Scenario 32 Flashcards
What is fine needle aspiration?
technique for obtaining cells for cytological diagnosis directly for palpable masses and radiologically guided for deep seated lesions
What are the two options for a tumour?
Malignant or benign
What is the 1-5 rating of lumps?
1- benign 5-cancer definite
What % of women at diagnosis have no overt metastatic disease?
95
What are the stages in the cell cycle?
G1 (G0)–>S–>G2–>M
What happens in G1?
Double internal structurees
What happens in G0?
Leave the cell cycle (eg neurones and cardiac muscle)
What happens in S?
Doubling the chromosomes
What happens in G2?
Check that things are copied correctly
How long does it take to go round the cycle?
Vaies- tumours take longer (24-72 hours)
What is the role of cyclin?
The activator present at different stages in the cycle (how it moves around the cycle)
What keeps cells in homeostasis?
The differentiation and specialisation that they have underfone, constraints by neighbouring cells, availability of metabolic substrates and the finite speed at which their internal metabolic pathways can function
What is hypertrophy?
Increase in cellular mass to maintain the higher levels of metabolic activity bought about by increasing the numbers of sub cellular organelles
What is hyperplasia?
Increase in number of cells in an organ or tissue which may lead to an increase in volume
Physiological- hormonal (breast), compensatory (liver)
Pathological- excessive hormonal stimulation of target cells (endometrium from oestrogen)
What is metaplasia?
Reversible change where one adult cell type is replaced by another
Eg- squamous metaplasia in the reap tract of smokers and at the cervix and glandular metaplasia in lower oesophagus
What are the morphological features of malignancy?
Increased cell proliferation and incomplete differentiation (irreversible change in the genome)
What is a neoplasm?
Abnormal mass of tissue, the growth of which exceeds and is coordinated with that of normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the change
Arises from just one cell
What are the basic components of a tumour?
Proliferating neoplastic cells that constitute the parenchyma and supportive stroma made up of CT, BV and lymphatics
What are malignant neoplasms of epithelial cell origin called?
Carcinomas
eg. squamous, adeno (glandular), basal cell
What are cancers arising from mesenchymal tissue called? (connective tissue)
Sarcomas
eg. lipo, fibro, osteo, chondro
What is the mechanism of cancer invasion?
Physical invasion, reduced adhesiveness and cohesiveness of tumour cells, increased motility of tumour cells, loss of ‘contact inhibition’ (2 layers of cells should touch and stop proliferating) and release of destructive enzymes
What is the difference in differentiation of benign and malignant neoplasm?
Benign are well differentiated and malignant range from well to un
What is the difference in rate of growth of benign and malignant tumours?
Most benign grow slowly where most malignant grow rapidly. Growth rate of tumours correlates with the level of differentiation.
How do tumours spread?
Benign tumours are encapsulated but malignant are never encapsulated are are characterised by infiltrative, erosive growth and extend crab like feel into adjacent tissues (invasiveness)
What are the two most reliable features to distinguish malignant from benign tumours?
Invasiveness and metastases
What is a cancer starting in a blood forming tissue called?
Leukaemia
What is a cancer that starts in cells of the immune system calles?
Lymphoma/myeloma
What is a cancer that starts in the brain or spine called
Glioma
How can a benign tumour be dangerous?
If it compresses things or releases hormones
What can a pit adenoma cause?
hypopituitarism and blindness
What can a glioma cause?
Increased intra cranial pressure, hemorhhage in brain stem that knocks out CV system
What are the 4 mechanisms of metastases formation?
Direct seeding, transplantation (surgeon cuts into tumour), lymphatic permeation, embolisation through blood vessels
What are the steps in metastases formation?
Primary neoplasm, progessive growth, vascularisation, invasion, detattchment, embolisation, survival in the circulation (avoid NK cells, lymphocytes, monocytes etc), arrest, extravasion, evasion of host defences, progressive growth, metastasis
Is metastasis episodic or continuous?
