Tumour Pathology Flashcards
What is a tumour?
Abnormal growing mass of tissue
Uncoordinated with surrounding normal tissue
Growth continues after stimulus removal, meaning it is an irreversible change
What are benign tumours of the glandular epithelium/squamous epithelium called?
Adenoma/Squamous papilloma
Malignant of glandular epithelium/squamous epithelium?
Adeno-carcinoma/Squamous carcinoma
Benign of bone/fat/fibrous tissue?
Osteoma/Lipoma/Fibroma
Malignant of bone/fat/fibrous tissue?
Osteo-sarcoma/Lipo-sarcoma/Fibro-sarcoma
What are tumours of the white blood cells/lymphoid tissue called?
Leukaemia/Lymphoma
Tumours of the CNS/PNS?
Astrocytoma/Schwannoma
Tumours of the germ cells?
Ovarian teratoma (usually benign) Testicular treatoma (usually malignant)
Give features of benign tumours
Non-invasive growth Well differentiated Encapsulated No metastases Rarely cause death
Give features of malignant tumours
Invasive growth Poorly differentiated Not encapsulated Metastases present Frequently cause death
Give feature of cancer cells
- altered genetics (tumour suppressor genes and oncogenes)
- altered cellular function (caused by tumour-related proteins)
- abnormal morphology
- loss of cell/cell and cell/matrix adhesion (for movement)
What are tumour related proteins?
Biomarkers whose presence predict the type of cancer present/prognosis/appropriate therapy
How is the presence of tumour biomarkers detected?
A specific cancer drug will only work when the biomarker is active in the body
Give some examples of tumour biomarkers and the cancers they can be used to predict
Kras - colorectal EGFR - lung Her2 - breast/gastric Braf - melanoma Alpha-fetoprotein - testicular/liver
What is angiogenesis?
Formation of new blood vessels to supple the tumour
Provides a mechanism for metastasis
What is metastasis?
Spreading of cancer cells following capsule degradation and transport in the blood/lymph
What is the term given to the special spread of cancer across a body cavity?
Trans-coelomic spread
What are common sites of metastasis?
Places of high blood flow;
Liver/lungs/brain/axial skeleton
What are uncommon sites of metastasis?
Spleen/heart/kidney
Where do the following tumours specifically metastasise to?
Breast
Colorectal
Prostate
Bone
Bone
Liver
What are the local effects of benign tumours?
Pressure and obstruction
What are the local effects of malignant tumours?
Pressure
Obstruction
Tissue destruction (ulceration and infection)
Bleeding (anaemia and haemorrhage)
Pain (pressure on nerves/pathological bone fractures)
What are the systemic effects of malignant tumours?
Normal and abnormal hormone secretion
What is ‘normal’ hormone secretion in relation to the systemic effects of malignant tumours?
Secretion by cancer cells where it is normally expected in physiology, but at an abnormal level
What is ‘abnormal’ hormone secretion in relation to the systemic effects of malignant tumours?
Secretions of unexpected origin; e.g. ADH/ACTH
What is dysplasia?
a pre-malignant change (organ/tissue enlargement), the earliest change in the malignancy process that can be detected
- in epithelium
- no invasion
- can progress to cancer
Give some features of dysplasia?
Increased nuclear size
Increased mitotic activity
Abnormal mitoses
How is the cell cycle externally controlled?
by:
- hormones
- growth factors
- cytokines
- stroma
How is the cell cycle intrinsically controlled?
by restriction points (R)
When does external control of the cell cycle occur?
before the restriction point
How is the cell cycle controlled after the restriction point?
autonomous control
What happens during the G0 stage of the cell cycle?
resting phase, no division occurring
G1 stage?
- cells increase in size
- G1 checkpoint control occurs
S stage?
DNA replication occurs
G2 stage?
- cells continue to increase in size
- G2 checkpoint control occurs
M stage?
- no more cell growth
- mitosis occurs
- metaphase checkpoint control occurs (to ensure cell is ready to complete division
What causes G1 to stop?
- inadequate cell size
- inadequate nutrient supply
- no external stimuli present
- DNA damage isn’t detected
What causes G2 to stop?
- inadequate cell size
- DNA damage isn’t detected
What causes S to stop?
- DNA isn’t replicated
What causes M to stop?
- chromosomes mis-align
What are checkpoints?
- cyclically active/inactive enzymes (CDK/cyclin complex)
- catalytic sub-units activated by regulatory sub-units
What are the catalytic sub-units called?
Cyclin-dependent kinases (CDKs)
What are the regulatory sub-units called?
Cyclins
What is the function of the CDK/cyclin complex?
- phosphorylates target proteins
- causes activation/inactivation of substrates
- regulates the next phase in the cell cycle
How are CDKs expressed?
constitutively in inactive form
What happens to cyclins in the cell cycle?
accumulate and are destroyed as the cycle progresses
What is the function of the retinoblastoma gene?
- encodes pRb (phosphoprotein) in almost every cell
- pRb is hypophosphorylated by CDK/cyclin complexes
- E2F transcription is inactivated by Rb
What is the function of active E2F?
- activates viral target genes
- stimulates cell cycle entry (potent; leads to cancer)
What causes carcinogenesis?
- mutation of genetic material that unbalances proliferation and apoptosis
- in genes that regulate division/apoptosis/DNA repair
- uncontrolled proliferation leads to cancer
How can this genetic damage occur?
- environmental
- inherited
How does environmental genetic damage occur?
- chemicals
- radiation
- oncogenes
How can chemicals give rise to carcinogenesis?
- DNA bases damaged by oxidising and alkylating agents
- chemical carcinogens/active metabolites react with DNA to form DNA adduct (covalent bonds)
- adducts at certain chromosomes can lead to cancer
How can radiation give rise to carcinogenesis?
- damages DNA bases
- when received in high doses e.g. UV rays/X-rays/Gamma radiation
What two pathways can carcinogenesis disrupt?
- cyclin D-pRb-E2F pathway (retinoblastoma)
- p53 pathway
What is the physiological function of p53?
- usually present in higher levels in damaged cells
- stops cell cycle at G1
- facilitates DNA repair/induces apoptosis
