Neoplasia 1 Flashcards
(192 cards)
1
Q
Where is the word neoplasia derived from?
A
Greek - ‘neo’ = new, ‘plasia’ = growth or formation
2
Q
Definition of neoplasia
A
uncoordinated growth of cells that persists after the initial stimulus is removed
3
Q
Description of normal cell growth
A
coordinated, controlled, responsive to stimuli, self-limiting, well-differentiated
4
Q
Description of neoplastic growth
A
autonomous growth that escapes normal regulatory mechanisms
5
Q
What is the result of neoplasia?
A
abnormal tissue masses (tumours/neoplasms)
6
Q
What are the 2 types of neoplasia?
A
benign or malignant
7
Q
What are the cells of benign neoplasms like?
A
well-differentiated cells that resemble the tissue of origin (e.g. if benign neoplasm is in epithelia, cells look like epithelial cells)
8
Q
What is the growth rate of benign neoplasms?
A
slow growth
9
Q
Metastasis definition
A
the spread of cancer cells from the primary tumour site to other parts of the body (via circulatory/lymphatic system)
10
Q
Can benign neoplasms metastasise?
A
no metastasis - local expansion rather than invasion
11
Q
What structural feature of benign neoplasms prevent invasion of surrounding tissue?
A
the borders are well defined - often encapsulated
12
Q
Are benign neoplasms life-threatening?
A
no unless in critical location
13
Q
Examples of benign neoplasms in oral cavity
A
fibroma, lipoma, papilloma
14
Q
What are the cells of malignant neoplasms like?
A
often poorly differentiated and variable/poor histological resemblance to normal tissue (look like stem cells rather than original tissue)
15
Q
What is the growth rate of malignant neoplasms?
A
rapid, uncontrolled growth
16
Q
Can malignant neoplasms metastasise?
A
yes due to poorly defined borders
17
Q
What does the absence of defined borders in malignant neoplasm allow?
A
Enables infiltrative growth and invasion of surrounding tissue
18
Q
Can malignant neoplasms be life-threatening?
A
malignant neoplasms are often fatal is untreated
19
Q
Is there a potential for recurrence after removing a benign neoplasm?
A
No - benign tumours are encapsulated so all the cells are removed
20
Q
Is there a potential for recurrence after removing a malignant neoplasm?
A
yes - cells may escape removal and reform tumour
21
Q
Examples of malignant neoplasms in the oral cavity
A
squamous cell carcinoma, mucoepidermoid carcinoma, salivary gland carcinoma
22
Q
What is the frequency of necrosis occurring in benign neoplasms?
A
rarely occurs
23
Q
What is the frequency of necrosis occurring in malignant neoplasms?
A
common
24
Q
Which type of neoplasm commonly exhibits ulceration?
A
malignant neoplasm (rare in benign)
25
Where does ulceration commonly occur in malignant neoplasms?
skin or mucosal surfaces
26
What is the direction of benign neoplastic growth on skin or mucosal surfaces?
often exophytic (projects outwards from surface - lump/ulcer may be present)
27
What is the direction of malignant neoplastic growth on skin or mucosal surfaces?
often endophytic (invades inwards)
28
Anaplasia definition
loss of cellular differentiation and reversion to a more primitive, stem-cell like form that often has an increased capacity for rapid cell division
29
Which type of neoplasia has anaplastic cells?
malignant neoplasms
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What changes do malignant cells undergo?
anaplasia, nuclear changes and cellular changes
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What are the nuclear changes that malignant cells undergo?
enlarged nuclei (high nucleus : cytoplasm ratio), hyperchromasia (so darkly staining), abnormal chromatin pattern, prominent nucleoli
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What cellular changes occur in malignant cells?
pleomorphism, abnormal mitotic figures, loss of polarity
33
Pleomorphism definition
variation in size and shape (of cell/nuclei)
34
What feature of a cell when disrupted can lead to loss of polarity?
cytoskeleton (maintains cell shape and structure)
35
Cell polarity definition
the intrinsic asymmetry observed in cells (shape, structure, cellular organisation)
36
What is the importance of cell polarity in epithelial cells?
cell polarity allows the formation of defined apical and basal membranes in epithelial cells
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What process is loss of cell polarity often associated with?
