L14: Neoplasia part 1 Flashcards
Define tumour?
A swelling
Detectable lumb or swelling
Define neoplasm?
New growth
Abnormal growth of cells that persists after the initial stimulus has been removed
Define oncology?
The study of tumours and neoplasms
Define hyperplasia?
Increase in cell number
Reversible
Stimulus removed goes back to normal
Define regeneration?
Increase in cell number back to normal
Define neoplasia?
Persistent abnormal growth
Genetic alterations lead to increased cell number
What is a benign neoplasm?
Gross and microscopic apperance are considered to be innocent, implying that it will remain localised and will not spread to other sites
What is cancer?
A malignant neoplasm
What is a malignant neoplasm?
Abnormal growth of cells that persists after the initial stimulus is removed and invaded surrounding tissue with the potential to spread to distant sites
What is a metastasis?
Malignant neoplasm that has spread from its original site to a new non-contiguous site
What is dysplasia? What is significant about them?
Pre-neoplastic alterations in which the cells show disordered tissue organisation
Reversible–> remove stimulus return to normal
Can exhibit pleomorphism (more than one distinct form of cells) with large hyperchromatic nuclei and high nuclear to cytoplasmic ratios
To summarise, what are the different types of tumours? What are the different subtypes?
Non-neoplastic and neoplastic
Neoplastic–> benign and malignant
Malignant–> primary or secondary
What is the difference between primary and secondary malignant neoplasms?
Primary–> original location-> biopsy contains cells from the location it was obtained
Secondary–> metastasis –> cells have moved to a different site
What is the difference between benign and malignant?
Benign–> remain localised, will not spread to different areas, considered innocent, do not produce metastases
Malignant–> invade and have the potential to metastasise
What is the difference in appearance between benign and malignant tumours?
Benign–> grow in a confined local area, pushing outer margin, rarely dangerous
Malignant–> irregular outer margin and shape, ulceration and necrosis and are infiltrative
What is the difference mode of growth between benign and malignant tumours?
Benign–> grow in a confined local area, pushing outer margin, rarely dangerous
Malignant–> irregular outer margin and shape, ulceration and necrosis and are infiltrative
Define differentiation?
The process of becoming different by growth or development
What is the difference in appearance between benign and malignant tumours?
Benign–> Well differentiated, closely resemble parent tissue
Malignant–> well to poorly differentiated, dependent on how closely they resemble the parent tissue
What are tissues that have no resemblance to the parent tissue called?
Anaplastic
What happens to the cells as the tissue become more poorly differentiated?
Worsening differentiation the individual cells have:
- Increasing nuclear size
- Increasing nuclear to cytoplasmic size
- Increasing nuclear staining (hyperchromasia)
- Increasing mitotic figures
- Abnormal mitotic figures (Mercedes Benz sign)
- Variation in size and shape of cells and nuclei (pleomorphism)
Compare and contrast benign and malignant tumours?
SLIDE 16
What are the different degrees of differentiation?
Different grades indicate the different degrees of differentiation
High grade–> poorly differentiated
Low grade–> well differentiated
What is the difference between an carcinoma in situ and a invasive carcinoma?
Carcinoma in situ is a irreversible tumour that has not breached the basement membrane and is therefore still localised –> not malignant
Invasive carcinoma has breached the basement membrane –> malignant
Why do we get neoplasias?
Carcinogenesis
Non-lethal genetic damage
Accumulated mutation in somatic cells
Why are the changes that result in neoplasia non lethal?
Lethal changes would causes the cell to apoptose and die
Wouldn’t get through the cell cycle or would alert the immune system and get removed
What causes mutations to appear in somatic cells?
Mutagenic agents –> initiators
- Chemicals –> smoking, alcohol consumption, diet and obesity
- Infectious agents–> HPV
- Radiation
- Inherited muations (BRAC1, BRAC2 genes)
How does a tumour form?
