2 Tumour behaviour and spread

Question 1

Define Metaplasia

Answer 1

Replacement of one fully differentiated cell type by another

Substituted cells are less sensitive to a particular stress
e.g. glandular –> squamous

Question 2

Define Dysplasia

Answer 2

Disordered cell growth

- dysplasia may involve squamous, glandular, or transitional epithelium

Question 3

List some risk factors for dysplasia

Answer 3

• Some metaplasia (barret’s)
• Some types of hyperplasia (endometrial hypoplasia)
• Chemicals, smoke causing squamous metaplasia to progress
• UV light - e.g. solar damage of the skin, causing squamous dysplasia
• Chronic irritation of the skin e.g. skin in a 3rd degree burn developing squamous dysplasia

Question 4

List the nuclear features of dysplasia

Answer 4

• Increased mitotic activity (high mitotic count)
• Increased nuclear size + chromatin
• Disorderly proliferation of cells with loss of cell maturation as cells progress to the surface

Question 5

Define pleomorphism

Answer 5

Pleomorphism is a term used in histology and cytopathology to describe variability in the size, shape, and staining of cells and/or their nuclei

• Therefore, cellular and nuclear pleomorphism is one of the earliest hallmarks of cancer progression and a feature characteristic of malignant neoplasms and dysplasia

Question 6

Describe carcinoma in situ

Answer 6

It defines cancer
- hence has metastatic potential but remain in situ

A group of abnormal cells that remain in the place where they first formed. They have not spread

• These abnormal cells may become invasive/metastatic cancer and spread into nearby normal tissue.
• AKA stage 0 disease

Question 7

List 4 cytological criteria of a malignant tumour

Answer 7

General
- uniform population of pleomorphic cells - can be assessed at low magnification

Nuclear

• Abnormal mitoses
• Variable nuclear size
• Variable nuclear/cytoplasmic ratios
• Multiple nucleoli
• Large irregularly shaped nucleoli
• Large irregularly shaped nucleoli
• Coarse chromatin patterns
• Irregular prominence of nuclear margin

Cytoplasmic

• Basophils
• Vacuolation

Structural

• Carcinoma: round to oval cells arranged in sheets of acinar patterns
• Sarcoma: spindle-shaped cells
• Discrete cell tumor

Question 8

Describe the nuclear features when compared to a normal cell of a malignant tumour

Answer 8

• Nucleus is larger, has irregular borders, and has more chromatin (hyperchromatic)
• Nucleolus is larger and has irregular border
• Mitoses have normal and atypical mitotic spindles

Question 9

Describe the first 2 stages of haematogenous (capillary) invasion by malignant tumours

Answer 9

1. shows primary tumours resting on basement membrane of a capillary (angiogenesis taken place), there has been clonal expansion of cells
2. Malignant cells to lose their cell-to-cell adhesion molecules (cadherins)

Question 10

What does a tumour use to degrade the basement membrane in the 3rd stage of haematogenous invasion

Answer 10

metalloproteinases

Question 11

What do cell receptors attach to in the ECM + to break it down in the 4th stage of haematogenous invasion

Answer 11

Fibronectin and other proteins

Question 12

Why do malignant cells produce cytokines in the 5th stage of haematogenous invasion

Answer 12

They stimulate locomotion

- so that they can move through basement membranes and the intracellular + extracellular matrices

Question 13

Describe the 6th stage of haematogenous invasion

Answer 13

Penetrate blood vessels (extravasation) to enter circulation

Question 14

What type of cells do the malignant cells encounter from the host defence, of which some malignant cells are destroyed in the 7th stage of haematogenous invasion

Answer 14

Cytotoxic T cells

Question 15

Describe the last 2 stages of haematogenous invasion of malignant cells (stages 8 + 9)

Answer 15

8. Those that survive the cytotoxic T cells are coated in fibrin + platelets - forming tumour emboli
9. Ends in target organ, attached to blood vessel wall and repeats step 6 (extravasation) in reverse

Question 16

List + describe the different types of metastasis
(most important criterion for malignancy - but, some cancers don’t metastasise
e.g. basal cell carcinomas)

Answer 16

Lymphatic spread
- (tumours of epithelial origin - carcinoma), move through regional nodes and dispense to capillaries to reach organ targets

Haematogenous spread
- direct invasion of blood vessels without lymphatic spread (common in sarcomas)

Question 17

List the different sites of deposition

Answer 17

• Malignant cells entering portal vein go to liver
• Malignant cells in vena cava go to lung

Both carcinomas and sarcomas have haematogenous dissemination; however, carcinomas invade regional lymph nodes before entering the systemic circulation

Question 18

List some other methods of metastasis

Answer 18

• Seeding

- Bone

Question 19

Describe seeding type metastasis

Answer 19

Seeding
- malignant cells exfoliate from a serosal surface and implant and invade tissue in a body cavity (pleural, pericardial, peritoneal)

Ovarian cancer is best example - with seeding to abdominal cavity and organs

• Peripherally lung cancers (usually adenocarcinoma) commonly seed the parietal and visceral pleurae > causing pleural effusion

Question 20

Describe bone type metastasis

Answer 20

• Most common site is vertebral Columbia
• Breast cancer is the most common cancer metastatic to bone; 2nd most common is prostate cancer
• Osteoblastic and osteolytic metastases
  > In osteolytic you get pathological fractures and hypercalcaemia

Question 21

List metastasis more common than primary tumour

Answer 21

• Lymph nodes (metals breast and lung cancer - carcinomas especially)
• Lungs (breast cancer most common cause)
• Liver (lung cancer most common cause)
• Bone (breast cancer most common cause)
• Brain (lung cancer most common case)