CAN Week 1 (lung Cancer) Flashcards
What is a pancoast tumour
Cancers that start in the apex of the lung. The tumour usually spreads into one or more structures in the upper thorax and neck, which include
- upper ribs in the thorax
- nerves in the upper thorax and neck
- bundles of nerves close to the spinal cord
- blood vessels that supply blood to the upper limb
Define neoplasia
A synonym for tumour :
An abnormal mass of tissue
The growth of which exceeds and is uncoordinated with that of normal tissues
And which persists in the same excessive manner after the cessation of the stimulus which has evoked the change
What triggers neoplasia
Neoplasia starts when a gene changes and makes one cell or a few cells begin to grow and multiply too much which can cause a tumour / neoplasm
Define hyperplasia
An increase in the number of cells in an organ or tissue. These cells appear normal under a microscope. They are not cancer but may become cancer
Define dysplasia
The presence of abnormal cells within a tissue or organ. Not cancer but may become cancer
Can be mild, moderate or severe depending on how abnormal the cells look under a microscope
What are the underlying principles that determine the complexity of cancer (hallmarks of cancer)
Avoiding immune destruction Deregulating cancer energetic Evading growth suppressors Activating invasion and metastasis Resisting cell death Enabling replicative immortality Genome instability and mutation Tumour promoting inflammation
What are malignant tumours
Show a particular type of behaviour which leads to severe illness and without treatment will cause death (cancer)
Define differentiation
The term to describe how different in appearance the cells of a tumour are to the cell type from which they derived
Failure to achieve cellular differential is a common feature of malignant
Define the 3 types of differentiation
Well differentiated tumour - composed of cells which very closely resemble the cell of origin
Poorly differentiated tumour - composed of cells which bear little resemblance to the cell of origin but just enough to enable the original cell type to be identified
Undifferentiated / anaplastic tumour - composed of cells which are so undifferentiated that their cell of origin is unknown
Compare benign and malignant tumours
Benign: do not infiltrate, grow by expansion, stay at their site of origin and do not spread to distant sites
Malignant: compress and invade adjacent tissue, can spread to distant sites of the body, will infiltrate, grow by expansion and infiltration,
What is metastasis
A malignant tumour can infiltrate and invade adjacent tissues and can spread to distant sites to form a separate Secondary tumour
It is this ability to invade ad destroy tissues and to spread to secondary sites causing further destruction there which makes malignant tumours potentially fatal
What are common metastatic sites
Brain Lymph nodes Lung Liver Bones
What are epithelial tumours called
Squamous benign: squamous cell papilloma
Squamous malignant: squamous cell carcinoma
Transitional benign: transitional cell papilloma
Transitional malignant: transitional cell carcinoma
Glandular benign: adenoma (colonic or thyroid)
Glandular malignant: adenocarcinoma (colonic, gastric or renal)
What are mesenchymal tumours called
Benign bone: osteoma Malignant bone: osteosarcoma Adipose benign: lipoma Adipose malignant: liposarcoma Cartilage benign: chondroma Cartilage malignant: chondrosarcoma Smooth muscle benign: leiomyoma Smooth muscle malignant: leiomyosarcoma Striated muscle benign: rhabdomyoma Striated muscle malignant: rhabdomyosarcoma
What are the names of tumours derived from different cells
Germ cell tumours are derived from germ cells in ovary and testis
Teratomas - germ cells containing representatives from all 3 embryological germ cell layers
Embryonal tumours - embryonic blast tissue
Glial cells of the CNS- gliomas
Melanoma - melanocytes usually in skin.