Episodic- groups of different sized ones seen in a tissue
Where does lung cancer commonly spread to?
Liver and adrenal
Where does breast cancer commonly spread to?
Lymph, skeleton, meninges, brain
Where does prostate cancer commonly spread to?
Obturator lymph nodes, lumbar spine
What decides where the cancer spreads to?
Not blood- kidneys would always be affected, depends on cell adhesion molecules
What are the local effects of a tumour on the host?
Pressure, destruction of tissue, hypercalcaemia , haemorrhage, infection
What are the systemic effects?
Fever (cytokine mediated from tumour cells or infiltrating macrophages), cachexia (loss of appetite, malabsorptuon, metabolic processes of tumour), immune defences compromised, haemotological effects (anaemia, increased RBC production), endocrine effects (appropriate hormone production or ectopic), non metastatic changes- clubbing, skin changes etc
What are the most common cancers in the UK?
Breast, lung, colorectal and prostate
What cancers are babies and children most likely to get?
Leukemia, brain/cns
What cancers are teens most likely to get?
First peak for hodgkins lymphoma
What cancer is most likely 25-49?
Breast cancer
What is the current breast, cervical and bowel screening?
Breast- every 3 years after 40, cervical every 3 years after 25, every 2 years after 60 for bowel
What is oncogenesis?
The process of transformation into cancer cells
What type of cancer are caused by nitrites in the soil
oesophageal carcinoma
What type of cancer are caused by soot?
Scrotal carcinoma (least washed)
What type of cancer are caused by viruses?
Hep B and C- hepatocellular carcinokma
Epstein-Barr virus- Burkett’s lymohoma
HHVH- Kaposi’s sarcoma
What type of cancer are caused by hormone levels?
Androgen levels- prostate cancer, oestogen- endometrial and breast cancer
What type of cancer are caused by mycotoxins and parasites?
Bile ducts and bladder?
If the host has a genetic risk factor will they definitely get cancer?
No- multistep not just a single insult, need initiation promotion and persistance
What are oncogenes?
Stimulate cell growth and division or inhibit apoptosis- normal gene is protooncogene
eg. philadelphia chronosome, RAS
Behave as a dominant trait- only need 1
What are tumour suppressor genes?
Behave as recessive genes- need to lose both
eg. p53 in thryoid, colonic and breast and BRCA 1 and 2 in ovarian and breast cancers
What changes occur in sporadic cancer?
Many DNA changes most environmental
What changes occur in familiar cancer?
Few mutations and environment not as important
When can surgery be used as a cancer treatment?
When detected early
What type of radiation does radiotherapy use?
Gamma
What cancer biology do we target using druga?
Target identification, oncogene actication, tumour suppressor genes
What is chemotherapy?
Cytotoxic therapy
Why does hair fall out and WBC count drop?
Because stem cell populations are damaged when cells are agents that damage DNA, target tubulin and antimetabolites
When can chemotherapy not be used?
Breast cancer after metastasis have formed
What non-cytotoxic therapies exist?
Inhibitors of tyrosine kinase, monoclonal antibodies to cell surface protein and immunotherapies
Why do we want to inhibit tyrosine kinase?
It is a molecule which takes signals from outside of cell in leading to gene expression. Tumours switch these on unnecessarily
How to tyrosine kinase inhibitors work?
Competitve to ATP binding site
Some people have a mutation around this site and in these cases the mutation responds very well but after 9 months become resistant- mutation
Can get rash/acne
What are monoclonal antibodies to cell surface proteins?
Highly specific to cancer cell surface proteins eg Herceptin
What immunotherapies could work?
APC activation of the CD28 signal is not good in cancer as they switch off T cells using PDL1 and CTLA4- need an autoantibody to these but problems with autoimmunity
What does tamoxifen do?
bLOCK OESTROGEN
What are the likely outcomes of different lymph node status’ in breast cancer?
Negative- 70% disease free in 10 years
1-3-40%
>10-10%
How much does herceptin reduce risk of relapse by?
35-50%
