Neoplasia Flashcards
What is the definition of neoplasia
An abnormal mass of tissue, the growth of which exceeds and is UNCOORDINATED
with that of normal tissues
and persists in the same excessive manner after cessation of the stimuli which evoke the change
How can u identify Neoplasia
-Loss of response to normal growth control mechanisms
- Continued proliferation even without a recognizable stimulus
- Loss of differentiation (especially for malignant neoplasm)
- Aberrant differentiation function (especially for malignant neoplasm)
- Expression of ‘embryonal’ characteristics (especially for malignant neoplasm)
Embryonic development is somehow similar to neoplasia in some way
How are they similar
How are they different
Both have rapid growth and are mitotic figures
Embryonic development is coordinated
What is hypertrophy
What is Hyperplasia
How are they different from neoplasia
Hypertrophy= Increase in size of cell (Muscle in response to exercise)
Hyperplasia= Increase in number of cell (uterine muscle in respoonse to pregnancy
They are cordianted and Reversible hence different from neoplasia
What are the difference between a benign and a maligant neoplasia in terms of their ability to invade
Benign is expansive yet limited by Basement membrane
malignant is infiltrative and expansive, and they can invade BEYOND Basement membrane
What are the difference in gross appearance between a benign and a malignant neoplasia
Benign is circumscribed and encapsulated
Malignant has a poorly defined margin
What are differences between benign and malignant neoplasia in terms of their rate of growth
Benign is slow and may cease
Malignant is fast, and it is common for it to outgrow it’s blood vessel supply to cause irregular necrosis
If a tumour has crab-foot like extensions, do u think it is benign or malignant
Malignant
How can benign and malignant neoplasia be classified according to microscopic appearance (6 difference)
Benign has
–> Normochromatic nuclei
–> Low Nucleus-to-cytoplasm ratio
-> well-differentiated and it closely resembles tissue of origin
–> It has regular cell shape
–> Mitosis is absent or scanty
–> It has mild architectural disturbance and with maintained polarity (ie they grow toward the same side)
Malignant is
–> Hyperchromatic nuclei
–> High nuclei-to-cytoplasm ratio
(The cytoplasm is small as it contains protien for function)
(The nuclei is enlarged due to replication, expression and division)
–> It has vary degree of differentiation (well/poor)
–> It shows cellular pleomorphism (Variation in size and shape of nucleus and overall cell)
–> It is active mitosis and there are abnormal mitosis (Indicated by tripolar or multipolar spindles)
–> it has lost the polarity and with marked architectural disturbance
Why the malignant neoplasia exhibits genetic instability
The nuclear sizes are irregular,
and the abnormal alignment of chromatin leads to unequal division of genetic materials in mitosis
For benign neoplasia,
What is meant by the term Polarity
What are the 2 situations called when benign tumour grows to increase the surface area
Polarity means they grow towards the same side
Grow outward to form papillary lesion: Papilloma
Invaginated: Adenoma
If a malignant cancer occurs at the epithelium, what will it usually do
Grows into the connective tissue and invade through the basement membrane
What is meant by the term differentiation
In embryonic development
And in neoplasia
It means the cell becomes specific cell types that performs specific functions
It means the cell resembles the tissue it originates both morphologically and functionally
What is the difference between the carcinoma and sarcoma in terms of the tissue they invade and the way they spread
Carcinoma: Epithelial . Spread by lymphatics
Sarcoma: Connective Tissue: Spread by blood
What is the term for
Benign
Malignant
At epithelium
Papilloma (B)
Adenoma (B)
Carcinoma (M)
Adenocarcinoma (M)
What is the term for
Benign
Malignant
At Fibrous tissue
Fibroma
Fibrosarcoma
What is the term for
Benign
Malignant
At Bone
Osteoma
Osteosarcoma (aka osteogenic sarcoma)
What is the term for
Benign
Malignant
At Fat
Lipoma
Liposarcoma
What is the term for
Benign
Malignant
At Cartilage
Chondroma
Chondrosarcoma
What is the term for
Benign
Malignant
At Smooth muscle
leiomyoma
leiomyosarcoma
What is the term for
Benign
Malignant
At Striated muscle
Rhabdomyoma
Rhabdomyosarcoma
What is the term for
Benign
Malignant
At blood vessel
Haemangloma
Angiosarcoma
What is the term for
Benign
Malignant
At Nervous tissue
Benign: Nil
Astrocytoma
Oligodendroglioma
Ependymoma
What is the term for
Benign
Malignant
At trophoblast
Hydatidiform mole
Chorion carcinoma
What is the term for
Benign
Malignant
At Totipotent cell of Embryonic tissue
Benign Teratoma
Malignant Teratoma
What is the term for
Benign
Malignant
At Pluripotent cell
