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Histopathology and Cytologic Techniques (Lecture) > Neoplasia (M) > Flashcards

Neoplasia (M) Flashcards

1
Q

What is the nationality and profession of Willis?

A

He is a British oncologist

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2
Q

As defined by Willis, what is neoplasia?

A

It is an abnormal mass of tissue the growth of w/c exceeds and is uncoordinated w/ that of normal tissue and persists in the same excessive manner after cessation of stimuli w/c evoked the change

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3
Q

What are the phases of cell cycle?

A

1) G0
2) G1 - presynthetic
3) S - synthetic
4) G2 - premitotic
5) M - mitotic

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4
Q

What are the grps of cells accdg to proliferative potentials?

A

1) Labile cells
2) Stable cells
3) Permanent cells

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5
Q

What are labile cells?

A

These are cells that are continuously dividing

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6
Q

What are stable cells?

A

These are also called as quiescent cells

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7
Q

What are permanent cells?

A

These are nondividing cells

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8
Q

Cell proliferation can be stimulated by what?

A

1) Injury
2) Cell death
3) Mechanical deformation of tissues

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9
Q

How can growth be accomplished?

A

It can be accomplished by shortening the cell cycle

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10
Q

What are the most impt factors in relation to growth?

A

Those that recruit resting or quiescent cells into the cycle

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11
Q

What are the fxns of molecular controls and what is its result?

A

Regulate and orchestrate events leading to cell division

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12
Q

What is involved in cascade of protein phosphorylation?

A

Cyclins

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13
Q

What are the fxns of set of checkpoints (present in the cell cycle)?

A

1) These monitor molecular events

2) These may delay the progression to the next phase of the cell cycle

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14
Q

What are the fxns of checkpoints?

A

1) These provides surveillance mechanisms

2) These causes cell cycle arrests

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15
Q

What is the purpose of providing surveillance mechanisms done by checkpoints?

A

For ensuring that critical transitions occur in the correct order w/ fidelity in their completion

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16
Q

How does checkpoints cause cell cycle arrests?

A

By promoting inhibitory pathways or inhibiting activation pathways

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17
Q

Why is p53 activated and what is its result?

A

In response to DNA damage w/c in turn activates p21

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18
Q

*What is p21?

A

It is a CDK inhibitor

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19
Q

What is the fxn of CDK1B complex?

A

It controls transition from G2 - M

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20
Q

*The fxn of CDK1B complex is done after what?

A

After completion degraded by ubiquitin-proteosome pathway

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21
Q

What is the action of CDK1B complex?

A

It may bind w/ CDK inhibitors

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22
Q

What is the definition of new growth?

A

Neoplasm

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23
Q

What is the definition of “onco”?

A

Tumor

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24
Q

What is cancer?

A

It is a malignant neoplasm

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25
Q

What is carcinoma?

A

It is a malignant epithelial tumor

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26
Q

What is sarcoma?

A

It is a malignant mesenchymal tumor

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27
Q

What is the meaning of salise?

A

To circumvent

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28
Q

What are the 6 fundamental physiological changes in the neoplastic cell?

A

SALISE

1) Self sufficiency in growth signals
2) Ability to invade and metastasize
3) Limitless replicative potential
4) Insensitivity to growth-inhibitory signals
5) Sustained angiogenesis
6) Evasion of apoptosis

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29
Q

*What are the danger signals of neoplasm (/ its clinical manifestation)?

A

CAUTION US

1) Change in bowel or bladder habits
2) A sore that does not heal
3) Unusual bleeding or discharge
4) Thickening or lump (breast or elsewhere)
5) Indigestion or difficulty of swallowing
6) Obvious change in a mole or a wart
7) Nagging cough or hoarseness
8) Unexplained anemia
9) Sudden unexplained weight loss

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30
Q

How can tumors be classified?

A

1) Based on biologic behavior

2) Based on tissue of origin

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31
Q

What are the classifications of tumors based on biologic behavior?

A

1) Benign

2) Malignant

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32
Q

What are the classifications of tumors based on tissue of origin?

