma/
MPNSTMPNST
VII] VII] METASTATICMETASTATIC
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TumorTumor MicroscopicMicroscopicAstrocytomaAstrocytoma Fibrillary background; Fibrillary background;
different cell typesdifferent cell types
Glioblastoma Glioblastoma Pseudopalisaded necrosis;Pseudopalisaded necrosis;microvascular proliferation microvascular proliferation (MVP)(MVP)
Oligodendroglioma Oligodendroglioma Mosaic/ poachedMosaic/ poached--egg egg appearanceappearance
Ependymoma Ependymoma Perivascular pseudorosettesPerivascular pseudorosettes
Medulloblastoma Medulloblastoma undifferentiated round cells; undifferentiated round cells; rosettes (Homerrosettes (Homer--Wright) Wright)
Meningioma Meningioma Whorls and psammoma bodiesWhorls and psammoma bodies
Diagnostic Tools: Histologic typing
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P Nair
Diagnostic Tools- Immunohistochemistry Glial: Glial: GFAPGFAP
Astrocytic / Astrocytic / oligodendroglial / ependymaloligodendroglial / ependymal
Neuronal: Neuronal: Synaptophysin / chromogranin / NSESynaptophysin / chromogranin / NSE
Vascular: Vascular: CD34, CD 31CD34, CD 31
Epithelial markersEpithelial markers-- EMA, CKEMA, CK
Proliferation markerProliferation marker-- MibMib--1 (Ki1 (Ki--67) 67) labeling indexlabeling index
Special stainsSpecial stains -- Reticulin / PTAH / PASReticulin / PTAH / PAS
Molecular markersMolecular markers -- 1p 19q del1p 19q del-- FISH FISH
EMEM: Ependymoma/ meningioma: Ependymoma/ meningioma
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GLIOMA
BIOLOGICALLYBIOLOGICALLY --
DiffuseDiffuse Young adults, Young adults,
cerebral hemisphere cerebral hemisphere and brainstemand brainstem
Astrocytoma II Astrocytoma II -- IV IV OligodendrogliomaOligodendroglioma
CircumscribedCircumscribed Children, Children,
characteristic characteristic location/ morphology)location/ morphology)
PA/ PXA/ SEGA/ PA/ PXA/ SEGA/ EpendymomaEpendymoma
No vascular changesNo vascular changes BBB intactBBB intact no edema / no edema /
enhancementenhancement
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GRADING
Nuclear atypia, Nuclear atypia,
Mitotic activityMitotic activity
Necrosis (sign of uncontrolled growth)Necrosis (sign of uncontrolled growth)
Vascular changes (tumor neovascularity; Vascular changes (tumor neovascularity; microvascular microvascular poliferationpoliferation-- MVP)MVP)
4tiered system4tiered system--
GRADE IGRADE I -- "Low"Low--Grade"Grade" -- Surgery curativeSurgery curative
GRADE IIGRADE II -- nuclearnuclear pleomorphismpleomorphism Surgery mainstay of treatmentSurgery mainstay of treatment RT for incomplete resectionRT for incomplete resection
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GRADING...
