Neoplasia Flashcards
What is a neoplasm?
Abnormal growth of cells that persists after the initial stimulus has been removed
What is a malignant neoplasm
Abnormal growth of cells that persist after stimulus removed AND invades surrounding tissue with potential to spread to distant sites
What’s a tumour
Clincally detectable lump or swelling
What is a cancer
Malignant neoplasm
What’s a metastisis
A malignant neoplasm that has spread from its original site to a new non contiguous site
What’s dysplasia
Pre neoplastic alteration in which cells show disordered tissue organisation. NOT neoplastic as this is reversible
What do benign tumours do re site?
Remain confined to site of origin
Describe the appearance of a benign tumour
Confined to local area with pushing outer margin
Describe a malignant tumour
Irregular outer margi and sharp and may show areas of necrosis and ulceration
What do benign neoplastic cells show under micoscope
Cells that closely resemble parent tissue (well differentiated )
What do malignant neoplasms look like under microscope
Well to poorly differentiated cells, all the way up to anaplastic cells
What’s a aplasia
Cells with no resemblance to parent tissue
What comes with worsening differntiation of individual cells?
Increasing nuclear size Increased nuclear to cytoplasm ratio More mitotic figures Hyperchromasia Increased variation in size and shape (pleomorphism)
What does the term grade indicate
Differentiation
What’s dysplasia
Altered differentiation
What causes mutations and what caused cell proliferation in regards to neoplasm
Initiations are mutagenic
Promoters are causing proliferation
The population of mutant cells are derived from one cell therefore
Monoclonal
What occurs after initiation and promotion
Progression
How do we know neoplasms are monoclonal?
Study of X linked G6PDH in women where lyonisation has occurred. Normal tissue would be patchwork. Cancer one cell type
What genetic alterations occur (type of gene) to promote neoplasm
Proto-oncogenes become abnormally activated
Tumour suppressor genes become inactivated
Both favour neoplasm
What do benign neoplasms end in
Oma
What does a epithelial malignant neoplasm end in
Carcinoma (90% of malignant tumours)
What does a sarcoma mean
It’s malignant and from some type of connective tissue
What is leukaemia
Malignant neoplasm of blood forming cells arising in the bone marrow
What is lymphoma
Malignant neoplasm of lymphocytes mainly affecting lymph nodes
What is myeloma
Malignant neoplasm of plasma cells
What’s a blastoma
Malignant neoplasm from immature precursor cells
What (generally) does invasion and mets lead to
Increased tumour burden
What are the 3 steps that need to occur for invasion and mets to be successful
- Grow and invade primary site
- Enter a transport system
- Grow at secondary (collinisation)
At all points avoiding immune system
What 3 changes are needed for invasion to be possible
Altered adhesion
Stromal proteolysis
Motility
If the 3 alterations of a carcinoma has occurred whats it called?
Epithelial to mesenchymal transition- new cell phenotype more like a mesencymal cell
What does altered adhesion between malignant cells require?
Reduction in E cadherin
What does altered adhesion between malignant cels and stromal proteins require?
Changes in integrin expression
What is needed for cells to degrade basement membrane and stroma to invade>
Expression of proteases notable matrix metalloproteinases MMP
How is altered motility achieved in cancer cells trying to invade
Changes in actin cytoskeleton
What’s a cancer niche?
Malignant cells taking advantage of nearby cells growth factors and proteases
How is signalling achieved in malignant cells?
Through integrins via small G proteins such as Rho family
What 3 roots can malignant cancers use?
Blood vessels
Lymphatic
Fluid in cavities- transcoelomic spread
What’s the greatest barrier to successful formation of mets
Failed collinisation
How can you explain the phenomenon of tumour dormancy
Micrometastases remain in disease free people
What determines the site of secondary?
- Regional drainage of blood, lymph of coelomic fluid
2. Seed and soil phenomenon
How do carcinomas typically spread
Via lymphatics initially
How do sarcomas tend to spread?
Via blood initially
What are common sites of blood borne mets?
