ICS Pathology Flashcards
What are the two categories of autopsy?
Hospital and Medico-legal
What are hospital autopsies used for?
Teaching, audit, research
Which type of autopsy is most common?
Medico-legal autopsies= over 90% of UK autopsies
What are the two types of medico-legal autopsy?
Coronial autopsies (where death is not due to unlawful action), and forensic autopsies (where death is thought to be unlawful)
What are the 4 questions to answer during a coronial autopsy?
- Who is the deceased?
- When did they die?
- Where did they die?
- What brought about their death?
What are the three categories for when deaths are referred to the coroner?
- Presumed natural but death is unknown and patient hasn’t seen doctor in 14 days prior
- Presumed iatrogenic such as peri/postoperative death, anesthetic deaths, complications of therapy etc
- Presumed unnatural such as accidents, suicide, unlawful killing, neglect, custody death etc
What do histopathologists do?
Perform hospital autopsies and some coronial autopsies including natural deaths, suicide, accidents, road traffic deaths, peri/post-operative deaths
What do forensic pathologists do?
Perform autopsies where the death could be due to the action of a third party such as homicide, death in custody or neglect
What are the parts of the coroners rules of 1984?
- Autopsy as soon as possible
- By a pathologist of suitable qualification
- Report findings promptly and only to coroner
- Autopsy only on appropriate premises
What are the rules of the coroners act of 1988?
- Allows coroner to order an autopsy where death is likely due to natural causes to obliviate need for inquest.
- Allows coroner to order an autopsy where death is clearly unnatural and inquest will be needed
What are the rules of the coronial legislation of 2005?
Pathologist must tell coroner precisely what material have been retained, coroner authorizes retention and sets disposal date. Coroner must inform family of retention. The family then has choices either to return material, retain for research/teaching or to respectfully dispose of.
What are the rules of the coroners and justice act of 2009?
Coroner can now defer opening the inquest and instead launch an investigation
What can be used to identify a body?
Formal identifies, body habitus, jewelry, body modification or clothing
What is inflammation?
A local physiological response to tissue injury that is either acute or chronic
List some benefits of inflammation
Destruction of invading microorganisms and walling off an abscess cavity to prevent the spread of infection
List some negatives of inflammation
Disease will compress surounding structures, Fibrosis may distort the surrounding tissues, digestion of normal tissues, swelling in dangerous places, inappropriate inflammatory responses
Give an example of acute inflammation?
Acute appendicitis
What are the 4 stages of acute inflammation?
- Changes in vessel calibre
- Fluid exudate
- Cellular exudate
- Chemotaxis
What is cellular exudate?
An accumulation of neutrophil polymorphs in the extracellular space
What causes the fluid exudate in acute inflammation?
- Sphincters in arteriolar walls relax thereby increasing blood flow into capillaries
- Capillary hydrostatic pressure is increased and there is escape of plasma proteins, increasing osmotic pressure in extravascular space
- Therefore more fluid leaves the vessels = fluid exudate
What are the 4 steps of neutrophil extravasation?
- Margination of neutrophils
- Pavementing of neutrophils
- Pass between endothelial cells
- Pass through basal lamina and migrate into adventitia
What is neutrophil extravasation?
The leakage of neutrophils from capillaries into the surrounding tissues during acute inflammation
What is neutrophil margination?
When neutrophils begin to flow at the peripheral zone of capillaries, near the endothelium, due to a loss of intravascular fluid and increase in plasma viscosity with slowing of flow at site of inflammation
What is pavementing of neutrophils?
At the site of acute inflammation, neutrophils begin to adhere to endothelium of venules due to its “sticky” wall
What is diapedesis?
When erythrocytes escape through the vessel walls passively during acute inflammation
What does large numbers of RBC in the extracellular space during inflammation imply?
Severe vascular injury
List some chemical mediators during acute inflammation
Histamine and Thrombin
What cells release histamine?
Mast cells, and basophil&eosinophil leucocytes
What are some effects of histamine?
Contraction of smooth muscle in the lungs, uterus and stomach, dilation of blood vessels thus lowering of blood pressure, gastric acid secretion etc.
What are the 4 enzymatic cascade systems in plasma?
Complement system
Kinin System
Coagulation factors
Fibrinolytic system
What is the purpose of the complement system?
To remove or destroy antigens either by lysis or oponization
What can activate the complement system?
Enzymes released from dying cells, endotoxins of bacterias etc.
What chemical mediators are secreted by tissue macrophages?
Interleukin-1 and TNF-alpha
Why do lymphatic channels become dilated in acute inflammation?
They drain away oedematous fluid of the inflammatory exudate
What is opsonization?
Making microorganisms more amenable to phagocytosis by either immunoglobulins of complement components
What are phagolysosomes?
When a particle is ingested by a phagocyte into a phagosome, which then fuses with a lysosome
What are the steps of phagocytosis?
