Neuropathology Flashcards
What are the most common primary tumours that spread to the Brain?
- Breast
- Melanoma
- Lung
- Kidney
- gut
- lymphoma /leukaemia
What are the symptoms of a space occupying lesion?
- fits
- Drowsiness
- Behavioural change
Breast cancer and spread to the brain
- Ductal and lobule carcinoma
* Ductal carcinoma is more likely to spread to the Brian
What is a triple negative breast cancer?
- No oestrogen receptor
- no HER2 target
- no progesterone receptor
What is the most common intracranial primary neoplasm?
Meningioma approx 1/3
What is most common neoplasm on the malignant spectrum?
Glioma
Intracranial peripheral nerve tumour
Acoustic schwannoma
Where do meningiomas develop?
At the sites of arachnoid
How do meningiomas cause damage?
They are not invasive but they are erosive and compressive
What are the symptoms of meningiomas?
- Fits
- Drowsiness
- Headaches
- Sometimes bleed
- Sometimes there is a personality change
What is the treatment of meningiomas?
- Surgical removal
* Radiation encouraged as can activate the tumour making it more metastatic
Which cells can gliomas develop from?
- Astrocytes
- Oligodendrocytes
- Ependyma/choroid plexus
- microglia
What are the types of gliomas?
- Astrocytoma - common
- Oligodendeoglioma
- Ependyma
- Medulloblastoma and PNET
Describe the WHO glioma grading
- I - localised (potentially curable)
- II - diffuse
- III anaplastic astrocytoma
- I glioblastoma multiforme
Describe the diagnostic and prognostic molecular and genetic testing
- BRAF fusion gene and V600E point mutations (astrocytoma)
- molecular analysis of LOH1p/19q in astrocytomas and oligodendrogliomas
- IDH1/2 mutations = better outlook
Describe prognostic and predictive molecular testing
- methylation of MGMT in malignant gliomas
* Molecular analysis of EGFR amplifications and EGFRvIII mutations in GBM
What are the peripheral nerve tumours?
- Nerve: neuroblastoma, ganglioneuroma
- Schwannoma or neurofibroma - benign
- CNVIII - vestibulocochlear: acoustic nerve
What is a Schwannoma?
- Tumour arising from the Schwann cell
- Compresses the nerve but potential for successful excision
- Can be painful as it presses on the nerve
What is a neurofibroma?
- Nerve sheath: non- myelinating Schwann cell (myelin sheath)
- Diffuse: fibrous like tissue: can’t be dissected out while preserving the nerve (leave alone unless symptomatic)
- Can be sporadic, possibly as result of trauma
Describe neurofibromatosis
- Autosomal dominant
- 50% spontaneous
- Mutation in gene NF1
- Multiple tumours growing in multiple locations
- Cafe au lait
What happens if neurofibromatosis is left untreated?
Can become malignant - neurofibrosarcoma
What are the problems of relying on pathology?
- Sampling error e.g. sampling wrong bit in a a temporal artery biopsy
- Accessibility of the tissue
- Often tissue is only available in late disease process e.g. post mortem
Describe the pathology of multiple sclerosis
- Recurrent inflammation due to a breakdown of the blood brain barrier
- Infiltration of inflammatory cells that go on to cause demyelination
- This tends to happen around fingers or venules, particularly around the paraventricular region of the brain and the corpus callous (Dawson’s fingers)
- Degree of recovery - demyelination, this leaves shadow plaques where there has been deposition but is thinner
- Astrocytes, fibrous plaques, hardened plaques
Describe the pathology of motorneuorone disease
- Degeneration of corticospinal tract - preservation fo the dorsal columns and sensory tracts
- Degeneration of hypoglossal nuclei (in the medial medulla)
What are the causes of peripheral neuropathy?
- Diabetes mellitus
- Idiopathic
- Toxic: alcohol, drugs
- Post infections
- Vitamin deficiency
- Paraneoplastic
- Leprosy
- Amyloid, other inflammation
What is the most common cause of inherited peripheral neuropathy?
• An abnormality in the peripheral myelin protein 22
What is the phenotype of Charcot Marie tooth?
Distal wasting and weakness resulting arched feet and champagne bottle legs
When would you carry out a sural nerve biopsy?
- To work out the cause of a neuropathy and determine if it is treatable
- Only do if there is a good reason for doing so as the patient will lose sensation beyond the point of biopsy and 30% will experience a burning neuropathic pain
What are slow twitch fibres innervated by?
alpha 2 motor neurones
What are fast twitch fibres innervated by?
Alpha 1 motor neurones
Out of slow and fast twitch fibres, which has a higher conduction velocity?
• Fast twitch
Describe motor unit recruitment
- Motor neurones are recruited in order of size
- Smallest alpha motor neurones, which belong to slow twitch are recruited first
- Largest alpha motor neurones which belong to fit twitch are recruited last
Describe the staining properties of slow and fast twitch fibres
- Slow twitch have myosin isoforms have low ATPase activity
* Fast twitch have myosin isoforms with high ATPase activity
In a muscle biopsy, which muscle is usually used?
- Deltoid
- Quadriceps
- Tibilais anterior
What is DMD?
- Duchenne muscular dystrophy
- X linked recessive, only affects boys
- Dystrophin - protein that links the cytoskeleton to the membrane
