Neoplasia 2

Question 1

What are the most lethal features of a malignant neoplasm

What do they lead to

Answer 1

Invasion and metastasis, lead to increased tumour burden

Question 2

Define Invasion and Metastasis

Answer 2

Invasion: Breach of 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

Question 3

What are the 3 steps taken by a tumour in the process of Invasion and Metastasis

What must the cell do at all points?

Answer 3

1. Grow and invade at the primary site
2. Enter a transport system and lodge at the secondary site
3. Grow at the secondary site to form a new tumour (colonisation)

Cells must evade immune destruction

Question 4

What 3 things must be altered for Invasion to occur?

What happens to the cell as it makes these alterations?

Answer 4

• Adhesion
• Stromal Proteolysis
• Motility

Epithelial to mesenchymal transition (takes on a phenotype more akin to a mesenchymal/ stromal cell than an epithelial cell)

Question 5

Describe how Adhesion is altered for Invasion of a tumour to occur in 2 ways

Answer 5

1. Reduction in E-Cadherin expression

2. Changes in Integrin expression

Question 6

Describe how Stromal Proteolysis is altered for Invasion of a tumour to occur in 2 ways?

What happens to nearby non-neoplastic cells? What do these cells form?

Answer 6

• Altered expressions of proteases, mainly MMPs (Matrix metalloproteinases)
• Degrade basement membrane and stroma to allow for invasion
• Malignant cells take advantage of nearby non-neoplastic cells, which provide growth factors and proteases

Non-neoplastic cells form a Cancer Niche

Question 7

Describe how Motility is altered for Invasion of a tumour to occur in 1 way?

Answer 7

Changes in actin cytoskeleton

Question 8

By what 3 routes does a tumour spread to distant sites?

Answer 8

• Blood
• Lymph
• Transcoelomic (Fluid in body cavities)

Question 9

What is the greatest barrier to successful metastasis?

Answer 9

Failed colonisation of tumour at secondary site

(Most malignant cells lodge at secondary sites as tiny clinically undetectable cell clusters that either die or fail to grow into detectable tumours)

Question 10

What are Micrometastases?

What do they cause?

Answer 10

Surviving microscopic deposits of malignant cells lodged at secondary sites, that fail to grow

Cause relapse of a malignant neoplasm

Question 11

What is Tumour Dormancy?

Answer 11

The presence of many metastases in an apparently disease-free person

Question 12

What 2 things determine the site of a metastasis

Answer 12

• Regional drainage of blood/ lymph or coelomic fluid

- ‘Seed and soil’ phenomenon

Question 13

What is the “Seed and soil phenomenon’?

What can it explain?

Answer 13

The interactions between malignant cells and local tumour environment (the niche) at the secondary site

May explain the unpredictable distribution of blood-borne metastases

Question 14

How do Carcinomas and Sarcomas spread to distant sites?

Answer 14

Carcinomas;

• Via Lymphatics first
• Via blood

Sarcomas;
- Via blood

Question 15

What are the 4 common sites of blood-borne metastases

Answer 15

• Lung
• Bone
• Liver
• Brain

Question 16

List the 5 common neoplasms that most frequently spread to bone

Answer 16

• Breast
• Bronchus
• Kidney
• Thyroid
• Prostate

Question 17

Describe the majority of bone metastases

Describe the bone metastases caused by prostate cancer

Answer 17

Osteolytic lesions due to destruction of bone tissue

Osterosclerotic, as production of disorganised abnormal bone is increased

Question 18

What do we mean by “ Malignant tumours have personalities”

Answer 18

Some malignant neoplasms are more aggressive and metastasise very early

(Small cell carcinoma of bronchus presents early with widespread systemic metasteses, Basal cell carcinoma of skin almost never metastasises)

Question 19

What is the likelihood of metastasis related to

Answer 19

Related to size of primary neoplasm

Question 20

What are 3 ways tumours can avoid the immune system?

Answer 20

• Loss of/ reduced expression of histocompatabilty antigens
• Expression of factors that suppress the immune system
• Failure to produce tumour antigen

Question 21

Identify 5 local effects of Neoplasms

Answer 21

• Raised pressure (tumour growth or swelling)
• Compression of adjacent structures
• Obstruction of tubes and orifices
• Ulceration at surface leading to bleeding
• Direct invasion and destruction of normal tissue

Question 22

List 12 systemic effects of Neoplasms

Answer 22

• Cachexia (Weakness and wasting of body)
• Malaise
• Immunosuppression
• Thrombosis
• Hormone production (by endocrine tumour)
• Neuropathies
• Skin problems (Pruritus, abnormal pigmentation)
• Fever
• Clubbing
• Myositis (Any condition causing muscle inflammation)
• Hypercalcaemia (most common)
• Paraneoplastic Syndromes

Question 23

What is a Paraneoplastic Syndrome? (Affect 10% of people with cancer)

Answer 23

A set of signs and symptoms in a cancer patient, that can’t readily be explained by the anatomical distribution of the tumour OR by the production of hormones from the tissue in which the tumour arise

Question 24

What are 3 significant things about Paraneoplastic syndromes

Answer 24

• May be the earliest manifestation of an occult neoplasm
• Can mimic metastatic disease
• Can confound treatment

Question 25

What is an occult neoplasm?

Answer 25

A metastatic tumour whose primary site can’t be identified