MoD Session 9 Flashcards Preview

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Flashcards in MoD Session 9 Deck (175):
0

What are the most lethal features of malignant neoplasm?

Invasion
Metastasis

1

Why is cancer said to be 'in remission' rather than 'cured' when a primary tumour is removed?

Any remaining micrometastases can spread and develop

2

What increases tumour burden?

Extra cells increasing metabolic demand

3

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

4

What must occur before a new metastasis is formed?

Colonisation

5

How does the body try to prevent metastasis?

Immune attack at each stage

6

If a cell can carry out some but not all of the steps of metastasis, will it metastasise?

Nope

7

What type of tumour has been used mainly to study metastasis?

Carcinomas

8

How does cancer in the peritoneal cavity cause uncomfortable breathing?

Exudate (ascites) splits abdomen

9

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

10

How is adhesion between malignant cells altered in carcinoma invasion?

Decreased E-Catherine expression

11

How is adhesion altered between malignant cells and stromal proteins in carcinoma invasion?

Changes in integrin expression

12

What does altering the integrin expression in carcinoma cells cause?

Actin production so the cell can fan out

13

How does integrin act as a signalling molecule?

Via G-proteins such as those in the Rho family

14

What is carried out by fibroblasts which allows stromal proteolysis?

Altered expression of Matrix Metalloproteinases (MMPs)

15

What must occur in stromal proteolysis for the carcinoma cells to invade surrounding tissue?

Degrade basement membrane and stroma

16

How are changes in motility achieved in invasion of carcinoma cells?

Changes in the actin cytoskeleton

17

What do altered adhesion, stromal proteolysis and motility cause the carcinoma cell phenotype to more closely resemble?

Mesenchyme

18

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

19

What do malignant cells take advantage of?

Nearby non-neoplastic cells

20

What is the cancer niche?

Inflammatory cells
Endothelial cells
Fibroblasts
Stroma

21

What provides growth factor and proteases to malignant cells?

Normal cells

22

What can malignant cells enter to be transported to distant sites?

BV
Lymphatic vessels
Fluid in body cavities

23

What is transcoelemic spread?

Spread of malignant cells via pleura, peritoneal, pericardial, or brain ventricles fluid

24

What precedes colonisation at a secondary site?

Extravasation

25

Why do many malignant cells that lodge at secondary sites not create clinically detectable tumours?

They die or fail to grow

26

How many cells are present in a micrometastasis?

10-15

27

What is tumour dormancy?

When an apparently disease-free person harbours many micrometastases

28

What can cause tumour dormancy?

Hostile secondary site
Decreased angiogenesis
Immune attack

29

What causes relapse even after an apparent cure?

Micrometastasis growth

30

Why do transplant patients have a higher risk of melanoma?

Transplant organs can harbour micrometastases which grow in the receipient as they are immunosuppressed

31

Which system probably has a prominent role in melanoma?

Immune system

32

What does the site of a predictable secondary tumour depend on?

Regional drainage of blood, lymph or coelomic fluid

33

Where would you expect to see a secondary tumour if spread is via the blood?

Next capillary bed encountered - lungs or liver

34

Where would you expect to see a secondary tumour if spread of malignancy is via lymph?

Regional lymph node

35

Where would you expect to find secondary tumours spread by coelomic fluid?

Elsewhere in the coelomic space/adjacent organs

36

Where is a common site of metastatic deposits?

Pouch of Douglas

37

What is the unpredictable spread of secondary tumours also known as?

Seed and soil

38

What determines unpredictable, distant site of secondary tumour?

Interaction b/w malignant cells and nice at secondary site

39

What is a common pathway of 'seed and soil' secondary tumour site location?

Bronchial to adrenal

40

How do carcinomas typically spread?

Into draining lymph nodes and blood-borne to distant sites

41

What distant sites do carcinomas typically spread to?

Lung
Bone
Liver
Brain

42

Define osteolytic.

Decrease in bone mass

43

What type of malignant neoplasm typically causes osteosclerotic bone metastases?