A

1) Epithelial
2) Mesenchymal
3) Mixed
4) Teratoma

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33
Q

Where does the biologic behavior of tumors depend?

A

1) Degree of differentiation
2) Rate of growth
3) Local invasion
4) Presence / absence of metastasis

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34
Q

What is the hallmark of malignancy?

A

Metastasis

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35
Q

What are the characteristics of a benign neoplasm?

A

1) It is well-circumscribed
2) It is encapsulated
3) It is well-differentiated
4) It pushes margins
5) There is no metastasis

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36
Q

What are the characteristics of a malignant neoplasm?

A

1) It is ill-defined
* 2) Irregular margins are present
3) It is anaplastic
4) There is invasion / metastasis

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37
Q

What are the 2 principles present in benign neoplasms?

A

1) Encapsulation

2) Differentiation

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38
Q

*What are the types of differentiation for malignant neoplasms?

A

1) Well-differentiated
2) Moderately differentiated
3) Poorly differentiated
4) Undifferentiated / anaplastic

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39
Q

What is the principle of differentiation?

A

The extent to w/c parenchymal cells resemble comparable normal cells, both morphologically and fxnally

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40
Q

What is dysplasia?

A

1) Disordered growth

2) Disordered maturation

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41
Q

What is anaplasia?

A

There is lack of differentiation

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42
Q

What is present in well-differentiated squamous cell CA?

A

Keratin pearls

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43
Q

What are the characteristics of anaplasia?

A

1) Pleomorphism
2) Hyperchromasia
3) Increased nucleo-cytoplasmic ratio
4) Abnormal (atypical) mitotic figures
5) Loss of polarity (loss of orientation)
6) Presence of multiple or enlarged nucleoli
7) Formation of tumor giant cells

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44
Q

How long does it take to produce a clinically overt tumor mass?

A

The original transformed cell (approx 10 um in diameter) must undergo at least 30 population doublings to produce 10^9 cells (weighing approx 1 g)

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45
Q

What is the smallest clinically detectable mass?

A

A transformed cell that weighs approx 1 g

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46
Q

What are the 3 factors that determines the rate of growth of a tumor?

A

1) The doubling time of tumor cells
2) The fraction of tumor cells that are in replicative pool
3) The rate at w/c cells are shed or die

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47
Q

*What are the 2 principles under biology of tumor growth?

A

1) Tumor angiogenesis

2) Tumor progression and heterogeneity

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48
Q

*What are the factors present / involved in tumor angiogenesis?

A

1) Vascular endothelial growth factor
2) Basic fibroblast growth factor
3) Anti-angiogenic factors

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49
Q

*What are the events present under tumor progression and heterogeneity?

A

1) Increased aggressiveness
2) Genetic instability / random mutations
3) Loss of p53, DNA repair genes

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50
Q

*What are the 2 types of local invasion?

A

1) In-situ

2) Invasive

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51
Q

What is the principle of local invasion that is in-situ?

A

Malignant cells confined to epithelial lining, limited by the basement membrane

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52
Q

*What are the 2 types of local invasion in-situ?

A

1) Intraepithelial

2) Intramucosal

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53
Q

What is the principle of local invasion that is invasive?

A

Malignant cells have breached basement membrane and are in the subepithelial stroma, lamina propia, or submucosa

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54
Q

Local invasion can be thru what?

A

1) Invasion thru basement membrane
2) Invasion thru lamina propia
3) Invasion thru muscularis mucosa

55
Q

What is metastasis?

A

It is the contiguous invasion to adjacent organ

56
Q

What can happen in metastasis?

A

Seeding of body cavities / surfaces

57
Q

What are the 2 types of spread (in relation to metastasis)?

A

1) Lymphatic spread

2) Hematogenous spread

58
Q

What are the sequence of events in invasion and metastasis?

A

1) Detachment of tumor cells
2) Attachment to matrix components
3) Degradation of extracellular matrix
4) Migration of tumor cells
5) Vascular / lymphatic drainage
6) Microenvironment

59
Q

What is responsible for detachment of tumor cells?

A

E-cadherins

60
Q

What are responsible for attachment to matrix components?