GRADE IIIGRADE III -- ANAPLASTICANAPLASTIC, + mitoses, + mitoses Surgery for HPR & debulking + RT +/Surgery for HPR & debulking + RT +/-- CTCT
GRADE IV GRADE IV -- MALIGNANTMALIGNANT, + �vascularity�/ MVP , + �vascularity�/ MVP +/+/-- necrosis: Glioblastoma multiformenecrosis: Glioblastoma multiforme
Surgery for debulking + RT + CT ( PCV/ Surgery for debulking + RT + CT ( PCV/ Temozolamide)Temozolamide)
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P Nair
PILOCYTIC ASTROCYTOMA [WHO I]
Cell of Origin:Cell of Origin: Astrocyte (biAstrocyte (bi--polar, hairlike) polar, hairlike)
Associations:Associations: in ON (optic nerve) w/ NFin ON (optic nerve) w/ NF--1 1
Location:Location: Cerebellum (85%), Cerebral Cerebellum (85%), Cerebral hemisphere (10%), Chiasm/ Hypothal, Optic hemisphere (10%), Chiasm/ Hypothal, Optic Nerve, Cx spinal cordNerve, Cx spinal cord
Circumscribed Circumscribed �� Enhancing; Enhancing;
Cyst with a mural noduleCyst with a mural nodule
Treatment: Surgery, patience (radiation and Treatment: Surgery, patience (radiation and chemotherapy uncommon) chemotherapy uncommon)
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P Nair
Pathology
Biphasic patternBiphasic pattern-- dense pilocytic glia dense pilocytic glia
Rosenthal fibers: Dense, eosinophilic fibers Rosenthal fibers: Dense, eosinophilic fibers (intermediate filaments )within cytoplasmic (intermediate filaments )within cytoplasmic processes of astrocytesprocesses of astrocytes
loose microcystic areas with EGBloose microcystic areas with EGB
Abnormal capillariesAbnormal capillaries-- pericystic MVPpericystic MVP +/+/-- necrosis, occasional mitosisnecrosis, occasional mitosis Degenerative nuclear changesDegenerative nuclear changes
Low gradeLow grade
Mib1 LI > 2%Mib1 LI > 2%-- risk of recurrencerisk of recurrence
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PILOCYTIC ASTROCYTOMA
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P Nair
ROSENTHAL FIBRES
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EGB
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MVP
Degenerative nuclear atypia
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DIFFUSE ASTROCYTOMA WHO II
(Fibrillary, Protoplasmic, Gemistocytic)(Fibrillary, Protoplasmic, Gemistocytic)
"Adult type" or "Hemispheric" "Adult type" or "Hemispheric" AstrocytomaAstrocytomaDiffusely infiltrate brain irrespective of Diffusely infiltrate brain irrespective of gradegrade
continuum from low continuum from low -- grade to high grade to high --grade; progress over timegrade; progress over timeGrade 2 Grade 2 3 3 4 (GBM)4 (GBM)
Imaging correlates with histologyImaging correlates with histology
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P Nair
Fibrillary Astrocytoma WHO grade II; Nuclear atypia +: WHO grade II; Nuclear atypia +: enlarged, irregular, hyperchromaticenlarged, irregular, hyperchromatic
No mitotic activity / necrosis/ MVPNo mitotic activity / necrosis/ MVP
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P Nair
GFAP
Mib1< 5%
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P Nair
Gemistocytic Astrocytoma [II]
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PROGRESSION
Astrocytoma IIAstrocytoma IILL-- 9p, 19q, 11p; CDK4 amplifiicn9p, 19q, 11p; CDK4 amplifiicn
(4(4-- 5 years)5 years)
Anaplastic Astrocytoma IIIAnaplastic Astrocytoma IIIPTEN mutn, MDM2 amplificn, PTEN mutn, MDM2 amplificn,
EGFR amplification*EGFR amplification*
(< 2 years)(< 2 years)
GBM (secondary)GBM (secondary); ; young adults, BS in young adults, BS in childrenchildren
* in Primary (de novo) GBM; * in Primary (de novo) GBM; older adults, rapid older adults, rapid progressionprogression
Mib1> 6 %
p53 +
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P Nair
Prognostic factors
GoodGood
YoungYoung Gross total resectionGross total resection
M/SM/S MicrocystsMicrocysts
PerivascularPerivascular
lymphocyteslymphocytes
PoorPoor
TP53 mutationTP53 mutation
MibMib--1 > 5%1 > 5%
M/SM/S Gemistocytes ++Gemistocytes ++
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P Nair
ANAPLASTIC ASTROCYTOMA
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P Nair Mib1 6- 10%
ANAPLASTIC ASTROCYTOMA
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GLIOBLASTOMA MULTIFORME
Pseudopalisaded necrosis
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P Nair