Mutations are causes by initiators-> mutagenic agents
Promoters cause cell proliferation
A tumour is formed by clonal expansion of a single precursor cell that has incurred genetic damage
What is the difference between germ line mutations and somatic mutations?
Germline mutations–> neoplastic cells get a head start, mutations exist within the population of cells
Cell population–> requires an initiator causes mutation, cell divides passing mutation onto daughter cell, requires more steps to get to the same number of mutated cells
What does monoclonal mean?
Collection of cells that have originated from a single founding cell
How do neoplasms arise from monoclonal cells?
Process called progression—> accumulation of mutations over cell generations
How does progression occur?
-Group of monoclonal cells
-Mutation arises—> confers growth advantage—> cells grow faster—> evade all checkpoints
-Bigger pool—> more mutations arise, further increasing growth
Accumulation of mutations allow a neoplasm to form
Unclear how many mutations are required to get a full malignant neoplasm
Which genes are normally affected resulting in the formation of neoplasms?
Normal regulatory gene
- Growth promoting proto-oncogenes
- Growth inhibiting tumour suppressor genes
- Genes that regulate programmed cell death (apoptosis)
- Genes involved in DNA repair
What are Proto-oncogenes? What happens when mutated?
Involved in signalling pathway to drive proliferation
Mutations usually activate them—> excessive increase in one or more normal functions, or can impart a completely new function
‘Gain of function’ mutations
What are oncogenes?
Created by mutations in proto-oncogenes
Encode oncoproteins—> promote cell growth in absence of normal growth promoting signals
Dominant over their normal counterpart
Transforms cells despite normal copy of same gene
Give an example of a oncogene that is present in a lot malignant melanomas? How can this oncogene be inhibited?
BRAF mutation (V600E). (—> 60% melanomas, 100% hairy cell leukaemia, colon adenocarcinomas, langerhans cell histiocytosis and papillary thyroid carcinoma)
BRAF inhibitors stop function
What are tumour supressor genes?
Normal function stop cell proliferation
Mutation—> Loss of function
Both alleles must be damaged for transformation to occur
Mutation—> failure of growth inhibition
What are apoptosis regulating genes?
Genes that regulate programmed cell death (apoptosis)
Mutation–> less cell death and enhanced survival
‘Dodgy’ cells can survive
What are DNA repair genes? What happens when they are mutated?
Normally involved in repair of genes
Mutations—> loss of function
Indirectly —> carcinogenesis
Impair—> cell recognition and repair of non-lethal genetic damage in other genes
What is the result of the mutations in regulatory genes?
Affected cells acquire mutation at accelerated rate
Mutator phenotype—> genomic instability
When naming neoplasms what is taken into account?
Site of origin
Benign or malignant
Gross morphology
What is the general rule when naming neoplasms?
Benign tumours–> -oma
Malignant tumours–>
-carcinoma (epithelial)
-sarcoma (stromal- CT of any origin)
How are benign epithelial neoplasms named?
Stratified squamous—> squamous papilloma (tumour with finger like projections)
Transitional—> transitional cell papilloma
Glandular—> Adenoma
How are malignant epithelial neoplasms named?
Stratified squamous—> squamous cell carcinoma
Transitional—> transitional cell carcinoma
Glandular—> adenocarcinoma
Other—> basal cell carcinoma (skin)
How are the anomalies named? What is different about the germ cell neoplasms?
Smooth muscle: leiomyoma (benign), Leiomysarcoma (malignant)
Stratified muscle Rhabdomyoma (benign), Rhabdomyosarcoma (malignant)
Blood cells–> Leukaemia
Lymphoid tissue –> Lymphoma
Plasma cells–> Myeloma
Germ cell
Testis –>
-Malignant teratoma
-Semioma (malignant neoplasm)
Ovary–>
-Benign teratoma–> dermoid cyst
Teratoma in testes always malignant in ovaries always benign
