MoD Session 9 Flashcards
Why is cancer said to be ‘in remission’ rather than ‘cured’ when a primary tumour is removed?
Any remaining micrometastases can spread and develop
What are the most lethal features of malignant neoplasm?
Invasion
Metastasis
What increases tumour burden?
Extra cells increasing metabolic demand
How does metastasis take place?
Tumour cells grow and invade at primary site
Enter transport system and lodge at secondary site
Grow at secondary site to form a new tumour
What must occur before a new metastasis is formed?
Colonisation
How does the body try to prevent metastasis?
Immune attack at each stage
If a cell can carry out some but not all of the steps of metastasis, will it metastasise?
Nope
What type of tumour has been used mainly to study metastasis?
Carcinomas
How does cancer in the peritoneal cavity cause uncomfortable breathing?
Exudate (ascites) splits abdomen
To prevent splitting of the abdomen in cancer in the peritoneal cavity a shunt is used to allow the ascite fluid into a great vein. How does what you expect to see in the lungs compare with what is actually seen?
Expect lots of metastases but actually very few, if any, are seen
How is adhesion between malignant cells altered in carcinoma invasion?
Decreased E-Catherine expression
How is adhesion altered between malignant cells and stromal proteins in carcinoma invasion?
Changes in integrin expression
What does altering the integrin expression in carcinoma cells cause?
Actin production so the cell can fan out
How does integrin act as a signalling molecule?
Via G-proteins such as those in the Rho family
What is carried out by fibroblasts which allows stromal proteolysis?
Altered expression of Matrix Metalloproteinases (MMPs)
What must occur in stromal proteolysis for the carcinoma cells to invade surrounding tissue?
Degrade basement membrane and stroma
How are changes in motility achieved in invasion of carcinoma cells?
Changes in the actin cytoskeleton
What do altered adhesion, stromal proteolysis and motility cause the carcinoma cell phenotype to more closely resemble?
Mesenchyme
What is epithelial-to-mesenchyme transition (EMT)?
Three changes seen in carcinoma invasion which cause the carcinoma cell phenotype to resemble mesenchyme more closely than epithelia
What do malignant cells take advantage of?
Nearby non-neoplastic cells
What is the cancer niche?
Inflammatory cells
Endothelial cells
Fibroblasts
Stroma
What provides growth factor and proteases to malignant cells?
Normal cells
What can malignant cells enter to be transported to distant sites?
BV
Lymphatic vessels
Fluid in body cavities
What is transcoelemic spread?
Spread of malignant cells via pleura, peritoneal, pericardial, or brain ventricles fluid
What precedes colonisation at a secondary site?
Extravasation
Why do many malignant cells that lodge at secondary sites not create clinically detectable tumours?
They die or fail to grow
How many cells are present in a micrometastasis?
10-15
What is tumour dormancy?
When an apparently disease-free person harbours many micrometastases
What can cause tumour dormancy?
Hostile secondary site
Decreased angiogenesis
Immune attack
What causes relapse even after an apparent cure?
Micrometastasis growth
Why do transplant patients have a higher risk of melanoma?
Transplant organs can harbour micrometastases which grow in the receipient as they are immunosuppressed
Which system probably has a prominent role in melanoma?
Immune system
What does the site of a predictable secondary tumour depend on?
Regional drainage of blood, lymph or coelomic fluid
Where would you expect to see a secondary tumour if spread is via the blood?
Next capillary bed encountered - lungs or liver
Where would you expect to see a secondary tumour if spread of malignancy is via lymph?
Regional lymph node
Where would you expect to find secondary tumours spread by coelomic fluid?
Elsewhere in the coelomic space/adjacent organs
Where is a common site of metastatic deposits?
Pouch of Douglas
What is the unpredictable spread of secondary tumours also known as?
Seed and soil
What determines unpredictable, distant site of secondary tumour?
Interaction b/w malignant cells and nice at secondary site
What is a common pathway of ‘seed and soil’ secondary tumour site location?
Bronchial to adrenal
How do carcinomas typically spread?
Into draining lymph nodes and blood-borne to distant sites
What distant sites do carcinomas typically spread to?
Lung
Bone
Liver
Brain
Define osteolytic.
Decrease in bone mass
What type of malignant neoplasm typically causes osteosclerotic bone metastases?
Pancreatic
Define osteosclerotic.
Decrease in bone mass
Which neoplasms most frequently spread to bone?
Breast Bronchus Kidney Thyroid Prostate
Give an example of a malignant neoplasm that metastasises very early in its course.