- Neutrophil ingests bacterium
- Bacterium lies within a phagosome
- Lysosome fuses with phagosome (phagolysosome), and digests the bacterium
- Bacterial debris is released
List some causes of acute inflammation
- Microbial infection
- Hypersensitivity reaction
- Physical agents
- Tissue Necrosis
How does tissue necrosis cause acute inflammation?
Peptides are released from the dead tissues which trigger inflammation
What are the 5 signs of acute inflammation?
Tumor (Swelling), Rubor (Redness), Calor (Heat), Dolor (Pain), loss of function
What causes swelling in acute inflammation?
Oedema, and formation of new connective tissue
What causes redness in acute inflammation?
Dilation of small blood vessels
What causes heat in acute inflammation?
Increased blood flow (Hyperaemia) and systemic fever
What causes pain in acute inflammation?
Stretching and distribution of the tissues to inflammatory oedema. Some chemical mediators also induce pain
What are the possible outcomes of acute inflammation?
- Resolution
- Suppuration
- Organisation
- Progression to chronic inflammation
What conditions favor resolution?
Minimal cell death and damage, in tissues capable of regeneration, rapid destruction of causal agent
What is suppuration?
Formation of pus
What conditions favour suppuration?
Persistant causative stimulus, and normally an infective agent, usually pyogenic bacteria
What is organisation?
When tissue is replaced with granulation tissue as part of the healing process - healing by fibrosis where there is substantial damage to connective tissue framework with excessive necrosis
When will acute inflammation progress onto chronic inflammation?
If the causative agent is not removed
What is pyrexia and how does it happen?
Fever= Neutrophils and macrophages produce endogenous pyrogens which act on the hypothalamus to set the thermoregulatory mechanisms at a higher temperature
List some systemic effects of inflammation
Pyrexia, malaise, anorexia, nausea, splenomegaly, weight loss, lymph node enlargement, anaemia
What is primary chronic inflammation?
Where there is no initial phase of acute inflammation
What are the histological features of chronic inflammation?
Cellular infiltrate consisting of lymphocytes, plasma cells and macrophages
Name an example of chronic inflammation
Tuberculosis
What is resolution?
Healing where the initiating factor is removed. Generally one single large injury such as a single fracture, liver damage through paracetamol overdose etc which is then left to repair. Can fully repair if in a cell population which can do so.
What is repair?
Healing where the initiating factor is still present. Generally a recurring injury/ disease such as fracture that it frequently moved, liver damage through recurrent alcohol intake etc. Won’t fully repair as there will be scar tissue
What is the role of B lymphocytes?
Production of antibodies
What is the role of T lymphocytes?
Cell-mediated immunity
What is a granuloma?
An aggregate of epithelioid histocytes- Part of type IV hypersensitivity
List some systemic granulomatosis diseases
TB, Sarcoidosis, Crohn’s disease, Leprosy, Schistosomiasis
How can you identify tuberculosis?
Use ziehl-neelsen stain, will get a bright red result if TB
What are the histological features of epithelioid histocytes?
Large vesticular nuclei
Plentiful eosinophilic cytoplasm
Elongated
Arranged in clusters
What are langerhans giant cells?
Giant cells with a horseshoe arrangement of peripheral nuclei at one pole. It is characteristically seen in TB.
What are foreign body giant cells?
Large cells with nuclei randomly scattered throughout their cytoplasm
What are touton giant cells?
Large cells with a central ring of nuclei, peripheral to which there is lipid material
What cells are involved in acute inflammation?
Neutrophils and macrophages
What cells are involved in chronic inflammation?
Lymphocytes, macrophages and plasma cells
What are labile cells?
Cells with a good capacity to regenerate e.g. epithelial cells
What are stable cell populations?
Cells that divide at a very slow rate normally, and still retain their capacity to divide when necessary. E.g. hepatocytes
What are permanent cells?
Cells with no effective regeneration
How does organisation occur?
Granulation tissue is formed in the early stages, which then contracts and gradually accumulates collagen. Granulation tissue is the combination of capillary loops and myofibroblasts. The organized area is firmer than normal
How do abrasions heal?
Scab forms over surface
Epidermis grows out from adnexa, protected by scam
Leads to a thin confluent epidermis
Final epidermal regrowth leading back to normal skin
What is healing by first intension?
- Fibrin deposited locally will weakly bind the two sides of the wound
- Coagulated blood on the surface will form a scab
- Capillaries then proliferate sufficiently to bridge the gap, and fibroblasts secrete collagen as they migrate into the fibrin network to form a strong collagen join
When can healing by first intension occur?
If there is a small incision with little damage to tissue either side of the cut.
What is healing by second intension?
- When there is tissue loss so the wound margins are not apposed.
- There is first phagocytosis to remove any debris
- Granulation tissue to fill in defects and repair specialised tissue lost
- There is finally epithelial regeneration to cover the surface
List some cells that can regenerate
Hepatocytes, Pneumocytes, all blood cells, epithelia, osteocytes
What cells cannot regenerate?
Myocardial cells, neurones
How is local inflammation due to injury (e.g. banging the ankle) treated?
