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17
Thrombosis, Embolism and Infarction
THROMBOSIS
A thrombus is dened as a solid mass formed in the living
circulation from the components of the streaming blood.
is is to be distinguished from clotting, which is solidi-
cation of the blood when it is:
• static
• outside a blood vessel
• outside a body
• within a vessel in a dead body.
Causes of Thrombosis
Several factors contribute to thrombus formation and these
are usually grouped together as Virchow’s triad, i.e.
• changes in the vessel wall
• changes in blood ow
• changes in the constituents of the blood.
Damage to Vessel Wall
• Arteries: atherosclerotic plaques or synthetic gras.
• Heart: congenital abnormalities or articial valves.
• Veins: local injury caused by pressure on the calves from
bed or operating table.
Arterial thrombosis
• e commonest cause is atherosclerosis.
• Vessels most commonly aected are the coronary arteries, abdominal aorta, mesenteric arteries, cerebral arteries, renal arteries and arteries of the lower limb.
• Arterial thrombosis is more associated with damage to
the vessel wall, as compared with venous thrombosis,
which is most associated with blood ow disturbances.
• Factors increasing the risk of atherosclerosis and thus
indirectly of thrombosis:
• family history
• male sex
• smoking
• hypertension
• hypercholesterolaemia
• diabetes mellitus
• homocysteinaemia.
Venous thrombosis
• e commonest cause is stasis.
• Mechanical damage due to pressure on calf veins during
surgery may be contributory.
• e main sites of venous thrombosis are calf veins and
pelvic veins.
• Emboli occur to the lungs via the right side of the
heart.
Alterations in Blood Flow
Normal laminar ow may change to a turbulent pattern.
is may occur with:
• prolonged inactivity following surgery, trauma or myocardial infarction
• cardiac failure
• proximal occlusion of venous drainage, e.g. pregnancy,
pelvic tumour.
Alterations of the Constituents of the Blood
ese include:
• increased number of platelets and increased adhesiveness of platelets following surgery or injury
• dehydration, which may increase viscosity
• thrombophilia: abnormal balance of clotting factors and
natural anticoagulants.
Stages in the Development of Thrombosis
• rombus may develop in heart, arteries or veins.
• First stage involves platelets sticking to damaged
endothelium.
• A dense layer of brin and leucocytes adheres to the
surface of the platelets.
• Blood clot (brin and red cells develop on this layer of
leucocytes and platelets).
• A secondary layer of platelets collects on the surface of
the blood clot.
• Gradual extension of thrombosis leads to a propagated
or consecutive thrombus.
• Organization then begins, with adherence to the vessel
wall as mural thrombus.
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SECTION III Pathology
• A second stage develops, with a further batch of platelets laid down over the initial aggregate, and then a further layer of blood clot.
• In this way, alternate layers of platelets and blood clots
form a lamina arrangement.
• is causes a dierential contraction of platelets and
brin and gives a rippled appearance, reminiscent of
rippling of sand on a beach.
• Ridges on the surface of the thrombi are known as the
lines of Zahn.
Fate of Thrombi
• Lysis (resolution): the thrombolytic system may remove
thrombi completely, especially if they are small.
• Recanalization: following organization, new vessels may
grow through the thrombus, eventually forming a single
or several new channels.
• Propagation: because the thrombus itself results in
slowing of the blood ow, it may cause further thrombosis and the clot may increase in length.
• Embolization: part of the thrombus or the whole
thrombus may become dislodged and move through
the circulation until arrested in a vessel which is
of similar size to itself, causing that vessel to be
occluded.
EMBOLISM
An embolus is an abnormal mass of undissolved material
which passes in the bloodstream from one part of the circulation to another, impacting in blood vessels too small to
allow it to pass.
Emboli may consist of:
• thrombus
• gas (air and nitrogen)
• fat
• tumour
• amniotic uid
• foreign body, e.g. i.v. cannula, particulate matter with
i.v. drug abuse
• therapeutic emboli, e.g. gel, foam and steel coils.
Thromboembolism
Venous Thromboembolism
• Venous thromboembolism gives rise to pulmonary
embolism.
• e overwhelming majority of emboli arise from
thrombi in the veins of the lower limb.
• ey travel through the inferior vena cava to the right
side of the heart and impact in the pulmonary artery or
one of its major branches, depending upon the size of
the embolus.