GLIOBLASTOMA MULTIFORME
Microvascular proliferation
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P Nair
GLIOBLASTOMA MULTIFORME
GoodGood
< 50 years< 50 years preop KPSpreop KPS Resection of Resection of
enhancing tumorenhancing tumor M/S:M/S:
Giant cellGiant cell Capillary MVPCapillary MVP Oligodendroglial Oligodendroglial
componentcomponent MGMTMGMT
PoorPoor
Mib1Mib1 Glomeruloid MVPGlomeruloid MVP Molecular Molecular
*VEGF+*VEGF+ *EGFR+*EGFR+ *her2 amplificn*her2 amplificn *PTEN/ Rb1 mutn*PTEN/ Rb1 mutn
* * Stealth invasion�Stealth invasion�-- hinders surgical disease controlhinders surgical disease control
* * CT/ RT resistanceCT/ RT resistance
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MODES OF SPREADMODES OF SPREAD
Natural passagesNatural passages
Along surfacesAlong surfaces-- leptomeningealleptomeningeal
Along tractsAlong tracts-- corona radiata, peduncles, corona radiata, peduncles, corpus callosum, anterior commissure, corpus callosum, anterior commissure, arcuate fibresarcuate fibres
Across the meningesAcross the meninges
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P Nair
Pleomorphic Xanthoastrocytoma WHO II
MeningocerebralMeningocerebral
Pleomorphic & foam cellsPleomorphic & foam cells
EGBEGB
Pericellular reticulinPericellular reticulin
Anaplastic PXA: III Mitoses > 5 / 10 HPFMitoses > 5 / 10 HPF
+/+/-- palisaded necrosis palisaded necrosis D/DD/D-- GBMGBM
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P Nair
PXA [ II]
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P Nair
Reticulin rich
�Mib-1 < 1%
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ASTROCYTOMA: 5 Year survival
0
10
20
30
40
50
60
70
80
GBM [IV] AA [III] LG A [I-II] JPA
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OLIGODENDROGLIOMA
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OLIGODENDROGLIOMA
GoodGood
Age: < 40yearsAge: < 40years
Low gradeLow grade
Gross total Gross total resectionresection
1p 19q del 1p 19q del ( a/w ( a/w better chemoresponse)better chemoresponse)
PoorPoor
MibMib--1 > 5%1 > 5%
Anaplasia Anaplasia Necrosis & Necrosis &
mitosis > 6/ 10 hpf)mitosis > 6/ 10 hpf)
P53 immunoexpP53 immunoexp
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P Nair
MIXED GLIOMA
OLIGOASTROCYTOMA OLIGOASTROCYTOMA ( II)( II) Conspicuous mixture of 2 distinct cell typesConspicuous mixture of 2 distinct cell types
At least one 100x field of oligo componentAt least one 100x field of oligo component
Origin from bipotential glial precursor cellsOrigin from bipotential glial precursor cells
CKDN 2A, occ EGFR amplificnCKDN 2A, occ EGFR amplificn
ANAPLASTIC OA (III)
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EPENDYMOMA
ChildrenChildren-- Infra/ supratentorialInfra/ supratentorial
AdultsAdults-- spinal cord*/ supratentorialspinal cord*/ supratentorial
Perivascular pseudorosettes/ True ependymal Perivascular pseudorosettes/ True ependymal rosettesrosettes
Poor prognosisPoor prognosis--
Child < 3years; Post fossaChild < 3years; Post fossa
Incomplete resectionIncomplete resection
AnaplasiaAnaplasia
MibMib--1 > 4%1 > 4%
CSF seedingCSF seeding
* * Most common glioma at this site, a/w NF2Most common glioma at this site, a/w NF2
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P Nair
EPENDYMOMA
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P Nair
ANAPLASTIC EPENDYMOMAANAPLASTIC EPENDYMOMA
De novo or rarely progress from preexisting grade IIDe novo or rarely progress from preexisting grade II
MYXOPAPILLARY EPENDYMOMA [I]MYXOPAPILLARY EPENDYMOMA [I] Almost exclusive in cauda equina/ Almost exclusive in cauda equina/ filum filum
terminale; good prognosisterminale; good prognosis
SUBEPENDYMOMA [I]SUBEPENDYMOMA [I] Slow growing, intraventricular grade I, favorable Slow growing, intraventricular grade I, favorable
prognosisprognosis
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P Nair
Myxopapillary EPENDYMOMA
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NEURONAL/ MIXED GLIONEURONAL TUMORS
RareRare
Favorable prognosis; usually low grade Favorable prognosis; usually low grade I/ III/ II
Variable neuronal & glial Variable neuronal & glial differentiationdifferentiation
Precise classification to avoid Precise classification to avoid unnecessary RT/CT unnecessary RT/CT
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P Nair