A

1) Laminin

2) Fibronectins

61
Q

What are responsible for degradation of extracellular matrix?

A

1) Collagenase

2) Cathepsin D

62
Q

What are the sequence of events present in the metastatic cascade?

A

1) Clonal expansion, growth, diversification, and angiogenesis
2) Metastatic subclone
3) Adhesion to and invasion of basement membrane
4) Passage through extracellular matrix
5) Intravasation
6) Interaction w/ host lymphoid cells
7) Tumor cell embolus
8) Adhesion to basement membrane
9) Extravasation
10) Metastatic deposit
11) Angiogenesis
12) Growth

63
Q

What are the simplified sequence of events present in metastatic cascade?

A

1) Loosening of intercellular junctions
2) Attachment
3) Degradation
4) Migration

64
Q

What are the concepts related to biology of CA?

A

1) Clonality
2) Progression
3) Proto-oncogenes

65
Q

What are the principles (/ principles related to clonality) of clonality?

A

1) Neoplastic cell arise from a single cell

2) 30 population doubling time produce 10^9 cells = 1 gram

66
Q

What is the principle of progression?

A

Acquisition of permanent, irreversible qualitative changes in 1 or more characteristics of a neoplasm

67
Q

What are the principles (/ principles related to proto-oncogenes) of proto-oncogenes?

A

1) Cellular genes that can become activated to become CA causing oncogenes
2) Encode proteins involved in normal differentiation / proliferation

68
Q

How does CA develop (/ also called as carcinogenesis)?

A

Gene damage -> clonal proliferation

69
Q

What are the concepts related to development of CA?

A

1) Point mutation
2) Chromosomal translocation
3) Chromosome deletion
4) Gene amplification

70
Q

What are the principles related to gene amplification (/ what are the events that occur in gene amplification?)

A

1) DNA-binding protein proto-oncogenes
2) myc family, present in all eukaryotes, bind to protein products are intranuclear and bind to DNA itself. They enable DNA synthesis
3) myc activation is usually by amplification (excess copies of a gene) and/or translocation rather than by mutation

71
Q

What are the characteristics of myc family?

A

1) Present in all eukaryotes
2) Its protein products are intranuclear
3) Its protein products bind to DNA itself

72
Q

What are the ways of how myc activation is done?

A

1) Via / by amplification (usual)

2) Translocation

73
Q

What are the targets of genetic damage?

A

1) Growth-promoting proto-oncogenes
2) Growth-inhibiting cancer suppressor genes
3) Apoptosis-regulating genes

74
Q

Provide an ex relating to the principle of growth-promoting proto-oncogenes as a target of genetic damage

A

The related neu (once erb2, now HER2) is amplified in many carcinomas, notably adenocarcinomas, especially of the breast, and the degree of amplification strongly correlates w/ bad outcome

75
Q

What is the characteristic of neoplasia?

A

It is a multi-step process

76
Q

What is the process related to neoplasia being a multi-step process?

A

Tumor progression

77
Q

What is the molecular biology of malignant transformation (accdg to Volgenstein’s Multistep Adenoma-Carcinoma Sequence)?

A

Normal Epithelium -> Hyperplastic Epithelium (Early Adenoma) -> Adenoma (Intermediate Adenoma) -> CANCER

Note: Early Adenoma -> Intermediate Adenoma

78
Q

What are the concepts present in normal epithelium?

A

1) Chromosome: 5q
2) Alteration: M / L
3) Gene: APC; MCC

Note:
Legend: M - mutation
L - loss

79
Q

What are the concepts present in the transition from hyperplastic epithelium to adenoma?

A

1) Chromosome: 12p
2) Alteration: M
3) Gene: ϰ-RAS

Note:
Legend: M - mutation
L - loss

80
Q

What are the concepts present in adenoma?

A

1) Chromosome: 18q
2) Alteration: L
3) Gene: DCC

Note:
Legend: M - mutation
L - loss

81
Q

What are the concepts present in the transition between adenoma to CA?

A

1) Chromosome: 17q
2) Alteration: L
3) Gene: p53

Note:
Legend: M - mutation
L - loss

82
Q

What are the mechanisms related to activation of proto-oncogenes?

