Histopathology - Neurooncology Flashcards
Tumours of the PNS
Small nerves
Large nerves
Small nerves - neurofibromas
Large nerves - schwanommas
Commonest type of CNS tumours in
adults
children
adults - secondary (metastases)
o Well demarcated, solitary or multiple with surrounding oedema
children - primary
Commonest extra-axial and intra-axial tumour
extra-axial - meningioma
intra-axial - glial cell tumour
Commonest malignant vs non-malignant primary CNS tumour
malignant - GBM
Non-malignant - non-malignant meningioma
Where does glioblastoma originate from?
Astrocytes
It is a neuroepithelial tumour
Neurofibromatosis chromosomes and tumours
NF1 - Chr 17
neurofibroma, pilocytic astrocytoma, optic glioma
NF2 - Chr 22
Schwannoma, meningioma, ependymoma, astrocytoma
Grade of gliomas and radiotherapy vs chemotherapy
Radiotherapy - low grade, high grade, mets, benign tumours
Chemotherapy - high grade, lymphomas
temozolomide
WHO classification of brain tumours
Tumour type (histological type - derived from cell of origin or lineage of differentiation)
Grade - based on morphological/ histological criteria and predicted natural clinical behaviour (does not consider response to treatment)
Grading tells us survival but does not tell us therapy response/disease spread/cell of origin
• Survival refers to the natural history of the tumour (i.e. if they are not treated)
Molecular profile - genetic profile, molecular markers
staging NOT used except for medulloblastoma
Which are the 3 gliomas
Astrocytes - astrocytoma (commonest)
oligodendrocytes - oligodendroglioma
ependyma - ependymoma
astrocytomas are more aggressive than oligodendroglioma
ependyma = the thin membrane of glial cells lining the ventricles of the brain and the central canal of the spinal cord.
(also
schwann cells
microglia
satellite cells)
What kind of tumour originated from Embryonal cells?
Medulloblastoma
Low grade vs high grade
low grade
grade 1 - benign, long term survival
grade 2 - >5y
high grade
grade 3 - <5y
grade 4 - <1y
Most common primary CNS tumour
Glioma
Which are the glial cells
Astrocytes oligodendrocytes ependymal cells schwann cells microglia satellite cells
Mutations in diffuse glial tumours that are good prognostic factors and are associated with long term survival
IDH1/2 mutations
associated with a longer survival + a better response to chemo/radio
Gliomas in adults vs children
adults - diffuse gliomas, supratentorial, grades >=2, malignant, IDH1/IDH2, H3 mutations
children - circumscribed gliomas, posterior fossa, grades 1-2, rarely malignant, MAPK pathway mutations (BRAF (50%), NF1, FGFR1)
most common brain tumour in children
second most common brain tumour in children
Pilocytic astrocytoma (grade 1) medulloblastoma (grade 4)
pilocytic astrocytoma buzzwords
location
mutation
MRI
Histopathology
circumscribed glioma
grade 1
most common child brain tumour
CEREBELLAR, optic-hypothalamic, brainstem
NF1 BRAF mutation (70%)
MRI - well circumscribed, cystic, enhancing lesion, little surrounding oedema
Histopathology
Piloid cell
Rosenthal fibres, granular bodies
Slow growing, low mitotic activity
Oligodendroglioma buzzwords
20-40y
Long history of neurological signs (e.g. seizures)
cytology –> fried eggs –> round cells with clear cytoplasm
soft, gelatinous, calcified
better prognosis than astrocytoma
(slow growth - can be resected, good response to chemo/radio)
IDH1/2 mutation + co-deletion of 1p/19p
How does astrocytoma present on an MRI
Non enhancing lesion
Histology of astrocytoma
low mitotic activity
low cellularity
no vascular proliferation or necrosis
where is astrocytoma found in
adults
children
adults - cerebral hemisphere
children - brainstem, cerebellum
Most common glioma
GBM
Most common primary CNS tumour
GBM
Most aggressive glioma in adults
GBM
How can a GBM have an IDH1 mutation?
