Session 8 ILO's Neoplasia 1 Flashcards
Neoplasm
Neoplasm = abnormal growth of cells that persists after the initial stimulus is removed (irreversible)
Dysplasia
Dysplasia = pre-neoplastic alteration in which cells show a disordered tissue organisation (technically reversible)
Tumour
Tumour = a swelling i.e. any clinically detectable lump or swelling
Cancer
Cancer = colloquial term for a malignant neoplasm which is: 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
Metastasis = a malignant neoplasm that has spread from its original site to a new, non-contiguous site
Anaplasia
Anaplasia = cells with no resemblance to any tissue; cells appear primitive and lack specialization along any particular cell line
Pleomorphism
Pleomorphism = variety in cell size or shape (i.e. a large hyper chromatic nucleus with a high nucleus to cytoplasm ratio)
Progression
Progression = process by which a neoplasm arises from monoclonal cells, followed by the accumulation of yet more mutations
Differentiation
Differentiation = the process of becoming different by growth or development
In situ
In situ = no invasion through epithelial basement membrane
Understand, explain and define the terms: neoplasm, dysplasia, tumour, cancer, metastasis, anaplasia, pleomorphism, progression, differentiation and in situ.
Neoplasm = abnormal growth of cells that persists after the initial stimulus is removed (irreversible)
Dysplasia = pre-neoplastic alteration in which cells show a disordered tissue organisation (technically reversible)
Tumour = a swelling i.e. any clinically detectable lump or swelling
Cancer = colloquial term for a malignant neoplasm which is: 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 = a malignant neoplasm that has spread from its original site to a new, non-contiguous site
Anaplasia = cells with no resemblance to any tissue; cells appear primitive and lack specialization along any particular cell line
Pleomorphism = variety in cell size or shape (i.e. a large hyper chromatic nucleus with a high nucleus to cytoplasm ratio)
Progression = process by which a neoplasm arises from monoclonal cells, followed by the accumulation of yet more mutations
Differentiation = the process of becoming different by growth or development
In situ = no invasion through epithelial basement membrane
Describe and understand the difference between in-situ and invasive malignancy.
In-situ = showing all the features of malignancy but no invasion through epithelial basement membrane
Invasive = penetrated through epithelial basement membrane and spreading to non-contiguous sites
Explain how proto-oncogenes are involved in the development of neoplasms (7)
- A proto-oncogene is a normal gene that is found in a cell
- They’re are loads of them and they have multiple different functions
- All these functions participate in some way in the signalling pathways that drive proliferation (growth promoting genes)
- If a mutation occurs in one of these, it can be permanently and abnormally tuned on (even when it is not supposed to be)
- This promotes an excessive increase in its normal function ie growth
- Sometimes a mutation can impart a completely new function on the affected gene
- These are known as gain-of-function mutations
- These changes favour neoplasm formation
Describe the science behind how porto-oncogenes work
- We have a proto-oncogene
- We get a mutation in it
- That forms an oncogene
- That oncogene will encode proteins, known as oncoproteins
- It is those oncoproteins that have the ability to continually promote cell growth in the absence of our normal cell growth promoting signals
- You only need 1 allele to be affected with that mutation for you to have that growth promotion (as oncogenes are dominant over their normal counterparts thus they can transform cells despite a normal copy of the same gene)
Example of Proto-Oncogene mutation
BRAF (v600e) mutation
Describe the normal function of tumour suppressor genes (3)
- Stop cell proliferation
- Help encourage repair damage to cellular DNA
- Cause damaged cells to undergo apoptosis
Explain how tumour suppressor genes are involved in the development of neoplasms
- Normal function is to stop cell proliferation and thus suppress neoplasm formation
- When they become altered or inactivated as a result of mutation, it leads to failure of growth inhibition in cells
- Cells also stop undergoing apoptosis (programmed cell death)
- Tumor supressor genes tend to be recessive, so both alleles have to be damaged in order for the transformation to occur
Explain how proto-oncogenes and tumour suppressor genes are involved in the development of neoplasms
Genetic alterations affect proto-oncogenes and tumour suppressor genes.