What is Ewing’s sarcoma
A malignant tumour of bone seen in young people probably derived from primitive neuroendocrine cels
What is Hodgkin’s disease
A malignant proliferation of lymphoid tissues classified as a subgroup of lymphomas
What is kaposi’s sarcoma
A malignant tumour derived from endothelium and driven by infection with herpes virus 8
Define cellular pleomorphism
Variation in size and shape of cells in tumour
Define nuclear pleomorphism
Variation in size and shape of nuclei in tumour cells
Define nuclear hyperchromatism
Very dark staining nuclei due to increased nuclear DNA
Define high mitotic count
Increased numbers of cells in mitosis including abnormal mitotic forms
How do malignant tumours spread
They can invade so can gain access to lymphatics, blood vessels and serosal surfaces
Common sites of blood borne metastasis
Brain and cerebrospinal fluid Lung Adrenals Bone Liver
What are some effects of benign tumours
Bleeding eg gut, bladder Pressure on adjacent vital structures eg in brain Obstruction eg in brain, bronchus Hormone secretion eg pituitary adenoma Conversion to a malignant tumour
What are adenomas / polyps / warts
Larger growths of dysplasic cells
What things have to go wrong in order for a cell to become cancerous
Proliferation: grow independently of signals
Immortality: avoid senescence / telomere shortening
Avoiding cell death: apoptosis, they don’t do it
Angiogenesis: they must be fed
Metastasis: many activities needed
What is the difference between sporadic and familial
Sporadic cancer is where there is no genetic link within the family for that specific cancer
Familial cancer is when patients inherit a predisposition to develop cancer
What is proliferation (cell cycle control)
Progression through the cell cycle is regulated by checkpoints
4 checkpoints are well characterised
- the restriction point in G1 phase
- DNA damage checkpoints in late G1 and G2
- metaphase checkpoint (spindle attachment checkpoint) in M
What are oncogenes and tumour suppressors
Oncogenes promote proliferation (via restriction point)
Tumour suppressors inhibit proliferation
What 2 processes play a role in the intrinsic limit in the number of times a cell lineage can divide
Senescence - cells in G0, don’t proliferate
Apoptosis- programmed cell death as a response to DNA damage and cell stress
What does excess telomere shortening lead to
Crisis: damage to the chromosomes will eventually make the cell unviable
- cells undergo apoptosis if they can
- genetic catastrophe is so severe it triggers apoptosis even in the absence of p53
What is sustained angiogenesis
O2 and other nutrients supplied by vasculature are essential for cell function and survival
Newly arisen tumours must promote angiogenesis to survive
Hypoxia induced factor 1
What is VEGF
Many cancers produce VEGF which induced new vessel growth and also production of endothelial precursor cells in bone marrow which travel to the tumour
Describe the vascularisation of a tumour
Disorganised, probably due to the imbalance of secreted factors stimulating growth over differentiation
Leaky due to imperfect cell cell junctions
What is the primary ramus
A branch of a spinal nerve. There are both ventral (anterior) and dorsal (posterior) primary rami.
Dorsal rami pass posteriorly to supply:
- a strip of skin (dermatone) extending either side of the midline of the neck or trunk and extensor muscles of the vertebral column
Ventral rami are larger and clinically more important
How are nerve plexus formed
All spinal nerves (except T2-12) their anterior rami branch and rejoin forming nerve plexuses
These plexuses are formed only by anterior (not posterior) rami and occurs in cervical, brachial, lumbar and sacral regions
How do nerve fibres regroup within a plexus
Branches may contain fibres from more than one spinal level (the principle of convergence)
A given spinal level may contribute to more than one branch (the principle of divergence)
Because of regrouping, damage to one spinal segment usually doesn’t lead to complete loss of function or sensation
Cardiac plexus
Innervates the heart. Sympathetic nerves arise from cervical and upper thoracic parts of sympathetic trunk. Parasympathetic supply derives from vagus (X cranial) nerve. These nerves also contribute to oesophagus plexus
Pulmonary plexus
Surrounds lung root and has branches from the upper thoracic sympathetic trunk and vagus nerve
What is the difference between sympathetic and parasympathetic fibres
Sympathetic fibres speed up heart and dilate coronary arteries. Afferent fibres are associated with pain (eg from impaired blood supply to myocardium)
Parasympathetic fibres reduce heart rate and constrict arteries. Afferent fibres take part in cardiovascular reflexes
Benefits and downsides of CT scans