epithelial-to-mesenchymal transition (EMT)
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What happens during epithelial-to-mesenchymal transition (EMT)?
epithelial cells lose their polarity and acquire mesenchymal characteristics which promotes cell migration and invasion
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How are benign tumours named?
cell/tissue of origin + suffix '-oma'
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How are malignant tumours named?
cell/tissue of origin + either carcinoma / sarcoma
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When would a malignant neoplasm have 'carcinoma' as a suffix?
if the malignancy is of epithelial origin
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When would a malignant neoplasm have 'sarcoma' as a suffix?
if the malignancy is of mesenchymal origin
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Name of benign neoplasm of surface epithelium
papilloma
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Name of malignant neoplasm of surface epithelium
squamous cell carcinoma
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Name of benign neoplasm of glandular epithelium
adenoma
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Name of malignant neoplasm of glandular epithelium
adenocarcinoma
47
Name of benign neoplasm of fibrous tissue
fibroma
48
Name of malignant neoplasm of fibrous tissue
fibrosarcoma (connective tissue is of mesenchymal origin)
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Name of benign neoplasm of adipose tissue
lipoma
50
Name of malignant neoplasm of adipose tissue
liposarcoma
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Name of benign neoplasm of cartilage
chondroma
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Name of malignant neoplasm of cartilage
chondrosarcoma
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Name of benign neoplasm of bone
osteoma
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Name of malignant neoplasm of bone
osteosarcoma
55
Where are epithelial tumours derived from?
epithelial tissues
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Examples of epithelial tumours
squamous cell carcinoma, basal cell carcinoma
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Where are mesenchymal tumours derived from?
connective tissues
58
Examples of mesenchymal tumours
osteosarcoma, chondrosarcoma, liposarcoma
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Where are hematopoietic tumours derived from?
blood forming tissues
60
Examples of hematopoietic tumours
leukaemia, lymphoma
61
Where are neural tumours derived from?
Neural tissues
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Examples of neural tumours
neurofibroma, schwannoma
63
Where are mixed tumours derived from?
more than one tissue type
64
Example of mixed tumour
pleomorphic adenoma of salivary glands
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What are the different types of genetic alterations?
point mutations, chromosomal translocations, gene amplifications, deletions
66
What happens during a point mutation?
one nucleotide/base is swapped
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What happens during chromosomal translocations?
part of a chromosome breaks and is reattached to a different chromosome (can lead to overexpression)
68
What happens during gene amplifications?
multiple copies of a gene is produced (leads to overexpression)
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What does the accumulation of genetic alterations result in?
uncontrolled proliferation, resistance to apoptosis, ability to invade and metastasise
70
What are the key genes that can lead to cancer if affected?
DNA repair genes, oncogenes, tumour suppressor genes
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Definition of oncogenes
genes that promote cell growth and division
72
How do oncogenes exist initially before they are overexpressed/mutated?
proto-oncogenes
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What are proto-oncogenes?
normal cellular genes that regulate cell growth
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What are the main functions of oncogenes?
promote cellular proliferation, survival and migration
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What are the mechanisms that activate oncogenes from proto-oncogenes?
chromosomal translocation, point mutations, gene amplification, insertion of promoter/enhancer
76
How may chromosomal translocation of the oncogene cause its activation?
the oncogene can be translocated from an untranscribed site to a position adjacent to an actively transcribed gene (e.g. Ig gene in B cell) which leads to inappropriate transcription of oncogene
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Example of neoplasia where chromosomal translocation involving an oncogene is the cause
Burkitt lymphoma (increased B cells)
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How can a point mutation within the oncogene lead to activation?
substitution of a single base is translated into an amino acid substitution resulting in a hyperactive oncogene
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How can gene amplification of the oncogene lead to neoplasia?
multiple excess copies of the oncogene are inserted stimulating cellular proliferation
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How may the insertion of a promoter/enhancer activate oncogenes?
insertion of promoter or enhancer sequence proximal to oncogene actives its expression
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Examples of oncogenes (inactive in health)
RAS (signal transduction), MYC (transcription factor), HER2/neu (growth factor receptor), BCL-2 (inhibits apoptosis)
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Definition of tumour suppressor genes
genes that inhibit inappropriate cell division and suppress growth
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What are the functions of tumour suppressor genes?
