Neoplasia Flashcards
(114 cards)
1
Q
What is a neoplasm?
A
Abnormal growth of cells that persists after the initial stimulus has been removed
2
Q
What is a malignant neoplasm
A
Abnormal growth of cells that persist after stimulus removed AND invades surrounding tissue with potential to spread to distant sites
3
Q
What’s a tumour
A
Clincally detectable lump or swelling
4
Q
What is a cancer
A
Malignant neoplasm
5
Q
What’s a metastisis
A
A malignant neoplasm that has spread from its original site to a new non contiguous site
6
Q
What’s dysplasia
A
Pre neoplastic alteration in which cells show disordered tissue organisation. NOT neoplastic as this is reversible
7
Q
What do benign tumours do re site?
A
Remain confined to site of origin
8
Q
Describe the appearance of a benign tumour
A
Confined to local area with pushing outer margin
9
Q
Describe a malignant tumour
A
Irregular outer margi and sharp and may show areas of necrosis and ulceration
10
Q
What do benign neoplastic cells show under micoscope
A
Cells that closely resemble parent tissue (well differentiated )
11
Q
What do malignant neoplasms look like under microscope
A
Well to poorly differentiated cells, all the way up to anaplastic cells
12
Q
What’s a aplasia
A
Cells with no resemblance to parent tissue
13
Q
What comes with worsening differntiation of individual cells?
A
Increasing nuclear size Increased nuclear to cytoplasm ratio More mitotic figures Hyperchromasia Increased variation in size and shape (pleomorphism)
14
Q
What does the term grade indicate
A
Differentiation
15
Q
What’s dysplasia
A
Altered differentiation
16
Q
What causes mutations and what caused cell proliferation in regards to neoplasm
A
Initiations are mutagenic
Promoters are causing proliferation
17
Q
The population of mutant cells are derived from one cell therefore
A
Monoclonal
18
Q
What occurs after initiation and promotion
A
Progression
19
Q
How do we know neoplasms are monoclonal?
A
Study of X linked G6PDH in women where lyonisation has occurred. Normal tissue would be patchwork. Cancer one cell type
20
Q
What genetic alterations occur (type of gene) to promote neoplasm
A
Proto-oncogenes become abnormally activated
Tumour suppressor genes become inactivated
Both favour neoplasm
21
Q
What do benign neoplasms end in
A
Oma
22
Q
What does a epithelial malignant neoplasm end in
A
Carcinoma (90% of malignant tumours)
23
Q
What does a sarcoma mean
A
It’s malignant and from some type of connective tissue
24
Q
What is leukaemia
A
Malignant neoplasm of blood forming cells arising in the bone marrow
25
What is lymphoma
Malignant neoplasm of lymphocytes mainly affecting lymph nodes
26
What is myeloma
Malignant neoplasm of plasma cells
27
What's a blastoma
Malignant neoplasm from immature precursor cells
28
What (generally) does invasion and mets lead to
Increased tumour burden
29
What are the 3 steps that need to occur for invasion and mets to be successful
1. Grow and invade primary site
2. Enter a transport system
3. Grow at secondary (collinisation)
At all points avoiding immune system
30
What 3 changes are needed for invasion to be possible
Altered adhesion
Stromal proteolysis
Motility
31
If the 3 alterations of a carcinoma has occurred whats it called?
Epithelial to mesenchymal transition- new cell phenotype more like a mesencymal cell
32
What does altered adhesion between malignant cells require?
Reduction in E cadherin
33
What does altered adhesion between malignant cels and stromal proteins require?
Changes in integrin expression
34
What is needed for cells to degrade basement membrane and stroma to invade>
Expression of proteases notable matrix metalloproteinases MMP
35
How is altered motility achieved in cancer cells trying to invade
Changes in actin cytoskeleton
36
What's a cancer niche?
Malignant cells taking advantage of nearby cells growth factors and proteases
37
How is signalling achieved in malignant cells?
Through integrins via small G proteins such as Rho family
38
What 3 roots can malignant cancers use?
Blood vessels
Lymphatic
Fluid in cavities- transcoelomic spread
39
What's the greatest barrier to successful formation of mets
Failed collinisation
40
How can you explain the phenomenon of tumour dormancy
Micrometastases remain in disease free people
41
What determines the site of secondary?
1. Regional drainage of blood, lymph of coelomic fluid
| 2. Seed and soil phenomenon
42
How do carcinomas typically spread
Via lymphatics initially
43
How do sarcomas tend to spread?
Via blood initially
44
What are common sites of blood borne mets?
Lung, liver, Bone, brain
45
What neoplasms most frequently spread to bone?
Breast, bronchus, kidney, thyroid, prostate
46
What is likelihood of mets determined by
Relative size of primary
47
What are the 2 classifications of effects caused by neoplasms
Direct local and systemic
48
What are paraneoplastic syndromes
Indirect systemic effects of neoplasm
49
What are the 3 main types of systemic effects of neoplasm (classes)
Tumour burden
Hormone secretion
Misc
50
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
51
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
52
What neoplasms tend to secrete hormones and why?
Benign as normally well differentiated, malignant can also eg bronchial SCC
53
What are some of the miscellaneous systemic effects of neoplasia
```
Neuropathies
Skin issues like pyuritis
Pigmentation
Fever
Finger clubbing
Myositis
```
54
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
```
55
What are the 3 main extrinsic factor categories and to what level are they the causes of cancer
Chemical, radiation and infections
| 85%
56
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
57
What is critical in the adminisirisation of promoters and initiators
The sequence, initiator->promoter ++
58
What does Ames test show is?