Pancreatic

44

Define osteosclerotic.

Decrease in bone mass

45

Which neoplasms most frequently spread to bone?

Breast
Bronchus
Kidney
Thyroid
Prostate

46

Give an example of a malignant neoplasm that metastasises very early in its course.

Small cell bronchial carcinoma

47

Does basal cell carcinoma of the skin metastasise?

No, almost never

48

Why is basal cell carcinoma of the skin considered malignant even though it almost never metastasises?

Has aggressive, invasive growth instead

49

What increases the risk of metastasis?

Cell number in the primary neoplasm

50

What is the basis of cancer staging?

Cell number in the primary neoplasm

51

What are the local effects of a neoplasm due to?

Primary or secondary neoplasm itself

52

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

53

How do mediastinum tumours present as an emergency?

Occlude SVC

54

How does a tumour lead to a stricture?

Tumour in wall --> contractures --> stricture

55

What causes systemic effects of neoplasm?

Increased tumour burden increasing metabolism

56

What causes massive protein loss by entry into a catabolic state in neoplasm?

Secreted hormone and cytokines

57

What effects can neoplasm have on appetite and weight?

Decrease

58

What is cachexia?

Wasting syndrome

59

What systemic effects other than massive protein loss are seen in neoplasm?

Malaise
Immunosuppression
Thrombosis

60

What local effect of neoplasm can cause immunosupression?

Direct bone marrow destruction

61

What happens to platelets as a result of the systemic effects of neoplasm?

They become more sticky

62

What will a thyroid adenoma secrete which would cause systemic effects due to the neoplasm?

Thyroxine

63

How can malignant tumours such as bronchial small cell carcinoma cause Cushing's or hyponatreamia?

Secretion of ACTH or ADH

64

How can bronchial squamous cell carcinoma cause hypercalcaemia?

Secretion of PTH-like hormone

65

How can a local effect of neoplasm cause hypercalcaemia?

Direct destruction of bone

66

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

67

What cells other than tumour cells invade?

Trophoblast invades uterine wall
Leucocytes invade tissues during inflammation

68

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

69

Why may happen if tumour cells reach a serosal surface?

Fall into it causing seeding

70

What proportion of patients have microscopic metastases by the time a diagnosis of cancer is made?

>50%

71

What is the most common portal of entry of tumour cells into the bloodstream?

Capillaries and veins

72

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

73

What shape do metastases tend to be?

Spherical

74

How are metastases described on chest X-Ray?

Single = coin lesion
Multiple = cannon balls

75

Where do tumours in organs drained by the portal system metastasise primarily to?

Liver

76

What acts as filters and receives 20-25% of cardiac output yet develops far fewer metastases than the smaller adrenal glands?

Kidneys

77

What tumours favour metastasising to the ovaries?

GI tumours

78

What are bilateral metastatic tumours of the ovaries called?

Kruckenberg tumours

79

How are some metastases to the vertebrae explained?

Presence of a system of veins in and around the spine - vertebral venous plexus

80

What method of spread is favoured by carcinomas?

Via lymphatics

81

How do malignant cells spread via the lymphatics?

Penetrate w/out destroying endothelium --> float to next lymph node --> settle in peripheral sinus --> grow

82

What is peau d'orange?

Slightly oedematous and puckering of the skin due to lymphatic obstruction common in carcinomas of the breast

83

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

84

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

85

How can seeding in the CSF occur?

With tumours of the CNS

86

Why is implantation on epithelial surfaces rare?

They are inhospitable, covered in mucus, cornfield cells and bacteria

87

What is a more histiologically atypical tumour more likely to do?

Invade and metastasise

88

Where does basal cell carcinoma appear?

Skin exposed to sunlight, especially the face

89

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

90

Can implantation of tumour cells along a needle track after biopsy occur?

Yes but it is rare

91

What must a metastatic cell escape in the blood in order to metastasise?