Relatively quick for scanning large areas of the body and readily available
Provides good anatomical information in multiple planes
Appropriate to assess for most acute clinical problems
Larger doses of ionising radiation
Risk of allergy to iodine based contrast
Contrast resolution is relatively poor for soft tissues
Benefits and downsides of MRI scans
- excellent anatomical detail of soft tissues
- multiple planes and sequences allow detailed evaluation
- radiation sparing investigation
- time consuming and expensive
- cannot be used in all patients
- poor assessment of air filled structures
Benefits and downsides of ultrasound
Quick, expensive, radiation sparing and portable
Allows for real time assessment
Excellent for assessment of superficial soft tissue
Highly user dependent
Poor assessment of deep structures, air filled structures and bone
Limited field of view at any one time
What scans are used for different elements of the neck
Bones- plain film and CT
Spinal cord and nerves - MRI
Soft tissues (glands, lymph nodes, muscles)- ultrasound, CT and MRI
Vessels - ultrasound, CT and MRI
What scans are used for different elements of the thorax
Lungs - plain film and CT
Heart- ultrasound and MRI
Bone- plain film and CT
What is the mediastinum divided into
Superior mediastinum - above the upper level of the pericardium and plane of Ludwig terminating at the thoracic inlet
Inferior mediastinum- below the plane of Ludwig
Anterior mediastinum - anterior to the pericardium
Middle mediastinum - within the pericardium
Posterior mediastinum - posterior to the pericardium and anterior to the vertebral column
Describe tumour origin n
- tumours arise from normal tissue
- any tissue type can develop into a cancer
- tissue type dictates type of cancer
General rules of tumour origins
- benign tumours have the suffix -oma (adenoma, leiomyoma)
- malignant epithelial tumours are usually regarded as carcinomas
- malignant mesenchymal tumours are usually regarded as sarcomas
- many malignant tumours have benign precursors
Tumour characteristics
- many normal tissues undergo continuous turnover
- new cells are produced by cell division from stem cells and old cells die by apoptosis (programmed cell death)
- an imbalance between the rates of cell division and cell death will cause tumour development
- growth control mechanisms ensure that cell division = apoptosis
- growth control can be mediated via a number of different mechanisms:
Levels of secreted growth factors, environmental growth inhibitory factors, levels of secreted growth inhibitors, intrinsic program of differentiation, tumour immune response
What features does a tumour need to survive and become malignant
- limitless replication / immortality
- angiogenesis
- invasion and metastasis
Hallmarks of cancer
- self sufficiency in growth signals
- insensitivity to anti growth signals
- evading apoptosis
- limitless replicative potential
- sustained angiogenesis
- tissue invasion and metastasis
Mechanisms of tumourigenesis
- tumours arise from cells which were normal but not have acquired new features (such as escape from growth control)
- acquisition of these features is mediated through disrupting gene function
- disrupting gene function occurs through gene mutation
How can gene mutation occur
- sequence change
- gene amplification
- gene deletion
- gene silencing (epigenetic)
- gene mutation is permanent
What does gene mutation result in
Chanel in protein structure or levels (or both)
This causes either gain of function (oncogenes) or loss of function (tumour suppressor genes)
What can evasion of apoptosis occur through
- upregulation of anti-apoptosic factors (Bcl2 is up regulated in follicular lymphomas due to the t(14;18) translocation
- down regulation or pro-apoptosis factors
Caspase 3 is down regulated in colorectal tumours - loss of function of pro-apoptotic factors
3 examples of tumour markers
HCG- human chorionic gonadotropin from tumours with trophoblast elements
AFP- alpha fetoprotein. Liver cancer, germ cell tumours
PSA- prostate- specific antigen from carcinoma of the prostate
What is the TNM system
Based upon the extent of local Tumour spread, regional lymph Node involvement and the presence of distant Metastases
Can be applied to many different types of tumour
What are the different stagings of tumours
TX- primary tumour cannot be assessed
T0- no evidence of primary tumour
Tis- carcinoma in situ
T1- tumour is 2cm or less across
T2- tumour is more than 2cm but not more than 5cm across
T3- tumour is more than 5cm across
T4- tumour of any size growing into the chest wall or skin (includes inflammatory breast cancer)
What is the staging of metastasis
MX- distant spread cannot be assessed
