43.1 Pathology of Neoplasia Flashcards
Describe the characteristics of benign tumours.
- Loss of growth control
- Limited to the site of origin, often encapsulated
- Clinical signs related to the occupying space or due to production of hormones/active molecules
- Often cured by surgery
Describe the characteristics of malignant tumours.
*Invasion
*Metastasis
*Progression
*Aberrant differentiation
*Pleomorphism and anaplasia
*Distinct from benign tumours
What is the difference in level of differentiation between benign and malignant tumours?
- Benign: well-differentiated, closely resemble normal structure and function (just high numbers of cells)
- Malignant: wide range of differentiation with significant alterations - such as different cell and nucleus sizes, hyperchromatic nuclei, loss of polarity
What are the examples of benign tumours that you need to know?
- Papilloma (warts) -> Epithelial tumour
- Gliomata -> Glial cell tumour (CNS)
- Adenoma (e.g. colonic polyps) -> Glandular tumour
- Leiomyoma (e.g. uterine fibroids) -> Smooth muscle tumour
- Lipoma -> Fat cell tumour
What are the examples of malignant tumours that you need to know?
- Squamous cell carcinoma -> Skin tumour
- Adenocarcinoma -> Glandular tumour
What are the potential damaging effects of benign tumours?
- Bleeding
- Pressure
- Endocrine toxicity (if glandular tissue affected)
- Possible progression to malignancy
How can glioma be harmful?
- Cause intracranial hypertension and headaches
- Impact local structures e.g. compress optic nerve –> visual disturbances
- Affect connectivity –> seizures
What % of deaths from cancer are caused by benign primary tumours?
10%
What is a benign tumour?
A local growth of cells that does not invade nearby tissues
What is a glioma?
A tumour of the glial cells in the CNS (astrocytes, oligodendrocytes, ependymal cells)
What is a leiomyoma? Give a specific example
A smooth muscle tumour
Uterine leiomyoma –> uterine fibroids
What is a papilloma?
A tumour of the skin usually derived from the keratinocytes in the stratum basale
= Wart
What is an adenoma? Give two specific examples
Arenal adenoma (Cushing’s disease)
Colonic polyps
What is lipoma?
Tumour of fat cells
Why do benign tumours not invade local tissues?
They are confined within a rim of compressed fibrous tissue (capsule)
They are confined within a rim of compressed fibrous tissue (capsule)
Grow into blood vessels –> rupture them
How does a malignant tumour cause local infection?
Local modulation of immune system, loss of protective structures such as barriers
Makes nearby structures more susceptible to infection
How does a tumour cause intussusception?
Tumour obstructs lumen, weight causes abnormal folding
Tumour serves as the leading edge of the fold
How does cancer cause anaemia?
Involves inflammation that reduces RBC production
What are examples of local effects of malignant tumours?
Direct:
- Pressure on other structures
- Occupation of space (e.g. intra-thoracic or intra-cranial)
- Obstruction of vessels/ducts
Indirect:
- Intussusception of gut
- Haemorrhage
- Infection
What is intussusception of the gut?
When part of the gut slides into another - like a crumpling sock
What are examples of systemic effects of malignant tumours?
- Cachexia (weight-loss, nausea, anorexia, lethargy)
- Hormonal effects
- Marrow destruction (leukaemias) leading to neutropenia –> infection, Bleeding (thrombocytopenia), or anaemia.
What are the hormonal effects that can be caused by malignant tumours?
Over-secretion, ectopic secretion (e.g. ACTH release from tumours in lungs), or destruction of endocrine tissue.
What is pleomorphism?
- The variability in the size, shape and staining of cells and/or their nuclei.
- Several key determinants of cell and nuclear size, like ploidy and the regulation of cellular metabolism, are commonly disrupted in tumours.
What is anaplasia?
- A condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to each other and to endothelial cells.
- This is a feature of malignant tumours.
- In other words, the cells become less differentiated in tumours.
What is invasion of tumours? Do all tumours do it?
[IMPORTANT]
- The direct extension and penetration by cancer cells into neighbouring tissues.
- It is a characteristic of malignant tumours.
What is meant by infiltration and permeation in cancers?
- Infiltration -> Spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues.
- Permeation -> Spread of cancer cells in continuous columns within the lymph vessels.
What is the benign to malignant transformation?
Benign → malignant transformation: Malignant acquire invasive, aggressive phenotype.
*Accumulation of more mutations (from genome instability/ loss of checkpoint reg etc)
*Benign → confined to origin site
*Malignant → rapid growth/ invasion/ destruction of surroundings.
- May metastasise + form 2o tumours.
How may an organ/tissue be made favourable for metastatic extravasation?
- Exosome delivery –> regulatory molecules that send many signals to recipient cells at once
- Growth factor release
- Cytokine release –> inflammation, immunosuppression
Overall: angiogenesis, vascular permeability, reprogrammed energy metabolism, modulated immunity, induced EMT
What are adenocarcinomas? Give examples
Tumours of specialised cells of epithelia that secrete substances into ducts or cavities
Examples:
lung, colon, breast, pancreas, stomach, ovary, prostate
What are squamous cell carcinomas? Give examples
Tumours of epithelial sheets that protect a cavity or channel and the underlying cell populations
Examples:
skin (keratinocytes), nasal, lung, oesophagus, cervix
What are micrometastases?