RICE
Rest, Ice, Compression, Elevation
How are bites treated?
Antihistamines, NSAIDs
How are chronic rashes treated?
Steroid creams
How do steroid creams work?
They bind to DNA and up regulate inhibitors of inflammation and down regulates chemical mediators of inflammation
What is an abscess?
A localized collection of inflammatory cells with a fibrotic wall
List two ways of investigating inflammation
- Localised aspiration
- Blood cultures
What is a thrombus?
The solidification of blood contents that forms within the vascular system during life
What are the three components of Virchow’s triad?
- Stasis of blood flow
- Endothelial injury
- Hypercoagulability
What is Virchow’s triad?
3 elements that predispose to thrombosis
What mechanisms prevent thrombus formation?
- Laminar flow (where cells travel in the centre of arterial vessels and don’t touch the sides)
- Endothelial cells which line vessels are not “sticky” when healthy
What are contained within alpha granules of platelets?
Platelet adhesion molecules such as fibrinogen, fibronectin and platelet growth factor
What are contained within the dense granules of platelets?
Adenosine diphosphate that cause platelets to aggregate
What is platelet aggregation?
Platelets release chemicals which cause other platelets to stick, and starts the cascade of clotting proteins
What is the process of arterial thrombosis formation?
- A fatty streak forms, which protrudes into the lumen causing turbulence in blood flow
- This turbulence eventually results in the loss of intimal cells and the exposed plaque surface is presented to the blood cells
- This results in fibrin deposition and platelet clumping due to exposed collagen
- This process may be self perpetuating, causing thrombi to grow
- This disrupts laminar flow
What is a fatty streak?
An early atheromatous plaque which is a slightly raised area on the luminal surface of an artery
What does arterial thrombus result in?
- Loss of pulse distal to thrombus
- Area becomes cold, painful and pale
- Eventually tissue dies and gangrene results
Does atheroma normally occur in arteries or veins?
Arteries, as veins are low pressure
How do venous thrombi normally occur?
Normally due to stasis
- At valves are there is a natural degree of turbulence here
- Or if blood pressure falls during surgery or following a MI
Where do venous thrombi normally occur?
95% occur in leg veins
What does a venous thrombus result in?
- Area becomes tender and causes general ischaemic pain
- Area becomes reddened
- Area becomes swollen
What are arterial thrombosis made up of?
Blood clot- Many platelets (White thrombus)
What are venous thrombosis made up of?
Blood clot- Mainly coagulation factors (Red thrombus)
What can arterial thrombosis lead to?
MI/Stroke
What can venous thrombosis lead to?
Deep vein thrombosis/ Pulmonary embolism
What is the treatment for arterial thrombosis?
Anti-platelets e.g. aspirin, clopidogerel
What is the treatment for venous thrombosis?
Anti-coagulants e.g. warfarin, heparin, NOACs
What is the commonest cause of arterial thrombosis?
Most commonly due to atheroma
What is the commonest cause of venous thrombosis?
Stasis- slowing of blood flow in veins
What is an embolus?
A mass of material in the vascular system able to lodge in a vessel and block its lumen
What things can cause an embolus?
Thrombus, air, cholesterol crystals from plaques, tumour amniotic fluid, fat after severe trauma etc.
Where will a venous embolism occur?
It will travel to the vena cava, then lodge somewhere in the pulmonary arteries causing a pulmonary embolism
What will be the outcome of a pulmonary embolism?
Small embolism= May be lysed in lung or remain unnoticed
Large embolism= Acute respiratory and cardiac problems (chest pain, shortness of breath)
Massive embolism= Sudden death
Where do arterial emboli normally occur?
Either from the heart on areas of damaged cardiac muscle, or from an atheromatous plaque
What is ischaemia?
A reduction in blood flow to a tissue or part of the body caused by constriction or blockage of the blood vessels supplying it
What is infarction?
The necrosis of part or whole of an organ that occurs when the artery supplying it becomes obstructed
Why are the liver, lung and brain less susceptible to infarction?
Dual blood supply
What is reperfusion injury?
When blood flow returns to an ischaemic area, there is removal of dead cells and activation of oxygen-dependent free radical systems. There are also intrinsic oxygen free radicals brought by WBC, resulting in more damage.
What is gangrene?
When areas of a limb or a region of the gut have their arterial supply cut off, and large areas of mixed tissue die in bulk
What is wet gangrene?
Where bacterial infection supervenes as a secondary complication and patient becomes septic
What is disseminated intravascular coagulation (DIC)?
Where there is minute thrombi and bleeding at multiple sites due to the consumption of clotting factors
What are causes of ischaemia?
Thrombi Spasms in smooth muscle in the vessel wall External compression of veins Hyperviscosity of blood Vasculitis
What is atherosclerosis?
An accumulation of lipid, macrophages and smooth muscle cells in intimal plaques in arteries
Do plaques occur in mainly high or low pressure systems?
Only occurs in high pressure systems
What can occlusive atheroma cause?