M0- no distant spread is found on X-rays (or other imaging tests) or by physical exam
M1- cancer has spread to distant organs (most often brain, bones, liver)
Describe dukes staging for colorectal carcinoma
Stage A- any tumour which does not extend beyond muscular is propia (no nodal involvement)
Stage B- tumour extends beyond the muscularis propia. No nodal involvement
Stage C- any depth of tumour. Tumour present in nodes
What is the two hit hypothesis for retinoblastoma
Phenotype of the mutant Rb allele is dominant at the level of the whole organism
However the phenotype of the mutant allele is recessive at the cellular level
Characteristic of the tumour suppressor gene
Why are tumour suppressor genes associated with a loss of heterozygosity in tumours
Because it is highly unlikely that both gene copies are inactivated by 2 successive mutational events
The second mutation occurs by a different mutational process with a higher frequency
(Eg Mitotic recombination)
Describe the importance of cloning the Rb gene
Showed that familial and sporadic cancers can share common mechanisms
Showed that theories relating to TS genes were correct
Suggested ways of identifying TS genes
- positional cloning of genes responsible for familial cancers
- scanning tumours for regions of LOH
How do the tumour suppressors Rb and P53 act
Apoptosis:
- when things go wrong, cells can commit suicide = programmed cell death (apoptosis)
- this is a key mechanism to avoid cancer
- proteins such as P53 can trigger cells to enter apoptosis if cell cycle / DNA synthesis fails
What stresses can P53 detect and what outcomes does it trigger
Stresses:
- dna damage
- hypoxia
- heat / cold shock
- mitotic spindle damage
Outcomes:
- cell cycle arrest
- DNA repair
- apoptosis
- senescence
How do oncogenes act
They undergo dominant activating mutations in tumours (gain of function)
What do oncogenes do and how are they activated
-Translocations
-cytogenetics: chromosomal arrangements creating a novel gene: common in haematologic tumours and sarcomas
Philadelphia chromosome in 90% of patients with chronic myeloid leukaemia
- ABL is a proto-oncogene
- BCR (breakpoint cluster region) produces a novel protein kinase. This acts on many downstream signalling pathways
How do carcinogens cause mutations
Reaction with free radicals (radiation)
Mechanisms of mutation: adducts, cross links, breaks etc
- increase the rate of mutation, DNA breaks or base changes
- leads to errors such as incorrect bases incorporated or misjoining of chromosome ends
Examples of infectious agents that can cause cancer
Helicobacter pylori bacterium - stomach cancer (930,000 cancers worldwide) - cure with antibiotics
Hepatitis B virus - liver cancer (450,000 worldwide)
Human papilloma virus - cervical cancer (490,000)
Epstein- Barr virus - nasopharyngeal cancer and lymphoma (100,000) (glandular fever but cancer with malaria)
Human immunodeficiency virus - kaposis sarcoma and other rarer tumours (57,000) - treat with antivirals
Mechanisms that cause cancer
Inflammation - viruses, asbestos
Immune suppression - immune suppressed individuals show small increase in cancer frequency (especially virus induced cancer)
Food, chemicals
Intrinsic causes: tissue growth- kids
Hormones
What is the principle of an inherited cancer predisposition
Inherited mutation in a gene causing a defect in the machinery that guards against genome damage, either monitoring or DNA damage repair
Examples of targeted therapies based on known features of cancer cells
Antibodies: to specific antigens eg herceptin, EGFR, breast cancer
Small molecule inhibitors eg Abl, leukaemias, BRAF, melanoma
Angiogenesis inhibitors: eg avastin, VEGF, colon cancer
What are the rotator cuff muscles (SITS)
Supraspinatus
Infraspinatus
Teres minor
Subscapularis
4 common physical signs of breast cancer
Skin dimpling
Abnormal contours
Edema (orange peal)
Nipple retraction / deviation
What do palpable and enlarged cervical lymph nodes suggest
These are glands in the neck which become enlarged in infection
If they are persistent they raise suspicion of cancer (breast, lung, stomach), TB, lymphoma
Most common symptoms of lung cancer
- cough: lung cancer can cause a new cough or a change in a chronic cough
- blood in sputum : hemoptysis- requires medical attention
- shortness of breath
- wheezing
- chest pain: can develop and may be dull, sharp or stabbing
- voice hoarseness
- headache and swelling of the face, arms or neck
- arm shoulder and neck pain: can be caused by a tumour in the top of the lungs (called a pancoast tumour). Other symptoms include weakening of the hand muscles (due to pressure on the nerve that stimulates the arm), a droopy eyelid and blurred vision
Differential diagnosis for Mr jones
Lung cancer
Tuberculosis
Pneumonia
Hodgkin’s lymphoma
