Neoplasia Flashcards
1
Q
differentiate between the definitions tumour, neoplasm and oncology.
A
- tumour : any clinically detectable lump or swelling.
- neoplasm : abnormal growth of cells that persists after initial stimulus removed.
- oncology : study of tumours and neoplasms.
2
Q
what is the difference between a benign neoplasm and malignant neoplasm?
A
- benign : gross and microscopic appearances that will remain localised, not spreading to other sites.
- pushes outer margins, closely resembles parent tissue.
- malignant : abnormal growth that persists after initial stimulus removed and invades surrounding tissue with potential to spread distally.
- may have ulcerations and necrosis, poorly differentiated mostly.
3
Q
define metastasis.
A
- malignant neoplasm that has spread from its original site to new non-contagious site.
4
Q
what is dysplasia?
what is anaplastic?
A
- pre-neoplastic alteration in which cells show disordered tissue organisation, reversible, pleomorphism seen, large hyper-chromatic nuclei and high nuclear:cytoplasmic ratio.
- cells with no resemblance to any tissue.
5
Q
how is neoplasia graded? what is taken into account?
A
- DIFFERENTIATION : higher grades indicate poor differentiation.
6
Q
why do we get neoplasia?
A
- carcinogenesis.
- genetic damage.
- accumulation of mutations.
- mutations caused by initiators and proliferation caused by promoters.
7
Q
give some examples of initiators.
A
- chemicals : smoking, alcohol, diet and obesity.
- infectious agents : HPV.
- radiation.
- inherited mutations.
8
Q
which genes being affected increases risk of neoplasia?
A
- growth promoting proto-oncogenes.
- growth inhibiting tumour suppressor genes.
- genes that regulate apoptosis.
- genes involved in DNA repair.
9
Q
what is the significance with proto-oncogene mutations?
A
- participates in signalling pathways that drive proliferation.
- ‘gain of function’ mutations and mutations in encode proteins called oncoproteins promote cell growth.
10
Q
what are tumour suppressor genes?
A
- stops cell proliferation, usually subject to ‘loss of function’ mutations.
- both alleles damaged for transformation to occur.
eg: TP53.
11
Q
what about apoptosis regulating genes and DNA repair genes?
A
- apoptosis ; less cell death and enhanced survival.
- DNA repair : ‘loss of function’ mutation, impairs ability to recognise and repair non-lethal genetic damage, accumulation of mutations.
12
Q
how would you generally name neoplasms?
A
- benign -oma.
- malignant : carcinoma if epithelial, sarcoma in stromal.
CHECK SLIDEZ.
13
Q
define invasion in terms of metastatic neoplasia.
A
- breach of basement membrane with progressive infiltration and destruction of surrounding tissue.
14
Q
describe the journey of metastases.
A
- grow, invade at primary site.
- enter transport system and lodge at secondary site.
- grow at secondary site to from new tumour.
15
Q
what are the 3 key events of carcinoma invasion?
A
- adhesion : reduction in E-cadherin expression to more motile, changes in integrin expression.
- stromal proteolysis : altered expression of enzymes, degrades basement membrane and stroma to allow invasion. surrounding tissue provide growth factors and proteases.
- motility : changes to actin cytoskeleton.
16
Q
how does it spread to distant sites?
A
- blood vessels, lymphatics, body cavity fluids.
17
Q
what is the significance of micrometaastases?
A
- failed colonisation deposits wait for optimum conditions such as immunosuppression to proliferate and invade.
18
Q
what determines site of secondary tumour?
A
- regional damage of blood, lymph etc.
- lymphatic metastases drain to lymph nodes.
- breast cancer ipsilateral axillary lymph nodes.
- blood-borne : next capillary bed.
19
Q
common neoplasms that spread to bone can be detected on plain films. what are some examples.
A
- breast, bronchus, kidney, thryroid, prostate.
- osteolytic lesions due to destruction of bone.
20
Q
what is meant by personalities of neoplasms.
A
- malignant more aggressive metastasises very early on.
- small cell carcinoma of bronchus v.aggressive.
- basal cell carcinoma on the other hand, almost never metastasises.