Cerebral infarction MI Aortic aneurysm Peripheral vascular disease Gangrene
What are the five types of arteries where atherosclerosis occurs?
Aorta (Normally descending) Cerebral arteries Common iliac arteries/ Femoral arteries Coronary arteries Carotid
What are the contents of a plaque?
Fibrous tissue cap with macrophages and lymphocytes
Central lipid core
Smooth muscle cells, cell debris, calcium, connective tissues, foam cells
What are foam cells?
Macrophages that have phagocytosed oxidised lipoproteins = appear foamy. Often at the border of a thrombogenic lesion
What are the risk factors for plaque formation?
- Hypercholesterolaemia
- Hyperlipidaemia
- Hypertension
- Smoking
- Poorly controlled diabetes
- Male gender
- Increasing age
- Social deprivation
How do atherosclerotic plaques form?
- Endothelial cell dysfunction
- High levels of LDL in the blood begin to accumulate
- Macrophages are attracted to the site of damage and take up lipid to form foam cells
- Formation of a fatty streak
- The activated macrophages release their own products- cytokines and growth factors
- Smooth muscle proliferation around the lipid core and formation of a fibrous cap
What things can damage endothelial cells?
- High cholesterol
- Smoking
- Hypertension
- Poorly controlled diabetes
How can someone prevent atherosclerosis?
Smoking cessation Control of blood pressure Weight reduction Low dose aspirin Statins
How does aspirin prevent thrombosis and atherosclerosis?
Inhibits platelet aggregation
What is the difference between atherosclerotic plaque and thrombi?
- Plaques= mainly lipid, macrophages, cholesterol etc
- Thrombi= Blood clot
What is an aneurysm?
A localised permanent dilation of part of the vascular tree
What is an aortic dissection?
Where blood is forced through a tear in the aortic intima to create a blood-filled space in the media
What is a berry aneurysm?
An aneurysm in the circle of willis causing a subarachnoid haemorrhage
What is a TIA?
A stroke that lasts for less than 24 hrs and is associated with complete clinical recovery
What is the normal cause of a intracerebral haemorrhage?
A rupture of the middle cerebral artery
What is the normal cause of a subarachnoid haemorrhage?
A rupture of a saccular aneurysm of the circle of willis
Define hypertrophy
An increase in size of organ or tissue due to an increase in the size of the cells
Give an example of hypertrophy
Example-Increase in skeletal muscle mass during exercise
Define hyperplasia
An increase in the size of an organ or tissue due to an increase in the number of cells
Give an example of hyperplasia
Benign prostatic hyperplasia
Define atrophy
Decrease in the size of an organ or tissue and results from a decrease in the mass of pre-existing cells, either by decrease in cell size or decrease in numbers of cells.
Give an example of atrophy
Atrophy of the endometrium
Define metaplasia
Replacement of one differentiated cell type by a different differentiated cell type
Give an example of metaplasia
Barretts oesophagus
Define dysplasia
Increased cell growth and decreased differentiation. Pathological a variation in size and shape of cells, with a high nuclear/cytoplasmic ration, and increased nuclear DNA
Give an example of dysplasia
Pre-cancerous state
Define apoptosis
Programmed cell death. Pathologically death of scattered single cells forming membrane-bound bodies eventually phagocytosed and broken down by adjacent unaffected cells
Give an example of apoptosis
Apoptosis between digits in utero
Define necrosis
Traumatic cell death which induces inflammation and repair
Give an example of necrosis
Gangrene
Do cells swell in apoptosis or necrosis?
Swell in necrosis, shrink in apoptosis
Are organelles damaged in apoptosis or necrosis?
Damaged in necrosis, undamaged in apoptosis
Is there inflammation in necrosis or apoptosis?
Inflammation in necrosis
Is apoptosis energy dependent or independent?
Energy dependent
What inhibits apoptosis?
Growth factors, extracellular cell matrix, sex steroids and some viral proteins
What induces apoptosis?
Growth factor withdrawal, glucocorticoids, some viruses, free radicals, ionising radiation, DNA damage, ligand-binding at death receptors
Briefly describe the intrinsic apoptotic pathway
- BCL2 proteins inhibit apoptosis, and Bax proteins enhance apoptosis
- Their ratio determines cell’s susceptibility to apoptotic stimuli
- The cell responds to stimuli
- P53 can then induce cell cycle arrest, or if there is severe damage in the cell, it can induce apoptosis
Briefly describe the extrinsic apoptotic pathway
- There are specific mechanisms for the activation of apoptosis characterised by ligand-binding at death receptors
- Receptors include members of the tumour necrosis factor receptor family
- Fas ligands bind to Fas receptors on the cell surface, which sends a signal into the cell and switches on caspases
Briefly describe the execution phase of apoptosis
- Caspases are activated by either the intrinsic or extrinsic pathway (Either by Fas binding, Bax, or by lower Bcl-2)
- This therefore induced degradation of the cytoskeletal framework and nuclear proteins
- This is then phagocytosed
How does necrosis induce inflammation?
