Session 8 Flashcards
Define neoplasia
An abnormal growth of cells that persists after the initial stimulus is removed
Define malignant neoplasm
An abnormal growth of cells that persists after the initial stimulus is removed and invades surrounding tissue with potential to spread to distant sites
Define tumour
Any clinically detectable lump or swelling
Define cancer
Any malignant neoplasm
Define metastasis
A malignant neoplasm that has spread from its original site (primary site) to a new non-contiguous site (secondary site)
Define dysplasia
A pre-neoplasticism alteration in which cells show disordered tissue organisation (reversible)
Compare dysplasia and neoplasia
Neoplasia = irreversible
Dysplasia = reversible
Do benign neoplasms produce metastases?
No - remain confined to their site of origin
Describe the appearance of a benign neoplasm to the naked eye with regards to its outer margin in particular
Has a regular ‘pushing’ outer margin and grows in a confined area
Benign neoplasms may push on local structures causing…
Inflammation
Describe the appearance of cells of a benign neoplasm under the microscope
Cells closely resemble the parent tissue - well differentiated
Do malignant neoplasms have the potential to metastasise?
Yes, by definition
Describe the appearance of a malignant neoplasm to the naked eye
Irregular outer margin and shape
May show necrosis/ulceration
Describe the appearance of the cells of a malignant neoplasm under a microscope
Cells range from well to poorly differentiated
What is meant by the term anaplastic?
Cells have no resemblance to any tissue
Compare the cells seen in malignant neoplasms with the cells seen in benign neoplasms
Benign - well differentiated cells (resemble parent tissue)
Malignant - poorly to well differentiated (a range)
Describe the varying degrees of differentiation seen in benign and malignant neoplasms under the microscope
Benign - cells well differentiated, closely resemble parent tissue
Malignant - cells range from well to poorly differentiated
Name 5 changes seen in cells due to worsening differentiation as seen in malignant neoplasms
Nuclear hyperchromasia
Increased nuclear:cytoplasm ratio
Increased mitoses (mitotic figures)
Larger nucleus
Cellular and nuclear size variation (pleomorphism)
What is nuclear hyperchromasia?
Increased nucleus staining due to increased DNA content
Clinicians use the term __________ to indicate differentiation
Grade
Clinicians use the term grade to indicate differentiation.
High grade = _________ differentiated
Poorly
Neoplasm is caused by an accumulation of _____________ in somatic cells
Mutations
What sort of factors are the most important causes of mutations?
Extrinsic/Environmental Factors
Mutations are caused by initiators and promoters.
What is the function of an initiator?
What is the function of a promoter?
Mutagenic agent - introduces mutation
Causes cell proliferation
Mutations are caused by initiators and promoters. In combination they result in…
An expanded, monoclonal population of mutant cells
Name the three main initiators of neoplasia
Infections
Chemicals
Radiation
A neoplasm emerges from a monoclonal population through a process called _______________ where there is an accumulation of ______________
Progression
Mutations
What is meant by the term monoclonal with regards to a cell population?
A collection of cells that all originated from a single founding cell
What is evidence that neoplasms are monoclonal?
From the study of x-linked gene for the enzyme G6PD in tumour tissue from women
Evidence from the study the of x-linked gene for the enzyme _________ in tumour tissue from women supports the theory that neoplasms are monoclonal
G6PD
Describe how the study of the x-linked gene for G6PD in tumour tissue from women provides evidence that neoplasms are monoclonal
Gene has several alleles encoding different isoenzymes
Early in embryogenesis one allele is randomly inactivated in EACH cell (lyonisation)
In women that have alleles coding for different isoenzymes, normal tissue will be a patchwork of each
In neoplastic tissues only one isoenzyme is expressed —> indicating monoclonal group
What is lyonisation? With regards to G6PD?
Random inactivation of the allele from one x chromosome
Early in embryogenesis, one allele coding for G6PD is randomly inactivated
Genetic alterations in neoplasms affect which two types of genes?
Proto-oncogenes
Tumour suppressor genes
Proto-oncogenes become abnormally activated forming…
Oncogenes
The formation of oncogenes from proto-oncogenes favours…
Neoplasm formation
In neoplasia, tumour suppressor genes which normally suppress neoplasm formation become…
Inactivated
The system for naming neoplasms can take into account (4)
Site of origin
Malignant or benign
Type of tissue that the tumour forms
Gross morphology (cyst or papilloma)
Benign neoplasms end in…
-oma
Malignant neoplasms end in -carcinoma if it is…
Epithelial
Malignant neoplasms end in -sarcoma if it is…
Stromal
-blastomas mainly occur in ____________ and are formed from…
Children
Immature precursor cells
The majority of malignant neoplasms are of which type? Give a rough percentage.
Carcinomas (epithelial origin)
~90%
Why are carcinomas more common than sarcomas?
