Role of the Lab in the Diagnosis and Management of Tumours

Question 1

What is the gold standard in the diagnosis of cancer?

Answer 1

Histology

Question 2

What % of the work of a histology lab is convered with the diagnosis and treatment of cancer?

Answer 2

70%

Question 3

Why is it important that cancer diagnoses are made correctly?

Answer 3

False positives and negatives are potentially disastarous and expensive

Question 4

Why might false positive cancer results be disasterous?

Answer 4

A diagnosis of cancer can lead to radical treatment that is disfiguring or harmful

Question 5

Why can false negative cancer results be potentially disastrous?

Answer 5

Because the patient will come back with more advanced tumours with a worse prognosis

Question 6

Why are most cancers easily diagnosed histologically?

Answer 6

Because most cases show histological features that are at either end of the benign-malignant spectrum

Question 7

What happens when cases are in the middle of the benign-malignant spectum histologically?

Answer 7

It produces problems of diagnosis, and therefore management

Question 8

What are the categories of samples sent for cancer diagnosis?

Answer 8

• Tissue
• Cytology

Question 9

What forms of tissue sample might be received for histological testing?

Answer 9

• Diagnostic biopsy
• Excisional specimen

Question 10

What is the main purpose of diagnostic biopsies?

Answer 10

Diagnosis

Question 11

Give two examples of methods of obtaining diagnostic biopsies

Answer 11

• Incisional
• Needle core

Question 12

What is the main purpose of obtaining excisional specimens

Answer 12

Done with curative intent

Question 13

What tissues are amenable to histological evaluation?

Answer 13

All

Question 14

What is evaluated in cytology?

Answer 14

Cells suspended in fluid

Question 15

What are the ways of obtaining cytology samples?

Answer 15

• Exfoliation
• Aspiration

Question 16

How can cells be exfoliated?

Answer 16

• Can be shed - cells fall off a surface
• Can be scraped off a surface

Question 17

Give 4 examples of fluids that cells are shed into

Answer 17

• Sputum
• Urine
• Pleural
• Ascitic

Question 18

What is the problem with using cells that have been shed in diagnosis?

Answer 18

Cells usually degenerate, so cancer pick-up rate is low

Question 19

How does the pick-up rate of cancer differ between shed cells and scraped cells?

Answer 19

The scraped cells are intact and viable, so the pick-up rate is higher

Question 20

When is an aspirate sample taken?

Answer 20

When no surface is available for exfoliation

Question 21

Give 3 locations that an aspirate sample would be taken from

Answer 21

• Accessible lump
• Breast
• Lymph node

Question 22

How is an aspirate sample collected? al

Answer 22

With a needle into a lump, free hand - without guidance

Question 23

How is an aspirate sample collected?

Answer 23

Under imaging guidance

Question 24

Give three locations where an aspirate sample would be obtained

Answer 24

• Inaccessible lump
• Liver
• Pancreas

Question 25

What is initially reported on when a histologist obtains a specimen?

Answer 25

A macroscopic description of; * Tumour * Apperance * Size * Spread

Question 26

Why is tissue resected during cancer surgery inked?

Answer 26

To demonstrate the excision margin when you look at it down the microscope

Question 27

What happens if a cancer extends to the excision margin?

Answer 27

Probably need further treatment

Question 28

How is the tumour specimen further divided from its original form?

Answer 28

Blocks are taken from areas of interest

Question 29

What happens to the tissue blocks cut from the specimen?

Answer 29

They are impregnanted with wax to support tissue, and 4μm sections are cut

Question 30

How are the 4μm sections prepared for microscope visualisation?

Answer 30

They are mounted on a glass slide and stained

Question 31

What factors will the histology report consider?

Answer 31

* Is there a lesion? * Is it malignant? * What sort of malignancy? * How malignant is it? *(Grade)* * How far has it spread? *(Stage)* * Is it all out?

Question 32

What are the categories in the histological criteria of malignancy?

Answer 32

* Tissue changes * Cytological changes

Question 33

What are the tissue changes in the histological criteria of malignancy?

Answer 33

* Dysplasia * Invasion * Infiltrative margin

Question 34

What are the cytological changes in the histological criteria of malignancy?