The rupture of the plasma membrane and spillage of cell contents, with some being immunostimulatory, which provokes an inflammatory response
What is caseous necrosis?
A pattern of necrosis where the dead tissue is structureless almost like soft cheese. It is characteristic of tuberculosis
What is gangrene?
A type of necrosis with the rotting of tissues, sometimes as a result of certain bacteria particularly clostridia. Affected tissue appears black
Why does gangrenous tissue appear black?
Deposition of iron sulphide from degraded haemoglobin
What is a congenital disease?
A disease present at birth and includes chromosomal disorders, hereditary and spontaneous genetic diseases etc.
What is a genetic disease?
Inherited diseases such as cystic fibrosis, such as sickle cell anaemia, or spontaneous such as Down’s syndrome
What is trisomy 21?
Down’s syndrome
What is acquired disease?
A disease caused by non-genetic environmental factors, such as TB, lung cancer, AIDS
What is multifactorial disease?
A disease due to many different factors, such as spina bifida. A common example is cleft palate
What is a homeobox gene?
A group of genes that control mutations
What is mendelian inheritance?
Single gene inheritance
What is autosomal inheritance?
Non-sex linked inheritance
What is polygenic disease?
Disease caused by multiple genes
What is acromegaly?
Excess growth hormone leading to increasing bone sizes mainly in hands, feet and face
What is the normal cause of acromegaly?
Pituitary tumour leading to growth hormone excess
What is achondroplasia?
A disorder of bone growth that prevents the changing of cartilage in bone. It is characterized by dwarfism, large head size, small fingers
Describe telomere length in aging
The telomere is the region at the end of each DNA sequence. They are not fully copied on division, thus gradually get shortened. Eventually they become so short that DNA polymerase cannot bind and thus the cell can’t replicate again.
What is sarcopaenia?
Muscle loss due to aging caused by decreased growth hormone, decreased testosterone, and icnreased acatabolic cytokines
How does deafness occur?
Loss of hair cells
How do cataracts form in aging?
UV damage results in cross-linking proteins in the eye
What causes osteoporosis in aging?
Oestrogen loss
What is dermal elastosis?
Wrinkling
What causes wrinkling?
UV damage resulting in less collagen and less elastin within the skin
What is progeria?
A disease of rapid aging in children.
Which cells produce collagen?
Fibroblasts
What is the main effector cell in acute inflammation?
Neutrophil Polymorphs
Give an example of primary chronic inflammation?
Transplant rejection
Name a drug that inhibits platelet aggregation
Aspirin
How can you cure basal cell carcinoma?
Complete local excision - basal cell carcinoma never metastasises
Where do sarcomas normally metastases to?
The lung
What is metastasis?
When tumours spread from their site of origin to tumours at distant sites
What are the possible routes of metastasis?
Haematogenous
Lymphatic
Transcoelomic
Where do breast cancers normally metastasis to?
Axillary lymph node then bone
What is haematogenous spread?
Via the blood stream
What carcinomas favour bone haematogenous metastasis?
Lung Breast Kidney Thyroid Prostate
What is lymphatic spread?
Via the lymph nodes
What is the most common route of spread for carcinomas?
Lymphatic spread
What is transcoelomic spread?
Via the peroneal cavitys
How is leukaemia treated and why?
Leukaemia is a cancer of bone marrow and thus white blood cells are affected. This means that the cancer is circulating, so would have to treat systemically (Chemotherapy)
What are some generalised cancer symptoms?
Weight loss, fever, frequent infections, easy shortness of breath, weakness, pain, fatigue, splenomegaly, night sweats
How is a breast carcinoma diagnosis confirmed?
Biopsy using a core biopsy needle. Can confirm if it has spread using ultrasound and core biopsy needle at lymph nodes and using full body scans
How is breast carcinoma normally treated?
Surgery with or without axillary lymph node clearance to remove the tumor. Radiotherapy to destroy microtumors. Chemotherapy if the cancer has spread further
What is carcinogenesis?
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
What is a carcinogen?
An environmental agent participating in the causation of tumours
What percentage of cancer risk is environmental?
85%
What are some problems with identifying carcinogens?
- Latent period may be decades
- Complexity of environment
- Ethical constraints
Where is hepatocellular carcinoma common and why?
Uncommon in UK/USA. Common in areas with high hep B and C (South Africa)
Where is oesophageal carcinoma common and why?
Japan and china due to consumption of carcinogenic chicken
Turkey and Iran due to drinking extremely hot coffee
What is the biggest risk for lung cancer?
Smoking
What population has increased risk of bladder cancer?
Those who have worked with aniline dye and rubber
What population has increased risk of scrotal carcinoma?
Chimney sweeps due to soot exposure
What are the categories of carcinogen?
- Chemical
- Viral
- Radiation
- Hormones, mycotoxins and parasites
- Misc
What are pro-carcinogens?
The pre-carcinogenic state of chemical carcinogens, which then require metabolic conversion into ultimate carcinogens
What viruses are associated with cancer?
Epstein-Barr
Human Papillomavirus
What type of cancers are associated with UVA and UVB?