Small cell bronchial carcinoma
Does basal cell carcinoma of the skin metastasise?
No, almost never
Why is basal cell carcinoma of the skin considered malignant even though it almost never metastasises?
Has aggressive, invasive growth instead
What increases the risk of metastasis?
Cell number in the primary neoplasm
What is the basis of cancer staging?
Cell number in the primary neoplasm
What are the local effects of a neoplasm due to?
Primary or secondary neoplasm itself
What are local effects of neoplasm?
Direct invasion and destruction of normal tissue
Ulceration at surface causing bleeding and potential perforation
Compression of adjacent structures
Blocking of tubes and orifices
How do mediastinum tumours present as an emergency?
Occlude SVC
How does a tumour lead to a stricture?
Tumour in wall –> contractures –> stricture
What causes systemic effects of neoplasm?
Increased tumour burden increasing metabolism
What causes massive protein loss by entry into a catabolic state in neoplasm?
Secreted hormone and cytokines
What effects can neoplasm have on appetite and weight?
Decrease
What is cachexia?
Wasting syndrome
What systemic effects other than massive protein loss are seen in neoplasm?
Malaise
Immunosuppression
Thrombosis
What local effect of neoplasm can cause immunosupression?
Direct bone marrow destruction
What happens to platelets as a result of the systemic effects of neoplasm?
They become more sticky
What will a thyroid adenoma secrete which would cause systemic effects due to the neoplasm?
Thyroxine
How can malignant tumours such as bronchial small cell carcinoma cause Cushing’s or hyponatreamia?
Secretion of ACTH or ADH
How can bronchial squamous cell carcinoma cause hypercalcaemia?
Secretion of PTH-like hormone
How can a local effect of neoplasm cause hypercalcaemia?
Direct destruction of bone
Name some miscellaneous systemic effects of neoplasm whose link to neoplasm is poorly understood.
Neuropathic so affecting brain and peripheral nerves Pruritis Abnormal pigmentation Fever Finger clubbing Myositis
What cells other than tumour cells invade?
Trophoblast invades uterine wall
Leucocytes invade tissues during inflammation
Why are hyaline cartilage and arterial walls rarely invaded by malignant tissue?
Malignant tissue tends to produce collagenase but not elastase so the elastin present in these tissues is not broken down
Why may happen if tumour cells reach a serosal surface?
Fall into it causing seeding
What proportion of patients have microscopic metastases by the time a diagnosis of cancer is made?
> 50%
What is the most common portal of entry of tumour cells into the bloodstream?
Capillaries and veins
How do renal cell carcinomas invade the right heart?
Tumour cells enter the large renal vein and grow within it as a continuous root through the IVC into the right heart
What shape do metastases tend to be?
Spherical
How are metastases described on chest X-Ray?
Single = coin lesion Multiple = cannon balls
Where do tumours in organs drained by the portal system metastasise primarily to?
Liver
What acts as filters and receives 20-25% of cardiac output yet develops far fewer metastases than the smaller adrenal glands?
Kidneys
What tumours favour metastasising to the ovaries?
GI tumours
What are bilateral metastatic tumours of the ovaries called?
Kruckenberg tumours
How are some metastases to the vertebrae explained?
Presence of a system of veins in and around the spine - vertebral venous plexus
What method of spread is favoured by carcinomas?
Via lymphatics
How do malignant cells spread via the lymphatics?
Penetrate w/out destroying endothelium –> float to next lymph node –> settle in peripheral sinus –> grow
What is peau d’orange?
Slightly oedematous and puckering of the skin due to lymphatic obstruction common in carcinomas of the breast
Why may lymph nodes downstream from a tumour swell but not be metastatic?
Secondary to antigens and irritating material that leach out from the tumour especially if it is necrotic, ulcerated or infected causing hyperplasia
Why do ascites develop?
Possibly secondary to factors produced by tumours causing fluid leakage from peritoneal membrane
Possibly secondary to fluid leaking from the surface of malignancy
How can seeding in the CSF occur?
With tumours of the CNS
Why is implantation on epithelial surfaces rare?
They are inhospitable, covered in mucus, cornfield cells and bacteria
What is a more histiologically atypical tumour more likely to do?
Invade and metastasise
Where does basal cell carcinoma appear?
Skin exposed to sunlight, especially the face
Why do tumours of the CNS rarely produce metastases for the rest of the body?
They are in a closed space so often kill before visceral metastases are detected
Can implantation of tumour cells along a needle track after biopsy occur?
Yes but it is rare
What must a metastatic cell escape in the blood in order to metastasise?
