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Pathology > Neoplasms, carcinogenesis and tumour classification > Flashcards

Neoplasms, carcinogenesis and tumour classification Flashcards

1
Q

What is neoplasia?

A

Unregulated and irreversible clonal growth that results in neoplasm/tumour formation

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2
Q

Why is neoplasia described as unregulated and irreversible?

A

Neoplasia continues after stimulus is removed

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3
Q

What is a neoplasm/tumour?

A

Lesion formed by abnormal autonomous growth of cells that persists in absence of a stimulus

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4
Q

What is meant by clonal growth to form a neoplasm/tumour?

A

All of the tumour cells are derived from the same single cell of origin

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5
Q

What are the 2 types of neoplasm/tumour?

A

Benign or malignant

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6
Q

What cell types can undergo neoplastic change?

A

All cell types

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7
Q

What is the most common cell type that undergoes neoplastic change?

A

Epithelial cell

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8
Q

What 2 factors can cause molecular change of genes in carcinogenesis?

A

Mutagens

Ageing

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9
Q

What are the 2 types of genetic change in carcinogenesis?

A

Genetic mutation

Epigenetic change

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10
Q

What is epigenetic change?

A

Modification of genes due to environment and behaviours eg. methylation

Gene sequence itself isn’t altered

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11
Q

What properties do genetic errors provide to cells in carcinogenesis?

A

Cancer hallmarks

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12
Q

How many cancer hallmarks are there?

A

6

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13
Q

What are the 6 cancer hallmarks of cancer cells developed in carcinogenesis?

A

Resisting apoptosis

Constant proliferation

Inducing angiogenesis and immune system evasion

Enabling replicative immortality

Evading growth suppressors

Activating invasion and metastasis

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14
Q

What 2 characteristic features of a cancer can be identified by examining its cancer hallmarks?

A

Natural history

Responses to therapies

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15
Q

When genetic error occurs in carcinogenesis, is this a type of DNA damage?

A

Yes

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16
Q

How is a mutagen different from a carcinogen?

A

Mutagens can be non-lethal, but carcinogens usually result in malignant tumours (cancer)

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17
Q

What is a carcinogen?

A

Agent that causes DNA damage that increases cancer risk

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18
Q

Give 2 examples of chemicals that are carcinogens?

A

Benzene

n-nitrosamine

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19
Q

Why is cigarette smoke a carcinogen?

A

It contains benzene

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20
Q

What bacteria is associated with gastric adenocarcinoma and lymphoma?

A

Helicobacter pylori

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21
Q

What type of infective agent is a liver fluke, that is also a carcinogen?

A

Parasite

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22
Q

Give 4 examples of oncogenic viruses?

A

HPV, EBV, HCV, HBV

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22
Q

Give 4 types of cancers that radiation is associated with?

A

Skin cancer, thyroid cancer, lymphoma, leukaemia

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23
Q

How is a clone of neoplastic daughter cells formed in carcinogenesis?

A

The cell which has undergone DNA damage overcomes DNA repair mechanisms and can transmit the genetic error to daughter cells, forming a clone

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24
Q

What occurs in progression during the molecular sequence of carcinogenesis?

A

A single daughter cell from the clone mutates to have a survival advantage, so natural selection favours this aggressive daughter cell and it dominates the population by forming its sub-clone

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25
Q

How does a tumour form a tumour microenvironment?

A

The tumour recruits normal cells

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26
Q

Where does a tumour form its tumour environment?

A

In the organ that it arises from

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27
Q

How do DNA mutations cause tumour growth, invasion of surrounding tissues and metastasis?

A

DNA mutations disrupt regulatory systems

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28
Q

What is the most commonly mutated proto-oncogene in the human body?

A

RAS (Rat Sarcoma virus)

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29
Q

What is a proto-oncogene?

A

Normal gene for cell growth and differentiation, that mutates into an oncogene

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30
Q

Give 5 examples of proto-oncogenes?

A

Growth factor
Growth factor receptor
Nuclear receptor
Cell-cycle receptor
Signal transducer

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31
Q

What does MAP Kinase pathway stand for?

A

Mitogen-Activated Protein Kinase pathway

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32
Q

What type of receptor does the growth factor bind to at the cell membrane in the MAP Kinase pathway?

A

Receptor tyrosine kinase

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33
Q

What inner membrane protein is activated by binding of growth factor to receptor tyrosine kinase in the MAP Kinase pathway?