• e eect of the embolism depends on its size:
• small emboli may be thrown o in showers and are
asymptomatic until their cumulative eect limits
respiration
• medium emboli may cause dyspnoea, respiratory
distress and chest pain
• large emboli may occlude both pulmonary arteries
and cause sudden death.
• If only one major pulmonary vein is blocked, severe
shortness of breath and circulatory collapse may occur.
is may be due to a vagal reex inducing spasm of
the coronary and pulmonary arteries associated with
peripheral vasodilatation.
Arterial Thromboembolism
• Systemic emboli from arteries deposit in arteries more
distally along the arterial tree.
• Total occlusion of such arteries may produce relative
ischaemia. A collateral supply may be available.
• If there is no collateral supply, infarction will take place.
• Arterial thromboembolism may come from the following:
• heart, e.g. le auricular thrombus in atrial brillation,
mural thrombus following myocardial infarction
• valvular disease, including prosthetic valves
• proximal atherosclerotic plaques
• aneurysms
• paradoxical: from the venous system via a right-to-
le shunt, e.g. patent interatrial septum.
Gas Embolism
Gas must be free within the bloodstream and not in solution. ere are two main causes of gas embolism: i.e. gas
entering the bloodstream usually as air, and gas dissolved
in the blood coming out of solution.
Gas entering the bloodstream:
• injection of air (100 mL or more)
• trauma to neck veins: low pressure during inspiration
causes air to ow in, especially with patient in erect sitting position.
Nitrogen embolism may occur in decompression sick-
ness when a diver ascends too rapidly:
• Nitrogen (previously in solution under high pressure)
forms bubbles within the circulation as pressure is rapidly reduced.
• Bubbles may also be found in ligaments and joints, causing
severe pain which causes the patient to lie and bend double
in an attempt to relieve the pain; hence, ‘the bends’.
Fat Embolism
• Most commonly associated with long bone fractures.
• Initially thought to be due to entry of globules of fat
into the circulation from the bone marrow, but now
CHAPTER 17 Thrombosis, Embolism and Infarction
313
considered more probably to be due to metabolic
changes.
• Can be demonstrated in about 90% of multiple fracture
cases, although signicant clinical consequences are rare.
• e emboli may pass through the pulmonary vessels and into the systemic circulation, where they may
become impacted in the capillaries of brain, kidneys,
skin and other organs.
• Symptoms consist of fever, respiratory distress and cerebral symptoms. Occasionally brain damage is sucient
to cause coma and death.
• Haemorrhagic skin eruptions may occur as may subconjunctival and retinal haemorrhages.
Tumour Emboli
• All malignant tumours tend to invade blood vessels at
an early stage, and isolated malignant cells are commonly present in the circulation.
• Various factors are responsible for survival of metastatic tumours within the bloodstream, and for the
ability to escape to surrounding tissues and to grow following impaction within a vessel bed of small enough
calibre to impede its further progress (see Chapter 18).
Amniotic Fluid Embolism
• Occurs in labour when the placenta is detached from
the uterine wall and amniotic uid enters the maternal
circulation.
• Rare event 1 : 50 000 deliveries.
• Eects may be produced by thromboplastins in amniotic uid.
• Onset is indicated by severe respiratory diculty with
shock and ts.
• Death is due to disseminated intravascular coagulation
in many cases.
Foreign Body Embolism
• Pieces of cannulae may break o during i.v.
instrumentation.
• Intravenous injection with undissolved drugs may also
be involved in i.v. drug abusers.
• Accidental intra-arterial injection may occur with arterial embolus and thrombosis.
Therapeutic Embolism
• erapeutic emboli such as gel, foam or steel coils may
occasionally be used to:
• stop haemorrhage
• thrombose aneurysms
• reduce vascularity of a tumour prior to surgical
removal
• treat arteriovenous stulae.
Non-Thromboembolic Vascular Insufficiency
Causes include:
• atheroma
• torsion
• spontaneous vascular occlusion, e.g. spasm in Raynaud’s
disease
• ‘steal’ syndrome, i.e. redirected blood supply
• external pressure occlusion, e.g. tumours, tourniquets,
fractures, tight plasters.
Atheroma
• Tends to occlude the lumen of arteries progressively.
• Risk of thrombosis occurring on atheromatous plaque.