90% of cases of GBM occur denovo and have wildtype IDH(poor prognosis)
10% occur secondary to astrocytoma progression and have the IDH mutation (positive prognostic factor)
GBM
MRI
Histology
MRI
HETEROGENOUS mass
enhancing post-contrast
histology high cellularity high mitotic activity microvascular proliferation (neoangiogenesis)* necrosis
- abnormal blood vessels –> typical of GBM
1st and 2nd most common CNS tumours in adults
1 glioma
2 meningioma
what kind of tumour is meningioma?
extra-axial
Meningioma
MRI
Histology
MRI
Extra-axial, isodense, contrast-enhancing
Histology
Psammoma bodies(round collection of calcium)
calcification
Most useful predictor of recurrence
Grading
Mitotic activity
grade 1
grade 2
grade 3
mitotic activity per HPF (high power field)
grade 1 <4
grade 2 4-20
grade 3 >20
How do we determine origin of brain mets?
Immunohistochemistry
Where is metastatic brain disease usually found and why?
• Located at grey/white matter junction +/or leptomeningeal disease (cortical – subcortical junction)
o As structure of cerebral blood vessels changes at this point (become smaller as they enter the white matter) -> neoplastic emboli tend to get stuck at this level and then start growing
Most frequent cancers causing mets to the CNS
Lung
Breast
Melanoma
Renal
Where does medulloblastoma originate from
Neuroepithelial cells or neuronal precursors of the cerebellum/ dorsal brainstem
Derived from periventricular tissue around the 4th ventricle
Medulloblastoma histopathology
Blue tumour “small blue round cell”*
Large hypochromic nuclei
Homer Wright rosettes*
https://www.bing.com/images/search?q=homer+wright+rosettes&form=HDRSC2&first=1&tsc=ImageHoverTitle
grow in sheets
express neuronal markers (i.e. very little differentiation) - synaptophysin, GFAP, Ki67
*features of primitive cell lines/primitive neuronal differentiation
What is methylome profiling and where is it used?
o Most tumours have characteristic patterns of DNA methylation of CpG islands
o The methylation signature is stable + reflects the tumour cell of origin –> Give information on tumour type
Helpful for atypical cases, rare entities, small biopsies, subtyping
Not used for grade/progression or targeted therapy
does not consider the histology/ does not require histological correlation
• Buzzwords
o NF2
o Ventricular tumour, hydrocephalus
o Indolent, childhood
o Soft, gelatinous, calcified
• Buzzwords
o NF2 – meningioma
o Ventricular tumour, hydrocephalus – ependymoma
o Indolent, childhood – pilocytic astrocytoma
o Soft, gelatinous, calcified - oligodendroma
a. Seizure following 2 weeks of left arm and leg weakness
b. MRI showing heterogeneous enhancing right frontal lesion, started on steroids
c. Partial response to steroids with improved dexterity of the left arm and leg
d. A tumour was partially resected
e. Glioblastoma (WHO grade IV)
f. Oligodendroglioma (WHO grade II)
g. Metastatic carcinoma
h. Diffuse astrocytoma (WHO grade II)
i. Answer – E
MRI showing HETEROGENOUS ENHANCING right frontal lesion, started on steroids
- year-old boy
a. Had headache and vomiting in the morning for 2 weeks
b. Symptoms worsened and the vision became blurred
c. Fundoscopic exam: papilledema
d. MRI showing cystic cerebellar lesion tumour was removed
e. Glioblastoma (WHO grade IV)
f. Medulloblastoma (WHO grade IV)
g. Oligodendroglioma (WHO grade II)
h. Pilocytic astrocytoma (WHO grade I)
i. Answer - H
Histology is of a low grade glial tumour, not a blue tumour (medulloblastoma)
d. MRI showing CYSTIC CEREBELLAR lesion