Antibodies Complement Macrophages Killer cells Toxic oxygen concentration Blood clotting
What must a tumour cell do once it has reached a vessel small enough to be embolised during spread via the blood?
Survive impact and mechanical squeeze
How do tumour cells penetrate BV?
Reverse diapedesis
Where is it most likely that tumour cells enter the bloodstream?
Vessels of the tumour itself rather than preformed surrounding vessels
How do tumour cells attach to basement membrane when entering a vessel with endothelial lining and basement membrane?
Laminin receptors
What can tumour cells become coated in within the blood which can help the metastatic process?
Platelets
Why is the mechanical impact of embolism fatal to many tumour cells?
They are larger and less deformable than WBCs
What is the possible explanation for why capillaries in the heart and skeletal muscle are rarely metastasised?
Bio mechanical trauma is too great due to squeezing with heart beat or muscular contraction
What is organ selection in metastasis?
Selection because they drain the blood of the primary tumour e.g. colon–> liver
Selection due to seed or soil properties
What are fistulae?
Abnormal communications between two distinct tissues e.g. B/w bladder and rectum
What is paraneoplastic syndrome?
Symptom complexes that accompany tumours and concern distant targets whether the mechanisms be hormonal, toxic, immunologic or unknown
What happens to paraneoplastic syndrome is the tumour is removed or destroyed?
It usually disappears
What may be the first sign of a hidden tumour and can help follow the regression or recurrence of a tumour?
Paraneoplastic syndrome
What are the most common offenders in ectopic hormone secretion?
Lung carcinomas
What can renal cell carcinomas produce that results in high haematocrit and symptoms related to high blood viscosity?
Erythropoietin
Why is a hypercoaguable state seen in 90-95% of cancer patients?
Platelets activated by tumour products e.g. ADP
Tumours secrete procoagulents
What is Trosseau’s syndrome?
Migratory thrombophlebitis where bouts of thrombophlebitis are seen in multiple locations without an apparent predisposing factor
Which types of cancer is Trousseau’s syndrome often seen in?
Pancreatic
Lung
Stomach
What is acanthosis nigricans?
Symmetric, brown, warty hyper pigmentation w/hyperkeratosis of the axilla and other flexural areas
What is the possible cause of acanthosis nigricans?
Transforming growth factor alpha
What does more than 50% of acanthosis nigricans occur in association with?
Internal malignancy - esp. GI carcinoma
What produces tumour necrosis factor which results in cachexia caused by tumour?
Macrophages
What causes changes in sense of taste in neoplasm?
Tumour
What is tumour lysis syndrome?
Extensive, acute necrosis of a tumour that is v. sensitive to X-Rays or chemotherapy which can cause life-threatening release of toxic amounts of potassium and uric acid
What is often seen in Burkitt’s lymphoma?
Tumour lysis syndrome
What limits tumour lysis syndrome to 5-7 days?
Wave of cell death ends
How does cancer kill?
Infection - cancer and its treatment are anti inflammatory Haemorrhage and thromboembolic phenomena Cachexia Respiratory failure Renal failure
What molecules are carcinogenic with a delay of 5-30 years?
Aromatic amines
Why are carcinogenic molecules described as electrophilic reactants?
They have relatively electron deficient sites which make them seek nucleophilic sites such as amine groups
How are nucleophilic groups relatively abundant in a cell?
As DNA, RNA and proteins
What happens to carcinogens in the body?
They are activated into an electrophilic state
What are procarcinogens?
Inactive carcinogens
Why does each carcinogen always affect the same organ?
Due to their need for modification before they are effective
What may the organ selectivity of carcinogens depend on?
Presence, absence or balance of enzymes that activate procarcinogens
Is alcohol carcinogenic?
Not directly but causes liver cirrhosis and liver nodules may become neoplastic
Where does alcohol increase risk of cancer for?
Mouth Pharynx Larynx Oesophagus Lung Rectum Breast
What two things interact to increase the risk of oesophageal cancer?
Alcohol and tobacco
What is the principal theory to explain gastric cancer?
Based on nitrosamine formation in the stomach
Where can nitrosamines come from?
Tobacco smoke
Sodium nitrite prescursor used as a food additive in cured meat and fish
What inhibits the production of nitrosamines from nitrites?
Adding ascorbic acid/increasing the amount of fruit and vegetables in the diet
What is produced by Aspergillus flavus which grows on grain stored in warm and humid conditions that is a very potent carcinogen?