• With thrombus formation, total occlusion may occur,
with development of gangrene.
Torsion
• May aect testis, ovary, bowel.
• As organ rotates on pedicle or mesentery, venous return
is aected rst.
• Arterial supply unaected initially and continues to
pump blood into organ, which becomes engorged and
swollen.
• Eventually with oedema, venous pressure equals arterial
pressure, ow ceases and there is impending infarction.
Spontaneous Vascular Occlusion
• May be due to vascular spasm.
• Spasm may occur in such vessels as coronary arteries
(myocardial infarction), peripheral arteries (Raynaud’s
disease).
• Spasm occurs due to contraction of smooth muscle in
vascular wall.
‘Steal’ Syndrome
• Occurs when blood is redirected preferentially along
one branch of a vessel to the detriment of the end territory of the branch.
• May be seen with proximal arteriovenous stula (usually created for dialysis) in the proximal part of a limb,
e.g. between brachial artery and cephalic vein at the
elbow. e ow from the brachial artery goes preferentially through the cephalic vein with very little blood
passing down the ulnar and radial arteries to the hand.
External Pressure Occlusion
• May be caused by tumours, tourniquets or tight plaster
of Paris cast.
• May also be caused by fractures, e.g. super-condylar
fracture of the femur where the distal fragment is drawn
backwards, compressing and damaging the popliteal
ar tery.
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SECTION III Pathology
ISCHAEMIA, INFARCTION AND GANGRENE
Ischaemia
Ischaemia is the condition of an organ or tissue where the supply of oxygenated blood is inadequate for its metabolic needs.
Causes
General
• Ischaemia may follow a sudden fall in cardiac output.
• Myocardial infarction occasionally results in symmetrical gangrene of the extremities.
• Dierent tissues are aected with dierent degrees of
severity, e.g. the brain is the most sensitive to ischaemia.
Local
• Arterial obstruction:
• atherosclerosis
• intra-arterial thrombosis
• embolism
• external pressure
• compartment syndrome.
• Venous obstruction:
• tissues become engorged with blood such that even-
tually arterial pressure and venous pressure equate
and arterial blood ow ceases
• strangulated hernias
• mesenteric venous thrombosis
• phlegmasia cerulea dolens: a severe form of deep
vein thrombosis with venous engorgement such that
venous gangrene may supervene.
• Small vessel obstruction:
• spasm, e.g. Raynaud’s phenomenon
• vasculitis
• frostbite
• microembolism
• precipitated cryoglobulins
• thrombocythaemia.
Severity of Ischaemia
is depends upon:
• speed of onset
• the extent of obstruction
• the extent and patency of collateral circulation
• the metabolic requirements of the tissues.
Infarction
Infarction is death of the tissue following acute ischaemia
when irreparable damage has occurred.
Sequence of Events
• Dead tissue undergoes progressive autolysis of parenchymal cells and haemolysis of red cells.
• Living tissue surrounding the infarct undergoes an
acute inammatory response.
• Demolition phase: when there is an increase in the polymorphs, and aer a few days, macrophage inltration.
• Repair phase: gradual ingrowth of granulation tissue
and the infarct is eventually organized into a brous
scar.
• Infarcts may either be described as red or white (pale).
• White infarcts are usually due to arterial occlusion
of ‘end’ arteries in solid tissues, e.g. heart, spleen,
kidneys.
• Red infarcts are due to venous infarcts and occur in
loose tissues, e.g. the lung, where the bronchial arteries
continue to pump in blood.
• In the long term, dystrophic calcication may occur in
some infarcts.
Systemic Effects of Infarcts
• Fever.
• Leucocytosis.
• Raised erythrocyte sedimentation rate (ESR).
• Rise in certain specic enzymes according to the tissue
aected, e.g. creatine kinase (CK) raised in myocardial
infarction.