Antibodies
Complement
Macrophages
Killer cells
Toxic oxygen concentration
Blood clotting

92

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

93

How do tumour cells penetrate BV?

Reverse diapedesis

94

Where is it most likely that tumour cells enter the bloodstream?

Vessels of the tumour itself rather than preformed surrounding vessels

95

How do tumour cells attach to basement membrane when entering a vessel with endothelial lining and basement membrane?

Laminin receptors

96

What can tumour cells become coated in within the blood which can help the metastatic process?

Platelets

97

Why is the mechanical impact of embolism fatal to many tumour cells?

They are larger and less deformable than WBCs

98

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

99

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

100

What are fistulae?

Abnormal communications between two distinct tissues e.g. B/w bladder and rectum

101

What is paraneoplastic syndrome?

Symptom complexes that accompany tumours and concern distant targets whether the mechanisms be hormonal, toxic, immunologic or unknown

102

What happens to paraneoplastic syndrome is the tumour is removed or destroyed?

It usually disappears

103

What may be the first sign of a hidden tumour and can help follow the regression or recurrence of a tumour?

Paraneoplastic syndrome

104

What are the most common offenders in ectopic hormone secretion?

Lung carcinomas

105

What can renal cell carcinomas produce that results in high haematocrit and symptoms related to high blood viscosity?

Erythropoietin

106

Why is a hypercoaguable state seen in 90-95% of cancer patients?

Platelets activated by tumour products e.g. ADP
Tumours secrete procoagulents

107

What is Trosseau's syndrome?

Migratory thrombophlebitis where bouts of thrombophlebitis are seen in multiple locations without an apparent predisposing factor

108

Which types of cancer is Trousseau's syndrome often seen in?

Pancreatic
Lung
Stomach

109

What is acanthosis nigricans?

Symmetric, brown, warty hyper pigmentation w/hyperkeratosis of the axilla and other flexural areas

110

What is the possible cause of acanthosis nigricans?

Transforming growth factor alpha

111

What does more than 50% of acanthosis nigricans occur in association with?

Internal malignancy - esp. GI carcinoma

112

What produces tumour necrosis factor which results in cachexia caused by tumour?

Macrophages

113

What causes changes in sense of taste in neoplasm?

Tumour

114

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

115

What is often seen in Burkitt's lymphoma?

Tumour lysis syndrome

116

What limits tumour lysis syndrome to 5-7 days?

Wave of cell death ends

117

How does cancer kill?

Infection - cancer and its treatment are anti inflammatory
Haemorrhage and thromboembolic phenomena
Cachexia
Respiratory failure
Renal failure

118

What molecules are carcinogenic with a delay of 5-30 years?

Aromatic amines

119

Why are carcinogenic molecules described as electrophilic reactants?

They have relatively electron deficient sites which make them seek nucleophilic sites such as amine groups

120

How are nucleophilic groups relatively abundant in a cell?

As DNA, RNA and proteins

121

What happens to carcinogens in the body?

They are activated into an electrophilic state

122

What are procarcinogens?

Inactive carcinogens

123

Why does each carcinogen always affect the same organ?

Due to their need for modification before they are effective

124

What may the organ selectivity of carcinogens depend on?

Presence, absence or balance of enzymes that activate procarcinogens

125

Is alcohol carcinogenic?

Not directly but causes liver cirrhosis and liver nodules may become neoplastic

126

Where does alcohol increase risk of cancer for?

Mouth
Pharynx
Larynx
Oesophagus
Lung
Rectum
Breast

127

What two things interact to increase the risk of oesophageal cancer?

Alcohol and tobacco

128

What is the principal theory to explain gastric cancer?

Based on nitrosamine formation in the stomach

129

Where can nitrosamines come from?

Tobacco smoke
Sodium nitrite prescursor used as a food additive in cured meat and fish

130

What inhibits the production of nitrosamines from nitrites?

Adding ascorbic acid/increasing the amount of fruit and vegetables in the diet

131

What is produced by Aspergillus flavus which grows on grain stored in warm and humid conditions that is a very potent carcinogen?

