CAN Week 1 (lung Cancer)

Question 1

What is a pancoast tumour

Answer 1

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

Question 2

Define neoplasia

Answer 2

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

Question 3

What triggers neoplasia

Answer 3

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

Question 4

Define hyperplasia

Answer 4

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

Question 5

Define dysplasia

Answer 5

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

Question 6

What are the underlying principles that determine the complexity of cancer (hallmarks of cancer)

Answer 6

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

Question 7

What are malignant tumours

Answer 7

Show a particular type of behaviour which leads to severe illness and without treatment will cause death (cancer)

Question 8

Define differentiation

Answer 8

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

Question 9

Define the 3 types of differentiation

Answer 9

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

Question 10

Compare benign and malignant tumours

Answer 10

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,

Question 11

What is metastasis

Answer 11

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

Question 12

What are common metastatic sites

Answer 12

Brain 
Lymph nodes 
Lung 
Liver 
Bones

Question 13

What are epithelial tumours called

Answer 13

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)

Question 14

What are mesenchymal tumours called

Answer 14

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

Question 15

What are the names of tumours derived from different cells

Answer 15

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.

Question 16

What is Ewing’s sarcoma

Answer 16

A malignant tumour of bone seen in young people probably derived from primitive neuroendocrine cels

Question 17

What is Hodgkin’s disease

Answer 17

A malignant proliferation of lymphoid tissues classified as a subgroup of lymphomas

Question 18

What is kaposi’s sarcoma

Answer 18

A malignant tumour derived from endothelium and driven by infection with herpes virus 8

Question 19

Define cellular pleomorphism

Answer 19

Variation in size and shape of cells in tumour

Question 20

Define nuclear pleomorphism

Answer 20

Variation in size and shape of nuclei in tumour cells

Question 21

Define nuclear hyperchromatism

Answer 21

Very dark staining nuclei due to increased nuclear DNA

Question 22

Define high mitotic count

Answer 22

Increased numbers of cells in mitosis including abnormal mitotic forms

Question 23

How do malignant tumours spread

Answer 23

They can invade so can gain access to lymphatics, blood vessels and serosal surfaces