Low-flow infarction
In some tissues, infarction may be due to impaired blood
ow (or oxygenation), rather than complete cessation of
ow. Areas involved include:
• ‘watershed’ areas
• splenic exure of the colon, which is situated between
the territories of the superior and inferior mesenteric
arteries (ischaemic colitis)
• the deep myocardium between the subendocardial
myocardium, oxygenated directly from the blood of the
ventricles and the remainder, which is perfused by the
coronary arteries
• tissues perfused by a portal vasculature, e.g. the anterior
pituitary, which is perfused by blood that has already
perfused the hypothalamus
• tissues distal to pathological arterial stenoses, e.g. arteriosclerotic narrowing of arteries may be sucient to
allow distal perfusion in normotensive individuals, but
in hypotension, the blood ow falls and the distal tissue
may become infarcted
• metabolically active tissues, e.g. cerebral neurons, in
which irreversible damage can occur within a few minutes of cessation of blood ow and oxygenation.
Gangrene
is is the death of tissue.
Two types of gangrene are recognized:
• Dry gangrene:
• tissue dies
• becomes mummied
• healing occurs above it
CHAPTER 17 Thrombosis, Embolism and Infarction
315
• eventually the dead area drops o below a line of
demarcation (auto-amputation), e.g. gangrenous
toes in diabetes.
• Wet gangrene:
• bacterial infection and putrefaction occur
• gangrene spreads proximally
• there is no line of demarcation
• proximal amputation is required where the blood
supply is better
• death may occur from overwhelming sepsis.
OSCE SCENARIOS
OSCE Scenario 17.1
A 42-year-old female on your ward develops a painful calf
ve days aer having a mastectomy and free ap reconstruction for breast cancer. She has a body mass index (BMI) of
25, is otherwise t and well, and takes no medications.
1. Take a brief history from this patient.
2. What is your diagnosis?
3. What specic risk factors does this patient have for a
deep vein thrombosis (DVT)?
4. What venous thromboembolism prophylaxis measures
would you check that she had received?
5. Outline your assessment and any investigations you
would perform.
e vital signs and blood tests were all unremarkable; however, the duplex Doppler reveals a DVT in the popliteal
vein of the aected calf.
6. Outline your management plan.
Specific Forms of Gangrene
• Gas gangrene.
• Meleney’s gangrene.
• Fournier’s gangrene.
• Necrotizing fasciitis.
ese conditions are dealt with in Chapter 21.
restored. e intensivists are concerned as he has a rising
serum lactate and acidosis despite good cardiac output and
no obvious evidence of infection. He has reduced bowel
sounds, though no abdominal distension exists. He has a
temperature of 38.1°C. His WCC is 14.2 × 109/L and his lactate is 5.6 mmol/L.
1. What is your dierential diagnosis?
2. A plain AXR is non-contributory and a CT scan is car-
ried out and is shown below (Fig. 17.3Q).
3. What other investigation could be carried out to estab-
lish the diagnosis?
4. Outline your management plan.
5. Explain to the examiners the likely cause of this patient’s
pathology.
OSCE Scenario 17.2
A 69-year-old male presents to A&E an hour aer developing acute pain in his le buttock, thigh and calf. He has a
history of angina and hypertension, and admits to episodes
over several months of cramp-like pain in the le buttock,
thigh and calf when walking uphill. On examination, his
le leg is paler and cooler and he complains of a ‘pins and
needles’ sensation in it.
1. What is the likely diagnosis?
2. An arteriogram is carried out (Fig. 17.2Q). What abnor-
malities are shown? Is there evidence that this is acute-
on-chronic rather than simply acute?
3. Outline your immediate management plan to the
examiners.
OSCE Scenario 17.3
You are asked to see a 60-year-old male in ICU who has
been intubated and ventilated for two days aer a cardiac arrest – attributed to a myocardial infarction. He had
approximately 45 minutes of CPR before a heartbeat was
Fig. 17.2Q The patient’s arteriogram.
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Fig. 17.3Q The patient’s CT scan. (From Pretoris ES, Solomon JA. Radiology Secrets Plus, 3rd edn. Mosby,
2011, with permission.)
SECTION III Pathology
OSCE Scenario 17.4
A 65-year-old smoker is referred to you due to episodes of
unsteadiness, blurred vision in the le eye and a numb le
arm. During your history you nd out he is a painter and
these symptoms occur only when he is painting or using his
arm for other physical tasks. He is le-handed.
1. What is the potential diagnosis?
2. Would you expect to nd a dierence in the blood pres-
sure of each arm and why? Are there any other signicant examination ndings?
