Session 9 Flashcards
What is a Malignant Neoplasm?
An abnormal growth of cells that persists after the initial stimulus is removed AND invades surrounding tissue, often in a destructive manner, with potential to spread to distant sites.
What is a Benign Neoplasm?
An abnormal growth of cells that persists after the initial stimulus is removed; growth is autonomous.
What is a Tumour?
Any clinically detectable lump or swelling.
Note: a neoplasm is just one type of tumour. A cancer is any malignant neoplasm.
NOTE: Clinicians may use tumour and malignant neoplasm and cancer synonymously.
What is a Metastasis?
A malignant neoplasm that has spread from its original site to a new non-contiguous site.
The original location is the primary site and the place to where it has spread is a secondary site.
What is meant by Dysplasia?
Pre-neoplastic alteration in which cells show disordered tissue organisation (altered differentiation).
It is not neoplastic because the change is reversible.
Often dysplasia with further altered differentiation can become neoplasia.
Describe the different behaviour benign and malignant neoplasms show
Benign neoplasms remain confined to their site of origin and do not produce metastases.
Malignant neoplasms have the potential to metastasise.
Benign tumours may gain further genetic alterations and become malignant.
Describe the macroscopic features of a benign neoplasm
Benign neoplasms grow in a confined local area and so have a pushing outer margin (grow without destroying surrounding tissue but compress and squash surrounding tissue).
Sometimes a pseudo-capsule forms.
This is why they are rarely dangerous - non-destructive.
Describe the macroscopic features of a malignant neoplasm
They have an irregular, jagged outer margin and shape and may show areas of necrosis and ulceration (if on a surface) because they tend to grow faster than their blood supply can provide.
Malignant tumours infiltrate and destroy the surrounding tissue.
Ulceration is due to the breakage of the epithelium.
As cancer spreads, tumour burden increases - a kg of tumour = very advanced disease, unlikely to be cured.
Metastasis themselves concede more metastasis.
What do neoplasms show under the microscope?
Varying levels of differentiation.
A benign tumour has cells that closely resemble the parent tissue, I.e. they are well-differentiated
Malignant neoplasms range from well to poorly differentiated.
Cells with no resemblance to any tissue are called ANAPLASTIC.
What changes can be seen with worsening differentiation?
Individual cells have increased nuclear size and nuclear to cytoplasmic ratio, nuclear hyperchromasia (abnormal chromatin/DNA - visible due to increased staining of the nucleus), more Mitotic figures and increasing variation in size and shape of cells and nuclei, which is called Pleomorphism.
Clinical use the term ‘grade’ to indicate differentiation, high grade being poorly differentiated.
Dysplasia also represents altered differentiation. Mild, moderate and severe dysplasia indicates worsening differentiation.
In normal tissue, cells are relatively uniform.
What does grading mean?
Generally high grades tend to correlate with a poorer outcome but this is more important/relevant in some cancers e.g. Grading does not really make a difference in skin cancer but is really important in breast cancer.
Describe differentiation in Dysplasia
Altered/abnormal differentiation.
Mild, moderate and severe dysplasia indicates worsening differentiation.
Severe dysplasia, under stimulus, can merge with carcinoma in situ (not yet invaded basement membrane) and then invasive carcinoma (invades basement membrane).
Dysplasia is reversible but neoplasia is irreversible.
What is Neoplasia caused by?
Accumulated mutations in somatic cells.
The mutations are caused by INITIATORs, which are mutagenic agents, and PROMOTERs, which cause cell proliferation.
In combination, initiators and promoters result in an expanded, monoclonal (all derived from the same parent cell) population of mutant cells.
Chemicals, infections particularly certain viruses, and radiation are the main initiators but some of these agents can also act as promoters.
In some neoplasms, mutations can be inherited rather than from an external mutagenic agent.
A neoplasm emerges from this monoclonal population through a process called progression, characterised by the accumulation of yet more mutations.
Which is more important, extrinsic factors (environment) or intrinsic (genetic) factors?
Environment plays a large role - ~85% of cancer risk is due to environment/extrinsic factors.
In a germ-line mutations, neoplastic cells get a head start because the mutation is present in all cells.
How do we know neoplasms are monoclonal?
A collection of cells is monoclonal if they all originated from a single founding cell.
Evidence that neoplasms are monoclonal came from the study of the X-linked gene for the enzyme glucose-6-phosphate dehydrogenase (G6PD) in tumour tissue from women.
The gene has several alleles encoding different isoenzymes. Early in female embryogenesis one allele is randomly inactivated in each cell (Lyonisation).
In heterogenous women that happen to have one allele encoding a heat stable isoenzyme, and one allele a heat labile isoenzyme, normal tissues will be patchwork of each type. However neoplastic tissues only express one isoenzyme indicating a monoclonal group of cells.