neuropathology of brain tumours · neuropathology of brain tumours ... neuropathology -approach to...
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Neuropathology of Brain Tumours
Dr Kathreena M Kurian
Consultant Neuropathologist/
Honorary Senior Lecturer, Bristol
Utube tutorial: Brain Tumour
Neuropathology -Approach to diagnosis of
common brain tumours
https://www.youtube.com/watch?v=Ln7FtHJ6nyk
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FRCPath Guidelines
Twenty cases will be provided in 10 pairs of haematoxylin and eosin
(H&E) stained slides in 20 minute slots over 3hrs 20 minutes on the
second morning. The cases are selected according to a blueprint and
include a balanced mixture of neoplastic and non-neoplastic material.
The cases are drawn from a wide range of organ systems including
upper and lower gastrointestinal tract, endometrial and non-
endometrial gynaecological pathology, breast, skin, soft tissue,
osteoarticular, respiratory, urological, lymphoreticular and endocrine
systems.
This list is not comprehensive and material from paediatric and
neuropathological areas may also be included from within the systems
listed above.
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The four essential clinical features for
histological diagnosis are:
age of the patient
location of the tumour
duration of symptoms and
the presence or absence of contrast enhancement
on radiology
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Differential Diagnosis in Children and Adults
Children Adults
Posterior Fossa
Medulloblastoma
Pilocytic Astrocytoma
Ependymoma
Choroid plexus tumour
Anterior Fossa
Diffuse astrocytoma
Anaplastic astrocytoma
Glioblastoma
Oligodendroglioma
Midline
Craniopharynioma
Germ Cell tumour
Dural-Based
Meningioma
Spinal cord
Ependymoma
Astrocytoma
Peripheral Nerve Sheath Tumours
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WHO Grading features of the more common
astrocytic tumours
Common
Astrocytic
Tumours
WHO
Grade
Mitotic
Figures
Microvascular
Proliferation
Necrosis
CHILDREN
Pilocytic
astrocytoma
I
+/-
+/-
+/-
CHILDREN and
ADULTS
Diffuse astrocytoma
Anaplastic astrocytoma
Glioblastoma
II
III
IV
-
+
+
-
-
+/-
-
-
+/-
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Immunohistochemical profile of the more
common NS tumours
Tumour category Helpful Immunohistochemistry
Astrocytoma GFAP (Glial Fibrillary Acidic Protein) less
positivity in poorly differentiated tumours
Oligodendroglioma Fried-eggs GFAP-negative
Minigemistocytes GFAP-positive
Ependymoma GFAP, S100, variable EMA dot-positivity
Medulloblastoma Synaptophysin, Neu N, focal GFAP
Meningioma EMA, vimentin
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Differential Diagnosis in Children and Adults
Children Adults
Posterior Fossa
Medulloblastoma
Pilocytic Astrocytoma
Ependymoma
Choroid plexus tumour
Anterior Fossa
Diffuse astrocytoma
Anaplastic astrocytoma
Glioblastoma
Oligodendroglioma
Midline
Craniopharynioma
Germ Cell tumour
Dural-Based
Meningioma
Spinal cord
Ependymoma
Astrocytoma
Peripheral Nerve Sheath Tumours
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Medulloblastoma WHO Grade
IV
Medulloblastoma comprising
small round blue cells with
increased mitotic and apoptotic
activity
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Pilocytic astrocytoma WHO Grade I
Figure 1 Pilocytic astrocytoma showing
elongated piloid cells and corkscrew
eosinophilic Rosenthal fibres (arrow)
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Differential Diagnosis in Children and Adults
Children Adults
Posterior Fossa
Medulloblastoma
Pilocytic Astrocytoma
Ependymoma
Choroid plexus tumour
Anterior Fossa
Diffuse astrocytoma
Anaplastic astrocytoma
Glioblastoma
Oligodendroglioma
Midline
Craniopharynioma
Germ Cell tumour
Dural-Based
Meningioma
Spinal cord
Ependymoma
Astrocytoma
Peripheral Nerve Sheath Tumours
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Diffuse astrocytoma WHO Grade II,
Anaplastic astrocytoma WHO Grade III
Figure 2: Diffuse astrocytoma showing
mildy pleomorphic bland oval nuclei
(arrow) with indistinct fibrillary cell
processes. No mitotic figures are present.
Figure 3: Anaplastic astrocytoma
showing increased cell packing
density, nuclear pleomorphism and
mitotic activity (circle).