MEDULLOBLASTOMA- [IV] Most common pediatric brain tumor (infratentorial)Most common pediatric brain tumor (infratentorial)
Std risk factorsStd risk factors-- > 3 years; cerebellar tumor; > 3 years; cerebellar tumor; no mets at presentation; little/ no no mets at presentation; little/ no residual (<1.5 cmresidual (<1.5 cm33))
All others are All others are HIGHHIGH riskrisk-- + intense CT+ intense CT
M</S: M</S: Cellular/ Round cell tumorCellular/ Round cell tumor HomerHomer--Wright rosettesWright rosettes Desmoplastic & MBENDesmoplastic & MBEN-- good prognosisgood prognosis Large cell variantLarge cell variant-- poorpoor IHCIHC-- Synaptophysin, chromogranin ++Synaptophysin, chromogranin ++ MibMib--1 : 1 :
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P Nair
Homer Wright rosette
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P Nair
Supratentorial -PNET
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P Nair
Mic2 +
Synapto +Chromo +
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P Nair
MENINGEAL TUMORS
MENINGIOMA: MENINGIOMA: Meningioma (typical) [I]Meningioma (typical) [I] Atypical Meningioma [II]Atypical Meningioma [II] Anaplastic (Malignant) Meningioma [III]Anaplastic (Malignant) Meningioma [III]
MESENCHYMAL (nonMESENCHYMAL (non--meningothelial) meningothelial)
Primary MELANOCYTIC Lesions Primary MELANOCYTIC Lesions UNCERTAIN Origin UNCERTAIN Origin
Hemangiopericytoma Hemangiopericytoma HemangioblastomaHemangioblastoma
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Arise from meningothelial cells of Arise from meningothelial cells of arachnoid granulationsarachnoid granulations
Adjacent to venous sinusesAdjacent to venous sinuses
Nodular, capsulated, slow growingNodular, capsulated, slow growing--BenignBenign
Form whorls of cells, Psammoma Form whorls of cells, Psammoma bodies in the centerbodies in the center
Pressure effectPressure effect
No brain infiltration or metastasis No brain infiltration or metastasis (Benign)(Benign)
MENINGIOMA
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P Nair
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P Nair
MENINGEAL TUMORS
TYPETYPE GRADEGRADE
MENINGIOMAMENINGIOMA II
ATYPICAL MENINGIOMAATYPICAL MENINGIOMA IIII Clear cell; chordoidClear cell; chordoid
(( mitosis 4 mitosis 4 -- 19/ 10HPF; OR 3 of foll19/ 10HPF; OR 3 of foll-- cellularity, cellularity, N:C, N:C, prominent nucleoli, patternless growth, spontaneous/ prominent nucleoli, patternless growth, spontaneous/ geographic necrosis)geographic necrosis)
ANAPLASTIC MENINGIOMAANAPLASTIC MENINGIOMA IIIIII Papillary; rhabdoidPapillary; rhabdoid
(( mitosis > 20/ 10HPF; appearance like carcinoma/ sarcoma/ mitosis > 20/ 10HPF; appearance like carcinoma/ sarcoma/ melanoma)melanoma)
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P Nair
Meningioma
IHC: EMA +; MibIHC: EMA +; Mib--1< 4 / 1< 4 / 8 8 / / 1515 %% EM: Interdigitating cell processesEM: Interdigitating cell processes
Surgery if feasibleSurgery if feasible--
RTRT Incomplete resectionIncomplete resection Recurrent diseaseRecurrent disease Atypical / invasive featuresAtypical / invasive features
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P Nair
Hemangiopericytoma
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P Nair
CD34 +
Reticulin
Hemangiopericytoma
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P Nair
Primary Brain LYMPHOMA
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P Nair
Craniopharyngioma [WHO I]
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Metastasis
Most common brain tumor in adultsMost common brain tumor in adults
Common primary sites: breast, lung, GI Common primary sites: breast, lung, GI tract, kidney & melanomatract, kidney & melanoma
Most are in cerebrum (MCA territory); Most are in cerebrum (MCA territory); at the greyat the grey--white junctions due to white junctions due to vascularityvascularity
Discrete, globoid, sharply demarcated Discrete, globoid, sharply demarcated tumorstumors
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P Nair
Metastatic carcinoma
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Tumor heterogeneityTumor heterogeneity
Limited biopsy material Limited biopsy material
Team effortTeam effort-- SurgeonSurgeon
RadiologistRadiologist
PathologistPathologist
Radiation oncologistRadiation oncologist
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