Lung, liver, Bone, brain
What neoplasms most frequently spread to bone?
Breast, bronchus, kidney, thyroid, prostate
What is likelihood of mets determined by
Relative size of primary
What are the 2 classifications of effects caused by neoplasms
Direct local and systemic
What are paraneoplastic syndromes
Indirect systemic effects of neoplasm
What are the 3 main types of systemic effects of neoplasm (classes)
Tumour burden
Hormone secretion
Misc
What are 4 main local effects of primary and secondary neoplasm
Direct invasion and destruction of normal tissue
Ulceration leading to bleeding
Compression of adjacent structures
Blocking of tubes and orrifices
What is the parasitic effect of neoplasm
Tumour using a lot of energy
Secreted factors such as cytokines causing reduced apetite and weight loss
Malaise
Immunosupression if bone marrow infiltrated
Thrombosis
What neoplasms tend to secrete hormones and why?
Benign as normally well differentiated, malignant can also eg bronchial SCC
What are some of the miscellaneous systemic effects of neoplasia
Neuropathies Skin issues like pyuritis Pigmentation Fever Finger clubbing Myositis
What are the 5 leading behavioural and dietary risks that attribute to 30% of cancer deaths
High BMI Lowe fruit and veg Lack of physical activity Tobacco use Alcohol use
What are the 3 main extrinsic factor categories and to what level are they the causes of cancer
Chemical, radiation and infections
85%
What did the malignant neoplasms caused by 2-napthylamine show us?
There is a long delay (sometimes decades between exposure and onset
Risk dependent on dose
Sometimes organ specific
What is critical in the adminisirisation of promoters and initiators
The sequence, initiator->promoter ++
What does Ames test show is?
Initiators are mutagens while promoters cause prolonged proliferation of target tissues
After promoters what is needed for a monoclonal cell to become fully malignant
Progression
Mutagenic chemical carcinogens can be what?
Polycyclic aromatic hydrocarbons Aromatic amines N nitroso compounds Alkylation get agents Diverse natural products
What’s a pro-carcinogen
One that is converted by the liver into carcinogen
What’s a complete carcinogen
One that acts as both initatior and promotor
How far does UV light penetrate
No deeper than the skin
How does ionising radiation damage cells
Strips them of electrons. Damage either direct or through free radical production
What does nuclear radiation comprise of?
Alpha+beta particles
Gamma rays
Where is most people exposure to ionising radiation coming from?
Background radiation from radon
How does ionising radiation directly damage cells
DNA bases damaged causing single and double strand breaks
What are the two main ways infections can be carcinogenic
Direct affect on genes controlling cell growth
Indirect by causing chronic tissue injury
How does chronic tissue injury from infection cause neoplasms
Regeneration that can act as a promotor for existing mutaton or new mutations through dna replication errors
How does HPV have such a link with cervical carcinoma?
Direct carcinogen as it inhibts p53 and pRB
How does hep B or C have an association with liver neoplasia
Liver cell injury and regeneration
What is Knudsons 2 hit hypothesis
The thought that 2 mutations are required for something that has 2 alleles coding for it. Explains why genetic predispositions arise as these have germ line 1 hit.
What do tumour suppressor genes code for
Things that inhibit neoplastic growth
What are oncogenes
Genes that enhance neoplastic growth (abnormally activated versions of proto-oncogenes)
Whats the difference between TSG and POG in regards to mutations
Only one hit of POG required to promote tumour growth, where as TSG requires 2
What is RAS (mutated in 1/3 of all malignant neoplasm)
Encodes a small G protein that relays signals to push cell past cell cycle restriction point
Mutant RAS encodes protein always active
What does the RB gene code for?
Restrains cell proliferation by inhibiting passage through the restriction point (inactivation of both alleles required)
What types of things can protooncogenes encode?
Growth factors, growth factor receptors, plasma membrane signal transducers, intracellular kinases, transcription factors, cell cycle regulators, apoptosis regulators
What do tumour suppressor genes encode
Proteins in the same pathways as proto-oncogenes but instead they have anti growth effects
What is Xeroderma pigementosum a mutation in? What doe sit lead to?