cell cycle regulation, apoptosis induction, DNA damage repair, maintain genomic stability
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How are tumour suppressor genes inactivated?
two hit hypothesis - both alleles (on both chromosomes) must be inactivated - tumour suppressor gene can still function is only one chromosome is affected
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What is the consequence of tumour suppressor genes being inactivated?
loss of cell cycle control leading to uncontrolled proliferation, genomic instability
86
Examples of tumour suppressor genes
Tp53, RB (retinoblastoma gene)
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What is the cause of DNA mutations/damage?
cariogenic stimuli
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Function of TP53 gene
'guardian of the genome' - maintains genome stability via the synthesis of p53
89
What happens to cells with DNA mutations that have a normal p53?
cell is arrested in G1 until the damage is repaired or apoptosis occurs if the damage is too severe
90
What happens in cells that have a DNA mutation and a defective p53 (due to TP53 mutation)?
no repair or apoptosis occurs and the cell proceeds to S phase. DNA damage is propagated to daughter cells, uncontrolled proliferation to form tumour
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What are retinoblastomas?
malignant tumours derived from the retina that occur almost exclusively in children
92
What are the two types of retinoblastomas?
inherited and sporadic retinoblastoma
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Which was the first tumour suppressor gene identified?
retinoblastoma gene (RB)
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What is the function of a normal retinoblastoma gene?
controls progression from G1 to S phase of cell cycle, bind and inactivates transcription factors (E2F family), prevents uncontrolled cell division
95
What must occur for retinoblastoma to take place?
both RB alleles must be inactivated (two-hit hypothesis)
96
What happens during retinoblastoma?
there is a loss of cell cycle control leading to uncontrolled proliferation
97
Which type of retinoblastoma is more common?
inherited retinoblastoma (one allele is already impaired)
98
Which type of retinoblastoma has a high risk for bilateral retinoblastoma?
inherited retinoblastoma (high possibility of at least one mutation occurring in any cell)
99
Which type of retinoblastoma causes unilateral retinoblastoma?
sporadic retinoblastoma
100
What happens in inherited retinoblastoma?
one of the paired RB1 genes is already mutated/absent. So mutation/loss of the remaining RB1 allele in any retinal cell will lead to retinoblastoma. Likely to occur more than once (high risk of bilateral retinoblastoma)
101
What happens in sporadic retinoblastoma?
mutations/deletions of both RB genes in the same cell or its daughters must occur (very rare and is unilateral - almost impossible for process to occur in both eyes!)
102
Carcinogens definition
agents that initiate or promote cancer development
103
What are the categories of carcinogens?
chemical, physical and biological carcinogens
104
Examples of chemical carcinogens
tobacco, asbestos, benzene
105
Examples of physical carcinogens
UV radiation, ionizing radiation
106
Examples of biological carcinogens
HPV, HBV, H. pylori
107
What tumour is associated with polycyclic aromatic hydrocarbons?
skin (mineral oil exposure) and lung cancer (smoking)
108
What tumour is associated with aromatic amines?
bladder cancer (in rubber and dye workers)
109
What tumour is associated with alkylating agents?
leukaemia
110
What tumour is associated with vinyl chloride?
liver angiosarcoma
111
Which biological carcinogen is associated with cervical and oropharyngeal carcinoma?
human papillomavirus
112
Which biological carcinogen is associated with nasopharyngeal cancer?
epstein-barr virus
113
What is carcinogenesis?
the multi-step process of cancer development
114
What are the steps in the theory of carcinogenesis?
1. initiation
2. promotion
3. progression
115
What happens during the initiation step of carcinogenesis?
carcinogen causes an irreversible alteration in DNA (of relevant genes e.g. oncogene/tumour suppressor gene)
116
What happens during the promotion stage of carcinogenesis?
a promoter stimulates proliferation of initiated cells via clonal expansion to form a benign tumour (reversible process)
117
What happens during the progression stage of carcinogenesis?
additional mutations are acquired which increases malignant potential and develops invasive and metastatic capabilities
118
Definition of latency period
time between exposure to carcinogen and development of cancer
119
How does cellular senescence normally work?
each time a cell divides, the telomeres become shorter until the chromosome is too short and the cell can no longer divide.