3. Can you explain his symptoms given the diagnosis?
4. You order a duplex ultrasound scan; can you describe
haematoma and broken right wrist. He is taken to theatre
early the next morning and has had his femur nailed to x
the fracture. You are called by the nurse caring for him to
tell you he is very confused – he is pulling away when the
nurse has tried to take a blood gas; he is making noises
and opens his eyes when you speak. In addition, his SpO2
is 88% and his chest is covered in a petechial rash.
1. What is the likely diagnosis and what is the cause? What
dierential diagnosis should you consider?
2. What tests would you order?
3. How would you treat this patient?
4. What is his GCS score?
the ndings you would expect to see?
OSCE Scenario 17.5
Answers in Appendix pages 470–473
A 29-year-old man is involved in a road trac accident and has a badly fractured right femur, a splenic
Please check your eBook at https://studentconsult.inkling.com/ for more self-assessment questions. See inside cover for
registration details.
18
Neoplasia
A neoplasm is a lesion resulting from abnormal growth of a
tissue, which is partly or completely autonomous of normal
growth controls, and persists aer the initiating stimulus
has been removed.
CLASSIFICATION OF TUMOURS
• Behavioural classication: benign or malignant.
• Histogenetic classication: cell of origin.
Behavioural Classification
e behavioural classication divides tumours into:
• benign
• malignant.
e pathological criteria for classifying a tumour as
benign or malignant are shown in Box 18.1.
Histogenetic Classification
• Classication by cell of origin.
• Histologically determined.
• Degree of histological resemblance allows tumour to
be graded.
• Grading correlates with clinical behaviour.
Major Categories of Tumour Origin
• From epithelial cells.
• From connective tissue cells (mesenchymal).
• From lymphoid and haemopoietic tissue.
Differentiation
e degree to which the tumour histologically resembles its
cell or tissue of origin. Degree of dierentiation determines
the tumour grade.
• Well-dierentiated: resembles parent tissue more than
poorly dierentiated tumours.
• Poorly dierentiated: may be so poorly dierentiated that
they lack easily recognizable histogenetic features. ey
are more aggressive than well-dierentiated tumours.
BOX 18.1 Behavioural Classification
Benign Malignant
Slow growing Rapidly growing
Low mitotic rate High mitotic rate
Resembles parent tissue Differs from parent site
Non-infiltrating Infiltrating
Cells normal Cells abnormal
Never metastasizes Frequently metastasizes
Often circumscribed or
encapsulated
Rarely ulcerates Frequent ulceration on
Rarely undergoes
necrosis
Only fatal if damaging
vital function, e.g.
cerebral tumour
• Moderately dierentiated: intermediate between welland poorly dierentiated tumours.
• Tumours defying histogenetic classication are called
anaplastic.
Often poorly defined or
irregular
skin/mucosal surfaces
Necrosis common
Always fatal if untreated
NOMENCLATURE OF TUMOURS
• All have the sux ‘-oma’.
• Benign epithelial tumours are either papillomas or
adenomas.
• Benign connective tissue tumours have a prex denoting the cell of origin, e.g. lipoma (fat), osteoma (bone).
• A carcinoma is a malignant epithelial neoplasm.
• A sarcoma is a malignant connective tissue neoplasm.
Examples of tumour nomenclature are shown in
Table 18.1.
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SECTION III Pathology
TABLE 18.1 Examples of Tumour Nomenclature
Tissue of origin Benign Malignant
Epithelium
Glandular Adenoma Adenocarcinoma
Squamous Squamous cell papilloma Squamous cell carcinoma
Transitional Transitional cell papilloma Transitional cell carcinoma
Mesenchyme
Fat Lipoma Liposarcoma
Striated muscle Rhabdomyoma Rhabdomyosarcoma
Smooth muscle Leiomyoma Leiomyosarcoma
Bone Osteoma Osteosarcoma (osteogenic sarcoma)
Cartilage Chondroma Chondrosarcoma
Blood vessel Angioma Angiosarcoma
Fibrous tissue Fibroma Fibrosarcoma
Epithelial Tumours
Benign Tumours
• Papilloma: benign tumour of non-glandular or nonsecretory epithelium, e.g. transitional or stratied squamous epithelium.
• Adenoma: benign tumour of glandular or secretory
epithelium, e.g. colonic adenoma.
Malignant Tumours
• Carcinoma: malignant tumour of epithelium, e.g. squamous cell carcinoma.