A

RAS (Rat Sarcoma virus)

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34
Q

In the MAP Kinase pathway, what molecule does RAS activate, and what it its function?

A

RAF (Rapidly Accelerating Fibroma), a signal transducer

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35
Q

In the MAP Kinase pathway, what molecule does RAF activate, and where is is found in the cell?

A

MEK, a cytoplasmic protein

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36
Q

In the MAP Kinase pathway, what molecule does MEK activate?

A

ERK

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37
Q

In the MAP Kinase pathway, what does ERK do after it travels to the nucleus?

A

Activates transcription factors controlling cell metabolism and growth

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38
Q

In the MAP Kinase pathway, how do the ERK-activated transcription factors affect cell-cycle proteins?

A

Cell-cycle proteins are switched off

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39
Q

When cancer arises, what step of the MAP Kinase pathway is different?

A

Cell-cycle proteins mutate to be permanently switched on, which causes uncontrollable transcription

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40
Q

What is the role of Her 2 in the MAP Kinase pathway, and what type of cancer is it amplified in?

A

Her 2 is a receptor tyrosine kinase that is amplified in breast cancer

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41
Q

What drug is given to inhibit Her 2 when it is amplified in breast cancer?

A

Herceptin

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42
Q

What type of drug is used to treat malignant melanoma, which involves the MAP Kinase pathway?

A

RAF inhibitor

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43
Q

What are tumour suppressor genes?

A

Genes that regulate cell growth by preventing tumour development

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44
Q

What hypothesis is used to explain how tumour suppressor genes are affected by DNA mutations and cause cancer?

A

Knudson’s two hit hypothesis

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45
Q

Explain how Knudson’s two hit hypothesis refers to mutated tumour suppressor genes in carcinogenesis?

A

Both maternal and paternal copies of the tumour suppressor gene must be mutated to cause cancer

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46
Q

What triggers p53 expression in a normal cell?

A

DNA damage

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47
Q

What does p53 activate to stop the cell-cycle at the G1 checkpoint?

A

p53 activates transcription factors to form CDKI p21, which blocks the CDK4/cyclin D, this stops cell-cycle progression

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48
Q

How does p53 trigger apoptosis when the cell has severe DNA damage?

A

Upregulates BAX, which disrupts BCL2 so that the mitochondrial membrane loses its stability and cytochrome C leaks out

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49
Q

What is retinoblastoma?

A

Tumour suppressor gene that regulates progression from G to S phase of cell-cycle

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50
Q

What are apoptosis regulators?

A

They stop normal cells from dying but promote apoptosis in mutated cells with irreparable DNA damage

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51
Q

How does BCL2 stabilise the mitochondrial membrane?

A

Blocks release of cytochrome C

52
Q

In follicular lymphoma, what chromosome mutation has occured?

A

Translocation of BCL2 gene from chromosome 18 to Ig heavy chain locus of chromosome 14

53
Q

In follicular lymphoma, how does the translocation of BCL2 gene cause enhanced stability of the mitochondrial membrane?

A

BCL2 is overexpressed

54
Q

In follicular lymphoma, what is the cancer hallmark produced by the enhanced mitochondrial membrane stability?

A

Malignant lymphocytes are immortal

55
Q

What is the macroscopic feature of follicular lymphoma?

A

Rubbery enlarged lymph nodes

56
Q

What is the characteristic microscopic feature of follicular lymphoma?

A

Large, pale nodules in lymph node called malignant lymphoid follicles

57
Q

What is the function of telomerase in normal cells?

A

Elongates telomeres, which are pieces of DNA that shorten with serial cell division and lead to cell senescence

58
Q

How is telomerase different in cancer cells?

A

Telomerase is upregulated

59
Q

How do cancer cells evade the immune system?

A

They produce factors that switch off the immune system

60
Q

What is the importance of angiogenic factors in carcinogenesis?

A

They form new blood vessels which are needed for tumour growth

61
Q

Give 2 examples of angiogenic factors used for tumour growth?

A

Fibroblast growth factor

Vascular endothelial growth factor

62
Q

Where are benign tumours located relative to their area of origin?

A

Remain localised to area of origin

63
Q

How can the growth rate of a benign tumour be compared to the growth rate of a malignant tumour?

A

Benign tumour has slow growth rate but malignant tumour has fast growth rate

64
Q

What is meant by malignant tumours being invasive?