Question 24

Common sites of blood borne metastasis

Answer 24

Brain and cerebrospinal fluid 
Lung 
Adrenals 
Bone 
Liver

Question 25

What are some effects of benign tumours

Answer 25

``` 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 ```

Question 26

What are adenomas / polyps / warts

Answer 26

Larger growths of dysplasic cells

Question 27

What things have to go wrong in order for a cell to become cancerous

Answer 27

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

Question 28

What is the difference between sporadic and familial

Answer 28

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

Question 29

What is proliferation (cell cycle control)

Answer 29

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

Question 30

What are oncogenes and tumour suppressors

Answer 30

Oncogenes promote proliferation (via restriction point) Tumour suppressors inhibit proliferation

Question 31

What 2 processes play a role in the intrinsic limit in the number of times a cell lineage can divide

Answer 31

Senescence - cells in G0, don’t proliferate Apoptosis- programmed cell death as a response to DNA damage and cell stress

Question 32

What does excess telomere shortening lead to

Answer 32

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

Question 33

What is sustained angiogenesis

Answer 33

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

Question 34

What is VEGF

Answer 34

Many cancers produce VEGF which induced new vessel growth and also production of endothelial precursor cells in bone marrow which travel to the tumour

Question 35

Describe the vascularisation of a tumour

Answer 35

Disorganised, probably due to the imbalance of secreted factors stimulating growth over differentiation Leaky due to imperfect cell cell junctions

Question 36

What is the primary ramus

Answer 36

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

Question 37

How are nerve plexus formed

Answer 37

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

Question 38

How do nerve fibres regroup within a plexus

Answer 38

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

Question 39

Cardiac plexus

Answer 39

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

Question 40

Pulmonary plexus

Answer 40

Surrounds lung root and has branches from the upper thoracic sympathetic trunk and vagus nerve

Question 41

What is the difference between sympathetic and parasympathetic fibres

Answer 41

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

Question 42

Benefits and downsides of CT scans

Answer 42

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

Question 43

Benefits and downsides of MRI scans

Answer 43

- 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

Question 44

Benefits and downsides of ultrasound

Answer 44

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

Question 45

What scans are used for different elements of the neck

Answer 45

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

Question 46

What scans are used for different elements of the thorax

Answer 46

Lungs - plain film and CT Heart- ultrasound and MRI Bone- plain film and CT

Question 47

What is the mediastinum divided into

Answer 47

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

Question 48

Describe tumour origin n

Answer 48

- tumours arise from normal tissue - any tissue type can develop into a cancer - tissue type dictates type of cancer

Question 49

General rules of tumour origins

Answer 49

- 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

Question 50

Tumour characteristics

Answer 50

- 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

Question 51

What features does a tumour need to survive and become malignant

Answer 51

- limitless replication / immortality - angiogenesis - invasion and metastasis

Question 52

Hallmarks of cancer

Answer 52

- self sufficiency in growth signals - insensitivity to anti growth signals - evading apoptosis - limitless replicative potential - sustained angiogenesis - tissue invasion and metastasis

Question 53

Mechanisms of tumourigenesis

Answer 53

- 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

Question 54

How can gene mutation occur

Answer 54

- sequence change - gene amplification - gene deletion - gene silencing (epigenetic) - gene mutation is permanent

Question 55

What does gene mutation result in

Answer 55

Chanel in protein structure or levels (or both) This causes either gain of function (oncogenes) or loss of function (tumour suppressor genes)

Question 56

What can evasion of apoptosis occur through

Answer 56

- 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

Question 57

3 examples of tumour markers

Answer 57

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

Question 58

What is the TNM system

Answer 58

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

Question 59

What are the different stagings of tumours

Answer 59

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)

Question 60

What is the staging of metastasis

Answer 60

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)

Question 61

Describe dukes staging for colorectal carcinoma

Answer 61

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

Question 62

What is the two hit hypothesis for retinoblastoma

Answer 62

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

Question 63

Why are tumour suppressor genes associated with a loss of heterozygosity in tumours

Answer 63

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)

Question 64

Describe the importance of cloning the Rb gene

Answer 64

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

Question 65

How do the tumour suppressors Rb and P53 act

Answer 65

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

Question 66

What stresses can P53 detect and what outcomes does it trigger

Answer 66

Stresses: - dna damage - hypoxia - heat / cold shock - mitotic spindle damage Outcomes: - cell cycle arrest - DNA repair - apoptosis - senescence

Question 67

How do oncogenes act

Answer 67

They undergo dominant activating mutations in tumours (gain of function)

Question 68

What do oncogenes do and how are they activated

Answer 68

-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

Question 69

How do carcinogens cause mutations

Answer 69

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

Question 70

Examples of infectious agents that can cause cancer

Answer 70

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

Question 71

Mechanisms that cause cancer

Answer 71

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

Question 72

What is the principle of an inherited cancer predisposition

Answer 72

Inherited mutation in a gene causing a defect in the machinery that guards against genome damage, either monitoring or DNA damage repair

Question 73

Examples of targeted therapies based on known features of cancer cells

Answer 73

Antibodies: to specific antigens eg herceptin, EGFR, breast cancer Small molecule inhibitors eg Abl, leukaemias, BRAF, melanoma Angiogenesis inhibitors: eg avastin, VEGF, colon cancer

Question 74

What are the rotator cuff muscles (SITS)

Answer 74

Supraspinatus Infraspinatus Teres minor Subscapularis

Question 75

4 common physical signs of breast cancer

Answer 75

Skin dimpling Abnormal contours Edema (orange peal) Nipple retraction / deviation

Question 76

What do palpable and enlarged cervical lymph nodes suggest

Answer 76

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

Question 77

Most common symptoms of lung cancer

Answer 77

- 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

Question 78

Differential diagnosis for Mr jones

Answer 78

Lung cancer Tuberculosis Pneumonia Hodgkin’s lymphoma