Neoplasia 2

Question 1

Define invasion

Answer 1

Breach of the basement membrane with the progressive infiltration and destruction of the surrounding tissue

Question 2

Define metastasis

Answer 2

Spread of tumour to sites that are physically discontinous from the primary tumour.

Marks tumour as malignant

Question 3

How do cells metastasise?

Answer 3

1. Grow and invade ( basement membrane ) at the primary site

2, they need to enter a transport system and lodge at a secondary site.

3. They need to grow at the secondary site to form a new tumour

Question 4

What does a carcinoma cell need to invade ?

Answer 4

1. Altered adhesion - they needs to be able to dissociate themselves from other cells. This occurs from a reduction in E-cadherin expression and changes in integrein expression ( integrin is what keeps it held onto basement membrane).
2. Stromal proteolysis - method used to invade the actual basement membrane. This occurs by altered expression of proteases. Degrade basement membrane and stroma to allow for invasion.
3. Motility - the cancer cells needs to be able to move into the stroma. This involves changes in the actin cytoskeleton.

Question 5

After the cancer cells have invaded the basement membrane into the stroma , how does it spread to distant sites ?

Answer 5

1. Blood vessel (usually veins instead of the heart) SARCOMAS tend to spread through bloodstream
2. Lymphatic vessels ( where it drains to their distant sites ). CARCINOMAS tend to spread via lymphatics first.
3. Fluid in body cavities - this is called transcoelomic spread. For example peritoneal fluid , pericardial fluid , pleurae

Once tumours reach a certain size , they need to develop their own blood vessels in order to survive.

Question 6

What occurs to the cancer cells once they have reached a secondary site ?

Answer 6

At the secondary site , the malignant cells have to grow.

Question 7

What is the greatest barrier to successful metastasis?

Answer 7

Failed colonisation - they often die on the way to their secondary sites.

This could be due to turbulent blood flow. Or apoptosis.

Question 8

Generally , why should say you that people are in ‘remission ‘ from cancer and not cured ?

Answer 8

Because 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 that are often dormant.

Micrometastases are more prevalent in melanoma.

Question 9

What determines the site of a secondary tumour ?

Answer 9

Regional drainage of blood , lymph or caulk mic fluid.

For example lymphatic metastasis this is predictably to draining lymph nodes. For example breast cancer goes to the ipsilateral axiallary lymph nodes.

For transcoelemic spread , this is predictably to other areas in thr coelmic 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 10

What is the seed and soil phenomenon?

Answer 10

This may explain the unpredictable distribution of the blood borne metastases.

The cancer cells need certain environments in the organ / blood / capillary bed in order for it to grow at the secondary site. This is due to interactions between malignant cells and the locks tumour environment at the secondary site.

For example , the stroma , fibroblasts , endothelial cells , inflammatory cells at the secondary environment

Question 11

What are common sites of blood borne metastasis ?

Answer 11

Lung

Bone

Liver

Brain

Question 12

What cancers are often cause bone metastasis?

Answer 12

Breast

Kidney

Bronchus

Thyroid

Prostate

Cancers !

Question 13

What do we mean by cancers having personalities ?

Answer 13

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

For example , small cell carcinoma of the bronchus is very aggressive and presents early it’s widespread systemic metastases.

Other neoplasms such as basal cell carcinoma of the skin never metastasise.

Question 14

Why are immunosuppressive patients at increased risk for development of cancer ?

Answer 14

Because tumour cells can be recognised by the immune cell as non self and destined. This is mediated by predominantly cell mediated mechanisms, for example tumour antigens are presented on the cell surface of MHC class 1 molecules and are recognised by CD8+ cytotoxic T cells.

Question 15

However , in immunocompetent patients , how can tumours avoid the immune system ?

Answer 15

The loss or reduced expression of histocompatibiltiy antigens
- expression of certain factors that suppress the immune. System

• failure to produced tumour antigen

Question 16

What are the local effects of tumours ?

Answer 16

1. Direct invasion an destruction of normal tissue
2. Ulceration at the surface leading to bleeding

3, compression of adjacent structures

4. Blocking tubes and orifices
5. Raised pressure due to tumour growth or swelling

Question 17

What are systemic effects of neoplasia ?

Answer 17

1. Increased tumour burden results in a parasitic effect on the host
2. Together with secreted factor such as cytokines : reduced appetite +weight loss ( cachexia) , malaise , immunosuppression , thrombosis ,

3, production of hormones : usually benign tumours

Question 18

What malignant neoplasms often cause lytic lesions ?

Answer 18

X

Question 19

What cancers caused osteosclerotic metastases?

Answer 19

Prostate cancers

This causes abnormal hardening of the bone.

Question 20

What is paraneoplastic syndromes ?

Answer 20

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

Approx 10% of people with cancer

This is important because may cause significant clinical problems and be fatal. And can mimic metastatic disease and confound treatment.

Question 21

What is the most common paraneoplastic syndrome ?

Answer 21

Hypercalcaemia

There are two processes : osteolysis ( induced by cancer due to either primary bone lesions such as myeloma or secondary metastases.

Question 22

What is endometrial hyperplasia ?

Answer 22

Endometrial glands proliferation

Obesity is a key risk factor to this condition because excess fat is converted into oestrogen which causes glands to proliferate.

Question 23

Why is tamoxifen used to treat breast cancer ?

Answer 23

Selective oestrogen selective modulator - it is an antagonist to oestrogen receptors in the breast tissue which prevents tumours from spreading.

However , negatives of this medication is the fact that it acts as an agonist to receptors in the uterus lining so can increase the risk of endometrial hyperplasia.

Question 24

What are long term conditions of endometrial hyperplasia ?

Answer 24

1. anaemia

2. Endometrial carcinoma