21
Q
how does the hosts defence respond to neoplasia?
A
- tumour antigens recognised by CD8+ cytotoxic cells.
- immunocompromised increased risk.
- however might be missed by CD8+ as loss of or reduced antigen presentation, expression of immuno-suppressions.
22
Q
what are the local effects of neoplasms?
A
- direct invasion and destruction of normal tissue.
- ulceration leading to bleeds.
- compression of structures.
- blocking of tubes and orifices.
- raised pressure due to tumour growth ( brain).
23
Q
what are some systemic effects of neoplasms?
A
- increased tumour burden.
- together with secretions like cytokines reduced apetite and weight loss (cachexia), malaise, immunosuppression, thrombosis.
- hormone production.
24
Q
what is a paraneoplastic syndrome?
A
- symptoms in cancer nearing individuals that cannot be explained by anatomic distribution of tumour or hormones from the tissue at tumour origin.
- important because early sign of occult neoplasm, cause complications, mimic metastatic disease and confound treatment.
25
what is the most common paraneoplastic syndrome?
- hypercalcaemia.
- osteolysis : induced by cancer due to primary bone lesions like myeloma or secondary metastases calcaemia humoral substances produced.
(miscellaneous : neuropathies, skin problems, fever, clubbing, myositis).
26
Name some carcinogenic factors but differentiate between intrinsic and extrinsic factors.
- intrinsic : hereditary, age, sex.
| - extrinsic : chemicals, radiations, infection, behaviour like smoking, obesity.
27
4/10 cancers can be prevented. what factors could be controlled to do this?
- smoking.
- maintain healthy weight.
- balanced diet.
- sun safety.
- cut back on alcohol.
- being active.
- OBESITY.
28
what cancers could smoking cuase?
- mouth, pharynx, nose, larynx, oesophagus, liver, pancreas, stomach, bowel, cervix etc.
29
what is the significance of chemical carcinogens and carcinogenesis?
- 2-napthylamine found in industrial dyes and cigarettes affects risks depending on dose nd there is a delay between exposure and malignancy onset.
- chemical carcinogenesis involved initiation and promotion, and 2-napthylamine is a complete carcinogen doing both.
30
how might radiation act as a risk factor for neoplasia?
- can damage DNA directly or indirectly by crashing into water molecules causing free radicals.
- eg : UV responsible for 1/4 of skin neoplasms, radon gas, medical test radiation.
31
how might infections play a role in neoplasia?
- indirectly due to chronic inflammation inducing constant fibrosis and regeneration.
- directly via HPV.
- indirectly via Hep B & C.
- reduced immunity via HIV.
32
why is HPV so significant in neoplasia?
- associated with cervical carcinoma.
- it creates 2 proteins, E6 and E7. E6 inhibits P53 which prevents cell from apoptosis.
- interferes with retinoblastoma protein which is an important cell cycle checkpoint!
- combined they increase uncontrolled proliferation.
33
how are proto-oncogenes, tumour suppressor genes, DNA repair genes, RAS gene and the retinoblastoma gene different?
- tumour suppressor : 'loss of function' mutation.
- proto-oncogenes : 'gain of function' leading to formation of oncogenes which make onco-proteins which increases cell proliferation.
- retinoblastoma : G1/S cell cycle checkpoint differentiation controller.
- RAS : human oncogene that the most commonly mutated. mutated in 15-20% of all malignant neoplasms.
- DNA repair genes : caretaker genes that prevent accumulation of DNA damage. liked with inherited cancers.
34
what can proto-oncogenes code for?
- growth factors, growth factor receptors, transcription factors (controls rate of transcription), intracellular kinases.
35
what is xeroderma pigmentosa?
- autosomal recessive.
- mutation in 7 genes that affect DNA nucleotide excision repair.
- very sensitive to UV damage and develops skin cancer at young age.
36
what is hereditary non-polyposis colon cancer (HNPCC) syndrome?
- autosomal dominant associated with colon cancer.
| - germ-line mutation that affects one of several DNA mismatch repair genes.
37
what is the genetic link in familial breast carcinoma?
