Session 8 - Neoplasia 1 and 2 Flashcards
Definitions:
- Hyperplasia
- Regeneration
- Tumour
- Neoplasia
- Oncology
- Hyperplasia: Increase in tissue or organ size due to increased cell numbers
- Regeneration: renewing or restoring something, especially after it has been damaged or lost
- Tumour: A swelling (remember from inflammation), any clinically detectable lump or swelling
- Neoplasm: Literally means ‘new growth’, just one type of tumour. A neoplasm is an abnormal growth of cells that persisits after the initial stimulus is removed.
- Oncology: The study of tumours and neoplasms
Definitions surrounding the word neoplasm:
- Benign neoplasm
- Malignant neoplasm
- Metastasis
- Cancer
- Dyplasia
- —- potential characteristics with dysplasia?
- Benign neoplasm: Gross and microscopic appearances are considered to be innocent, implying that it will remain localised and will not spread to other sites
- Malignant neoplasm: An abnormal growth of cells that persists after the initial stimulus is removed and invades surrounding tissue with the potential to spread to distant sites
- Metastasis: Malignant neoplasm that has spread from its original site to a new non-contiguous site
- Cancer: a malignant neoplasm (colloquial)
Primary vs secondary - define
- The original location of the malignant neoplasm is the primary site
- The place to which it has spread is the secondary site.
Benign vs malignant
- differences in characteristics
- differntiation…
Benign vs malignant:
Differences in — • Behaviour • Appear different to the naked eye • Differentiation
- Benign neoplasms remain confined to their site of origin and do not produce metastases
- Malignant neoplasms invade and have the potential to metastasise
Type/mode of growth:
Benign tumours
•Grow in a confined local area
•They have a pushing outer margin
•Rarely dangerous (location)
Malignant tumours
•Irregular outer margin and shape
•May have ulcerations and necrosis
•Infiltrative
Differentiation = the process of becoming different by growth or development (PIC below)
•Benign neoplasms closely resemble the parent tissue – well differentiated •Malignant neoplasms range from well to poorly differentiated, dependent on how closely they resemble the cell of origin.
•Cells with no resemblance to any tissue are called anaplastic
Differntiation
With worsening differntiation, the individual cells have…
- Increasing nuclear size
- Increased nuclear to cytoplasmic size
- Increased nuclear staining (hyperchromasia)
- Increased mitotic figures
- Abnormal mitotic figures (Mercedes Benz)
- Variation in size and shape of cells and nuclei (pleomorphism)
Differntiation scales…
- Grade
- Prostate (name of grading system)
- Brest (name of grading system)
Dyplasia - more detail
- Define and characteristics
- Stages of dysplasia in the epidermis
Dyplasia = Dysplasia is the abnormal maturation of cells within a tissue, the cells show disordered tissue organisation, and it is reversible. It can be pre-neoplastic.
- — Characteristics: considerable pleomorphism, larger hyperchromatic nuclei and high nuclear to cytoplasmic ratio
- — Mild, moderate and severe - worsening differention
Order:
Normal -> Dyplasia -> Carcinoma in situ -> invasive cancer (invasive cancer - the basement membrane has been invaded)
Dysplasia - example of the cervix and scoring system
CIN I - cervical intra-epithelial neoplasia 1 (dyplasia affects the lower third of the epithelium first) CIN II: Lower 2 thirds CIN III (also called carcinoma in situ): Full thickness of epithelium
How do we get neoplasms?
Carcinogenesis (NON-lethal genetic damage)
Accumulation of mutations in somatic cells
- Mutations are caused by initiators, mutagenic agents
- Promoters then cause cell proliferation
- A tumour is formed by the clonal expansion of a single precursor cell that has incurred genetic damage
Initiators -> Promotors -> Proliferation -> Porgression
- A neoplasm then emerges from this group of cells by a process called progression, this is characterised by the accumulation of even more mutations.
