8. Neoplasia 1 & 2 Flashcards
Define neoplasia
An abnormal growth of cells that persists after initial stimulus is removed
Define dysplasia
Abnormal maturation of cells within a tissue - disordered. Preneoplastic.
What is a malignant neoplasm?
Cancer - abnormal growth of cells that persists after initial stimulus is removed…and invades surrounding tissue with potential to spread to distant sites.
What is the difference between a benign neoplasia and a malignant neoplasm?
Benign remain at site of origin
Malignant have metastasise potential
What does anaplastic mean and when is it seen?
No resemblance of tissue, in very poorly differentiated cancers cells.
How would you expect a benign neoplasm to look macroscopically?
Pushing outer margin
How would you expect a malignant neoplasm to look macroscopically?
Irregular outer margin
Ulceration
Necrosis
How would you expect benign and malignant tumours to differ microscopically?
Benign - well-differentiated
Malignant - worsening differentiation, anaplasia
What is an in situ malignancy, how does it differ from invasive?
In situ = no invasion of basement membrane
Invasive = penetrated basement membrane
What does the grade of a tumour measure?
Differentiation
What 3 things are considering when determining the grade of a tumour?
Nuclear size
Nuclear:cytoplasmic ratio
Mitotic figures
What will a high grade tumour look like?
Poorly differentiated. Large nuclei High NC ratio Hyperchromasia (increased nuclear staining) More mitotic figures Pleomorphic
What is another name for mutagenic agents.
Initiators
In addition to initiators, what else is required to cause neoplasia?
Promotors over a period of time
What type of expansion is seen in neoplasia?
Monoclonal - from same founding cell
Why might some mutations have no effect?
Non-coding regions, unimportant genes
What is an example of an internal promotor?
Inflammation
What is progression?
The accumulation of further mutations which leads to the emergence of a neoplasm from monoclonal population
Which genes become abnormally activated in neoplasms?
Proto-oncogenes
Which genes become inactivated in neoplasms?
Tumour suppressor genes
Which genes only require one allele to be affected in order to promote neoplasia?
Proto-oncogenes - one allele activate will be enough to drive the cell cycle and promote growth
If one allele of a TSG is mutated, what effect will it have?
None. Both alleles must be inactivated in order to result in increased growth.
What is an adenoma?
benign glandular neoplasm
What is a papilloma?
Benign neoplasm of squamous epithelium- skin and mucosa
Finger-like projections
What is an adenocarcinoma?
Cancer of glandular tissue
What 3 steps must a tumour go through in order to metastasise?
- Grow and invade at primary site
- Enter a transport system and lodge at a secondary site
- Grow at the secondary time to form a new tumour
Explain why the process is inefficient?
Many cancer cells are destroyed in the blood stream by shear forces while others reach the secondary site but are unable to grow there.
What 3 important alterations are needed for tumour invasion?
- Altered adhesion
- Altered proteolysis
- Altered motility
What is the name given to the process which changes a carcinoma phenotype to appear like a mesenchymal cell?
Epithelial-to-mesenchymal transition (EMT)
Explain how adhesion alters in a cancer cell to promote metastases.
Reduction in E-cadherin expression (cell-cell) and changes in integrin expression (to stroma)
Which protease is expressed by cancer cells to degrade basement membranes and stroma?
Matrix metealloproteinases (MMPs)
What is a cancer ‘niche’ and how can it be advantageous to the cancer cells?
The cancer cells take advantage of nearly non-neoplastic cell types which produce some growth factors and proteases.
What protein is involved in increasing motility of cancer cells?
Actin
What are the 3 transport routes for cancer cells?
- Blood vessels via capillaries and venues
- Lymphatic vessels
- Transcoelomic spread in body cavities - pleura,peritoneal,pericardial
What is colonisation?
Growth at a secondary site to form a metastasis.
What are micro-metastases and why are they significant?
Surviving microscopic deposits of cancer cells that fail to grow at secondary site, are sub-clinical and not detected in scans.
= tumour dormancy, can initiate relapse years later
What 3 factors are thought to help micro-mets remain dormant?
Immune attack
Reduced angiogenesis
Hostile secondary site
What 2 theories are there which explain the secondary site of a metastasis?
- Regional drainage
2. ‘Seed and soil’ phenomenon
According to regional drainage, where are blood-borne metastasis likely to spread to?
The next capillary bed that the cells encounter - lung and liver
According to regional drainage, where are lymphatic metastasis likely to end up?
Local lymph nodes
Where are cancers that spread by transcoelemic spread likely to end up?
Other areas in the coelomic space or adjacent organs
What is the ‘seed and soil’ phenomenon?
The site of metastasis is due to interaction between malignant cells and the local tumour environment (niche) at the secondary site.
Which cancers spread to lymphatics first?
Carcinomas
Which cancers spread via the blood stream?
Sarcomas
What are the common sites of blood borne metastasis?
Lung, bone, liver and brain
Which neoplasms most frequently metastasise to bone?
Thyroid, Kidney, Lung, Prostate and breast
Which type of lung cancer is very aggressive and tend to metastasise very early?
Small cell bronchial carcinoma
Which skin cancer almost never metastasises?
Basal cell carcinoma
What are the local effects of neoplasms (both benign and malignant)?
- Pressure/compression
- Invasion and destruction
- Ulceration and bleeding
- Obstruction/blocking of tubes and orifices
What are paraneoplastic syndromes?
Systemic effects of neoplasms
What are the main categories of systemic effects of neoplasms?
- Tumour burden
- Endocrine
- Haematological
- Neurological
- Dermatological
- General
What is tumour burden?
Increased number of cancer cells results in increased number of metabolically active cells and has a parasitic effect on the host.
What symptoms can an increased tumour burden lead to?
reduced appetite, cachaxia, malaise, immunosuppression, thrombosis
Which tumours typically produce hormones?
Benign neoplasms of endocrine glands as they are well differentiated
Give an example of a malignant tumour that is known to secrete hormones.
Bronchial small call carcinoma may secrete ACTH and ADH
What is exophytic growth?
Growth outwards e.g protruding into lumen
What is endophytic growth?
Growth inwards e.g proliferating in the interior of an organ
Why are polyps removed?
tend to benign adenoma’s initially but demonstrate dysplastia so can accumulate mutations to progress to a carcinoma.
What is a common tumour of the uterus smooth muscle cells of the myometrium?
Fibroid
At what age do osteosarcoma’s commonly present?
Teenagers (<20)
What is a teratoma, why does it contain such a range of tissues?
Germ cell tumour - arises from all 3 germ cell lines: ectoderm, endoderm and mesoderm.
How do ovarian and testicular teratomas behave differently?
Ovarian tend to be benign, testes tend to be more malignant
What are common tumours of soft tissue?
Lipomas and leiomyomas
What are malignant tumours of soft tissue referred to as?
Sarcomas
Which organ is recognised as a site of metastasis from gastric cancer?
Ovaries
What hormone can testicular teratomas produce?
HCG