Aflatoxin B1
What is a major factor in the high incidence of liver cancer in Africa and Asia and appear in conjunction with hepatitis B?
Aflatoxin B1
What dietary agents inhibit mutations and tumour formation?
Fibre
Vitamin A
Vitamin C
Certain seeds
How does obesity cause an increased risk of endometrial cancer?
Adipose tissue converts androgens to oestrogens
What type of cancer can the contraceptive pill cause?
Liver adenomas
What protects against breast cancer?
Early first pregnancy and bearing a child at all
What are approximately 10% of breast cancers due to?
Genetic predisposition often associated w/BRCA1 and BRCA2
How does asbestos cause cancer?
Fibres inhaled and produce fibrosis and malignant tumours of mesothelium of the pleura, pericardium and peritoneum
What acts synergistically with cigarette smoke to cause cancer?
Asbestos
What is involved in carcinogensis by ionising radiation?
Free radicals
What is given to women during pregnancy to stop bleeding and can cause adenocarcinoma of the vagina in the daughters of treated women?
Diethylstillboestrol
What are the only two types of radiation that are carcinogenic?
Ultraviolet
Ionising
How do UV rays behave as complete carcinogens on repeated exposure?
Damage DNA strands by forming dimers and cross-links
How many exposures of ionising radiation are needed to cause cancer?
One
What genetic predisposition can individuals be born with which increases their risk of developing cancer?
Mutation in one allele so they only need one more ‘hit’ to cause a cancer that is caused by mutations of both alleles of a gene
Which are the most sensitive cells to radiation injury causing shortened cell survival?
Bone marrow
Intestinal epithelial
(Both have high mitotic rates)
Which common worldwide tumour is the only one to be virus induced?
Hepatocellular carcinoma
Where does schistosoma cause cancer in humans?
Bladder
How do retroviruses work?
Transduce cellular genes and turn them into cancer genes
What unique enzyme do retroviruses possess?
Reverse transcriptase
Why are viral copies of transduced cellular genes not perfect?
Reverse transcriptase is a highly error-prone mechanism
What are proto-oncogenes?
Normal genes with important growth-related functions in a cell’s normal activity
About how many oncogenes are known to exist?
70
What is one-step oncogenesis?
Where the oncogene acts alone
Which DNA viruses can cause neoplasm?
Hep B
HPV
EBV
Molluscum contagiosum (forms benign molluscum bodies)
Which retrovirus can cause leukaemia and lymphoma?
Human T-cell leukaemia virus
How does Burkitt’s lymphoma usually present?
Large mass in the upper or lower jaw
What is the most common cause of infectious mononucleosis?
Epstein Barr virus
What does Epstein Barr virus do?
Parasitises B lymphocytes
Parasitises epithelium of upper pharynx
What does the distribution of Burkitt’s lymphoma in Africa coincide with?
Distribution of malaria
What do all Burkitt’s lymphomas show?
Chromosome translocations known to activate the oncogene c-myc
What does nasopharyngeal carcinoma always contain?
DNA of the EBV
How do DNA viruses produce tumours?
Carry genes that transform cells
Act indirectly by depressing genes that normally inhibit cell growth
What are RNA oncogene viruses also called?
Acute transforming proteins
How quickly can RNA oncogene viruses produce a leukaemia?
In a matter of days or weeks
Describe human T-cell lymphocytic virus-I.
A relative of the AIDS virus
Like HIV it affects helper lymphocytes (T4+)
What two types of neoplastic associations does the AIDS virus have?
Tumours related to immunosupression
Kaposi’s sarcoma
How does Kaposi’s sarcoma appear?
Bluish-red plaques or nodules on skin and mucosae seen in multiple locations due to multi centric origin not metastasis causing widespread involvement of internal organs
What is the likely cell of origin in Kaposi’s sarcoma?
Endothelium
How can Helicobacter pylori cause stomach cancer?
Causes chronic gastritis therefore may cause cancer due to chronic stimulus to regenerate
What are liver flukes?
Parasites that live in bile ducts causing hyperplasia and sometimes cholangiocarcinoma
How do Schistosoma haematobium cause cancer?
Larvae burrow into skin from infected water –> enter bloodstream and travel to liver where they mature into adult flukes –> migrate and breed in bladder –> constant regeneration of bladder epithelium –> squamous cell carcinoma of the bladder
How is water contaminated by Schistosoma haematobium?
Human host eliminates eggs in urine where they can enter the water supply
What happens to the eggs of Schistosoma Haematobium once they have been eliminated in the urine?
Hatch into miracidia and enter snail host which releases larvae into the water
