Neuropathology 2 Brain Tumours Flashcards
What are 3 ways even slow-growing, well-differentiated tumours in the brain can cause serious problems?
1.) Compression or destruction of smaller, critical brain areas such as the medulla
2.) Tumours that are difficult to isolate from normal brain tissue can result in extensive destruction when they are removed
3.) Damage to the blood-brain barrier or development of epilepsy due to the tumour or its removal
What is the most common glioma?
astrocytomas
Astrocytomas range from I-IV. The higher-grade tumours exhibit:
1.) greater anaplasia
2.) greater invasion into the surrounding tissues
3.) increased necrosis and more sites of hemorrhage/BBB incompetence
Naming conventions for different grades:
I, II, III, IV
Grade I – pilocytic astrocytoma (commonly-used name)
Grade II – diffuse astrocytoma
Grade III – anaplastic astrocytoma
Grade IV – glioblastoma multiforme (commonly-used name)
Which grade of astrocytomas tends to occur in children and young adults?
Grade I aka pilocytic astrocytomas
Where are Grade 1 astrocytomas often found? What kind of mass? Well differentiated? Easy to separate? Size? How many processes? Hemorrhagic areas? Necrosis? BBB? What
cerebellum, optic nerves, 3rd ventricle
solid or cystic mass
Well-differentiated, easy to separate from surrounding normal brain tissue
Large, 2 processes
Few hemorrhagic areas, less necrosis, preservation of BBB
Grade I astrocytomas is usually due to excessive activation of what?
Raf
Which grade of astrocytomas is more common in adults, found above the tentorium in the cerebrum?
Grade II & III
Grade III are similar to grade II in that they are both poorly differentiated cells and invade surrounding brain. But how are they different?
More mitotic figures, larger cells
What are mutations of grade II and III?
1.) PTEN: inactivated PTEN –> excessive signaling through the PI3K pathway
Increased EGF or PDGF receptor activity or expression
Epidermal growth factor, platelet-derived growth factor
P16, p14 or p53 inactivation
IDH mutations – isocitrate dehydrogenase mutations that produce a metabolite (2-hydroxyglutarate) that “dysregulates” epigenetic signaling in the glial cell excessive activation of the RAS pathways
Which brain tumour in adults in the most common?
Grade IV astrocytomas aka glioblastoma multiforme
Which brain tumour has the worst prognosis?
Grade IV
Which brain tumour has prominent hemorrhage, necrosis, rapid growth, and tendencies to invade the adjacent tissue more than other types?
Grade IV
Which mutations are more common in grade IV?
p53, EGFR (epidermal growth factor receptor) mutations are more common
What are the signs and symptoms of astrocytomas?
Headache (worse in the morning), intensified by straining and coughing, nausea, vomiting, 6th cranial nerve palsy, focal changes caused by invasion/damage of normal brain tissue (seizures, hemiparesis (one-sided weakness), ataxia, memory loss)
What percent of astrocytomas are grade II-IV?
80%
What is the median survival for Grade II?
5-6 year
What is the median survival rate for Grade IV?
less than 1 year
Worse prognosis is associated with what 3 things?
1.) infiltration of normal tissue
2.) hemorrhage and necrosis
3.) rapid cell division
What is the best imaging method?
MRI
What treatment methods are commonly used? Is treatment for all types the same?
Radiation, chemotherapy, and surgery
no
What are the signs/symptoms of increased intracranial pressure?
1.) Slowing of mental capacity
2.) headaches (especially if more severe in the morning)
3.) vomiting (more likely in the morning)
4.) blurred and/or double vision
5.) blurred = optic nerve atrophy due to papilledema, double vision = 6th cranial nerve palsy (usually)
6.) In kids – precocious puberty, stunted growth due to hypothalamic impairment
7.) Difficulty walking (spasticity)
Which cranial nerve causes double vision?
CN VI palsy
Which type of herniate are more likely with cerebral masses?
sub-falcine and transtentorial
What percent of gliomas are Oligodendrogliomas? What age group?
5-15%
40’s and 50’s
Where are Oligodendrogliomas found?
cerebral hemispheres, around white matter areas
Which mutations are common in Oligodendrogliomas?
IDH
Are Oligodendrogliomas a quick onset or slowly increasing in intracranial pressure
slowly increasing
Are seizures common in Oligodendrogliomas?
Yes
Is the treatment of Oligodendrogliomas similar or different to astrocytomas?
similar
Is the prognosis of Oligodendrogliomas better or worse than that of astrocytomas?
better
Where do Ependymomas arise from?
ependymal cells of the ventricular system
In kids, which ventricle is frequently blocked? Which canal?
4th ventricle, central
Because Ependymomas can produce a lot of CSF, what can they cause?
communicating (excess CSF) or non-communicating (blockage of CSF movement) hydrocephalus
What location are Ependymomas easier to remove from?
spinal cord
Ependymomas in which ventricle have a worse prognosis?
4th ventricle/posterior fossa
Signs and symptoms of Ependymomas are typical of what condition?
hydrocephalus and elevated intracranial pressure if in the cranium
If Ependymomas have spinal cord compression, what signs/symptoms are present?
paresis, pain, sensory deficits
Which tumors are usually fairly benign and in adults?
meningiomas
Where are Meningiomas attached and where do they often arise from?
attached to dura, arise from the meningothelial cell of the arachnoid
What percent of all primary brain tumours do Meningiomas make up?
20%
Where are Meningiomas found?
along the external surfaces of the brain and within the ventricular system
What are the pathological findings of Meningiomas?
rounded masses with a dural base that compresses underlying brain but are easily separated from it by a thin fibrous capsule
Sometimes extension into the overlying bone or “sheet-like” spreading through the brain
Meningiomas pathogenesis? Clinical features? Prognosis (FYI???)
Loss of the NF2 gene – regulates signaling through a variety of receptors that are involved in growth and the cell cycle
We’ll see it again in the disease neurofibromatosis
Clinical Features
Symptoms/signs of elevated intracranial pressure
Symptoms/signs caused by compression of
The cortex near the falx cerebri
Wing of the sphenoid
Foramen magnum
Interestingly, meningiomas tend to grow quite rapidly during pregnancy (not sure why)
Prognosis tends to be good – they tend to grow slowly and do not usually invade adjacent tissue
Surgery main treatment
What is a tumour with very poorly-differentiated, “primitive-looking” cells with rapid growth, highly anaplastic and can metastasize widely and even extend all the way into the cauda equina?
Medulloblastomas
Who does Medulloblastomas occur in?
children and adults
Where do medulloblastomas occur?
cerebellum
Due to encroachment on the 4th ventricle by Medulloblastomas, what can happen?
Obstruction of CSF flow
What are the signs/ symptoms of Medulloblastomas similar to?
hydrocephalus due to impaired CSF and damage to cerebellum
What kind of treatment is Medulloblastomas very responsive to?
radiation therapy
Does Medulloblastomas have a good prognosis?
Yes
What is a non primary brain tumour called? Where are they often found? (2)
metasteses
meninges
deep into cortical structures
