Intro to neoplasia Flashcards
Define neoplasia
Process of abnormal (increased) cell proliferation
Define neoplasm
Abnormal mass of tissue due to abnormal cell proliferation
Also known as a tumour
What are the 3 types of neoplasm/tumour?
Benign
Pre-malignant
Malignant (cancer)
Define oncogenesis
process of gradual steps toward tumour development
What is the difference between pre-malignant and malignant tumours?
The basement membrane is still intact and the tumour has not spread to other tissues in pre-malignant
How do we determine if a mass is neoplasia?
Take a sample for histology
What should we examine when determining if a sample is neoplasia?
Organisation of tissue structure
Degree of cellularity
Nuclear to cytoplasmic ratio
Nuclear morphology
Necrosis
Mitotic index
Individualisation of cells
Invasiveness of cells
What is the difference between benign and malignant tumours
Benign tumour = non-invasive
Malignant tumour = invades surrounding tissue
What are the characteristics of benign tumours. Give an example.
Slow-growing mass
Good demarcation from surrounding tissue (capsule)
Does not spread (no metastasis)
Minimal necrosis
Describe the characteristics of malignant tumours. Give an example
Can grow rapidly
Invasiveness to surrounding tissue
Can spread to other sites in body (metastasis)
Increased necrosis
Why does necrosis occur in malignant tumours?
Tumours grow too rapidly for the blood supply to support the centre of the mass => death of cells
Why do tumours often get infected?
Loss of blood supply to centre => no WBCs
What is the cytological criteria of malignancy?
Complete this table comparing the features of benign vs malignant tumour cells
Fill in this table comparing the features of benign and malignant tumours
Which genes control cell proliferation?
Proto-oncogenes - promote proliferation
Tumour suppressor genes - suppress proliferation or induce cell death
How does cell proliferation become dysregulated?
Proto-oncogenes mutate into oncogenes
Oncogenes code for oncoproteins that promote cell division despite absence of promotion signals and presence of normal check point controls to suppress division
Tumour suppressor genes can become mutated so they no longer supress cell division => neoplasia
What factors contribute to oncogenesis?
Genetic
Epigenetic
Environmental
Why does cancer occur more commonly in older patients?
Multiple hit hypothesis - one mutation not enough to cause neoplasia on its own - takes time for mutations to develop and accumulate
What are the hallmarks of cancer cells?
What is carcinogenesis?
Some some of mutation in a cell that causes neoplasia
What is an intrinsic factor of mutagenesis?
Normal by-products of cell metabolism that cause DNA damage
e.g. reactive oxygen species (ROS) a.k.a free radicals
What are some extrinsic factors of mutagenesis?
Describe direct-acting chemical agents that act as an extrinsic factor of mutagenesis
Cause mutagenesis in the form in which they enter the body
e.g. nitrosamines in tobacco smoke
Describe indirect-acting chemical agents that act as an extrinsic factor of mutagenesis
Need to be activated by enzymes in the body to cause mutagenesis (Most important enzyme is cytochrome P450 in the liver)
Also called procarcinogens
e.g. ptaquiloside in bracken fern => bladder tumours in cattle
Describe physical agents as an extrinsic factor of mutagensesis
Cause direct DNA damage and ROS generation - ROS can cause G to T transversion
Key physical agent is radiation
Describe radiation as an extrinsic factor of mutagenesis
All types of radiation are complete carcinogens
- Initiators of oncogenesis
- Also promoters of oncogenesis through continued exposure
Describe ultraviolet radiation (sunlight) as an extrinsic factor of mutagenesis
Ultraviolet radiation (sunlight) causes:
- Pyrimidine dimer formation (results in misreading during transcription)
- ROS generation
Describe the direct mechanisms of oncogenic viruses
Dominant oncogene mechanism
- Mutation in viral gene causes host cells to produce oncoprotein
e.g. Feline leukaemia virus
Insertional mechanism
- No oncogene in virus
- Insertion of viral DNA into host cells activates proto-oncogenes => oncogenes
e.g. Avian leukosis virus
Describe indirect mechanisms of oncogenic mechanisms
Suppress host immune system
e.g. Gallid herpesvirus-2 (Marek’s disease)
Directly stimulate host cell proliferation
e.g. Leporipoxvirus (Squirrel fibroma virus)`
Define metastasis
movement of cancer cells from one tissue or organ to another
Describe the process of metastasis
Cancer cells break away from primary tumour
Cells travel through blood and lymphatic vessels (usually) to new tissues/organs distant from primary tumour
Secondary tumours (metastases) develop in new organs
Define metastases
new cancerous growths at distant sites
Give an example of a highly metastatic and poorly metastatic tumour
Some tumours highly metastatic e.g. melanoma
Some are poorly metastatic e.g. squamous cell carcinoma
Why is it important to identify a tumour when it is small?
Generally- the bigger the tumour, the more likely it is to metastasise
What are the 3 pathways of metastasis?
haematogenous
lymphatic
transcoelomic
Describe the haematogenous pathway of metastasis
Cancer cells travel in blood vessels
Usually thinner-walled veins rather than arteries
Most common route for sarcomas
Ultimately enter lungs and liver
Describe the lymphatic pathway of metastasis
Cancer cells travel in lymphatic vessels
Lymph node(s) closest to the tumour are colonised first
These first lymph nodes develop the largest tumours
Most common route for carcinomas
Describe the transcoelomic pathway of metastasis
Cancer cells spread across the surface of abdominal and thoracic structures
Route used by mesotheliomas and ovarian adenocarcinomas
What are the fundamental steps of metastasis?
Intravasation - into vessels
Extravasation - out of vessels at new site
Colonisation - expansion into macroscopic masses
