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TUMORES DEL SNC
- CLASIFICACIÒN -
DR. RICARDO THEAUX
UNIDAD DE NEUROPATOLOGÌA
CLÌNICA REINA FABIOLA
UNIVERSIDAD CATÒLICA DE CÒRDOBA
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GLIOMAS CLASIFICACIÒN ( WHO-EORTC-2007)
• ASTROCITOMAS
- PILOCÌTICO
- FIBRILAR
- PROTOPLASMÀTICO
- GEMISTOCÌTICO
- XANTOASTROCITOMA
- ASTRO CÈLS. GIGANTES
- ANAPLÀSICO
• OLIGODENDROGLIOMAS
- CLÀSICO
- ANAPLÀSICO
• EPENDIMOMAS
- CLÀSICO
- MIXOPAPILAR
- SUBEPENDMOMAS
- ANAPLÀSICO
• TUMOR PLEXO COROIDEO
- CLÀSICO
- ANAPLÀSICO
- CARCINOMA
• OLIGOASTROCITOMAS
- ANAPLÀSICO
• COMPUESTOS (NEURONAL Y GLIAL)
- GANGLIOGLIOMAS
- DNET
• GLIOBLASTOMAS
- PRIMARIOS
- SECUNDARIOS A …
• GLIOSARCOMAS
• GLIOMATOSIS CEREBRI
• TUMORES EMBRIONARIOS
ASTROBLASTOMAS
EPENDIMOBLASTOMAS
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TUMORES GRADO I
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CÉLS. GLIALES
ASTROCITOS
OLIGODENDROCITOS
CÈLS. EPENDIMARIAS
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GLIOMAS
ASTROCITOMA PILOCíTICO (I)
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GLIOMAS
• CÈLULAS EPENDIMARIAS
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GLIOMAS
• EPENDIMOMA MIXOPAPILAR ( I )
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GLIOMAS
• PAPILOMA PLEXO COROIDEO ( I )
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TUMORES DEL SNC
NEURONALES
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GLIOMAS
GANGLIOCITOMA ( I )
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TUMORES DEL SNC
MIXTOS
GLIO-NEURONALES
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GLIOMAS MIXTOS ?
• TUMOR NEUROEPITELIAL
DISEMBRIOPLÀSTICO ( I )
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TUMORES DEL SNC
CÈLS. MENÌNGEAS
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•MENINGIOMA ( I )
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TUMORES GRADO II
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GLIOMAS
• ASTROCITOMAS DIFUSOS (II)
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GLIOMAS
• OLIGODENDROGLIOMA ( II )
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GLIOMAS
• OLIGODENDROCITOS Y ASTROCITOS
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GLIOMAS
• OLIGOASTROCITOMA ( II )
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GLIOMAS
• EPENDIMOMAS ( II )
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TUMORES DEL SNC
NEURONALES
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GLIOMAS
NEUROCITOMA CENTRAL (II )
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TUMORES DEL SNC
MIXTOS
GLIO-NEURONALES
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GLIOMAS
• GANGLIOGLIOMA ( II )
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TUMORES DEL SNC
CÈLS. MENÌNGEAS
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•MENINGIOMA ATÍPICO ( II )
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TUMORES GRADO III
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TUMORES DEL SNC
ANAPLÀSICOS ( III )
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TUMORES GRADO IV
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GLIOMAS
• GLIOBLASTOMA ( IV )
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GLIOMAS
• GLIOBLASTOMA
SECUNDARIO A ….. ( IV )
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TUMORES DEL SNC
NEURONALES
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GLIOMAS
MEDULOBLASTOMA ( IV )
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TUMORES DEL SNC
MENÌNGES
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•FIBROSARCOMA ( IV )
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TUMORES DEL SNC
LINFOMAS
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GLIOMAS
• METASTASIS CEREBRALES ( IV )
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TUMORES DEL SNC
INMUNOHISTOQUÌMICA
-TIPIFICAR LA CÈLULA QUE PROLIFERA:
- GFAP - NSE
- S100 - NF
- VIM - SYN
- NF - ANHIDRASA CARBÓNICA
- GRADO DE PROLIFERACIÒN CELULAR:
MIB 1 KI67
PCNA
P105
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GLIOMAS
GENÈTICA TUMORAL
COLABORA EN:
1- CONTROVERSIAS HISTOGENÈTICAS
2- POTENCIAL DIAGNOSTICO
3- MARCADOR PREDICTIVO DE PRONOSTICO Y RESPUESTA AL
TRATAMIENTO
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H-E EGFR
(CISH)
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EGFR-Glioblastoma
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Cr. 1p36 – CISH
Deleción
Oligodendroglioma
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Oligodendroglioma. Cr. 19q –CISH
Deleción significativa
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P53
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BIOLOGÍA MOLECULAR
P53 sobrexpr.
PDGFR sobrexpr.
P14 metil.
MGMT metil.
ASTROCITOMAS DIFUSOS II
IHQ
GFAP ++
S100 ++
VIM +
CK +
CAM5.2
MIB1-Ki67 < 3 %
IDH1/2 mut
TP53 mut.
Cr.7q gan.
Cr. 5p gan
Cr. 9 gan.
Cr. 19 gan.
Cr. 6 del.
Cr.19q pérd.
Cr. 22q LOH - Louis DN, Ohgaki H, Wiestler OD, Cavenee WK.
