S8: neoplasia (1) + neoplasia (2) Flashcards
Define neoplasm
An abnormal growth of cells that persists after the initial stimulus is removed
Define dysplasia
Pre-neoplastic alteration in which the cells show disordered tissue organisation
Reversible
Define tumour
Any clinical detectable lump or swelling
Define cancer
Malignant neoplasm
Abnormal growth of cells that persists after the initial stimulus is removed & invades surrounding tissue with the potential to spread to distant sites
Define metastasis
Malignant neoplasm that has spread from its original site to a new non-contiguous site
Define anaplasia
Cells with no resemblance to any tissue
Define pleomorphism
Variation in size and shape of cells and nuclei
Define progression
Stepwise accumulation of yet more complimentary mutations over time that provide the cell with a survival advantage
Define differentiation
The process of becoming different by growth or development
Describe the macroscopic and microscopic features of benign tumours
Grow in a confined local area
Pushing outer margin
Rarely dangerous (location)
Retain functions of their cells of origin
Closely resemble the parent tissue – well differentiated
Describe the macroscopic and microscopic features of malignant tumours
Irregular outer margin & shape
May have ulcerations and necrosis
Infiltrative & potential to metastasise
Less likely to retain functions of origin & sometimes acquire unexpected functions
Individual cells have: increasing nuclear size, increased nuclear to cytoplasm size, increased nuclear staining (hyperchromasia), increased mitotic figures, abnormal mitotic figures & pleomorphism
Describe and understand the difference between in-situ and invasive malignancy
In-situ = no invasion through epithelial basement membrane Invasive = penetrated through basement membrane
Explain how proto-oncogenes are involved in the development of neoplasms
All participate in signalling pathways that drive proliferation
Mutations cause an excessive increase in one or more normal functions -> gain of function mutations
Oncogenes are created by mutations in proto-oncogenes -> encode proteins (oncoproteins) that can promote cell growth in the absence of normal growth promoting signals
Transform cells despite a normal copy of the same gene (dominant over their normal counterparts)
Explain how tumour suppressor genes are involved in the development of neoplasms
Normal function is to stop cell proliferation
Loss of function mutation
Both alleles must be damaged for transformation to occur in most cases
Mutations lead to failure of growth inhibition
Explain the concept of clonality
Monoclonal = a collection of cells that all originated from a single founding cell
Neoplasm then emerges from this group of cells by progression (accumulation of more mutations)
List the nomenclature given to benign and malignant neoplasms
Naming depends on the site of origin Benign tumours end in -oma Malignant tumours end in -carcinoma (if epithelial) -sarcoma (if stromal) EXCEPT: Burkitt’s lymphoma, Hodgkin’s lymphoma, Ewing’s sarcoma & Kaposi’s sarcoma
List the histological characteristics of squamous cell carcinoma
Eosinophilic cytoplasm
Pleomorphic nuclei
Mitotic figures
List the histological characteristics of adenocarcinoma
Low grade – well differentiated resembling normal glandular structure
High grade – appear abnormal compared to surrounding tissues
List the histological characteristics of malignant melanoma
Atypical mitoses
Nests of melanocytes with variable size and shape
Consumption of epidermis
List the types of cancers that occur in different organs
Squamous cell carcinoma – oesophagus, skin, lung & cervix
Adenocarcinoma – oesophagus, stomach/bowel, lung, breast/prostate & thyroid/pancreas/uterus
Bladder – transitional cell carcinoma
Skin – malignant melanoma, basal cell carcinoma
Lung – small cell carcinoma
Brain – astrocytoma
Define invasion
Breach of the basement membrane with progressive infiltration & destruction of the surrounding tissues
Define metastasis
Spread of tumour to sites that are physically discontinuous from the primary tumour
Marks a tumour as malignant
Describe the three steps of metastasis
1) tumour must grow & invade at the primary site
- initiation & promotion
- progression
- cancer cells are under attack by the immune system
2) enter a transport system
- inefficient process: majority of cells will die & not metastasise
3) grow at the secondary site to form a new tumour = COLONISATION
Describe the cellular alterations that are required for invasion to occur
1) Altered adhesion = reduction in expression of e-cadherin that normally glues epithelial cells together; changes in integrin expression
2) Stromal proteolysis = altered expression of proteases; degrade basement membrane & stroma to allow for invasion
3) Motility = involves changes in actin cytoskeleton; allows for locomotion of cells to propel them through degraded basement membrane