Basal cell carcinoma and squamous cell carcinoma
Why are Ukranian children more prone to thyroid cancer?
Chernobyl caused excess ionising Iodine which is taken up by the thyroid to form thyroxine
What types of cancers is oestrogen associated with?
Mammary and endometrial cancer
What type of cancer is associated with steroids?
Hepatocellular carcinoma
What type of cancer is associated with Schistosoma?
Bladder cancer
How can race affect cancers?
Darker skinned people have more melanin and thus are more protected from the carcinogenic effect of UV
What is the most common cancer in males?
Prostate
What is the most common cancer in women?
Breast cancer
What premalignant lesions give a predisposition for cancer?
Colonic polyps
Cervical dysplasia
Undescended testicles
What dietary factors are linked to cancer?
Fat= Colorectal cancers Alcohol= breast and oesophageal cancer
What is a neoplasm?
A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed
Where does colon cancer normally metastasise to and why?
It invades the veins and travels through the portal system into the liver
Can neoplasms arise form erythrocytes?
No- they don’t have a nucleus
How do neoplastic cells relate to their parent cells?
Their synthetic activity is related (if parent cells produce hormones they will too), their growth patterns are also related to the parent cell
What are the types of tumours?
Neoplasm, inflammation, hypertrophy, hyperplasia
What is angiogenesis?
The ability of a tumour to induce blood vessels. It is induced by factors secreted by tumour cells such as vascular endothelial growth factor
What things promote angiogenesis?
Vascular endothelial growth factor, basic fibroblast growth factor
What things inhibit angiogenesis?
Angiostatin, endostatin, vasculostatin
Why is abnormal coagulation common in patients with hepatitis?
Hepatitis damages the liver, which means it cannot produce clotting factors.
What coagulation products does the liver produce?
Factor I, II, VII, IX
Proteins C and S for inhibition of coagulation
Anti-thrombin III which impairs coagulation
What is a prothrombotic state?
A state of abnormal coagulation that increases the chances of thrombosis
How can drug use cause embolism?
Filler material can build up in the venous system, normally in very small fragments
How can DVT be avoided post-surgery?
TED stockings
Anti-coagulants
If very high risk- can have a IVC cage and anticoagulants
What are the three main coagulation tests?
APTT
PT
TT
What is an APTT test?
Activated partial thromboplasmin time
Uses contact activation which provides a large surface area for plasma contact. Extra phosopholipid is added.
What does an APTT measure?
Activated partial thromboplasmin time
Measures all clotting factors except VII and XIII
What is a PT test?
Prothrombin time
Tissue factor and phospholipid are added to patient serum
What does PT measure?
Prothrombin time
Assesses factor II, V, VII, X, and fibrinogen
What is a TT test?
Thrombin time
Blood test to measure the time for clot formation. An excess of thrombin is added directly to blood to measure the speed of coagulation.
What are the three steps of carginogenesis?
- Initiation= Carcinogen induces genetic change
- Promotion= Stimulation of clonal proliferation of the transformed cell
- Progression= The process culminating in malignant behaviour, characterised by invasion
What genetic alterations are needed to transform a cell into a neoplastic cell?
- Expression of telomerase leading to immortalisation
- Loss or inactivation of tumour suppressor genes
- Activation or abnormal expression of oncogenes
Why do mutations occur in cells?
- By chance mutations
- By direct inheritance of faulty genes from parents
- As a consequence of toxic insult delivered to the cell
What is a gatekeeper gene?
A gene that inhibits the proliferation or promote the death of cells with damaged DNA e.g. P53
What is the HER2 gene?
A gene that can play a role in the development of breast cancer
What is a caretaker gene?
A gene that repairs DNA damage e.g. BRCA1
What is a MDT meeting?
Multidisciplinary team meeting - where cases are discussed with various staff members
What is P53?
A caretaker gene on chromosome 17 which is the most frequently mutated. It normally repairs damaged DNA before S phase by arresting the cell cycle in G1 until the damage is repaired, or will cause cell death if there is extensive damage
What are oncogenes?
Genes driving the neoplastic behaviour of cells
What is the mechanism of activation of oncogenes?
A) Translocation= The oncogene is translocated to an actively transcribed gene
B) Point mutations= A specific base is translated into an oncogene to make it hyperactive
C) Amplification= Insertion of multiple copies of the oncogene
Describe benign tumours
They do not invade the basement membrane, and are often exophytic (Grows outwards). They have a low mitotic activity, and are well circumscribed. Necrosis/ulceration is rare. They bare a close resemblance to normal tissue.
What are the risks of benign tumours?
- Can cause pressure on adjacent structures
- Obstruct flow
- Produce hormones
- Can cause anxiety
- Can possibly transform into malignant tumours
Describe malignant tumours
They invade the basement membrane, and are often endophytic (grows inwards). They have a high mitotic activity, and are poorly circumscribed. Necrosis/ ulceration is common. They have pleomorphic nuclei (vary in size and shape), and do not resemble the parent cell.