120
What are the 3 genetic mechanisms in carcinogenesis?
1. expression of telomerase
2. loss/inactivation of both TSG copies
3. activation of oncogenes
121
How does telomerase expression contribute to carcinogenesis?
telomerase prevents telomeric shortening with each cell division hence preventing cellular senescence, making the cell immortal
122
How does inactivation of tumour suppressor genes contribute to carcinogenesis?
the loss of TSG function permits mutations (DNA repair is impaired) and removes inhibitory growth control
123
How does the activation of oncogenes contribute to carcinogenesis?
results in cell proliferation via autocrine growth stimulation
124
Epigenetics definition
the study of changes in organisms caused by modification of gene expression rather than an altered gene code
125
How do epigenetic mechanisms contribute to carcinogenesis?
either normally repressed genes are abnormally expressed or normally active genes are repressed (silenced)
126
What are the 3 epigenetic mechanisms that contribute to carcinogenesis?
- hypermethylation
- histone modifications
- microRNA
127
How may hypermethylation contribute to carcinogenesis?
gene silencing results from the hypermethylation of promotor DNA sequences
128
How can histone modification contribute to carcinogenesis?
histone modifications usually to histone tails can alter chromatin structure leading to gene up- or downregulation
129
How does microRNA contribute to carcinogenesis?
increased microRNA leads to reduced mRNA translation and protein expression whereas decreased microRNA enhances protein expression
130
What is microRNA?
short sequences of inhibitory RNA that binds to mRNA transcripts
131
What are some host factors that can contribute to carcinogenesis?
race/ethnicity, diet and obesity, constitutional factors (sex, inherited risks..), transplacental exposure, premalignant lesions
132
What are premalignant lesions of the oral cavity referred to as?
Oral Potential Malignant Disorders (OPMD)
133
Examples of premalignant lesions of the oral cavity
leukoplakia, erythroplakia, oral submucous fibrosis
134
Definition of leukoplakia
white patch that cannot be characterised clinically or pathologically as any other disease
135
What is the malignant transformation rate of leukoplakia?
3-17%
136
Definition of erythroplakia
red patch that cannot be characterised clinically or pathologically as any other disease
137
What is the malignant transformation rate of erythroplakia?
14-50%
138
What is oral submucous fibrosis characterised by?
fibrosis and restricted mouth opening
139
What is associated with causing oral submucous fibrosis?
areca nut/betel quid chewing
140
How is the risk of cancer of premalignant lesions predicted?
checking for dysplasia in biopsy of premalignant lesion
141
What are the factors affecting tumour growth?
cell proliferation rate, cell death rate (apoptosis), angiogenesis, stromal interactions
142
How does angiogenesis affect tumour growth?
blood vessels supply nutrients and oxygen, provides route for metastasis
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What is the growth pattern for benign tumours?
expansile growth (pushes surrounding tissues aside, encapsulated, distinct border)
144
What is the growth pattern for malignant tumours?
infiltrative growth (invasion of surrounding tissues, irregular/ill-defined borders, destruction of normal architecture)
145
How is growth rate / aggression of a tumour estimated clinically?
using tumour doubling time
146
What is meant by tumour heterogeneity and clonal evolution?
diverse cell populations in tumours, selection pressures leads to emergence of aggressive clones, has implications for treatment resistance
147
Use the development of adenocarcinoma as a model of tumour progression
1. a single epithelial cell of the mucosal gland is transformed into a tumour cell by a carcinogen (initiation)
2. the abnormal cell proliferates to produce clones populating one gland (promotion)
3. further proliferation forms a benign adenoma protruding from mucosal surface (exophylic)
4. further genetic and epigenetic changes result in the transformed cells becoming invasive - lesion is now malignant (carcinoma)
5. metastases - malignant cells invade blood vessels and lymphatics and area carried to the liver and lymph nodes to form secondary tumours
148
Definition of angiogenesis
formation of new blood vessels from existing vasculature
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What diameter of a tumour requires angiogenesis?
tumours with a diameter beyond 1-2mm
150
Why is angiogenesis critical for tumours?
allow tumour growth to be supported by perfusion and provide a path for metastasis
151
What happens when vascularised tumours outgrow their blood supply?
central necrosis occurs, slower growth
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What is the angiogenic switch?
balance between pro- and anti-angiogenic factors
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What are the key pro-angiogenic factors?
