Introduction to neoplasia

Question 1

Define neoplasia

Answer 1

Process of abnormal cell proliferation

Question 2

Define neoplasm

Answer 2

Abnormal mass of tissue due to abnormal cell proliferation

(AKA tumour)

Question 3

What are the 3 types of neoplasm/tumours

Answer 3

Question 4

Define oncogenesis

Answer 4

Process of gradual steps towards tumour development

Question 5

What is the difference between pre-malignant and malignant tumours?

Answer 5

in pre-malignant tumour basement membrane is still intact & tumour has not spread to other tissues

Question 6

How do we determine if a mass is neoplasia?

Answer 6

Take a sample for histology

Question 7

What should we examine in a histological sample to look for neoplasia

Answer 7

Organisation of tissue structure
Degree of cellularity
Nuclear to cytoplasmic ratio
Nuclear morphology
Necrosis
Mitotic index
Individualisation of cells
Invasiveness of cells

Question 8

How do you differentiate between a benign vs malignant tumour?

Answer 8

Question 9

What are some characteristics of benign tumours

Answer 9

Slow-growing mass

Good demarcation from surrounding tissue (capsule)

Does not spread (no metastasis)

Minimal necrosis

Question 10

What are some characteristics of malignant tumours

Answer 10

Can grow rapidly

Invasiveness to surrounding tissue

Can spread to other sites in body (metastasis)

Increased necrosis

Question 11

Fill in the table of features of benign vs malignant tumours

Answer 11

Question 12

Why does necrosis often occur in malignant tumours?

Answer 12

Tumours grow too rapidly for blood supply to support centre of the mass => death of cells

Question 13

Why do tumours often get infected?

Answer 13

Loss of blood supply to centre => no WBCs

Question 14

What is the cytological criteria of malignancy

Answer 14

Question 15

Fill in the table with features of benign vs malignant tumour cells

Answer 15

Question 16

Which genes control cell division/proliferation?

Answer 16

Proto-oncogenes - promote proliferation

Tumour suppressor genes - suppress proliferation or induce cell death

(dysregulation of these mechanisms = neoplasia)

Question 17

How does cell proliferation become dysregulated?

Answer 17

1. Proto-oncogenes mutate into oncogenes
2. Oncogenes code for oncoproteins that promote cell division despite:
   - absence of promotion signals
   - presence of normal check point controls to suppress division

Tumour suppressor genes can become mutated so they no longer suppress cell division => neoplasia

Question 18

What factors contribute to oncogenesis?

Answer 18

Genetic factors
Epigenetic factors
Environmental factors

Question 19

Why does cancer occur more commonly in older patients?

Answer 19

Multiple hit hypothesis - 1 mutation not enough to cause neoplasia on its own - takes time for mutations to develop & accumulate

Question 20

What are the hallmarks of cancer cells?

Answer 20

Question 21

What is mutagenesis/carcinogenesis?

Answer 21

Initiating factor(s) causing genetic change

This genetic change makes cells more likely to divide in uncontrolled way in right conditions

Caused by intrinsic and extrinsic factors

Question 22

define mutagen & carcinogen

Answer 22

Mutagen = agent that damages DNA

Carcinogen = mutagen that causes neoplasia

All carcinogens are mutagens, but not all mutagens are carcinogens

Question 23

What are the intrinsic factors of mutagenesis?

Give an example.

Answer 23

Normal by-products of cell metabolism that cause DNA damage

e.g. reactive oxygen species (ROS) a.k.a free radicals

Question 24

What are the extrinsic factors of mutagenesis?

Answer 24

Environmental agents
- Chemical
- Physical

Oncogenic viruses

Question 25

Describe direct- vs indirect-acting chemical agents that act as extrinsic factors of mutagenesis | Give examples

Answer 25

Direct-acting - Cause mutagenesis in form in which they enter body - e.g. nitrosamines in tobacco smoke Indirect-acting - Need to be activated by enzymes in body to cause mutagenesis - Most important enzyme is cytochrome P450 in the liver - Also called procarcinogens - e.g. ptaquiloside in bracken fern => bladder tumours in cattle

Question 26

How do physical agents contribute to mutagenesis? Give an example.

Answer 26

Cause direct DNA damage or generate reactive oxygen species (ROS) ROS can induce mutations (e.g. G → T transversion) Radiation is the key physical agent - Acts as a complete carcinogen (initiator and promoter)

Question 27

Describe ultraviolet radiation (sunlight) as an (physical agent) extrinsic factor of mutagenesis

Answer 27

Ultraviolet radiation (sunlight) causes: - Pyrimidine (C &T) dimer formation (results in misreading during transcription) - ROS generation

Question 28

describe the direct mechanisms of oncogenic viruses

Answer 28

Dominant oncogene mechanism: - Mutation in viral gene causes host cells to produce oncoprotein - e.g. Feline leukaemia virus Insertional mechanism: - No oncogene in virus - Insertion of viral DNA into host cells activates proto-oncogenes => oncogenes - e.g. Avian leukosis virus

Question 29

describe the indirect mechanisms of oncogenic viruses | give examples

Answer 29

Suppress host immune system - e.g. Gallid herpesvirus-2 (Marek’s disease) Directly stimulate host cell proliferation - e.g. Leporipoxvirus (Squirrel fibroma virus)

Question 30

Define metastasis

Answer 30

Movement of cancer cells from one tissue/organ to another (key feature of malignancy)

Question 31

Describe the process of metastasis

Answer 31

Process can take years, but can also be rapid 1. Cancer cells break away from primary tumour 2. Cells travel through blood & lymphatic vesselsto new tissues/organs distant from primary tumour 3. Secondary tumours (metastases) develop in new organs Metastases –new cancerous growths at distant sites

Question 32

Give an example of a highly metastatic and poorly metastatic tumour

Answer 32

Some tumours highly metastatic e.g. melanoma Some are poorly metastatic e.g. squamous cell carcinoma

Question 33

Why is it important to identify tumours when they're small?

Answer 33

Generally- the bigger the tumour, the more likely it is to metastasise

Question 34

What are the pathways of metastasis

Answer 34

Haematogenous - Cancer cells travel in blood vessels - Usually thinner-walled veins rather than arteries Lymphatic - Cancer cells travel in lymphatic vessels - Lymph node(s) closest to tumour are colonised first - These first lymph nodes develop largest tumours Transcoelomic- less common - Cancer cells spread across surface of abdominal & thoracic structures

Question 35

What are the fundamental steps for metastasis

Answer 35

Intravasation Extravasation Colonisation