Histopathology Flashcards
Where do non-traumatic intraparenchymal haemorrhages tend to occur most frequently?
Basal ganglia
Define cavernous angioma.
Well-defined malformative lesion composed of closely-packed vessels with no parenchyma interposed between vascular spaces
NOTE: it is similar to an arteriovenous malformation but there is no brain substance wrapped up amongst the vessels
NOTE: these tend to bleed at lower pressure causing recurrent small bleeds
NOTE: shows target sign on MRI
What is the biggest cause of death in people < 45 years?
Traumatic brain injury
Describe the Braak stages of Alzheimer’s disease.
Stage 1: tau pathology in the transentorhinal cortex
Stage 2: posterior hippocampus
Stage 3: immunostaining is visible by eye, affects substantia nigra
Stage 4: superior temporal gyrus
Stage 5: peristriate cortex
Stage 6: striate cortex
NOTE: clinically, symptoms tend to arise in stage 3 or 4
What is the diagnostic gold standard for Parkinson’s disease?
Alpha-synuclein immunostaining
What are three important differentials to consider in a patient with Parkinson’s disease?
Multiple system atrophy
Corticobasal degeneration
Progressive supranuclear palsy
What is multisystem atrophy?
It is an alpha-synucleinopathy like Parkinson’s disease which targets glial cells
It presents similarly to Parkinson’s disease
It mainly affects the cerebellum so the patients are more likely to present with falls
What are the main histological features of Pick’s disease?
Marked gliosis and neuronal loss
Balloon neurones
Tau-positive Pick bodies
NOTE: mutations in tau are associated with a fronto-temporal dementia phenotype often associated with Parkinson’s disease
NOTE: there are 17 autosomal dominant syndromes resulting from mutations in tau
Which gene encodes tau?
17q21
Describe how the types of tau present in Alzheimer’s disease is different from CBD, PSP and Pick’s disease.
Alzheimer’s – when the tau is put through a Western blot, it will form 3 dense bands. If this is dephosphorylated it will show all 6 isoforms of tau
CBD and PSP – produces 2 dense bands which, when dephosphorylated, are shown to be made up of only 4R tau (i.e. it is a 4R tauopathy)
Pick’s disease – it is a 3R tauopathy
What is a characteristic feature of frontotemporal dementia associated with progranulin mutations?
Atrophy tends to be unilateral
Which other protein is thought to be implicated in some types of fronto-temporal dementia?
TDP-43 (trafficking protein)
On a cellular level, what insult results in ARDS?
Acute damage to the endothelium and/or alveolar epithelium
The basic pathology is the same regardless of cause: diffuse alveolar damage
Outline the pathophysiology of ARDS.
Exudative phase – the lungs become congested and leaky
Hyaline membranes – form when serum protein that is leaked out of vessels end up lining the alveoli
Organising phase – organisation of the exudates to form granulation tissue sitting within the alveolar spaces
Describe how the pattern of alveolar damage is different with smoking compared to alpha-1 antitrypsin deficiency.
Smoking – centrilobular damage
Alpha-1 antitrypsin deficiency – panacinar (throughout the lungs)
Where is the CFTR gene found?
7q31.2
What are the histopathological stages of lobar pneumonia?
Stage 1: congestion (hyperaemia and intra-alveolar fluid)
Stage 2: red hepatisation (hyperaemia, intra-alveolar neutrophils)
Stage 3: grey hepatisation (intra-alveolar connective tissue)
Stage 4: resolution (restoration of normal tissue architecture)
Describe the histological appearance of atypical pneumonia.
Interstitial inflammation (pneumonitis) without accumulation of intra-alveolar inflammatory cells NOTE: causes include Mycoplasma, viruses, Coxiella and Chlamydia
Where do squamous cell carcinomas tend to arise?
Centrally – arising from the bronchial epithelium
NOTE: there is an increasing incidence of peripheral squamous cell carcinomas (possibly due to deeper inhalation of modern cigarette smoke)
What is the precursor lesion for adenocarcinoma of the lung?
Atypical adenomatous hyperplasia (proliferation of atypical cells lining the alveolar walls)
Which mutations are associated with adenocarcinoma in smokers?
Kras
Issues with DNA methylation
P53
Which mutations are associated with adenocarcinoma in non-smokers?
EGFR
EML4-ALK
List some common mutations seen in small cell lung cancer.
P53
RB1
Which molecular changes are important to test for in adenocarcinoma?
EGFR (responder or resistance)
ALK translocation
Ros1 translocation
NOTE: it is important to correctly identify the type of lung cancer because of treatment implications. E.g. bevacizumab can cause fatal pulmonary haemorrhage in squamous cell carcinoma