Neuropathology of Brain Tumours · Neuropathology of Brain Tumours ... Neuropathology -Approach to...

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

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.

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

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

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

-

+

+

-

-

+/-

-

-

+/-

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

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

Medulloblastoma WHO Grade

IV

Medulloblastoma comprising

small round blue cells with

increased mitotic and apoptotic

activity

Pilocytic astrocytoma WHO Grade I

Figure 1 Pilocytic astrocytoma showing

elongated piloid cells and corkscrew

eosinophilic Rosenthal fibres (arrow)

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

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).

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)

Oligodendroglioma WHO grade

II

Figure 4 Oligodendroglioma showing

‘fried egg’ tumour cells separated by

thin-walled vessels

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)

Case 1

• 56 year old man presents with unilateral

hearing loss, and vertigo

• After his operation the patient was left

with a facial droop

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

? Diagnosis

S100

Case 2

• 56 year old man presents with a subtle

slow onset of memory and problems with

his speech

A poorly demarcated tumour diffusely invades the left

temporal lobe and thalamus, resulting in midline shift

neoplastic astrocytes reactive astrocytes

GFAP- glial fibrillary acidic protein

Case 3

• A 35 year old man presents with subtle

personality changes and motor weakness in

the right arm

This infiltrating neoplasm expands gyri and deep white

matter in the frontal lobe, distorting striatum and lateral

ventricles causing subfalcine herniation

GFAP ‘fried eggs- negative, minigemistocytes- positive’

Case 4

• 4 year old boy presents acutely with

nausea and vomiting

A soft homogenous mass destroys and occupies the

fourth ventricle

Marker of proliferation

MIB1 ~Ki67

Case 5

• 70 year old woman presents with slow

onset of visual disturbances

A fleshy dural-based midline tumour has compressed the inferior

part of the frontal lobes

EMA- epithelial membrane antigen

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

Genetics and epigenetics

Cancer stem cell theory

Frontiers in glioma research

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

.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

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.

Kurian KM, Cover Nature Reviews Clinical Oncology 2012

Glioma-derived Cancer Stem cells generate tumours following

xenotransplantation

In collaboration with Steve Pollard, Peter Dirks

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

Neoplastic astrocytes are

strongly GFAP positive (x20)

G26 original: Glioblastoma WHO Grade IV

Neoplastic astrocytes showing

Focal multinucleation (arrow) (H

and E x20)

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)

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.

Thank you