One of the 7 genes of DNA nucleotide excision repair
Very sensitive to UV damage therefore skin cancer at young age
What is hereditary non polyposis colon cancer a mutation in
One of several DNA mismatch repair genes
Familial breast carcinoma is associated with what? What is there normal purpose
BRCA1 BRCA2 important in repair of dna double strand breaks
What are caretaker genes
Tumour suppressor genes that maintain genetic stability
What does the adenocarcinoma sequence illustrate?
Multiple accumulation of mutations required to process to malignant neoplasm
What is the stead accumulation of multiple mutations termed?
Progression
What are the 6 hallmarks of cancer
- Self sufficient in growth signals
- Resistance to growth stop signals
- No limit in times it can divide (immortalisation)
- Sustained ability to produce blood vessels (angiogenessis)
- Resistant to apoptosis
- Ability to invade and metastisis
What is a summary of the cancer pathogenesis
Somatic cells exposed to carcinogens (initiator and promoter)
Monocloncal population (inherited mutation may be present)
Hallmark changes occur
Genetic instability
What cancers account for over half of all new cancers in the uk
Breast, lung, prostate, bowel
Children younger than 14 are more likely to have what cancers
Leukaemia
Central nervous system tumours
Lymphomas
What’s the biggest cause of cancer deaths in the uk
Lung
What are some predicting outcome for cancer
Tumour type Grade Stage Treatments Age and general health
What does the TNM staging describe
T is size of primary 1-4
N is mets to lymph 0-3
M is distant mets 0-1
How is cancer staging worked out generally
Conversion of TNM to stage 1- local small 2- local big 3-node mets 4- distant mets
What staging does lymphoma have? What is it
Ann Arbor
- single node
- 2 nodes one side of diaphragm
- Spread to both sides of diagram
- Spread to extra lymphatic organs like bone or lung
What is Dukes staging used in? What is it
Colorectal carcinoma A- invasion but not through bowel B- invasion through bowel wall C- involvement of lymph nodes D- distant mets
What are the tumour grades?
G1- well differntiatied
G2- moderately differentiated
G3- poorly differentiated
G4 anaplastic
When is grading used a lot in neoplasms
Squamous cell and colorectal
What grading system is used for breast cancer
Bloom-Richardson- looks at tubule formation, nuclear variation, number of mitosis
When can tumour grade be more important than stage
Soft tissue sarcoma, primary brain tumours, lymphomas, breast and prostate
What are some cancer treatments
Surgery Chemo Hormone Radio Targeted treatment
What’s an adjuvant treatment
Given after surgical removal to eliminate sub-clinical disease
What’s neoadjuvant treatment
Pre surgery to reduce size of primary prior to surgery
How does radiation therapy work
Kills proliferating cells by triggering apoptosis or interfering with mitosis
Why is a fractioned dose of radiotherapy given
Minimise normal tissue damage
How does ionising radiation preferential kill dividing cells
Direct or free radical dna damage detected by cell cycle checkpoints triggering apoptosis s
What are 4 types of chemo?
Antimetabolites
Alkylating
Antibiotics
Plant derived
What’s an issue with chemotherapy
Affects proliferating cells but is non specific
When is tamoxifen used? What is it an example of?
Hormone receptor positive breast cancer
Blocks oestrogen binding
Hormone therapy
When is herceptin used? How does it work?
Used for breast cancer with over expression of her 2 receptor
Her Epstein blocks its signalling (oncogene targeting)
When is imatinib used?
In chronic myeloid leukaemia, it inhibits the fusion of protein
What are tumour markers main use?
Monitoring tumour burden
Also have a role in diagnosis
What are some types of tumour markers
Hormones, onvogetal antigens, specific proteins and mucins
What are screening programs looking for in cancer?
Early signs in healthy people when curative chance is highest
What are some problems with cancer screening
Lead time biase, length bias and overdiagnosis