Epithelial cells are at the surface and rapidly turnover so are more likely to be mutated
Carcinomas can be either… (2)
In-situ
Invasive
Compare an in-situ carcinoma with an invasive carcinoma
In-situ - no invasion of epithelial basement membrane
Invasive - penetrated through basement membrane
Is leukaemia malignant or benign?
Is lymphoma malignant or benign?
Malignant
Malignant
What type of cancer is leukaemia? Which cells are affected? Where does it arise?
MALIGNANT neoplasm affecting BLOOD-FORMING CELLS arising in the BONE MARROW
What type of cancer is lymphoma? What cells does it affect? What part of the body does it mainly affect?
MALIGNANT neoplasm affecting lymphocytes. Mainly affects lymph nodes.
Germ cell neoplasms arise from…
What parts of the body do they mainly affect?
Pluripotent cells
In the testis or ovary
Neuroendocrine tumours arise from…
Specialised neuroendocrine cells
‘Papillomas’ refers to any tumour with…
Finger-like projections
What name is given to a benign neoplasm of the stratified squamous epithelium? Where can this cancer be seen?
Squamous papilloma
Skin
What name is given to a benign neoplasm of the transitional epithelium? Where in the body can this be seen?
Transitional cell papilloma
Bladder mucosa
What is the name given to a benign tumour of glandular epithelium?
Adenoma
Give an example of an adenoma you might see in the body
Adenomatous polyp of the COLON
What name is given to a malignant neoplasm of the stratified squamous epithelium?
Squamous cell carcinoma
Name two parts of the body you may see squamous cell carcinoma
Skin
Larynx
Oesophagus
Lung
What name is given to a malignant neoplasm of the transitional epithelium?
Transitional cell carcinoma
Name two parts of the body where you may see a transitional cell carcinoma
Bladder
Uterus
What is the name given to a malignant neoplasm of glandular epithelium?
Adenocarcinoma
Name two locations you may see an adenocarcinoma
Stomach
Colon
Pancreas
What is the name given to a benign neoplasm of the…
Smooth muscle Fibrous tissue Bone Cartilage Fat Nerve Nerve sheath Glial cells
Leiomyoma
Fibroma
Osteoma
Chondroma
Lipoma
Neuroma
Neurofibroma
Glioma
What is the name given to a malignant neoplasm of the…
Smooth muscle Bone Fibrous tissue Cartilage Fat Glial cells
Leiomyosarcoma
Osteosarcoma
Fibrosarcoma
Chondrosarcoma
Liposarcoma
Malignant glioma
Lymphoid and haematopoietic neoplasms are all regarded as…
Malignant
Lymphoid neoplasms are called…
Lymphoma
Haematopoietic neoplasms are called…
Where in the body do they arise?
Leukaemia (acute/chronic)
Bone marrow
Give two examples of germ cell neoplasms in the testis
Seminoma
Malignant teratoma
Is seminoma malignant?
Yes
Give an example of a benign neoplasm affecting the ovary?
Benign teratoma
What is the colloquial name for a benign teratoma of the ovary?
Dermis cyst
______________ and _____________ metastasis are the most lethal features of a malignant neoplasm
Invasion
Metastasis
How does invasion and metastasis of a malignant neoplasm to distant sites affect the tumour burden of a patient?
Greatly increases tumour burden
Do benign tumours metastasise?
No
What are the 3 steps that malignant cells must undergo to get from a primary site to a secondary site?
At which steps do the inefficiencies of malignant cells to form metastases mainly lie?
Grow and invade at the primary site
Enter a transport system and lodge at a secondary site
Grow at the secondary site (colonisation)
Steps 2 & 3
Is the process of forming metastases generally efficient or inefficient?
Inefficient - number of viable cells able to form metastases is very low
Name three reasons why the process of forming metastases from malignant cells is inefficient
The cells must evade destruction by immune cells through all the steps of the process
Many cancer cells are sheared in capillaries and cannot survive in blood vessels
Many cannot grow at secondary site and instead form micro deposits of cancer cells
Invasions into surrounding tissues by carcinoma cells requires altered… (3)
Adhesion
Stromal proteolysis
Motility
The altered adhesion, stromal proteolysis and motility shown by cancer cells that invade surrounding tissues result in…
Carcinoma cells that appear more like mesenchymal cells than an epithelial cell
What are mesenchymal cells?
Multi-potent stromal cells
The process of altered adhesion, stromal proteolysis and motility that causes carcinoma cells to appear as mesenchymal cells rather than epithelial cells is called…
Epithelial-to-Mesenchymal Transition (EMT)
Describe what is involved in the altered ADHESION allowing carcinoma cells to invade surrounding tissue
Altered adhesion BETWEEN malignant cells involves a reduction in E-Cadherin expression
Altered adhesion between malignant cells and stromal proteins involves changes in Integrin expression
Altered adhesion between malignant cells involves…
A reduction in E-Cadherin expression
Altered adhesion between malignant cells and stromal proteins involves…
Changes in Integrin expression
Describe what is involved in the altered STROMAL PROTEOLYSIS which allows carcinoma cells to invade surrounding tissues
Cells degrade basement membrane/stroma to invade with altered expression of proteases - especially matrix metalloproteinases (MMPs)
How is the basement membrane/stoma degraded to allow carcinoma cells to invade surrounding tissue?