Proto-oncogenes become abnormally activated (when they are then called oncogenes), favouring neoplasm formation.
Tumour suppressor genes, which normally suppress neoplasm formation, become inactivated.
Describe and understand the difference between benign and malignant tumours including macroscopic and microscopic features and biological behaviour.
Macroscopic/Microscopic differences:
Benign: (5)
- Cells are uniform throughout tumour
- Normal or mild increase in nuclear to cytoplasmic ratio
- Few mitoses
- Well differentiated (closely resemble parent cell/tissue)
- They have a pushing outer margin
Malignant: (5)
- Cells/nuclei vary in size and shape (pleomorphism)
- High nuclear to cytoplasmic ratio
- Many mitoses including abnormal forms
- Range from well to poorly differentiated(depends on proximity to origin) but in general, failure to differentiate fully
- Irregular outer margin and shape
Biological behaviour :
Benign Tumours: (4) •Grow in a confined local area •Do not produce metastases •Rarely dangerous (location) •Retained functions of their cells of origin
Malignant tumours: (5) •Expansive and invasive •Potential to metastasise •May have ulcerations and necrosis •Infiltrative •Less likely to retain functions of cells of origin and may sometimes acquire unexpected functions due to derangements in differentiation
Understand the reasoning behind the nomenclature given to benign and malignant neoplasms and the exceptions to this rule
Benign - end in ‘oma’ regardless of cell type
Malignant - ends in ‘carcinoma’ (if epithelial) or ‘sarcoma’ (if stromal)
Testicular neoplasms are the exceptions
A malignant tumours of the testis = all end in ‘Oma’
e.g. teratoma and seminoma = malignant
In the ovary, a teratoma is benign (ie dermoid cyst) so rule is not exception in ovaries
Identify the types of cancers that most commonly arise in certain organs and why
- Bladder
- Oesophagus
- Stomach/Bowel
- Skin
- Lung
- Breast/Prostate
- Brain
- Thyroid/Pancreas/Uterus
- Cervix
FIND OUT WHY
- Bladder – transitional cell carcinoma
- Oesophagus – squamous cell carcinoma, adenocarcinoma
- Stomach/Bowel – adenocarcinoma
- Skin – squamous cell carcinoma, malignant melanoma,
basal cell carcinoma - Lung – adenocarcinoma, squamous cell carcinoma, small cell carcinoma
- Breast/Prostate – adenocarcinoma
- Brain –astrocytoma
- Thyroid/Pancreas/Uterus – adenocarcinoma
- Cervix – squamous cell carcinoma
Explain the concept of clonality of neoplasm
Clonality: the concept that a collection of cells is monoclonal if they all originated from a single founding cell.
Neoplastic cells tend to be monoclonal.
Neoplasia is caused by accumulated mutations in somatic cells; mutations are caused by initiators (mutagenic agents) and promoters (cause cell proliferation). Together, initiators and promoters result in an expanded, monoclonal population of mutant cells.
Hall Marks of Malignancy
With worsening differentiation the individual cells have:
- Increasing nuclear size
- Increased nuclear to cytoplasmic size
- Increased nuclear staining (hyperchromasia)
- Increased numbers of mitotic figures
- Abnormal mitotic figures (Mercedes Benz)
- Variation in size and shape of cells and nuclei (pleomorphism)
Recognise the histological characteristics of certain common neoplasms e.g. squamous cell carcinoma, adenocarcinoma, melanoma.
COME BACK TO WHEN IPAD PENCIL WORKS
- We have a proto-oncogene
- We get a mutation in it
- That forms an oncogene
- That oncogene will encode proteins, known as oncoproteins
- It is those oncoproteins that have the ability to continually promote cell growth in the absence of our normal cell growth promoting signals
- You only need 1 allele to be affected with that mutation for you to have that growth promotion (as oncogenes are dominant over their normal counterparts thus they can transform cells despite a normal copy of the same gene)