A

1) Point mutation
2) Chromosome rearrangements
3) Gene amplification

83
Q

What are oncogenes?

A

These are DNA sequences within eukaryotic cells that seem to be involved in the development and maintenance of tumors

84
Q

What is the action of oncogenes?

A

These genes direct the synthesis of proteins that under some conditions transform a benign host cell into a CA cell

85
Q

What is the action of tumor suppressor genes?

A

These encode proteins that normally inhibit cell proliferation

86
Q

What are the proteins related to tumor suppressor genes?

A

1) Cell surface protein

2) Signal transduction protein

87
Q

Provide an ex of cell surface protein

A

DCC

88
Q

What is the action of DCC?

A

Cell adhesion

89
Q

Provide an ex of signal transduction protein

A

NF - 1

90
Q

What is the action of NF - 1?

A

GTPase activator

91
Q

What is the characteristic of most oncogenic ras?

A

Most oncogenic ras are mutations w/ a single base pair change that alters an AA at position 12, 13, or 61 in the protein product

92
Q

What is the action of oncogenic ras?

A

It destroys GTP-ase activity but retains GTP-binding activity, and current thinking is that these stay locked “on”, telling the transformed cell, “Keep dividing!”

93
Q

What are the proteins that regulate transcription (in relation w/ tumor suppressor genes)?

A

1) p53

2) pRb

94
Q

What is apoptosis?

A

It is the programmed cell death

95
Q

Provide a gene that is involved in apoptosis

A

Bcl-2

96
Q

What is the action of Bcl-2?

A

It is an inhibitor of apoptosis

97
Q

What is the action of tumor suppressor genes?

A

These keep cells benign, even when the oncogenes are activated

98
Q

What should be done to lose the anti-CA effect of tumor suppressor genes?

A

Both copies must be altered

99
Q

What is viral oncogene?

A

It is a proto-oncogene minus its regulatory sequences, or w/ a characteristic mutation, or in an excessive # of copies (“amplification”)

100
Q

What is the action of viral oncogene?

A

They are capable of causing CA by themselves, and hence are very different from their normal counterparts (i.e., have been damaged several times)

101
Q

What virus (/ viral oncogene) causes squamous cell carcinoma of the cervix?

A

Human papilloma virus (HPV | types 16 / 18)

102
Q

What is the virus (/ viral oncogene) that causes genital warts?

A

HPV (types 6 / 11)

103
Q

What is the virus (/ viral oncogene) that causes Burkitt’s lymphoma?

A

Epstein-barr virus (EBV | t [or types] [8;14])

104
Q

What is the virus (/ viral oncogene) that causes nasopharyngeal carcinoma and lymphoma in AIDS?

A

EBV

105
Q

What is the virus (/ viral oncogene) that causes hepatocellular carcinoma?

A

Hepatitis B virus (HBV)

106
Q

What is the principle of immune surveillance?

A

Recognition and destruction of NON-SELF tumor cells upon their appearance

107
Q

What are the cells / mechanisms related to immune surveillance?

A

1) CD8+ cytotoxic T cells (CTLs)
2) Natural killer (NK) cells
3) Macrophages
4) Humoral mechanism

108
Q

What are the mechanisms of how immunosurveillance tumor cells escape?

A

1) Selective outgrowth of Ag negative variants
2) Loss / reduced expression of HLA Ags
3) Tumor-induced immunosuppression
4) No co-stimulation / no sensitization
5) Apoptosis of cytotoxic T-cells

109
Q

What are the mechanisms of the role of p53 in maintaining the integrity of the genome?

A

1) The p53 gene product is a sequence-specific binder to DNA that prevents mitosis during times of cell injury, so that there will be more time for DNA repair
2) Sometimes (gamete, lymphocyte, chemotherapy) p53 even tells an injured cell to undergo apoptosis

110
Q

How is nomenclature for benign tumors of mesenchymal origin done?