Initiators are mutagens while promoters cause prolonged proliferation of target tissues
59
After promoters what is needed for a monoclonal cell to become fully malignant
Progression
60
Mutagenic chemical carcinogens can be what?
```
Polycyclic aromatic hydrocarbons
Aromatic amines
N nitroso compounds
Alkylation get agents
Diverse natural products
```
61
What's a pro-carcinogen
One that is converted by the liver into carcinogen
62
What's a complete carcinogen
One that acts as both initatior and promotor
63
How far does UV light penetrate
No deeper than the skin
64
How does ionising radiation damage cells
Strips them of electrons. Damage either direct or through free radical production
65
What does nuclear radiation comprise of?
Alpha+beta particles
| Gamma rays
66
Where is most people exposure to ionising radiation coming from?
Background radiation from radon
67
How does ionising radiation directly damage cells
DNA bases damaged causing single and double strand breaks
68
What are the two main ways infections can be carcinogenic
Direct affect on genes controlling cell growth
| Indirect by causing chronic tissue injury
69
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
70
How does HPV have such a link with cervical carcinoma?
Direct carcinogen as it inhibts p53 and pRB
71
How does hep B or C have an association with liver neoplasia
Liver cell injury and regeneration
72
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.
73
What do tumour suppressor genes code for
Things that inhibit neoplastic growth
74
What are oncogenes
Genes that enhance neoplastic growth (abnormally activated versions of proto-oncogenes)
75
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
76
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
77
What does the RB gene code for?
Restrains cell proliferation by inhibiting passage through the restriction point (inactivation of both alleles required)
78
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
79
What do tumour suppressor genes encode
Proteins in the same pathways as proto-oncogenes but instead they have anti growth effects
80
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
81
What is hereditary non polyposis colon cancer a mutation in
One of several DNA mismatch repair genes
82
Familial breast carcinoma is associated with what? What is there normal purpose
BRCA1 BRCA2 important in repair of dna double strand breaks
83
What are caretaker genes
Tumour suppressor genes that maintain genetic stability
84
What does the adenocarcinoma sequence illustrate?
Multiple accumulation of mutations required to process to malignant neoplasm
85
What is the stead accumulation of multiple mutations termed?
Progression
86
What are the 6 hallmarks of cancer
1. Self sufficient in growth signals
2. Resistance to growth stop signals
3. No limit in times it can divide (immortalisation)
4. Sustained ability to produce blood vessels (angiogenessis)
5. Resistant to apoptosis
6. Ability to invade and metastisis
87
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
88
What cancers account for over half of all new cancers in the uk
Breast, lung, prostate, bowel
89
Children younger than 14 are more likely to have what cancers
Leukaemia
Central nervous system tumours
Lymphomas
90
What's the biggest cause of cancer deaths in the uk
Lung
91
What are some predicting outcome for cancer
```
Tumour type
Grade
Stage
Treatments
Age and general health
```
92
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
93
How is cancer staging worked out generally
```
Conversion of TNM to stage
1- local small
2- local big
3-node mets
4- distant mets
```
94
What staging does lymphoma have? What is it
Ann Arbor
1. single node
2. 2 nodes one side of diaphragm
3. Spread to both sides of diagram
4. Spread to extra lymphatic organs like bone or lung
95
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
```
96
What are the tumour grades?
G1- well differntiatied
G2- moderately differentiated
G3- poorly differentiated
G4 anaplastic
97
When is grading used a lot in neoplasms
Squamous cell and colorectal
98
What grading system is used for breast cancer
Bloom-Richardson- looks at tubule formation, nuclear variation, number of mitosis
99
When can tumour grade be more important than stage
Soft tissue sarcoma, primary brain tumours, lymphomas, breast and prostate
100
What are some cancer treatments
```
Surgery
Chemo
Hormone
Radio
Targeted treatment
```
101
What's an adjuvant treatment
Given after surgical removal to eliminate sub-clinical disease
102
What's neoadjuvant treatment
Pre surgery to reduce size of primary prior to surgery
103
How does radiation therapy work
Kills proliferating cells by triggering apoptosis or interfering with mitosis
104
Why is a fractioned dose of radiotherapy given
Minimise normal tissue damage
105
How does ionising radiation preferential kill dividing cells
Direct or free radical dna damage detected by cell cycle checkpoints triggering apoptosis s
106
What are 4 types of chemo?
Antimetabolites
Alkylating
Antibiotics
Plant derived
107
What's an issue with chemotherapy
Affects proliferating cells but is non specific
108
When is tamoxifen used? What is it an example of?
Hormone receptor positive breast cancer
Blocks oestrogen binding
Hormone therapy
109
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)
110
When is imatinib used?
In chronic myeloid leukaemia, it inhibits the fusion of protein
111
What are tumour markers main use?
Monitoring tumour burden
| Also have a role in diagnosis
112
What are some types of tumour markers
Hormones, onvogetal antigens, specific proteins and mucins
113
What are screening programs looking for in cancer?
Early signs in healthy people when curative chance is highest
114
What are some problems with cancer screening
Lead time biase, length bias and overdiagnosis