A

Malignant tumours can directly enter surrounding tissues and travel to distant sites, which is metastasis

65
Q

To what extent do benign tumours resemble their origin tissue?

A

Closely resemble their origin tissue

66
Q

What are 2 ways in which malignant tumours can resemble their origin tissue?

A

Well-differentiated malignant neoplasms closely resemble origin tissue

Poorly-differentiated malignant neoplasms don’t closely resemble origin tissue

67
Q

Are benign tumours encapsulated, and what does this mean?

A

Benign tumours are encapsulated, so they are compact and confined to a specific area

68
Q

Are malignant tumours encapsulated or not?

A

No, they have irregular margins, so they aren’t compact and aren’t confined to a specific area

69
Q

Give one example of a malignant tumour that doesn’t usually metastasise?

A

Basal cell carcinoma, a malignant skin cancer

70
Q

Describe the nuclear to cytoplasmic ratio in benign cells compared to malignant cells?

A

In benign cells there is a low nuclear to cytoplasmic ratio

In malignant cells there is a high nuclear to cytoplasmic ratio

71
Q

Why do malignant cells have a high nuclear to cytoplasmic ratio?

A

They have nuclear pleomorphism (irregularities in nuclear shape and size), which makes the nuclei very large

72
Q

Why do benign cells have a low nuclear to cytoplasmic ratio?

A

They don’t have nuclear pleomorphism, so all nuclei are similar size

73
Q

Do malignant and benign cells have hyperchromasia?

A

Malignant cells have hyperchromasia

Benign cells don’t have hyperchromasia

74
Q

What is hyperchromasia?

A

Stained nucleus appears dark, opaque, smudged

75
Q

How is chromatin distributed in benign cells compared to malignant cells?

A

In benign cells, chromatin is distributed evenly

In malignant cells, chromatin is distributed irregularly and is vesicular/clumped

76
Q

Do benign and malignant cells have distinct nucleoli?

A

Benign cell has no distinct nucleolus

Malignant cell might have distinct nucleolus

77
Q

Describe the nuclear membranes in benign cells compared to in malignant cells?

A

Smooth nuclear membrane in benign cell

Irregular nuclear membrane in malignant cell

78
Q

What is dysplasia?

A

Disordered growth that is the precursor to carcinoma (malignant tumour of epithelium)

79
Q

Is dysplasia reversible?

A

Potentially, if stressors are removed in early dysplasia

80
Q

Why does dysplasia become irreversible carcinoma?

A

Stressor persists

81
Q

What 2 long-standing conditions does dysplasia arise from?

A

Metaplasia, hyperplasia

82
Q

What is another name for dysplasia?

A

Intraepithelial neoplasia

83
Q

What is Barrett’s oesophagus?

A

Metaplastic change of stratified squamous epithelial cells of lower lining into simple columnar epithelium cells that compose glands

84
Q

How can Barrett’s oesophagus result in dysplasia?

A

Glands become more abnormal and undergo dysplasia

85
Q

What kind of dysplasia can endometrial hyperplasia lead to?

A

Cervical intraepithelial neoplasia

86
Q

How can you obtain a sample of cells from the outer surface of the cervix to test for dysplasia?

A

Smear test, where cells on surface are brushed off

87
Q

What is dyskaryosis?

A

Abnormal change in squamous epithelial cell characterised by irregular chromatin and hyperchromasia

88
Q

What is pyknosis?

A

Irreversible condensation of chromatin in nucleus of cell undergoing apoptosis/necrosis

89
Q

In cells of cervical dysplasia, would there be dyskaryosis, and why?

A

Yes, because they are stratified squamous epithelial cells

90
Q

What classification system is first used to classify a tumour?

A

Histogenic classification

91
Q

Why is histogenic classification important when classifying and identifying the origin of a cancer?

A

Different cell types can develop different tumours

92
Q

What are the 4 main classes of origin cell types in histogenic classification of cancers?

A

Lymphocyte, Haematopoietic cell, epithelial cell, connective tissue/mesenchymal cell

93
Q

Give 4 examples of tumours derived from epithelial cells?

A

Carcinoma
Adenoma
Adenocarcinoma
Squamous cell carcinoma

94
Q

What is a carcinoma?

A

Malignant tumour derived from epithelial cells

95
Q

What is a squamous cell carcinoma?

A

Malignant tumour derived from squamous epithelial cells

96
Q

What is an adenoma?

