Neoplasia.- “A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change
Differentiation – the degree to which a cell becomes specialised. Undifferentiated cells have potential to become a variety of different cell types.
Anaplasia. – undifferentiated cells
Pleomorphism. – variation in size and shape of cells and nuclei
Dysplasia – abnormal change in cell type – increased mitoses, abnormal nuclear morphology, loss of polarity
Grading – extent of differentiation and number mitoses to give an indication of likely behaviour, aggressiveness, speed of growth
Staging.- description of neoplasm based on the size of primary tumour and degree of local or metastatic spread. Has implication for mode of treatment.
Metaplasia – change in cell type, reversible eg barretts oesophagus(squamous to columnar).
Metaplasia can reverse, the cell can lose its normal protective function, the persistent irritant that causes the metaplasia may initiate a malignant transformation.
Metastasis – distant spread of a neoplasm – malignancy. Can be via blood, lymphatics or direct innoculation
Characteristics of benign and malignant neoplasms.
|Well differentiated||Poorly differentiated|
|Cohesive and expansile||Locally invasive|
|Well demarcated||Poorly demarcated|
|Slow growing||Rapid growth – haemorrhage, necrosis|
|Non invasive, no mets||metastases|
- Genes that promote autonomous growth in the absence of normal mitogenic signals. Eg RAS oncogene
- Normal counterpart is the protooncogene.
- Tumour may begin to produce their own growth factors.
- A multistep process at phenotypic and genetic level called tumour progression. Caretaker and gatekeeper. Loss of mechanisms that counteract malignancies leads to multiple cancer syndromes
- HNPCC – inactivation of mismatch repair gene
- Familial polyposis –
- Li Fraumeni – abnormal p53
- MEN 1 – inactivation of mismatch repair gene
- MEN 2 – RET mutation – adrenals, thyroid and parathyroid
- Familial susceptibility
- BRACA 1 and 2
- Carcinogens – asbestos, tobacco, arsenic, benzene, vinyl chloride
- Microbial eg HPV
- Chronic inflammation
- Nonlethal genetic damage
- Clonal expansion of the tumour cell with the genetic damage
- Targets for gene damage is usually protooncogenes, tumour suppresor genes, genes involved in apoptosis, genes for DNA repair.
- Cytotoxic T cells can identify abnormal intracellular proteins on MHC1 and initiate cell death via apoptosis in possibly neoplastic cells.
- Can be evaded by making cell not produce MHC1, by producing factors that inhibit T cell activation or not displaying intracellular proteins on surface.
Clinical features of tumours.
- Tumour cell invasion of ECM
- Detachment of tumour cells from each other(break intercellular bonds)
- Attachment to ECM components via laminin and fibronectin receptors
- Degradation of ECM via type 4 collagenase and plasminogen to create pathways
- Migration of tumour cells which may lead to vascular dissemination
- Mechanisms that influence distribution of metastasis
- Chemokines for target tissues
- Chemoattractants from target tissues
- Tumour cell adhesion molecules such as ligand preferentially expressed on target organ cells.
- Endocrinopathies or other symptoms not explained by distant metastases or hormonal secretions of a neoplasm
- Eg SIADH in small cell lung cancer or cushings in pancreatic Ca, HPOA in bronchogenic Ca
- Enzymes, hormones or antigens that indicate presence or likely presence of a neoplasm. Can be used to monitor progress or reoccurance
- PSA – prostate
- HCG – trophoblastic disease, testicular tumours
- Ca 125 Ovarian Ca