Cancer as a disease: Cellular Pathoglogy of cancer Flashcards
Define Metaplasia
A reversible change in which one adult cell type (usually epithelial)is replaced by another adult cell type
Adaptive
Describe physiological metaplasia
Cervix during pregnancy – the cervix opens up and the columnar epithelium of the endocervical canal is exposed to the acidic uterine fluids making it squamous
pH of cervix is the key stimulus here
Describe pathological metaplasia
Barrett’s Oesophagus – gastro-oesophageal reflux (regurgitated stomach acid) can change the stratified squamous epithelium of the distal oesophagus to simple columnar
Reversible and adaptive to changes in pH (I.,e if you treat GERD- the epithelium will return to squamous)
Ultimately, what is meant by an adaptive response in metaplasia
ADAPTIVE response where cells sensitive to the stressful stimulus – reflux of acid, cigarette smoke, etc – and are replaced by cells which can withstand the adverse environment e.g. respiratory columnar ciliated epithelium changes to squamous, squamous oesophageal to columnar/ intestinal.
What are the two types of metaplasia that can take place in Barrett’s Oesophagus?
Gastric metaplasia – stratified squamous to simple columnar (but no goblet cells)
Intestinal metaplasia – goblet cells begin to appear (becomes columnar too)
What else can cause metaplasia
Or reprogramming of stem cells (reserve cells) to differentiate along a different pathway in response to signalling by cytokines, growth factors and extracellular matrix components.
Define dysplasia
an abnormal pattern of growth in which some of the cellular and architectural features of malignancy are present
pre-invasive stage with
intact basement membrane - hence non-invasive
What is important to remember about dysplasia
Cells are dysplastic before invasive (so it is the step before cancer). The cells show many of the cytoplasmic, genetic and molecular features of cancer- but the BM is intact and the cells themselves are not invasive yet.
Morphological correlation of molecular changes is seen in dysplasia.
Describe the clinical importance of detecting cells
Easier to treat and treatment will be 100% effective due to the lack of invasion
Therefore it is associated with a better prognosis
Aim of screening programmes.
List the key features of dysplasia
Large nuclei (and hyperchromatic) Increased mitoses Abnormal mitoses Increased nucleo-cytoplasmic ratio Loss of architectural orientation Loss of uniformity of individual cells
Why are the nuclei hyperchromatic in dysplasia
Due to the increased concentration of DNA in the cell
Why does the nuclear: cytoplasmic ratio increase in dyslaisa
Because the nucleus grows without the cell itself growing (hence the percentage of the cell that is nucleus increases).
What is meant by the loss of architectural orientation
Lose the normal differentiation of squamous epithelium.
Should go from basal - mature- keratinised- but this pathway of differentiation is lost in dysplasia.
What is dysplasia common in
CERVIX – HPV infection BRONCHUS – Smoking COLON – Chronic Ulcerative Colitis LARYNX – Smoking STOMACH -Pernicious Anaemia (chronic inflammatory process) OESOPHAGUS-Barret’s metaplasia
Describe the basis of screening for cervical cancer
Previously looking for dysplastic changes
Now moved to looking at genotypes of HPV.
What is important to remember about the relationship between metaplasia and dysplasia
Often occur in the same sites
metaplasia first- then dysplasia
why you can get squamous carcinomas of the lung (first metaplastic change from columnar, then the squamous cells become dysplastic and then cancerous)
Compare low grade dysplasia to high grade dysplasias
Low grade- lower risk of progression and more likely to revert back to normal spontaneously
high grade- darker- due to increased nuclei:cytpolasm ratio.
Define neoplasia, tumour and malignancy
A tumour is an abnormal, autonomous proliferation of cells which are unresponsive to normal control mechanisms governing their growth, and which persists in proliferating even when whatever stimulus started it going has stopped.
What are the characteristics of benign tumours
do not invade do not metastasise encapsulated usually well differentiated slowly growing normal mitosess
first one is absolute- functional classification of benign tumours, the rest are just descriptive and help with the diagnosis.
Describe non-encapsulated tumours that are benign
§ Encapsulated – note NOT always like this – i.e. Leiomyomas are NOT encapsulated but ARE benign
i.e fibroids in the uterus are not encapsulated but are benign.
Describe fibrous adenoma of the breast
Benign
Encapsulated- sharp, well demarcated edge, so can be resected easily
Can move around easily upon palpation- not adherent to skin or pectoral muscle (good thing)- less likely to be invasive