Through altered expression of proteinases (especially MMPs)
Which protease is particularly involved in the degradation of the basement membrane/stroma that allows carcinoma cells to invade surrounding tissue?
Matrix Metalloproteinases - MMPs
What is meant by a cancer niche?
Where malignant cells take advantage of nearby non-neoplastic cells that provide the malignant cells with some growth factors and proteases
Describe what is involved in the altered MOTILITY that allows the invasion of surrounding tissues by carcinoma cells
Changes in the actin cytoskeleton
Signalling through integrins allows changes in the actin cytoskeleton resulting in altered motility. Signalling occurs via…
Small G proteins such as members of the Rho family
In cancer niches the non-neoplastic cells supply the malignant cells with… (2)
Growth factors
Proteases
Transport of malignant cells to distant sites can occur via which 3 routes?
Blood vessels via capillaries/venules
Lymphatic vessels
Fluid in body cavities
What is the name given to spread/transport of malignant cells via fluid in body cavities?
Transcoelomic spread
Malignant cells must GROW at a secondary site to form a clinical metastasis in a process called…
Colonisation
What is considered the greatest barrier to successful metastasis formation?
Failed colonisation
What is the most common reason for failed colonisation?
Many malignant cells lodge at secondary sites BUT the tiny clusters of cells either die or fail to grow (micrometastases)
What are micrometastases?
Microscopic deposits of surviving cancer cells that fail to grow
An apparently disease-free person may harbour many micrometastases, this is known as…
Tumour dormancy
When a malignant neoplasm relapses after years it is typically due to…
One or more micrometastases starting to grow
Give 3 possible reasons for tumour dormancy
Immune Attack
Reduced Angiogenesis
Hostile Secondary Site
State two factors that influence the site of a secondary tumour
Regional drainage of blood, lymph or coelomic fluid
Seed and soil phenomenon
Regional drainage makes the site of metastasis more predictable.
Where is the typical site of lymphatic metastasis?
Draining lymph nodes
Regional drainage makes the site of metastasis more predictable.
Where is the typical site for transcoelomic spread?
Other areas in the coelomic space
Adjacent organs
Regional drainage makes the site of metastasis more predictable.
Where is the typical site for blood-borne metastasis?
Next capillary bed that the cells encounter (more unpredictable)
Describe what is meant by the seed and soil phenomenon
States that site of metastasis (secondary site) is due to interactions between malignant cells and the niche (local tumour environment) at the secondary site
By which route do carcinomas typically spread?
Lymphatics
Why which route do sarcoma typically spread?
Blood stream
State 4 common sites of BLOOD BORNE METASTASIS
Brain
Lungs
Liver
Bone
Neoplasms that spread to bone are most commonly… (5)
Breast Bronchus Kidney Thyroid Prostate
What is meant by tumour personalities?
Different characteristics commonly shown by different types of cancer
Give an example of a malignant neoplasm that is very aggressive and metastasises very early in its course
Small Cell Bronchial Carcinoma (SCLC)
Give an example of a malignant neoplasm that almost never metastasises
Basal cell carcinoma of the skin
The likelihood of metastasis is related to the size of…
The primary neoplasm
A substantially sized primary tumour is required to form…
Metastases
Give 4 LOCAL effects of primary/secondary neoplasms
Direct invasion/destruction of normal tissue
Ulceration at a surface leading to bleeding
Compression of adjacent structures
Blocking tubes/orifices
The systemic effects of neoplasms are as a result of either… (3)
What umbrella term can be given to systemic effects caused by these factors?
Increasing tumour burden
Secreted hormones
Miscellaneous systemic effects
Paraneoplastic syndromes
What systemic effects are caused by an increasing tumour burden?
Parasitic effect on host - cytokines contribute to reduced appetite and weight loss, malaise, immunosuppression and thrombosis
Cytokines released as a result of an increasing tumour burden can have a parasitic effect on the host.
State 4 symptoms this can cause in a patient
Malaise
Immunosuppression
Thrombosis
Decreased appetite + weight loss
Do both benign and malignant neoplasms secrete hormones that can have systemic effects on a host?
Give examples where necessary
Benign neoplasms consist of well differentiated cells so typically produce hormones
Thyroid adenoma —> Thyroxine
Malignant neoplasms sometimes produce hormones
Small Cell bronchial carcinoma —-> ACTH/ADH
Give 4 examples of a miscellaneous systemic effects of primary/secondary neoplasms
Neuropathies affecting the brain and peripheral nerves
Skin problems - e.g. Abnormal pigmentation and pruritus
Fever
Myositis
What is pruritus?
What is a neuropathy?
What is myositis?
Severe itching of the skin
A problem involving nerves
Inflammation/swelling of the muscles