Vascular Endothelial Growth Factor (VEGF), Basic Fibroblast Growth Factor (BFGF), Platelet-Derived Growth Factor (PDGF)
154
What are the characteristics of tumour vasculature?
disorganised structure, permeable vasculature, abnormal blood flow
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What is a therapeutic action to target angiogenesis in tumour growth?
anti-angiogenic therapy
156
Metastasis definition
spread of malignancy to distant organs
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What structure must be breached before metastasis can occur?
basement membrane
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What are the routes of metastasis (4)?
lymphatic, hematogenous, transcoelomic and perineural spread
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Which cancers commonly undergo lymphatic spread?
carcinomas
160
Which cancers commonly undertake hematogenous spread?
sarcomas
161
What is the route of lymphatic spread?
from regional lymph nodes to distant sites
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What is the route of hematogenous spread?
via bloodstream to distant organs
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What is the route of transcoelomic spread?
Across body cavities such as pleural, pericardial and peritoneal cavities
164
What is the route of perineural spread?
along nerve sheaths
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Which cancers commonly undergo perineural spread?
head and neck cancers
166
What are the routes of metastasis for colorectal cancer?
hematogenous spread to liver, lymphatic spread to lymph nodes, transcoelomic spread to peritoneum
167
What are the key steps in metastasis?
1. invasion through basement membrane
2. intravasation into blood/lymph vessels
3. survival in circulation
4. extravasation at distant site
5. colonisation of distant site e.g. lymph node
168
What is a major cause of cancer-related mortality?
metastasis (progresses faster than can be removed)
169
How are tumour cells able to migrate to initiate metastasis?
tumour cells detach from their neighbours (loss of adhesion molecules)
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How do tumour cells survive in circulation?
evading host defence mechanisms (e.g. natural killer cells, T lymphocytes) by reducing MHCI expression and releasing ICAM-1 which blocks TCR
171
What are the clinical effects of tumours?
Local effects, metabolic effects and metastatic effects for malignant tumours
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What are the causes of local effects of tumours?
compression, invasion, ulceration or destruction of adjacent structures
173
What may cause metabolic effects of tumours?
neoplastic cell products e.g. overproduction of specific protein
174
What are the histological features of neoplasms?
loss of differentiation, loss of cellular cohesion, nuclear enlargement, pleomorphism and hyperchromasia, and increased mitotic activity
175
What is nuclear pleomorphism?
variation in nuclear size, shape and chromatin staining patterns
176
What us hyperchromasia?
dark staining nuclei
177
What findings are tumour gradings based on?
based on the microscopic appearance of cells (histological examination)
178
What features are examined when determining the grading of tumours?
degree of differentiation/anaplasia, nuclear features, mitotic activity
179
Anaplasia definition
lack of differentiation in neoplastic cells
180
What is the description of a grade I tumour?
well differentiated
181
What is the differentiation of a grade II tumour?
moderately differentiated
182
What is the differentiation of a grade III tumour?
poorly differentiated
183
What is the definition of a grade IV tumour?
undifferentiated/anaplastic
184
What findings are used to identify the stage of a tumour?
clinical and radiographic findings
185
What does the staging of tumours describe?
the extent of spread
186
How does the grade and stage of a tumour differ?
the grade is based on the microscopic appearance of cells whereas the stage is based on the extent of the spread found using clinical and radiographic findings
187
What system is used to stage cancers?
TNM staging system
188
What does the T in the TNM staging system refer to?
size and extent of the primary tumour
189
What does the N in the TNM staging system refer to?
number of regional lymph nodes containing metastasis
190
What does the M in the TNM staging system refer to?
presence of distant metastasis
191
What is the use behind staging tumours?
the stage determines treatment approach and prognosis
192
What are the implications of a higher stage tumour?
shows there is more extensive disease which leads to worse prognosis
