Introduction to neoplasia Flashcards
Define neoplasia
Process of abnormal cell proliferation
Define neoplasm
Abnormal mass of tissue due to abnormal cell proliferation
(AKA tumour)
What are the 3 types of neoplasm/tumours
Define oncogenesis
Process of gradual steps towards tumour development
What is the difference between pre-malignant and malignant tumours?
in pre-malignant tumour basement membrane is still intact & tumour has not spread to other tissues
How do we determine if a mass is neoplasia?
Take a sample for histology
What should we examine in a histological sample to look for neoplasia
Organisation of tissue structure
Degree of cellularity
Nuclear to cytoplasmic ratio
Nuclear morphology
Necrosis
Mitotic index
Individualisation of cells
Invasiveness of cells
How do you differentiate between a benign vs malignant tumour?
What are some characteristics of benign tumours
Slow-growing mass
Good demarcation from surrounding tissue (capsule)
Does not spread (no metastasis)
Minimal necrosis
What are some characteristics of malignant tumours
Can grow rapidly
Invasiveness to surrounding tissue
Can spread to other sites in body (metastasis)
Increased necrosis
Fill in the table of features of benign vs malignant tumours
Why does necrosis often occur in malignant tumours?
Tumours grow too rapidly for blood supply to support 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
Fill in the table with features of benign vs malignant tumour cells
Which genes control cell division/proliferation?
Proto-oncogenes - promote proliferation
Tumour suppressor genes - suppress proliferation or induce cell death
(dysregulation of these mechanisms = neoplasia)
How does cell proliferation become dysregulated?
- Proto-oncogenes mutate into oncogenes
- Oncogenes code for oncoproteins that promote cell division despite:
- absence of promotion signals
- presence of normal check point controls to suppress division
Tumour suppressor genes can become mutated so they no longer suppress cell division => neoplasia
What factors contribute to oncogenesis?
Genetic factors
Epigenetic factors
Environmental factors
Why does cancer occur more commonly in older patients?
Multiple hit hypothesis - 1 mutation not enough to cause neoplasia on its own - takes time for mutations to develop & accumulate
What are the hallmarks of cancer cells?
What is mutagenesis/carcinogenesis?
Initiating factor(s) causing genetic change
This genetic change makes cells more likely to divide in uncontrolled way in right conditions
Caused by intrinsic and extrinsic factors
define mutagen & carcinogen
Mutagen = agent that damages DNA
Carcinogen = mutagen that causes neoplasia
All carcinogens are mutagens, but not all mutagens are carcinogens
What are the intrinsic factors 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 the extrinsic factors of mutagenesis?
Environmental agents
- Chemical
- Physical
Oncogenic viruses
Describe direct- vs indirect-acting chemical agents that act as extrinsic factors of mutagenesis
Direct-acting
- Cause mutagenesis in form in which they enter body
- e.g. nitrosamines in tobacco smoke
Indirect-acting
- Need to be activated by enzymes in 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 that act as extrinsic factors of mutagenesis
Cause direct DNA damage & ROS generation
- ROS can cause G to T transversion
Key physical agent is radiation
- All types of radiation are complete carcinogens
- Initiators of oncogenesis
- Also promoters of oncogenesis through continued exposure
Describe ultraviolet radiation (sunlight) as an (physical agent) extrinsic factor of mutagenesis
Ultraviolet radiation (sunlight) causes:
- Pyrimidine (C &T) 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 the indirect mechanisms of oncogenic viruses
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/organ to another
(key feature of malignancy)
Describe the process of metastasis
Process can take years, but can also be rapid
- Cancer cells break away from primary tumour
- Cells travel through blood & lymphatic vesselsto new tissues/organs distant from primary tumour
- Secondary tumours (metastases) develop in new organs
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 tumours when they’re small?
Generally- the bigger the tumour, the more likely it is to metastasise
What are the pathways of metastasis
Haematogenous
- Cancer cells travel in blood vessels
- Usually thinner-walled veins rather than arteries
Lymphatic
- Cancer cells travel in lymphatic vessels
- Lymph node(s) closest to tumour are colonised first
- These first lymph nodes develop largest tumours
Transcoelomic- less common
- Cancer cells spread across surface of abdominal & thoracic structures
What are the fundamental steps for metastasis
Intravasation
Extravasation
Colonisation