What are some risks of malignant tumours?
- They can metastasise
- Can have paraneoplastic effects such as ACTH from small cell lung cancer
- Can cause anxiety
- Pain
- Blood loss
- Pressure on adjacent tissue
What are borderline neoplasms?
Fairly rare tumours that defy precise classification- neither benign or malignant
What is the histological appearance of malignant tumours?
- High mitotic activity
- Pleomorphism
- Hyperchromatic nuclei
- Poorly defined border
Describe the TNM grading system
T= Primary tumour N= Lymph node status M= Anatomical extent of distant metastases
What is a carcinoma?
A tumour of epithelial cells
What is a sarcoma?
A tumour of connective tissues
What is a lymphoma?
A tumour of lymphoid tissues
What is a leukaemia?
A tumour of haemopoietic organs
What is the grading system of malignant tumours?
Grade 1= Well differentiated, closely resembles parent tissue
Grade 2= Moderately differentiated
Grade 3= Poorly differentiated, more aggressive
Anaplastic= lack recognisable histogenic features and extremely aggressive
What is histogenesis?
The specific cell of origin of a tumour
What is a papilloma?
Benign tumour of non-glandular, non-secretory epithelium, with the prefix of the cell type of origin e.g. squamous cell papilloma
What is an adenoma?
Benign tumour of glandular or secretory epithelium with the prefix of the cell type of origin e.g. Colonic adenoma
What is a carcinoma?
Malignant neoplasm of epithelial cells, prefixed with the name of epithelial cell type .e.g transitional cell carcinoma
What is an adenocarcinoma?
Malignant tumour of glandular epithelium, coupled with the name of the tissue of origin, e.g. adenocarcinoma of the prostate
What is a lipoma?
Benign tumour of adipocytes
What is a rhabdomyoma?
Benign tumour of striated muscle
What is a leiomyoma?
Benign tumour of smooth muscle cells
What is a chondroma?
Benign tumour of cartilage
What is a osteoma?
Benign tumour of bone
What is an angioma?
Benign vascular tumour
What is a neuroma?
Benign tumour of nerve
What is a liposarcoma?
Malignant tumour of adipocytes
What is a rhabdomyosarcoma?
Malignant tumour of striated muscle
What is a leiomyosarcoma?
Malignant tumour of smooth muscle cells
What is a chondrosarcoma?
Malignant tumour of cartilage
What is an osteosarcoma?
Malignant tumour of bone
What is an angiosarcoma?
Malignant vascular tumour
What is a neurosarcoma?
Malignant tumour of the nerve
What is a melanoma?
Malignant neoplasm of melanocytes
What is a mesothelioma?
Malignant tumour of mesothelial cells
What is a lymphoma?
Malignant neoplasm of lymphoid cells
What is a teratoma?
Neoplasm of germ cell origin that forms representing all three germ cell layers of the embryo
What is a carcinosarcoma?
Mixed malignant tumours showing characteristics of epithelium and connective tissue
What is brukitt’s lymphoma?
B cell lymphoma caused by epstein Barr virus
What is Ewing’s sarcoma?
A malignant tumour of bone
What is Hodgkins lymphoma?
Malignant lymphoma characterised by the presence of Reed-Sternberg cells
What is Kaposi’s sarcoma?
Malignant neoplasm derived from vascular endothelium, commonly associated with AIDs
How is carcinoma in situ treated?
Local excision as it isn’t moving so won’t spread
Why do cancerous cells produce meltalloprotinases?
To digest the basement membrane to allow for invasion
What factors influence invasion?
- Decreased cellular adhesion
- Secretion of proteolytic enzymes
- Abnormal or increased cellular motility
What are collagenases used for in neoplastic cells?
Degrade types I, II and III collagen to invade surrounding tissue
What are TIMPs?
Tissue inhibitors of metalloproteinases (counteracts meltalloprotinases)
How do neoplastic cells evade host immune defense?
- Tumour cells aggregate with platelets to surround themselves and thus go under the radar
- Shedding of surface antigens
- Adhesion to other tumour cells
What is the mechanism of metastasis?
- Detachment of tumour cells from their neighbours
- Invasion of surrounding tissue through basement membrane
- Intravasation into the lumen of vessels
- Evasion of host defense mechanisms
- Adherance to endothelium at a remote location
- Extravasation of the cells
What are some side effects of chemotherapy?
- Myelosuppression
- Hair loss
- Diarrhoea
What is targetted chemotherapy?
Chemotherapy that exploits some of the difference between cancer cells and normal cells to target the drugs to the cancer cells
Briefly describe the adeno-carcinoma sequence in the colorectum
- Mutation in the APC gene= polyposis
- Oncogenes are altered- normally KRAS and c-MYC
- Deletion of the accompanying allele results in complete loss of the tumour suppressor function
What is a germline mutation?
A mutation in sex or germ cells
What is a somatic mutation?
A spontaneous mutation in body cells. It cannot be passed on
What is lead-time bias?
