MOD S10 - Neoplasia II Flashcards
Define metastasis
The spread of a malignant tumour into a distant (aka non-adjacent) site
Define invasion
The ability of cells to break through the basement membrane and spread into other tissue
What are the mechanisms facilitating cell invasion and metastasis
Altered cell adhesion
Altered enzyme synthesis and interaction
Angiogenesis
Describe how altered cell adhesion assists the invasion and metastasis of cells
Cell to cell interactions: reduced expression of cadherins (which usually bind cells together) allow cells to move apart
Cell to stromatolites interactions: reduced expression of integrins in malignant cells allows movement
Describe how altered enzyme synthesis and interaction facilitates invasion and metastasis
Metastatic cells produce matrix metalloproteinases which digest collagen
This allows the cell to digest the extracellular matrix to reach and break through the basement membrane
Give specific examples of matrix metalloproteinases
MMP1 acts on type I collagen
MMP2/9 acts on type IV collagen
Describe how angiogenesis facilitates invasion and metastasis of cells
Once a tumour reaches 1-2mm cubed, it’s growth is halted by lack of nutrients and oxygen
This causes the tumours micro environment to become hypoxic, triggering the up regulation of pro-angiogenesis factors eg angiopoietin, VEGF
This causes the growth of new, thin walled blood vessels, allowing continued tumour growth and providing opportunity for metastasis
What are the common routes of metastasis?
Lymphatics
Vascular
Describe metastasis via lymphatics
Spread to local and distant lymph nodes
Frequent route for carcinoma spread
Can involve lymphatics of the lung
Describe metastasis via the vascular system
Spread through capillaries and veins to various organs
Common sites are bone, brain, lung and liver
What cancers commonly metastasise to the lung?
Sarcomas eg osteosarcoma
Carcinomas eg breast, stomach, large intestine
Kidney
Testis eg malignant teratoma
What cancers commonly metastasise to the liver?
Carcinomas eg breast, bronchial, large intestine
Very common from the large intestine as the metastases travel via the portal vein
What cancers commonly metastasise to bone and what are the common effects of this?
Carcinoma eg bronchial, breast, renal, thyroid
(These usually cause destruction of bone leading to pathological fractures)
Prostate (can cause production of dense bone aka osteosclerosis)
What cancers commonly metastasise to the brain and what are the common effects?
Carcinoma eg breast, bronchial, testicular
Melanoma
Act as a space-occupying lesion (SOL) and cause a wide range of neurological symptoms
Describe the local effects of a benign neoplasm
Cause compression which can lead to pressure atrophy or altered function (eg in the pituitary)
Can cause complete obstruction in a hollow viscus
Ulceration of surface mucosa
Space occupying lesion (eg brain)
Describe the local effects of malignant neoplasms
Tend to destroy surrounding tissues
Can cause complete obstruction in a narrow viscus
Ulceration
Infiltration into and around nerves, vasculature and lymphatics
Space occupying lesion (eg brain)
Describe the systemic haematological effects of a neoplasm
Anaemia - due to malignant infiltration of bone marrow (leukaemia, metastasis)
Low WBC and platelet count - as a consequence of treatments or infiltration of bone marrow
Thrombosis - seen in carcinoma of the pancreas
Describe the systemic endocrine effects of neoplasia
Excessive secretion of hormones - benign and malignant neoplasms of endocrine glands can produce PTH or corticosteroids
Ectopic hormone secretion - eg ACTH production by bronchial small cell carcinoma
Describe the systemic skin effects if neoplasia
Increased pigmentation - many carcinomas
Pruritis (itching) - jaundice, Hodgkin’s disease
Herpes zoster - lymphoma
Dermatomyositis - bronchial carcinoma
Describe the systemic neuromuscular effects of neoplasia
Problems with balance Sensory/sensorimotor neuropathies Myopathy and myasthenia Progressive multifocal leucoencephalopathy *Not due to metastasis to the brain*
Define cachexia
Loss of weight, muscle atrophy and loss of appetite in someone who is not actively trying to lose weight
Define malaise
A general discomfort or uneasiness
Define pyrexia
Fever
How can neoplasms kill?
Locally: raised ICP, perforation, haemorrhage (benign or malignant)
Systemically: replacement of essential body organs eg bone marrow, lung tissue, liver parenchyma (malignant neoplasms)