- BRCA1/BRCA2 genes involved in repairing double strand DNA breaks.
- found in sporadic malignant neoplasms.
38
is chromosome aggregation normal?
- this happening in mitosis is abnormal in malignant cells, this accounts for accelerated mutation rate known as genetic instability.
- caretaker genes maintain the genetic stability.
39
name some hallmarks of cancer.
- self sufficient growth signals.
- resistance to stop signals.
- cell immortalisation, no limit to times of division.
- sustained ability to induce angiogenesis.
- resistance to apoptosis.
- ability to invade and metastasise.
40
what are the commonest types of cancer in adults and children?
- in adult males prostate shows high incidence and in women breast cancer, then lung cancers and bowel cancers common in both.
- children younger than 14, Leukaemia, CNS tumour and lymphomas are common.
41
what are the leading causes of cancer related death?
- pancreatic, lung, brain cancers have the lowest survival rates.
42
what factors are important in predicting the outcome?
- age, general health, tumour site, tumour type, differentiation, tumour stage.
43
what staging system is used for solid tumours?
- TNM staging system used worldwide for solid tumours.
- T : size of primary tumour.
- N: extent of regional lymph node involvement.
- M : metastatic spread via blood.
* Ann Arbor staging for lymphoma.
* Dukes staging system for bowel cancer.
44
what is the significance of the tumour stage?
- a measure of overall burden of malignant neoplasm.
- converted to a stage 1-4.
- 1 : early localised disease.
- 2 : advanced local disease.
- 3 : regional metastasis.
- 4 : advanced disease with distant metastasis.
(contains levels within the stages too depending on tumour size, metastases state etc).
45
what is the significance of grading in neoplasia?
- grades describe the degree of differentiation of neoplasm.
- G1 : well-differentiated.
- G2 : moderately differentiated.
- G3 : poorly differentiated.
- G4 : undifferentiated or aplastic.
* depending on grading at diagnosis prognosis varies.
46
what are the principles of treatment for cancer?
- surgery.
- radiotherapy.
- chemotherapy.
- hormone therapy.
- treatments that target specific molecular alterations.
- immunotherapy.
47
differentiate between adjuvant vs neoadjuvant treatment.
- adjuvant treatment is given after surgical removal of primary tumour to eliminate subclinical disease, post curative treatment.
- neoadjuvant is given prior to surgical excision to to reduce size of primary tumour, prior to curative.
48
describe how radiation therapy works in battling cancer.
- kills proliferating cells by triggering apoptosis via interfering with mitosis.
- small doses given to kill rapidly dividing cells in G2, causing direct or free-radical induced DNA damage detected at checkpoints triggering apoptosis.
49
describe how chemotherapy works in battling cancer.
- antimetabolites mimic normal substrates involved in DNA replication.
- alkylating and platinum based drugs (cisplatin) that cross link 2 DNA strands.
- antibiotics to inhibit enzymes needed for DNA synthesis.
- plant derived drugs that block spindle formation.
*hair loss, trouble breathing, nausea, weakened immunity, bruising, rashes, neuropathy side effects.
50
describe how hormone therapy works in battling cancer.
- selective oestrogen receptor modulators that bind to oestrogen receptors preventing binding at cancer cells.
- used to treat hormone receptor positive breast cancer.
51
how would targeting oncogenes help treat cancer?
- helps create drugs that specifically target cancer cells.
| eg : imatinib.
52
describe how immunotherapy works in battling cancer.
- target immune system to help fight cancer by recognising and attacking.
- is burden overwhelming this won't fully help.
53
what is the significance of tumour markers?
- various substances released by cancer cells into circulation can be measured.
- sometimes used for diagnosis, to monitor tumour burden, as treatment assessments, recurrence assess.
eg : prostate specific antigen in prostate carcinoma.
54
what is the importance of cancer screening?
| Give some examples of screening programmes available in UK.
- meant for healthy people with no symptoms, as an attempt to detect cancers as early as possible.
- as early diagnosis means high chance of cure.
Breast screening : 47-73 ages women, Cervical : 25-64 women, bowel screening : 60-74 men and women.