Benign: Nil
Malignant:
Nephroblastoma
Hepatoblastoma
What is the term for
Benign
Malignant
At Unipotent cell
Benign: Ganglioneuroma
Malignant
Medulloblastoma
Retinoblastoma
Neuroblastoma (Sympathetic nerve)
What is dysplasia
It has cellular change similar to malignant neoplasia but there is no evidence of invasion and actual tumour formation
Does dysplasia Has maintained it’s polarity and architecture
It has maintained the polarity
And preserved Architecture
How can we define the seriousness of dysplasia
Graded as mild/ moderate/ severe:
- Mild/ moderate: some reluctance to differentiate, but will differentiate when forced without increase in size or any mass effect
Moderate dysplasia is still considered
- Severe: nuclear pleomorphism, hyperchromatism up to surface, mitosis in upper layers and also refuse to differentiate (but no loss of polarity yet, architecture preserved)
What is the situation when dysplasia involves the whole thickness of surface epithelium
Carcinoma-in-situ
What is the problem of dysplasia
It increase chance for invasive carcinoma
It maybe reversible
For colorectal cancer, what are the genes and chromosomes affected
APC gene: A Tumour suppressor gene
Ras gene: A oncogene, activated to benign adenoma with dysplasia
Chromosome 18q is needed
p53 is inactivated (Tumour suppressor)
What is the Concept of clonality and heterogeneity in malignant neoplasm
- By the time a malignant tumour is formed, the malignant cells are usually clonal in origin but have developed heterogeneity with varying ability to invade and metastasize
- Clonality in some situation helps us to distinguish a neoplastic from a hyperplastic situation clinically
- E.g. lymphoid hyperplasia in reaction to
antigen are polyclonal, whereas
lymphoid neoplasm are monoclonal →
distinguished by a clonality marker
How is the idea of clonal and heterogenity affect the treatment for cancer
Treatment induces new selection pressure
- Since there is variation within the tumour cell population, some cells will
survive the selection pressure and undergo clonal expansion again →
recurrence
How can the carcinoma or adenocarcinoma invade through the Connective tissue
it cleaves the basement membrane with enzymes like Type IV Collagenase
It also pause the anoikis (a strong program which signals the epthelial cell to die if not attached basement membrane/ neighbouring cell
Hence it can survive after detached from the Basement membrane and in the connective tissue
How is the metestatis done.
The tumour can find a vessel and invade it to enter the blood
Platelet will clot it while the host immune cells will attack it but it is uneffective
it then adhere to the basement membrane of the blood vessel and do extravasation.
It then induce the formation of new blood vessel via angiogenesis to establish colony
Name 3 media for tumour to do metastatis ead and what is the speed
Via lymph: Slow
Via blood: Quick
via transcoelomic spread (pleural cavity or peritoneal cavity)
Other than metastatis, name 2 ways for it to spread
Local invasion
Nerve invasion
What is the movement of tumour when it spread along lymph
Primary organ –> regional lymph node -> More central lymph node
What is the movement of tumour in haematogenous route
Veins to heart to organs
What is the route of peritoneal metastatis
Invasde through muscle wall then disseminate in the peritoneal cavity
What is the route of pagetoid spread
Crawling along the epithelium as each individual gland cell can invade a single layer or stratified squamous epithelium
What is the route of Perineural spread
Less resistant in nerves, easier to travel along them
What are the T N M staging of cancer
T: extent of Local invasion
N: Extent of lymph node metastatis
M: Extent of distant metastatis
What are the instrinsic factor for tumour growth
Cell proliferation rate, Cell death, cell maturation and stop dividing
What contributes to the net growth rate of a neoplasia
Balance between the proliferation and differentation
Tumour enhances Proloferation and avoids differentiation and cell death
What are the hall marks of the neoplasia
- Deregulate the cellular energy requirement
- Resist cell death
- Activate invasion and metastasis mechanisms
- Promote inflammation
- Enable them to replicate limitlessly (telomeres)
- Sustain proliferation signal
- Evade growth suppressive signal
- Avoid immune destruction
- To induce angiogenesis
- Show genomic instability and increased mutation rate to facilitate the development of
heterogeneity to overcome environmental constraints - [DRAPE SEATS or GRAPE CGI II]
What are the term of Normal gene for proliferation and differentiation
Cancer-causing gene
Gene that prevent development of tumour
Proto-oncogene
Oncogene
Tumour Suppressor gene/ antioncogene
How can
Viral infection
Chromosomal arrangement
Mutation
Gene amplification