A

Root word + “oma”

111
Q

Provide exs of nomenclature for benign tumors of mesenchymal origin

A

1) Fat = lipoma
2) Blood vessel = hemangioma
3) Smooth muscle = leiomyoma
4) Skeletal muscle = rhabdomyoma
5) Fibrous tissue = fibroma
6) Cartilage = chondroma
7) Bone = osteoma

112
Q

How is nomenclature done for benign tumors of epithelial origin w/ glandular pattern?

A

Adenoma

113
Q

How is nomenclature done for benign tumors of epithelial origin w/ finger-like projections?

A

Papilloma

114
Q

How is nomenclature done for benign tumors of epithelial origin w/ large cystic masses?

A

Cystadenoma

115
Q

How is nomenclature done for benign tumors epithelial origin visible projection above a mucosal surface?

A

Polyp

116
Q

How is nomenclature for malignant tumors of mesenchymal origin done?

A

Root word + “sarcoma”

117
Q

Provide exs of malignant tumors for mesenchymal origin

A

1) Fat = liposarcoma
2) Blood vessel = hemangiosarcoma
3) Smooth muscle = leiomyosarcoma
4) Skeletal muscle = rhabdomyosarcoma
5) Fibrous tissue = fibrosarcoma
6) Cartilage = chondrosarcoma
7) Bone = osteosarcoma

118
Q

Provide an ex of nomenclature for malignant tumors of epithelial origin w/ glandular microscopic pattern done?

A

Adenocarcinoma

119
Q

Provide an ex of nomenclature for malignant tumors of epithelial origin w/ squamous cells arising in any epithelium done

A

Squamous cell carcinoma

120
Q

What are the types of tumors based on tumor composition?

A

1) Simple tumors
2) Mixed tumors
3) Compound tumors

121
Q

What are simple tumors?

A

1 parenchymal cell type

122
Q

What are mixed tumors?

A

1 > neoplastic cell type usually from 1 germ layer

123
Q

What are compound tumors?

A

1 > neoplastic cell type from 1 > germ layer

124
Q

What are the exs of tumors of mesenchymal origin?

A

1) Connective tissues and derivatives
2) Endothelial and related tissues
3) Blood cells and related cells
4) Muscle
5) Bone
6) Cartilage

125
Q

What are the exs of tumors of epithelial origin?

A

1) Stratified squamous
2) Basal cells of the skin
3) Epithelial lining (gland or ducts)
4) Respiratory epithelium
5) Neuroectoderm
6) Renal epithelium
7) Liver cell
8) Urinary tract epithelium
9) Placental epithelium
10) Testicular epithelium

126
Q

What are the 10 leading CA sites (for males and females) accdg to Philippine Cancer Figures (2018)?

A

1) Breast
2) Lung
3) Colorectal
4) Liver
5) Prostate
6) Cervix uteri
7) Thyroid
8) Leukemia
9) Ovary
10) Corpus uteri

127
Q

What are the 10 leading CA sites in males?

A

1) Lung
2) Liver
3) Colorectal
4) Prostate
5) Stomach
6) Leukemia
7) Nasopharynx
8) Thyroid
9) Lymphomas
10) Oral cavity

128
Q

What are the 10 leading CA sites in females?

A

1) Breast
2) Cervix
3) Lung
4) Colorectal
5) Ovary
6) Liver
7) Thyroid
8) Uterus
9) Stomach
10) Leukemia

129
Q

What are the 6 leading CA sites in children?

A

1) Leukemia
2) Brain and spinal cord
3) Retinoblastoma
4) Lymphoma
5) Bone and soft tissues
6) Gonadal / germ cell site

130
Q

What are the 2 concepts related to neoplasia?

A

1) Grading

2) Staging

131
Q

What is the characteristic of grading?

A

It depends on the differentiation of tumor

132
Q

How is grading done?

A

1) Well differentiated
2) Moderately differentiated
3) Poorly differentiated

133
Q

What are the concepts related to staging?

A

1) Tumor size
2) Node involvement
3) Presence or absence of metastasis

TNM system

134
Q

What is the characteristic of TNM system (/ staging)?

A

It is a better method for prognostication

Histopathology and Cytologic Techniques (Lecture) (17 decks)

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