S8: neoplasia (1) + neoplasia (2)

Question 1

Define neoplasm

Answer 1

An abnormal growth of cells that persists after the initial stimulus is removed

Question 2

Define dysplasia

Answer 2

Pre-neoplastic alteration in which the cells show disordered tissue organisation
Reversible

Question 3

Define tumour

Answer 3

Any clinical detectable lump or swelling

Question 4

Define cancer

Answer 4

Malignant neoplasm
Abnormal growth of cells that persists after the initial stimulus is removed & invades surrounding tissue with the potential to spread to distant sites

Question 5

Define metastasis

Answer 5

Malignant neoplasm that has spread from its original site to a new non-contiguous site

Question 6

Define anaplasia

Answer 6

Cells with no resemblance to any tissue

Question 7

Define pleomorphism

Answer 7

Variation in size and shape of cells and nuclei

Question 8

Define progression

Answer 8

Stepwise accumulation of yet more complimentary mutations over time that provide the cell with a survival advantage

Question 9

Define differentiation

Answer 9

The process of becoming different by growth or development

Question 10

Describe the macroscopic and microscopic features of benign tumours

Answer 10

Grow in a confined local area
Pushing outer margin
Rarely dangerous (location)
Retain functions of their cells of origin
Closely resemble the parent tissue – well differentiated

Question 11

Describe the macroscopic and microscopic features of malignant tumours

Answer 11

Irregular outer margin & shape
May have ulcerations and necrosis
Infiltrative & potential to metastasise
Less likely to retain functions of origin & sometimes acquire unexpected functions
Individual cells have: increasing nuclear size, increased nuclear to cytoplasm size, increased nuclear staining (hyperchromasia), increased mitotic figures, abnormal mitotic figures & pleomorphism

Question 12

Describe and understand the difference between in-situ and invasive malignancy

Answer 12

In-situ = no invasion through epithelial basement membrane 
Invasive = penetrated through basement membrane

Question 13

Explain how proto-oncogenes are involved in the development of neoplasms

Answer 13

All participate in signalling pathways that drive proliferation
Mutations cause an excessive increase in one or more normal functions -> gain of function mutations
Oncogenes are created by mutations in proto-oncogenes -> encode proteins (oncoproteins) that can promote cell growth in the absence of normal growth promoting signals
Transform cells despite a normal copy of the same gene (dominant over their normal counterparts)

Question 14

Explain how tumour suppressor genes are involved in the development of neoplasms

Answer 14

Normal function is to stop cell proliferation
Loss of function mutation
Both alleles must be damaged for transformation to occur in most cases
Mutations lead to failure of growth inhibition

Question 15

Explain the concept of clonality

Answer 15

Monoclonal = a collection of cells that all originated from a single founding cell
Neoplasm then emerges from this group of cells by progression (accumulation of more mutations)

Question 16

List the nomenclature given to benign and malignant neoplasms

Answer 16

Naming depends on the site of origin 
Benign tumours end in -oma
Malignant tumours end in 
-carcinoma (if epithelial)
-sarcoma (if stromal)
EXCEPT: Burkitt’s lymphoma, Hodgkin’s lymphoma, Ewing’s sarcoma & Kaposi’s sarcoma

Question 17

List the histological characteristics of squamous cell carcinoma

Answer 17

Eosinophilic cytoplasm
Pleomorphic nuclei
Mitotic figures

Question 18

List the histological characteristics of adenocarcinoma

Answer 18

Low grade – well differentiated resembling normal glandular structure
High grade – appear abnormal compared to surrounding tissues

Question 19

List the histological characteristics of malignant melanoma

Answer 19

Atypical mitoses
Nests of melanocytes with variable size and shape
Consumption of epidermis

Question 20

List the types of cancers that occur in different organs

Answer 20

Squamous cell carcinoma – oesophagus, skin, lung & cervix
Adenocarcinoma – oesophagus, stomach/bowel, lung, breast/prostate & thyroid/pancreas/uterus
Bladder – transitional cell carcinoma
Skin – malignant melanoma, basal cell carcinoma
Lung – small cell carcinoma
Brain – astrocytoma

Question 21

Define invasion

Answer 21

Breach of the basement membrane with progressive infiltration & destruction of the surrounding tissues

Question 22

Define metastasis

Answer 22

Spread of tumour to sites that are physically discontinuous from the primary tumour
Marks a tumour as malignant

Question 23

Describe the three steps of metastasis

Answer 23

1) tumour must grow & invade at the primary site
- initiation & promotion
- progression
- cancer cells are under attack by the immune system
2) enter a transport system
- inefficient process: majority of cells will die & not metastasise
3) grow at the secondary site to form a new tumour = COLONISATION

Question 24

Describe the cellular alterations that are required for invasion to occur

Answer 24

1) Altered adhesion = reduction in expression of e-cadherin that normally glues epithelial cells together; changes in integrin expression
2) Stromal proteolysis = altered expression of proteases; degrade basement membrane & stroma to allow for invasion
3) Motility = involves changes in actin cytoskeleton; allows for locomotion of cells to propel them through degraded basement membrane

Question 25

What determines the site of a secondary tumour?

Answer 25

Regional drainage of blood, lymph or caulomic fluid
Lymphatic metastasis: draining lymph nodes
Transcoelemic spread: other areas in the space or adjacent organs
Blood-borne metastasis: sometimes to the next capillary bed malignant cells encounter

Question 26

Explain the ‘seed and soil’ phenomenon

Answer 26

Explains the unpredictable distribution of blood-borne metastases
Due to interactions between malignant cells & local tumour environment at the secondary site (different conditions than primary site)
Some tumour cells will not be able to survive in certain environments

Question 27

List the transportation routes for malignant cells

Answer 27

1) Blood vessels
2) Lymphatic vessels
3) Transcoelomic spread

Question 28

Identify the neoplasms that most frequently spread to the bones and the difference between lytic and sclerotic lesions

Answer 28

Breast, bronchus, kidney, thyroid & prostate
Majority are osteolytic lesions = destruction of bone tissue
EXCEPT prostate cancer = sclerotic lesions as it causes increased production of disorganised abnormal bone

Question 29

List the local effects of neoplasms

Answer 29

Direction invasion & destruction of normal tissue
Ulceration at a surface leading to bleeding
Compression of adjacent structures
Blocking tubes and orifices
Raised pressure due to tumour growth/swelling (intracranial pressure in brain)

Question 30

List the systemic effects of neoplasms

Answer 30

Increased tumour burden in a parasitic effect on the host
Reduced appetite & weight loss (cachexia)
Malaise
Immunosuppression
Thrombosis
Production of hormones (usually benign tumours)
Paraneoplastic syndromes (signs & symptoms cannot readily be explained by distribution of tumour)
Neuropathies
Hypercalcaemia

Question 31

List the 4 common sites for blood bourne metastases

Answer 31

Lung
Bone
Liver
Brain