Turns an protooncogene into Oncogene
a virus may insert own promoter above 5’-end of protooncogene
→ activity of proto-oncogene become controlled by the viral
promoter leading to aberrant activation
Chromosomal arrangement/ gene fusion – chromosomes break and
another fragment of the chromosome is connected to the 5’-end of the gene,
so the hybrid gene activity is controlled by an active cellular gene that is
normally active in certain cell types → uncontrolled activity
aberrant activation of proto-oncogenes
copies of proto-oncogene is duplicated (up to 30-40 copies of the same gene in the genome) and contributes to the net overactivity
how to inactivate the tumour suppressor gene
- Deletion (whole or part of the gene)
- Truncating mutation (frameshift, nonsense or splice site mutation) [shortening]
- Point mutation
- Promoter methylation
How does accumulation of multiple events cause the development of tumour
- Cells have altered, overactive oncogenes and loss of regulator tumour suppressor genes
- If there is growth advantage, there will be clonal expansion of the cells that have accumulated these changes
- Lead to a population of cells that divide faster and lead to additional genomic instability
(acquire additional genetic alterations more rapidly) - Development of heterogeneity
What is the major type of cancer in Child
46% leukaemia/lymphoma (hematopoietic or lymphoid
cells), 28% CNS tumours
What is the most 5 prevalent type of cancer in Male
Colorectal, lung, prostate, liver, stomach
What is the most 5 prevalent type of cancer in Female
Breast, colorectal, lung, corpus uteri, thyroid
What can chemical agents do to cause cancer
Under what circumstances will clonal expansion occur
Electrophilic, mutagenic, cause rapid irreversible DNA alteration in isolated cells
- Only when they are pushed to divide can they form clonal expansion/ pass mutation to the progeny
What does Pott suggest
Soot can enhance the risk of Scrotal cancer
Name 4 characteristics of chemical carcinogens
Long latent period
- Great individual variation in susceptibility
- Many are indirect carcinogens requiring metabolic activation but can also be destroyed by
detoxification pathway
- Hereditary factors may contribute to mild difference in activity of these pathways
How can Radiation cause Cancer
- DNA damage, if unrepaired, can cause cancer
- Depend of linear energy transfer (e.g. UV, gamma irradiation)
- UV is much weaker, so required very long exposure to cause mutations in DNA that can
develop into cancer - Related cancer types: e.g. Leukaemia, osteogenic sarcoma
Name 4 virus-linked cancer
Human papilloma virus (HPV) and cervical cancer
Epstein-barr virus and nasopharyngeal carcinoma
Hepatitis B virus and hepatocellular carcinoma
Epstein-barr virus and Burkitt lymphoma
What is the characteristic of Viral DNA when it is corporated into the host genome to cause cancer
incorporated and remains in cells as
they develop into cancer (viral DNA integration into the host genome)
Site of viral DNA integration into host genome not constant but clonal
- Every progeny cells have the virus in the same integration site
- Process is very critical in the early events of the cancer development
How does HBV cause hepatocellular carcinoma
The HBV induces chronic injury to the liver, which enhances cellular proliferation
The viral DNA integrated to the host DNA in clonal form, and activate proto-oncogenes and PKC
How can hormones induce Neoplasia
Name an example
Hormones are involved in stimulating the proliferation of the target
organs → increased risk of mutations or genetic aberrations →
increased incidence of specific cancer types
- E.g. Endometrial carcinoma and high oestrogen level
Name 2 other factors causing cancer
-Chronic irritation and trauma
- Immunological
How can one inherit Neoplasia
They receive defective tumour suppressor gene
What is the Knudson’s Hypothesis
2 Hit inactivation of antioncogene can allow unrestricted cell proliferation
Does oncogene need 1 or more copies to activate neoplasia
1 is alrd enough
For Lynch Syndrome
What is the gene mutated
What is the cancer caused
Why the offspring of Lynch syndrome is more prone to the cancer
MLH1 (a DNA repair mismatch gene)
Colorectal cancer
They have inherited a defective copy of MLH 1
For Familial Adenomatous polyposis (FAP)
is that autosomal dominant or recessive
What is the gene affected
What is the Cancer associated
Dominant
APC gene
adenocarcinoma (at colon epithelial cell)
What is microsatellite
How can we detect microsatellite
a tract of repetitive DNA
Measure length of satellite – in normal situations, the length of cancer and normal bands should be the same
- If there are multiple loci showing the phenomenon (displacement/ unequal length) then there is
microsatellite instability
Is Inherited Neoplasia Dominant or recessive
mostly dominant