• Adenocarcinoma: malignant tumour of glandular epithelium, e.g. adenocarcinoma of the stomach.
Carcinoma In Situ
A lesion with all the cytological features of cancer but no
evidence of invasion through the epithelial basement membrane, e.g. ductal carcinoma in situ (DCIS) of the breast.
Connective Tissue Tumours
Tumours of connective tissue are named according to the
cell of origin and behavioural classication.
Teratomas
A teratoma is a germ cell neoplasm representing all three
germ cell layers, i.e. ectoderm, mesoderm and endoderm.
Ovarian teratomas tend to be benign and cystic. Testicular
teratomas tend to be malignant and solid.
Embryonal Tumours (Blastomas)
ese bear a histological resemblance to the embryonic
form of the organ from which they arise.
• Nephroblastoma: Wilms’ tumour; kidney.
• Neuroblastoma: adrenal medulla, autonomic ganglia.
• Retinoblastoma: eye (inherited predisposition).
• Hepatoblastoma: liver.
Apudomas and Carcinoid Tumours
• APUD (amine content and/or precursor uptake and
decarboxylation).
• Describes cells of diuse (neuro-) endocrine system.
• Examples of apudomas and their clinical manifestations
are:
• insulinoma: episodes of hypoglycaemia
• gastrinoma: extensive peptic ulceration (Zollinger–
Ellison syndrome)
• phaeochromocytoma: paroxysmal hypertension
• carcinoid: if metastases are present, ushing, palpita-
tions and pulmonary valve stenosis.
Mixed Neoplasm
A neoplasm showing more than one neoplastic component;
usually both epithelial and mesenchymal, e.g. pleomorphic adenoma of the parotid (glandular tissue in a cartilaginous or mucinous matrix), broadenoma of the breast.
Carcinosarcomas are most common in the female genital
tract.
Hamartomas
A hamartoma is a tumour-like lesion which lacks autonomy
but in which the elements are fully dierentiated and are normally found in the tissue of origin. ey usually contain two
or more mature cell types native to the organ of origin but the
constituent parts are abnormally organized, e.g. pigmented
CHAPTER 18 Neoplasia
319
naevi, pulmonary hamartomas, which consist of a mixture
of cartilage and bronchial epithelium.
Poorly Named Tumours (Misnomas!)
• Lymphoma: malignant, therefore lymphosarcoma.
• Hepatoma: malignant, therefore hepatocellular carcinoma.
• Melanoma: malignant, therefore melanocarcinoma.
TUMOUR GROWTH PATTERNS
• Sessile, polypoid and papillary tumours are likely to be
benign (but not always).
• Fungating, ulcerating, annular and inltrating tumours
are likely to be malignant.
• Ulcerated tumours can oen be distinguished from
benign ulcers. e latter have sloping edges while the
former have rolled, everted edges, e.g. squamous cell
carcinoma.
• Encapsulated tumours tend to be benign. Beware the
false capsule of compressed connective tissue, e.g. pleomorphic adenoma of the parotid. ‘Shelling out’ this
tumour would leave residual tumour.
Histological Pattern
Malignant features include:
• loss of dierentiation
• disordered growth pattern
• variability in cell size
• variability in nuclear size
• high nuclear:cytoplasmic ratio
• increased mitotic activity
• abnormal nucleoli may be multiple
• abnormal chromatin pattern.
CARCINOGENESIS
• is is the process by which normal cells are converted
into cells capable of forming neoplasms.
• A carcinogen is an agent known or suspected to participate in the causation of tumours. Such agents are said to
be carcinogenic (cancer-causing) or oncogenic (tumourcausing). Strictly speaking, carcinogenesis applies to the
causation of malignant tumours, whereas oncogenesis
includes all tumours, benign and malignant.
• e main classes of carcinogen are:
• chemicals
• radiation
• viruses
• hormones
• bacteria, fungi, parasites
• other agents.
Chemicals
• Polycyclic aromatic hydrocarbons:
• scrotal cancer in chimney sweeps due to exposure to
polycyclic aromatic hydrocarbons in soot (of historical interest)
• 3,4-benzpyrene in tobacco smoke. Carcinogenic
on direct contact, e.g. smoking, but absorbed into
bloodstream, which may explain why smokers have
higher incidence of cancer at other sites, e.g. kidney,
bladder
• carcinogenic components of tar, which can cause
skin cancers by direct contact.