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Glioblastoma WHO Grade IV
Figure 3a) macroscopic appearance
showing diffuse tumour with
haemorrhage, cystic change, midline
shift and spread
b) pseudopalisading of tumour
nuclei around an area of
necrosis (arrow)
c) microvascular proliferation
showing multilayering of cells in
a vessel forming a glomeruloid
structure (arrow)
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Oligodendroglioma WHO grade
II
Figure 4 Oligodendroglioma showing
‘fried egg’ tumour cells separated by
thin-walled vessels
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Meningioma WHO Grade I
Figure 7 a Meningioma showing
whorls of cells with an intranuclear
pseudoinclusion (arrow)
Figure 8 b Meningioma with
Psammoma bodies (arrow)
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Case 1
• 56 year old man presents with unilateral
hearing loss, and vertigo
• After his operation the patient was left
with a facial droop
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Case 2 macro:
A wedge of temporal bone containing the internal auditory meatus:
A pale fleshy tumour mass was present arising from the eighth cranial
nerve
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? Diagnosis
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S100
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Case 2
• 56 year old man presents with a subtle
slow onset of memory and problems with
his speech
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A poorly demarcated tumour diffusely invades the left
temporal lobe and thalamus, resulting in midline shift
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neoplastic astrocytes reactive astrocytes
GFAP- glial fibrillary acidic protein
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Case 3
• A 35 year old man presents with subtle
personality changes and motor weakness in
the right arm
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This infiltrating neoplasm expands gyri and deep white
matter in the frontal lobe, distorting striatum and lateral
ventricles causing subfalcine herniation
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GFAP ‘fried eggs- negative, minigemistocytes- positive’
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Case 4
• 4 year old boy presents acutely with
nausea and vomiting
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A soft homogenous mass destroys and occupies the
fourth ventricle
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Marker of proliferation
MIB1 ~Ki67
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Case 5
• 70 year old woman presents with slow
onset of visual disturbances
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A fleshy dural-based midline tumour has compressed the inferior
part of the frontal lobes
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EMA- epithelial membrane antigen
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Frontiers in neurooncology
Kurian KM
Research Group
3 PhDs
Dr Harry Haynes: Pathological Society of Great Britain and Ireland/
Jean Shanks Foundation started PhD sept 2014
searchsearch
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Genetics and epigenetics
Cancer stem cell theory
Frontiers in glioma research
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Brain tumours
Loss of 1p/19q Oligodendroglioma predicts chemosensitivity
MGMT methylation status Glioblastoma predicts resistance to
alkylating agents
Isocitrate dehydrogenase (IDH1/2) mutations
Vaccine to EGFRvIII
IDH mutation analysis in gliomas as a diagnostic and prognostic biomarker. Kurian KM, Haynes HR, Crosby C, Hopkins
K, Williams M. Br J Neurosurg. 2013 Aug;27(4):442-5
EGFR and EGFRvIII analysis in glioblastoma as therapeutic biomarkers.Faulkner C, Palmer A, Williams H, Wragg
C, Haynes HR, White P, DeSouza RM, Williams M, Hopkins K, Kurian KM.Br J Neurosurg. 2014 Aug 20:1-7.
Genetics and epigenetics
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.Prognostic and predictive biomarkers in adult and pediatric gliomas: toward personalized treatment.
Haynes HR, Camelo-Piragua S, Kurian KM.Front Oncol. 2014 Mar 24;4:47
Cancer Genome Atlas: large scale multidimensional
analysis- DNA copy no, gene expression, DNA
methylation aberrations in 206 glioblastomas
Whole genome sequencing: personalised medicine
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Cancer Stem Cell Theory
The impact of neural stem cell biology on CNS carcinogenesis and tumor types.
Kurian KM.
Patholog Res Int. 2011;2011:685271. Epub 2011 May 19.
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Kurian KM, Cover Nature Reviews Clinical Oncology 2012
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Glioma-derived Cancer Stem cells generate tumours following
xenotransplantation
In collaboration with Steve Pollard, Peter Dirks
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Induction of pluripotent stem cells from adult human
fibroblasts by defined factors.
Takahashi K, Tanabe K, Ohnuki M et al Cell 2007
4 factors including cmyc reprogramme mature
skin fibroblast into pluripotent cell ‘IPS’ cell
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Neoplastic astrocytes are
strongly GFAP positive (x20)
G26 original: Glioblastoma WHO Grade IV
Neoplastic astrocytes showing
Focal multinucleation (arrow) (H
and E x20)
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i26 subcutaneous 13.1 A4283
Mesenchymal muscle
differentiation ( H and E x20)
Primitive endodermal glandular
structure (H and E x20)
Primitive ectodermal hairfollicle
(H and E x20)
Immature teratoma with areas of
necrosis (arrow)
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Widespread resetting of DNA methylation in
glioblastoma-initiating cells suppresses malignant
cellular behaviour in a lineage- dependent manner
Stricker SH, Feber A, Engström PG, Carén H, Kurian
KM, Takashima Y, Watts C, Way M, Dirks P,
Bertone P, Smith A, Beck S, Pollard SM.
Genes Dev. 2013 Mar 15;27(6):654-69. doi:
10.1101/gad.212662.112.
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Thank you