Small metastatic deposits that stay dormant for months/years
What are the four key features of malignant tumours that benign tumours do not have?
- Dedifferentiation (anaplasia)
- High rate of growth
- Local invasion
- Metastasis
What are the most common sites of secondary tumours?
- Lungs
- Liver
- Lymph nodes
- Bones
- Brain
- Skin
What are the three routes of metastasis?
- Grow directly into surrounding tissue (infiltration)
- Travel through bloodstream to distant locations
- Travel through lymph system to nearby or distant lymph nodes
What are the two events after local invasion?
Intravasation (entry into circulation)
Extravasation (leaving circulation)
Explain the seed and soil hypothesis of metastasis. What are its shortcomings?
(Paget, 1889):
- The theory that metastatic tumor cells will metastasise to a site where the local microenvironment is favorable, similar to how a seed grow only if it lands on fertile soil.
- This has been shown to be largely true and we now know that endosomes released by tumour cells can influence which sites in the body become favourable for metastasis development (see flashcards).
- However, the theory does not account for why the contralateral organ is rarely a site of metastasis (e.g. one lung to the other), since it would be
Summarise the main theories about what determines the location of metastatic tumour formation.
- Seed and soil hypothesis -> The theory that metastatic tumor cells will metastasise to a site where the local microenvironment is favourable. How favourable a site is is largely determined by exosome release (from tumour cells), which bind to a specific tissue based on their integrins and create a pre-metastatic niche there.
- Mechanical mechanisms hypothesis -> The theory that patterns of blood flow determine the site of tumour formation.
Neither of these can fully explain trends for all metastatic tumours seen clinically, so it is likely that both contribute somewhat.
What is the half-life of a circulating tumour?
1-2.4 hours
What is the key event to allow local invasion?
*Remodelling of b.membrane enables invasion
- Due to protease secretion (e.g. MMP) + changes in cell-cell/ matrix adhesion molecules.
*EMT = key phenotype switch allowing cancer cells to detach from 10 tumour + intravasate into lumen of blood/ lymphatic vessel.
What is thrombocytopenia?
Low platelet count
Which processes permit tumour extravasation?
- Adhesion molecules
- Local thrombin proteolysis which retracts the endothelial membrane - allows tumour cells through
- Local proliferation and secretion of proteases - can lead to eventual membrane rupture
Why are certain sites more common for secondary tumour growth?
More easily reachable from the primary tumour
Why are micro-metastases not destroyed by antimitotic chemo- or radiotherapy?
They are negative for markers of replication
Why do most metastatic tumours die before extravasation?
- High shear forces in circulation
- Loss of cell-cell contact; less signalling etc
Why is spread via lymphatics more likely than via blood vessels?
Less shear force
Is metastasis always the same?
It is common and serious, but variable
How can immunodeficiency give an increased risk of digestive tract tumours?
- More likely to get chronic infections of H. pylori - which is potentially carcinogenic
- H. pylori induces upregulation of oncogenes and silencing of tumour suppressor genes
- Also generates inflammatory response - that releases ROS that induce DNA breaks
- Increased levels of nitrate –> promotes progression to intestinal metaplasia/dysplasia
How can immunodeficiency give an increased risk of lymphomas?
- More likely to get infections that increase risk of developing lymphoma - e.g. HIV, which invades lymphocytes and may cause DNA changes
–> increases risk of Burkitt lymphoma, Hodgkin lymphoma, and more - More likely to get infections that make immune system overactive and make too many lymphocytes
How can immunodeficiency give an increased risk of virus-associated tumours?
More likely to get infected by potentially carcinogenic viruses
How do lymphomas cause immunodeficiency/suppression?
- Lymphocytes are growing rapidly and lose normal function
- Take up space in bone marrow so there are less other types of immune cells too
- Lymphoma cells use excessive energy –> affects general immune system’s ability to work well
What % of global cancer burden is attributable to viral infection?
15%
What are examples of virus-associated tumours?
- Cervical carcinoma (HPV)
- Kaposi’s sarcoma (HHV-8)
- Hepatocellular carcinoma (HBV)
Which three types of tumours are at a higher risk of developing when a person has immunodeficiency or immunosuppression?
- Lymphomas
- Digestive tract tumours
- Virus-associated tumours
Which type of carcinomas is there an immunisation program in the UK for?
Papilloma-associated carcinomas…
Cervical carcinoma
Ano-genitcal carcinomas
Head and neck squamous cell carcinoma
Generally, what is the ending for the names of mesenchymal malignant tumours?
-sarcoma
Generally, what is the ending for the names of parenchymal malignant tumours?
-carcinoma
Generally, what is the ending for the names of parenchymal or mesenchymal benign tumours?
-oma
Give examples of mesenchymal benign tumours
Fibroma, lipoma, chondroma, osteoma
Give examples of mesenchymal malignant tumours
Fibrosarcoma, liposarcoma, chondrosarcoma, osteosarcoma
Mesenchymal refers to…
Connective tissue
Parenchymal refers to…
epithelium
What is the term for a benign glandular epithelial tumour?
Adenoma
What is the term for a benign surface epithelial tumour?
Papiloma
What is the term for a malignant glandular epithelial tumour?
Adenocarcinoma
What is the term for a malignant surface epithelial tumour?
Carcinoma
What is the term for benign OR malignant bone marrow tumours?
Leukaemia
What is the term for benign OR malignant lymphoid tumours?
Lymphoma
