Neoplasia 2

Question 1

Definitions

Invasion

Metastasis

Answer 1

Invasion - Breach of the basement membrane with progressive infiltration and destruction of the surrounding tissues

Metastasis - Spread of tumour to sites that are physically discontinuous from the primary tumour (e.g. primary cancer is bone, there is now tumor in the lungs) - Unequivocally marks a tumour as malignant

Question 2

Forming of tumours is a multi step journey

Answer 2

1. Grow and invade at the primary site - i.e. cross past the basement membrane
2. Enter a transport system (blood vessels or lymph) and lodge at a secondary site (most cells that invade blood steam dont survive to form a new site)
3. Grow at the secondary site to form a new tumour (colonisation/metastaisis)

Question 3

What does a carcinoma cell need to invade?

Answer 3

Invasion involves three key events:
Altered adhesion
Stromal proteolysis
Motility
In doing so the cell takes on a phenotype more akin to a mesenchymal cell/stromal cell than an
epithelial cell and this is epithelial to mesenchymal transition

Adhesion - Reduction in E-cadherin expression, Changes in Integrin expression

Stromal proteolysis - Altered expressions of proteases, notably increase in matrix metalloproteinases (MMPs), which degrade basement membrane and stroma to allow for invasion
Malignant cells take advantage of nearby non-neoplasticism cells, which provide growth factors and proteases

Motility - involves changes in the actin of the cytoskeleton

Question 4

How does neoplasm spread to disband sites

Answer 4

Blood vessels - most typically seen in carcinomas - usually in veins (they are better at allowing for tumor spread)

Lymphatic vessels - will follow normal lymphatic system - e.g. in breast cancer - lymph nodes in breast cancer are next ones to get this cancer (axillary lymph nodes with breast cancer)

Fluid in body cavities (transcoelomic spread) - spreads through the cavities and space - e.g. ovarian cancer - can spread through to the peritoneum and there can be widespread peritoneal ‘seeding’

Secondary Site - At the secondary site the malignant cells have to grow - Colonisation
Failed colonisation is considered to be the greatest barrier to successful metastasis
Most malignant cells lodge at secondary sites as tiny clinically undetectable cell clusters that either die or fail to grow into detectable tumours

Surviving microscopic deposits that fail to grow are called micrometastases.
Some cancers are prone to relapse as they form from micrometastases - breast cancer

What determines the site of a secondary tumour?
Regional drainage of blood, lymph or caulomic fluid
For lymphatic metastasis this is predictably to draining lymph nodes E.g Breast cancer goes to the ipsilateral axillary lymph nodes

For transcoelemic spread this is predictably to other areas in the coelemic space or to adjacent organs 

For blood-borne metastasis this is sometimes (but not always) to the next capillary bed that the malignant cells encounter.

Question 5

Seed and soil phenomenon

Answer 5

May explain the unpredictable distribution of blood-borne metastases

Due to interactions between malignant cells and the local tumour environment at the secondary site
E.g. spleen has large blood supply but vary rarerly do you get a splenic metastasis - not a hospital environment for metastatic cancers

Carcinomas tend to spread via lymphatics first
Sarcomas spread via blood stream
Common sites of blood borne metastasis are lung, bone, liver and brain

Important to know the more common neoplasms that spread to the bone as these can be detected on plain films and be the presenting symptom
	Breast 
	Bronchus 
	Kidney 
	Thyroid 
	Prostate

Majority are osteolytic lesions due to destruction of the bone tissue
Prostate cancer actually causes osteosclerotic metastases as it causes increased production of disorganised abnormal bone

Question 6

Personalities

Answer 6

Some malignant neoplasms are more aggressive and metastasise very early in their course

Small cell carcinoma of the bronchus for example is very aggressive and presents early with widespread systemic metastases or is at the very least locally advanced

Others almost never metastasise e.g. basal cell carcinoma of the skin

Question 7

Evasion of host defences

Answer 7

Tumour cells can be recognised by the immune system as non-self and destroyed.

This is mediated by predominantly cell mediated mechanisms

Tumour antigens (antigens released by the tumour) are presented on the cell surface of major histocompatibility complex molecules (CD4+ helper cells and are recognised by CD8+ cytotoxic T cells which go and kill cells expressing this antigen)

Immunosuppressed patients are at increased risk for the development of cancer - due to lack of the above

How

Question 8

Effects of neoplasia

Answer 8

Usually has Direct local effects And Indirect systemic effects such as
Increasing tumour burden
Secreted hormones
Miscellaneous effects

Local effects of neoplasms -

1. Direct invasion and destruction of normal tissue
2. Ulceration at a surface leading to bleeding
3. Compression of adjacent structures
4. Blocking tubes and orifices
5. Raised pressure due to tumour growth or swelling (brain)

Systemic effects of neoplasia
Increased tumour burden results in a parasitic effect on the host
Together with secreted factor such as cytokines
Reduced appetite and weight loss (cachexia)
Malaise
Immunosuppression
Thrombosis
Production of hormones
Usually benign tumours

Question 9

Paraneoplastic syndromes

Answer 9

Some cancer bearing individuals develop signs and symptoms that cannot readily be explained by the anatomic distribution of the tumour or by the production of hormones from the tissue in which the tumour arose.

Affect approximately 10% of people with cancer

Important because: May be the earliest manifestation of an occult neoplasm (tumor where the primary site (original tumor) is unknown)
Can cause significant clinical problems and be fatal, Can mimic metastatic disease and confound treatment

Hypercalcaemia – Probably the most common
– 2 processes:
Osteolysis