Aflatoxin B1

132

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

133

What dietary agents inhibit mutations and tumour formation?

Fibre
Vitamin A
Vitamin C
Certain seeds

134

How does obesity cause an increased risk of endometrial cancer?

Adipose tissue converts androgens to oestrogens

135

What type of cancer can the contraceptive pill cause?

Liver adenomas

136

What protects against breast cancer?

Early first pregnancy and bearing a child at all

137

What are approximately 10% of breast cancers due to?

Genetic predisposition often associated w/BRCA1 and BRCA2

138

How does asbestos cause cancer?

Fibres inhaled and produce fibrosis and malignant tumours of mesothelium of the pleura, pericardium and peritoneum

139

What acts synergistically with cigarette smoke to cause cancer?

Asbestos

140

What is involved in carcinogensis by ionising radiation?

Free radicals

141

What is given to women during pregnancy to stop bleeding and can cause adenocarcinoma of the vagina in the daughters of treated women?

Diethylstillboestrol

142

What are the only two types of radiation that are carcinogenic?

Ultraviolet
Ionising

143

How do UV rays behave as complete carcinogens on repeated exposure?

Damage DNA strands by forming dimers and cross-links

144

How many exposures of ionising radiation are needed to cause cancer?

One

145

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

146

Which are the most sensitive cells to radiation injury causing shortened cell survival?

Bone marrow
Intestinal epithelial
(Both have high mitotic rates)

147

Which common worldwide tumour is the only one to be virus induced?

Hepatocellular carcinoma

148

Where does schistosoma cause cancer in humans?

Bladder

149

How do retroviruses work?

Transduce cellular genes and turn them into cancer genes

150

What unique enzyme do retroviruses possess?

Reverse transcriptase

151

Why are viral copies of transduced cellular genes not perfect?

Reverse transcriptase is a highly error-prone mechanism

152

What are proto-oncogenes?

Normal genes with important growth-related functions in a cell's normal activity

153

About how many oncogenes are known to exist?

70

154

What is one-step oncogenesis?

Where the oncogene acts alone

155

Which DNA viruses can cause neoplasm?

Hep B
HPV
EBV
Molluscum contagiosum (forms benign molluscum bodies)

156

Which retrovirus can cause leukaemia and lymphoma?

Human T-cell leukaemia virus

157

How does Burkitt's lymphoma usually present?

Large mass in the upper or lower jaw

158

What is the most common cause of infectious mononucleosis?

Epstein Barr virus

159

What does Epstein Barr virus do?

Parasitises B lymphocytes
Parasitises epithelium of upper pharynx

160

What does the distribution of Burkitt's lymphoma in Africa coincide with?

Distribution of malaria

161

What do all Burkitt's lymphomas show?

Chromosome translocations known to activate the oncogene c-myc

162

What does nasopharyngeal carcinoma always contain?

DNA of the EBV

163

How do DNA viruses produce tumours?

Carry genes that transform cells
Act indirectly by depressing genes that normally inhibit cell growth

164

What are RNA oncogene viruses also called?

Acute transforming proteins

165

How quickly can RNA oncogene viruses produce a leukaemia?

In a matter of days or weeks

166

Describe human T-cell lymphocytic virus-I.

A relative of the AIDS virus
Like HIV it affects helper lymphocytes (T4+)

167

What two types of neoplastic associations does the AIDS virus have?

Tumours related to immunosupression
Kaposi's sarcoma

168

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

169

What is the likely cell of origin in Kaposi's sarcoma?

Endothelium

170

How can Helicobacter pylori cause stomach cancer?

Causes chronic gastritis therefore may cause cancer due to chronic stimulus to regenerate

171

What are liver flukes?

Parasites that live in bile ducts causing hyperplasia and sometimes cholangiocarcinoma

172

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

173

How is water contaminated by Schistosoma haematobium?

Human host eliminates eggs in urine where they can enter the water supply

174

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