• Aromatic amines:
• β-naphthylamine: high incidence of bladder cancer
in dye and rubber industry.
• Nitrosamines:
• gut cancers in animals.
• Azo dyes:
• bladder and liver cancers in animals.
• Alkylating agents, e.g. cyclophosphamide:
• small risk of leukaemia in humans.
Radiation
• UV light is a major cause of skin cancer.
• Exposure to ionizing radiation is associated with
increased risk of cancer at many sites, e.g.
• carcinoma of the thyroid aer childhood irradiation
of the neck
• increased incidence of leukaemia and carcinoma of
breast, lung and thyroid aer nuclear explosions at
Hiroshima and Nagasaki during the Second World
War
• cancer of thyroid aer Chernobyl disaster, which
released radioactive iodine
• leukaemia and liver neoplasms developing years aer
exposure to thorium-containing contrast medium
(thorotrast)
• angiosarcoma developing at the sites of previous radio-
therapy treatment for breast cancer
Viruses
• HPV:
• common wart
• cervical carcinoma, strong association with HPV
type 16 and 18.
• EBV:
• Burkitt’s lymphoma
• nasopharyngeal carcinoma
• B-cell lymphoma in immunosuppressed patients.
• Hepatitis B virus:
• hepatocellular carcinoma.
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SECTION III Pathology
• HIV:
• Kaposi’s sarcoma.
• HTLV-1:
• T-cell lymphoma/leukaemia.
Hormones
• Experimentally, oestrogens can be shown to promote
formation of breast and endometrial carcinoma.
• Increased incidence of endometrial carcinoma in postmenopausal women treated with oestrogen-containing
compounds.
• Androgenic and anabolic steroids are known to induce
hepatocellular tumours in humans.
Bacteria, Fungi, Parasites
• Helicobacter pylori implicated in the pathogenesis of
gastric lymphoma.
• Aatoxins (B1) produced by Aspergillus avus have
been linked to high incidence of hepatocellular carcinoma in certain areas of Africa.
• Schistosoma is strongly implicated in the high incidence
of bladder cancer where infection (schistosomiasis) is
rife, e.g. Egypt.
• Clonorchis sinensis (liver uke): dwells in bile ducts
where it may cause cholangiocarcinoma.
Other Agents
• Asbestos:
• mesothelioma (strong association)
• carcinoma of the bronchus.
• Metals:
• nickel exposure is associated with nasal and bron-
chial carcinoma.
• Betel nut:
• chewing betel nut is associated with increased risk of
neoplasms of oral cavity.
HOST FACTORS AND CARCINOGENESIS
• Race.
• Diet.
• Inherited predisposition.
• Age.
• Sex.
Race
• Precise role unknown due to coincidence with diet,
habit and location.
• Incidence of oral cancer high in India and South East
Asia, but probably related to chewing betel nut.
• High incidence of hepatocellular carcinoma in Africa
and South East Asia, but is probably related to exposure
to dietary carcinogens and viral hepatitis.
• Immigrant groups tend eventually to assume the disease
prole of their adopted country.
Diet
• Aatoxins and hepatocellular carcinoma.
• Diet low in bre in colorectal cancer.
• High dietary fat in breast cancer.
Inherited Predisposition
• Some diseases appear to run in families (‘cancer
families’).
• A woman whose mother and one sister have breast cancer stands a 50% probability of developing the disease.
• Examples of familial cancer are shown in Table 18.2.
Age
• e incidence of cancer increases with age.
• is reects the cumulative eects of exposure to carcinogens with age.
• Eects of immune defences may be lost with old age.
Syndrome Gene Affected Resultant Neoplasms
Li–Fraumeni p53 Breast and ovarian carcinomas, astrocytomas, sarcomas
Retinoblastoma Rb1 Retinoblastoma, osteosarcoma
Familial polyposis coli APC GI tract carcinomas; mainly colon
von Hippel–Lindau VHL Renal carcinoma, phaeochromocytoma, haemangioblastoma
Multiple endocrine neoplasia
syndromes (I–III)
Familial breast cancer BRCA1, BRCA2 Breast, ovarian syndrome, prostatic carcinomas
RET, others Tumours of pituitary parathyroids, thyroid, pancreas, adrenal glands
(combination depends on which syndrome)
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