Earlier detection does not affect the inevitable fatal outcome, but prolongs the apparent survival time
What is length-bias?
Preferential detection of slow growing tumours with intrinsically better prognosis
What is overdiagnosis bias?
Diagnosis of lesions that, although histologically malignant, are clinically relatively harmless
What is selection bias?
Volunteers for screening are more at risk of good-prognosis tumours
What are the main screening programmes?
- Pregnancy screening
- Newborn screening
- Diabetic eye screening
- Cervical screening
- Breast screening
- Bowel cancer screening
- AAA screening
Which of the following tumours never metastasises?
a. Malignant melanoma
b. Small cell carcinoma of the lung
c. Basal carcinoma of the skin
d. Breast cancer
Correct answer= C
What is the name of a malignant tumour of striated muscle?
Rhabdosarcoma
Which of the following tumours doesn’t commonly metastasise to bone?
a. Breast
b. Lung
c. Prostate
d. Liposarcoma
D
What term describes a cancer that has not invaded the basement membrane?
Carcinoma in situ
What is the name of a benign tumour of glandular epithelium?
Adenoma
Which one of these tumours does not have a screening programme in the UK?
a. Breast cancer
b. Colorectal
c. Cervical
d. Lung
Correct answer= D
Which of the following is not known to be a carcinogen in humans?
a. Hepatitis C virus
b. Ionising radiation
c. Aromatic amines
d. Aspergillus niger fungus
Correct answer=D
What is the name of a benign tumour of fat cells?
Lipoma
What is the name of a malignant tumour of glandular epithelium?
Adenocarcinoma
Which one of the following is not a feature of malignant tumours?
a. Vascular invasion
b. Metastasis
c. Increased cell division
d. Growth related to overall body growth
Correct answer= D
True or false: A transitional cell carcinoma of the bladder is a malignant tumour?
True
True or false: A leiomyoma is a benign tumour of smooth muscle?
True
What is the commonest organ in the body that has benign tumours of smooth muscle?
Uterus (Fibroids)
True or false: Radon gas is a cause of lung cancer?
True
True or false: Asbestos is a human carcinogen?
True
What cancer does asbestos normally cause?
Mesothelioma
Which lifestyle factor is most likely to cause cancer
a. Drinking half a bottle of wine a day
b. Being obese
c. Running for 20 mins twice a week
d. Smoking 20 cigarettes a day
Correct answer= D
Which tumour has the shortest median survival
a. Basal cell carcinoma of the skin
b. Malignant melanoma of the skin
c. Breast cancer
d. Anaplastic carcinoma of the thyroid
Correct answer= D
True or false: Ovarian cancer commonly spreads in the peritoneum
True
What is the predominant inflammatory cell seen in appendicitis?
Neutrophil polymorph
A man breaks his leg and it is plastered for 6 weeks. When the plaster is removed, the leg is much thinner than the other leg. What has happened? a) Atrophy b) Hyperplasia c) Hypertrophy d) Metaplasia D) Dysplasia
Correct answer=A
Acute inflammation actively involves A) Constriction of arterioles B) Capillary endothelial cell enlargement C) Influx of macrophages D) Influx of mast cells E) Influx of neutrophils
Correct answer= E
Benign tumour of glandular origin is called: A) Adenoma B) Adenocarcinoma C) Sarcoma D) Rhabdomyoma E) Leiomyoma
Correct answer= A
Aside from increased mitotic activity, give 2 histological findings you might find when examining a malignant tumour (2 marks)
Pleomorphism
Hyperchromatic nuclei
Poorly defined border
Name 2 routes of metastasis (2 marks)
Lymphatic
Haematogenous
Transcoelemic
Name two cancer screening programmes in the UK
Breast, Bowel, Cervical
Name 2 types of cancers which commonly spread to the bone (2 marks)
Myeloma
Prostate, Breast, Kidney, Thyroid, Lung
You suspect a patient has Sarcoidosis, which blood marker do you investigate?
ACE – released by granulomas
Give the classes of drug used to treat i) arterial thrombosis ii) venous thrombosis
Arterial Thrombosis- Anti-Platelets e.g Aspirin/Clopidogrel
Venous Thrombosis- Anti-Coagulants e.g Warfarin, Heparin, NOAC
What is PSA a tumour marker for?
Prostate cancer
What is calcitonin a tumour marker for?
Medullary carcinoma of the thyroid
What is CA 15.3 a tumour marker for?
Breast cancer
What is CA 19.9 a tumour marker for?
Colon and pancreatic cancer
What is Ann Arbor used to stage?
Lymphoma
What is Duke’s classification used to stage?
Colon cancer
What is The Enneking system used to stage?
Bone tumour
What is the FIGO staging system used to stage?
Cervical cancer staging
What is alpha-fetoprotein a tumour marker for?
Hepatocellular carcinoma and germ cell cancer of the gonads
What is CEA a tumour marker for?
Colorectal cancer
What is beta-hCG a tumour marker for?
Choriocarcinomas, germ cell tumours and lung cancer
