Pathology - Neoplasia Flashcards
What is the pathological definition of cancer?
Uncontrolled cell proliferation and growth that can invade other tissues
What is a tumour?
A growth
What is a neoplasm?
A new growth which is not in response to any stimulus
What does malignant mean?
Metatastic potential
Invaded through the basement membrane
What dies metastases mean?
Spread to other sites through blood or lymphatics
What is dysplasia?
Disordered growth
No invasion of basement membrane
What is carcinoma in-situ?
Dysplasia affecting the whole of the epithelium
Still no invasion at this point - last stage before invasion
What is metaplasia?
Change form one the of mature epithelium to another
Usually in response to injury
Why are sites of metaplasia associated with cancer?
The epithelium is changing and constantly being damaged, and so is unstable
This makes it more likely to undergo dysplasia
How is hyperplasia associated with cancer?
Can become autonomous and no longer require a stimulus (uncontrolled growth)
Why are obese individuals more prone to cancer (e.g. endometrial cancer)?
Structure of steroid hormones is similar to cholesterol
Although women stop producing oestrogen post-menopause, cholesterol can still act as a stimulus for endometrial growth
if growth becomes permanently switched on, cancer risk increases
What factors can contribute to cancer?
Inherited predisposition Chemicals Radiation Infections Inflammation Lifestyle factors
What is the double hit hypothesis?
One working gene is enough
Two faulty copies will result in functional problem
Why are people with an inherited predisposition more t risk?
If you have already inherited one faulty copy of a gene, you will be at increased risk (“one hit left”)
What chemicals can cause cancer?
Smoking carcinogens = Lung, bladder, head and neck, cervical (alongside HPV)
Aflatoxin (fungus on peanuts) = Liver
Beta-naphthylamine (chemical dyes) = Bladder
Nitrosamines (food preservatives)
Arsenic
How does UV radiation cause cancer?
UVB
Causes DNA damage. Initially, this can be repaired, but on repeat exposure the mechanisms are overwhelmed
What kinds of radiation exposure can cause cancer?
UV
Atomic Bombs (high incidence of leukaemia in Japan)
X-Ray/CT
Which method of imaging gives highest risk of radiation exposure?
CT
More susceptible to leukaemias and thyroid cancers
Which viruses are know to cause cancers?
HPV = Cervical cancer, head and neck cancers EBV = Burkitt-lymphoma, B-cell lymphomas, Hodgkin lymphoma, Nasopharyngeal carcinoma
How does chronic inflammation cause cancer?
Must be very long term and intense
Causes many lymphomas due to constant lymphocyte reproduction - this may lead to errors
Other tumours can be caused as the tissue is replicating so often it becomes unstable
Often in the context of metaplastic change (e.g. permeant catheterisation, chronic gastritis etc.)
What are the four main groups of cancer development?
Oncogenes - Promote growth
Destroy tumour suppressors - Avoid inhibition of growth
Evade apoptosis - Avoid death
Spell checkers - Turned off by malignant cells. Allows accumulation of mutation and allows these to evade apoptosis
What is MMP (matrix metalloproteinases)?
Substances produced by malignant cells to digest connective tissue
What is angiogenesis?
The ability of tumours to create their own blood supply
Tumours often have mutations which allow them to produce proteins encouraging new vessel growth
e.g. vascular endothelial growth factor, platelet derived growth factor
What are the three stages of cancer development?
Initiation
Promotion
Persistance
What does the initiation stage involve?
A mutation to one of the four main groups
This is where the first mutation is acquired, and involves single cells/groups of cells
What does the promotion stage involve?
Further accumulation of mutations
Additive effect = increased growth
Often results in “pre-malignant” phase i.e. dysplasia
What does the progression stage involve?
Cell has developed mutations that allows to grow autonomously and unregulated
Cell has also developed the ability to invade connective tissue and blood vessels
MALIGNANCY
What are oncogenes?
Genes which promote cell growth
In cancer, these are generally unregulated and cells received uncontrolled growth signals
What are the three categories of growth receptors?
Receptors with intrinsic tyrosine kinase activity
7 transmembrane G protein-coupled receptors
receptors without intrinsic tyrosine kinase activity
What is Myc?
One of the last points in the MAPK/ERK pathway
Nuclear transcription factor that promotes growth
Common in lymphoma, neuroblastoma, SCC in the lung
What is PI3K?
Most commonly mutated kinase in cancer
Give an example of cancer caused by a mutation to a 7 transmembrane G protein-coupled receptor pathway?
Wnt/APC/beta catenin
APC is one of the first mutations in colorectal cancer
Give an example of a mutation to a non-intrinsic TK receptor pathway causing cancer?
JAK-STAT
JAK2 mutations can cause leukaemia and some lymphomas
What are tumour suppressor genes?
Lots of proteins that inhibit cell cycle
p53 is most commonly mutated in cancers
What roles does p53 play in the cell cycle?
Cell cycle arrest when abnormalities sensed
Induced apoptosis if DNA repair not possible
Other than p53, give examples of tumour suppressor genes and conditions they give rise to when mutated?
von-Hippel Lindau = VHL syndrome, renal cancers
PTEN = Inhibits PI3K/AKT pathway, giving uncontrolled proliferation
Give examples of DNA repair genes?
MLH1, MLH2, PMS1, PMS2, BRCA1, BRCA2
Which gene is anti-apoptotic and which type of cancer can it caused when switched on?
Bcl2
Lymphoma
How is a benign tumour likely to appear?
Round, symmetrical, homogenous, encapsulated
Due to slow growth, likely to be larger with unbroken skin
How is a magnet tumour likely to appear?
Irregular, heterogenous, haemorrhages, necrosis
What is the histopathology of a benign tumour?
Low N:C ratio
Regular shape, size, colour etc.
Well differentiated
What is the histopathology of a malignant tumour?
High N:C ratio
Pleomorphism (different shapes, size, colour etc.)
Poorly differentiated
Hyperchromasia (more DNA so much darker)
From which group is a tumour found in a child likely to belong to?
Mesenchyme
Leukaemia
CNS
What is the general name for cancer of the epithelium?
Carcinoma
What are the names for benign and malignant glandular epithelial cancers?
B = Adenoma M = Adenocarcinoma
What are the names for benign and malignant squamous epithelial cancers?
B = Papilloma M = Squamous Cell Carcinoma
What is the name for malignant bladder epithelial cancer?
Transitional cell carcinoma
aka, urothelial cell carcinoma
What is the general name for cancers of the mesenchyme?
Sarcomas
What are the names for benign and malignant fat cancers?
B = Lipoma M = Liposarcoma
What are the names for benign and malignant bone cancers?
B = Osteoma M = Osteosarcoma
What is the names for benign cartilage cancer?
Enchondroma
What are the names for benign and malignant skeletal muscle cancers?
B = Rhabdomyoma M = Rhabdomyosarcoma
What are the names for benign and malignant smooth muscle cancers?
B = Leiomyoma M = Leiomyosarcoma
What is the name for benign nerve cancer?
Neurofibroma
What are the names for benign and malignant blood vessel cancers?
B = Haemangioma
M = Angiosarcoma
Kaposi’ sarcoma (caused by HPV, common in AIDs patients)
How are CNS cancers defined?
Graded on severity of malignancy
How are blood cancers defined?
Technically they are all malignant
What is the stage of a tumour?
The level of metastases
What is the grade of a tumour?
The level of differentiation