A

Benign tumour derived from epithelial cells that shows gland formation

97
Q

What is an adenocarcinoma?

A

Malignant tumour derived from epithelial cells, of glandular origin or showing gland formation

98
Q

How can you tell from the name of a tumour derived from epithelial tissue, if it is malignant or benign?

A

Malignant ends in ‘carcinoma’

Benign ends in ‘oma’

99
Q

Give 2 microscopic features of a squamous cell carcinoma?

A

Desmosomes linking tumour cells

Keratin production (pink material)

100
Q

Give 2 microscopic features of an adenocarcinoma?

A

White lumen of malignant glands

Mucin in cytoplasm

101
Q

How can you tell from the name of a tumour derived from connective/mesenchymal tissue, if it is malignant or benign?

A

Malignant tumour ends in ‘sarcoma’

Benign tumour ends in ‘oma’

102
Q

What are the names of malignant and benign tumours derived from adipose tissue?

A

Malignant: liposarcoma

Benign: lipoma

103
Q

What are the names of malignant and benign tumours derived from blood vessels?

A

Malignant: angiosarcoma

Benign: haemangioma

104
Q

What are the names of malignant and benign tumours derived from skeletal muscle?

A

Malignant: rhabdomyosarcoma

Benign: rhabdomyoma

105
Q

What are the names of malignant and benign tumours derived from smooth muscle?

A

Malignant: leiomyosarcoma

Benign: leiomyoma

106
Q

What are the names of malignant and benign tumours derived from schwann cells?

A

Malignant: Malignant Peripheral Nerve Sheath Tumour

Benign: schwannoma

107
Q

What are the names of malignant and benign tumours derived from fibroblasts?

A

Malignant: fibrosarcoma

benign: fibroma

108
Q

What is a lymphoma?

A

Malignant tumour derived from lymphocytes, that is commonly found in lymph nodes and enlarges them

109
Q

How does a lymphoma relate to lymph nodes?

A

Lymphoma commonly found in lymph node and causes it to have enlarged appearance

110
Q

When a malignant tumour derived from lymphocytes is leukaemia, where is it found?

A

Peripheral blood or bone marrow

111
Q

What is the malignant tumour derived from haematopoetic cells?

A

Leukaemia

112
Q

Give 2 microscopic features of follicular lymphoma?

A

Oval pale nodules that are malignant lymphoid follicles

Medullary sinuses can’t be seen anymore

113
Q

What characteristic feature does the blood film of chronic lymphocytic leukaemia (CLL) show?

A

Small lymphocytes

114
Q

What is tumour grade?

A

How closely a tumour resembles the origin tissue

115
Q

How do you interpret high and low tumour grades?

A

The higher the grade, the more poorly differentiated the tumour is (resembles origin tissue less), so the tumour is more aggressive and spreads more rapidly

116
Q

In a grade 3 tumour, how can you identify the origin tissue?

A

Immunohistochemistry, where antigens from the tumour are identified by observing their colour reactions with specific, labelled antibodies

117
Q

In normal breast tissue, what structures are found in the lobes?

A

Lobules, which are composed of acini (glands) that have epithelial lining and open lumen

118
Q

In a grade 1 breast adenocarcinoma, what would you see in the microscopic image?

A

Well-differentiated and acini resemble those of normal breast tissue

119
Q

In a grade 3 breast carcinoma, what would you expect to see in the microscope image?

A

Poorly-differentiated and no acini

120
Q

What is the most common malignant tumour found in breast tissue?

A

Adenocarcinoma

121
Q

What is tumour stage?

A

Extent of tumour spread

122
Q

What system is used to determine the tumour stage?

A

TNM system 8th edition

123
Q

What 3 types of examinations are needed to determine tumour stage?

A

Pathological, radiological, clinical

124
Q

What does T represent in the TNM system 8th edition?

A

Size/extent of local invasion of primary tumour

125
Q

What does N represent in the TNM system 8th edition?

A

Whether metastasis to lymph node has occurred, which drains parent organ of tumour

126
Q

What does M represent in the TNM system 8th edition?

A

Whether metastasis to distant site has occurred

127
Q

In oesophageal cancer, when does T score of TNM system increase?

A

With increasing involvement of layers of oesophageal wall

128
Q

In oesophageal cancer, when does N score of TNM system increase?

A

With increasing number of positive lymph nodes (lymph nodes that have cancer)

Pathology (17 decks)

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