WHO Classif. Tumours CNS; 2007
-Killela et al. Oncotarget 2014
-Weller et al. Molec Classif Gliomas 2015
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BIOLOGÍA MOLECULAR
ASTROCITOMA ANPLASICO III
IHQ
GFAP ++
S100 ++
VIM ++
CK +
CAM5.2
MIB1-Ki67 5-10 %
IDH1/2 mut
TP53 mut.
PTEN mut.
.
Cr. 6q LOH
Cr. 10q LOH
Cr.17p LOH
Cr. 19q LOH
Cr. 22q LOH
EGFR amplif.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK.
WHO Classif. Tumours CNS; 2007
-Killela et al. Oncotarget 2014
- Weller et al. Molec Classif Gliomas 2015
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BIOLOGÍA MOLECULAR
GLIOBLASTOMA IV IHQ
GFAP ++
S100 ++
VIM ++
CK +
CAM5.2
MIB1-Ki67 > 10 %
TP53 mut.
PTEN mut
Cr. 1 del.
Cr. 6q LOH
Cr. 10q LOH
Cr.15p LOH
Cr. 17p LOH
Cr. 18q LOH
Cr. 22q LOH
Cr. “Y” pérd.
P14 del.
P16 del.
TERT Prom mut
EGFR amplif
MDM2 amplif
.
EGFRvIII sobrexpr.
MDM2 sobrexpr.
VEGF sobrexpr.
Cr. 7 gan.
P14 metil.
P16 metil.
Louis DN, Ohgaki H, Wiestler OD.,
WHO Classif. Tumours CNS; 2007
- Killela et al. Oncotarget 2014
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Diagnóstico Diferencial de Glioblastomas
SECUNDARIOS
Mujeres
Menor edad
(+) tiempo de síntomas
EGFR amplif. bajo
PTEN mut. bajo
Cr. 10q pérd.
Cr. 19q pérd.
MGMT metil.
sobrexpres.
P53 mut. Aumento
IDH1/2 mut.
PRIMARIOS
Varones
Mayor edad
(-) tiempo de síntomas
EGFR amplif. Au
PTEN mut. Au
P16 del.
DMBT-1 del.
MDM2 sobrexpres.
P53 mut. Bajo
TERT promoter mut
Cr. 10 LOH au
Cr. 1p LOH au
P14 del. au
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BIOLOGÍA MOLECULAR
OLIGODENDROGLIOMA II
IHQ
No hay marcador
específico
S100 +
PBM +
GFAP +
PLP +
MAG +
HNK1 +
VIM +
Anhidr. Carbonica C+
Neuronales en bordes
MIB1-Ki67 < 5 %
TP53 mut.
rara
Cr. 4 pérd.
Cr. 6 pérd.
Cr.14 pérd.
Cr. 22q LOH
IDH1/2 mut.
TERT promot mut
1p del.
19q del.
Cr. 7 gan.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK.
WHO Classif. Tumours CNS; 2007
EGFR sobrexpr
PDGF/PDGFR sobrexpr.
EGFR amplif.
FGF
TGF-B
IGF-1
NGF
VEGF/VEGFR - Killela et al. Oncotarget 2014
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BIOLOGÍA MOLECULAR
Cr. 7 gan.
Cr. 15q gan. TP53 mut.
Cr. 4q pérd.
Cr. 6 pérd.
Cr. 9p pérd.
Cr. 10q pérd.
Cr.11 pérd.
Cr. 13q pérd.
Cr. 18 pérd.
Cr. 22q pérd.
OLIGODENDROGLIOMA ANAPLÁSICO III
IHQ
VIM +++
MIB1-Ki67 > 5 %
IDH1/2 mut
TERT prom mut
1p del.
19q del.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK.
WHO Classif. Tumours CNS; 2007
P14 metil.
RB1 metil.
VEGF/VEGFR sobrexpr.
EGFR amplif.
PDGFRA amplif.
MDM2 amplif.
CDK4 amplif. - Killela et al. Oncotarget 2014
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OLIGODENDROGLIOMA II
BIOLOGÍA MOLECULAR
CAMBIOS EPIGENÉTICOS:
CDKN2 A y B
P14 ARF
RB1
DAPK-1
ESR 1
THBS
TIMP-3
MGMT
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK., WHO Classif. Tumours CNS; 2007
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TUMORES DEL SNC
ESTEREOTAXIA
COMPUTARIZADA
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BASES MOLECULARES DEL CANCER
• ONCOGENES
- Factores de crecimiento y sus receptores:
- PDGFRA
- EGFR
- VEGFR
- bFGF
- Proteínas transductoras de señales:
- P21
- Proteínas reguladoras nucleares
• GENES SUPRESORES DEL CANCER
Mut. TP53 - P53 mutante
MDM2 amplif.
INHIBIDORES DE LA APOPTOSIS
- Sobreexpresa Bcl-2
Proliferación
y/o
grado
biológico
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GLIOMAS
GENÈTICA TUMORAL
OLIGODENDROGLIOMAS:
Pèrdida Cr 1 p = QTX sensible
+
pèrdida CR 19q = larga respuesta al tratamiento.
ASTROCITOMAS: Astrocitos + Mut. P53 + LOH 17p: ASTROCITOMA
ASTROCITOMA + Mut. Rb y LOH 13p y LOH 19q: ASTROCITOMA ANAPLÀSICO
AA + AMPLIF. EGF-R Y LOH 10: GLIOBLASTOMA