List of potential initiators
- Recap of difference between initiators and promotors
• Chemicals:
- Smoking
- Alcohol consumption
- Diet and obesity
• Infectious agents
- HPV
• Radiation
• Inherited mutations
*Many initiators can also act as promoters
Initiator: Induce first mutation
Promoter: Increase population size
Some carcinogens are initiators and promoters, some are one or the other
Which genes are affected - mutations here to occur in key genes…
There are FOUR class of normal regulatory genes:
- • Growth promoting proto-oncogenes
- • Growth inhibiting tumour suppressor genes
- • Genes that regulate programmed cell death (apoptosis)
- • Genes involved in DNA repair
- Proto-oncogenes
- explain
- examples
- Multiple functions but all participate at some level in signalling pathways that drive proliferation
- Mutations that activate these generally cause an excessive increase in one or more normal functions
- Sometimes they impart a completely new function on the affected gene
- “Gain-of-function” mutations
- Oncogenes are created by mutations in proto-oncogenes and encode proteins called oncoproteins that have the ability to promote cell growth in the absence of normal growth promoting signals
- They can transform cells despite a normal copy of the same gene
- Oncogenes are dominant over their normal counterparts
Protooncogene or oncoprotein mutation -> Oncogenes (oncogenes have the ability to promote cell growth in the absence of normal growth promoting signals)
Examples: BRAF mutation
- Tumour Suppressor Genes
- Explain
- Example - Apoptosis Regulating Genes
- Explain
- Tumour Suppressor Genes:
• Normal function is to stop cell proliferation
• Generally cause a ‘loss-of-function’
• In most instances both alleles must be damaged for transformation to occur
• Abnormalities in these genes leads to failure of growth inhibition
Examples - p53 (a tumour suppressor gene)
- Apoptosis Regulating Genes
• May acquire abnormalities that result in less cell death and enhanced survival of cells
- DNA Repair Genes
- Explain
- Loss of function mutations
- Contribute indirectly to carcinogenesis
- Impair the ability of the cell to recognise and repair non-lethal genetic damage in other genes
- As a result affected cells acquire mutations at an accelerated rate, a state referred to as a mutator phenotype and is marked by genomic instability
Naming Neoplasms
- What does this take into account?
- In general - Benign tumour, Malignant tumour name
Naming -
Takes into account:
• The neoplasms site of origin
• Benign or malignant
• Sometimes the gross morphology
General:
• Benign tumours end in –oma
• Malignant tumours end in
= carcinoma (if epithelial) – 90% of neoplasms
= sarcoma (if stromal)
Overarching names
- Benign
- Malignant
Tissue of origin:
Blood vessel
Lymph vessels
Smooth muscle
Striated muscle
Stratified squamous epithelium
Epithelial lining of glands or ducts
Urinary tract epithelium
Blood cells
Lymphoid tissue
Plasma cells
Germ cell neoplasms
- Testis
- Ovary
Definitions
- Invasion
- Metastasis
- Tumour burden
- Invasion: Breach of the basement membrane with progressive infiltration and destruction of surrounding tissue
- Metastasis: Spread of tumour to sites that are physiocally discontinous from the primary tumour (unequivocally marks a tumour as malignant)
- Tumour burden: for malignant neoplasms - overtime, increasing tumour burden
How does a neoplasm invade and metastasise?
- Grow and invade at the primary site
- Enter a transport system and lodge at a secondary site
- Grow at the secondary site to form a new tumour (colonisation)
What does a carcinoma cell need in order to be ‘successful’ at invasion?
For malignant cells to invade in to surrounding tissues they require:
-
Altered cellular adhesion
- Decreased expression of E-cadherin reduces the cell-cell adhesion.
- Changes to expression of integrin receptors alters the adhesion between cells and extracellular matrix.
-
Increased secretion of proteolytic enzymes
- Matrix metalloproteinases (MMPs) are enzymes secreted by malignant cells to enable them to breakdown surrounding connective tissue.
-
Increased cellular motility
Involves changes in the actin cytoskeleton
In doing so the cell takes on a phenotype more akin to a mesenchymal cell/stromal cell than an epithelial cell and this is epithelial to mesenchymal transition
Effects of neoplasms
- local
- systemic
- paraneoplastic
- hypercalcaemia
- miscellaneous
- *Local effects: LOCATION IS KEY**
1. Direct invasion and destruction of normal tissue
2. Ulceration at a surface leading to bleeding
3. Compression of adjacent structures
4. Blocking tubes and orifices
5. Raised pressure due to tumour growth or swelling (brain)
Systemic effects:
• Increased tumour burden results in a parasitic effect on the host
• Together with secreted factor such as cytokines:
– Reduced appetite and weight loss (cachexia)
– Malaise
– Immunosuppression
– Thrombosis
• Production of hormones
– Usually benign tumours
Paraneoplastic Syndromes:
Some cancer bearing individuals develop signs and symptoms that cannot readily be explained by the anatomic distribution of the tumour or by the production of hormones from the tissue in which the tumour arose.
Affect approximately 10% of people with cancer
Important because:
- May be the earliest manifestation of an occult neoplasm
- Can cause significant clinical problems and be fatal
- Can mimic metastatic disease and confound treatment
Hypercalcaemia:
– Probably the most common
– 2 processes:
• Osteolysis – induced by cancer due to either primary bone lesions such as myeloma or secondary metastases
• Production of calcaemic humoral substances by extraosseous neoplasms
Miscellaneous:
– Neuropathies affecting brain and peripheral nerves
– Skin problems e.g. pruritus and abnormal pigmentation
– Fever
– Clubbing
– Myositis