Answer 34

* Nuclear pleomorphism * Nuclear size * Nuclear shape * Nuclear staining * Increased proliferation * Increased number of mitotic figures * Abnormal mitotic figures

Question 35

What are tumours named from?

Answer 35

The tissue in which they are derived

Question 36

What are the potential histogenic classifications of tumours?

Answer 36

* Squamous * Glandular * Lymphoid * Melanocytic

Question 37

What kind of classification may be more useful than histogenic classification in the future?

Answer 37

Molecular classification, *e.g. Braf +ve, HPV associated etc*

Question 38

Histologically, what can help determine what sort of malignancy it is?

Answer 38

* Architectural arrangement * Cytological differentiation

Question 39

What features are considered in cytological differentiation?

Answer 39

* Morphology * Protein expression

Question 40

What may be found when looking at morphology of malignant cells?

Answer 40

* Desmosomes * Mucin * Melanin

Question 41

What may be found when looking at protein expression in malignant cells?

Answer 41

* Filaments * Low or high molecular weight cytokeratins * Specific protein products * Thyroglobulin * Enzyme production

Question 42

What is the importance of the cancers grade?

Answer 42

It provides important prognostic information about some cancers

Question 43

What is a cancer grade based on?

Answer 43

Degree of differentiation

Question 44

How is a cancer grade determined?

Answer 44

Mixture of score and subjective assessment, considering; * Proliferation * Architectural differentiation * Pleomorphism

Question 45

What is the best predictor of prognosis in most cancers?

Answer 45

Stage

Question 46

What does stage consider?

Answer 46

The extent of the spread

Question 47

What is the importance of knowing the cancer stage?

Answer 47

It provides vital information for making management decisions

Question 48

Where to carcinomas spread to first?

Answer 48

Lymph nodes

Question 49

Where do sarcomas spread to first?

Answer 49

Blood stream

Question 50

How do sarcomas spread?

Answer 50

Via the blood stream

Question 51

What needs to be assessed in order to determine the cancer stage?

Answer 51

* Primary tumour * Draining lymph nodes * Distant spread

Question 52

What happens when you cannot assess the primary tumour?

Answer 52

It is considered to be Tx

Question 53

What happens if lymph nodes are found to be involved in cancer?

Answer 53

Clearance

Question 54

What happens if no involved nodes are found on examination or imaging?

Answer 54

Targeted lymph node sampling

Question 55

What is typically done to lymph nodes in breast cancer?

Answer 55

Axillary clearance

Question 56

What is the problem of axillary clearance treatment in breast cancer?

Answer 56

There is significant morbidity from lymphoedema

Question 57

When is sentinal lymph node biopsy conducted in breast cancer?

Answer 57

In clinical and USS negative cases

Question 58

What cancers is sentinal lymph node biopsy routinely used for?

Answer 58

* Breast * Melanoma * Penile SCC * Head and neck SCC

Question 59

What happens in a sentinal lymph node biopsy?

Answer 59

You inject the tumour with a dye containing a short half life radioactive isotope to determine the first draining lymph node. You would then remove and assess this lymph node. If there is no cancer, then the patient does not need a lymph not clearance. If there is, need lymph node clearance

Question 60

What should be reported on when considering the margins in cancers?

Answer 60

How big the margins are, and if the margins are cleared, close, or involved

Question 61

When might the margins in cancer exicision be left intentionally small?

Answer 61

When there is intent for plastic surgery - *have to balance getting clearance with serious deformity*

Question 62

Give an example of a technique that can be employed when trying to make margins as small as possible

Answer 62

Moh's micrographic surgery

Question 63

What happens when the margins are involved?

Answer 63

Further excision or radiotherapy

Question 64

Other than light microscopy, what other lab techniques can be used to investigate a tumour?

Answer 64

* Histochemical stains * Electron microscopy * Immunohistochemistry * PCR * *In situ* hydridisation * Cytogenetics

Question 65

How can histochemical stains be useful in the diagnosis of cancer?

Answer 65

* Can help characterise the tissue components, *e.g. collagen, melanin* * Can detect infection

Question 66

How can PCR be useful in the diagnosis of cancer?

Answer 66

* Can detect monoclonality * Can detect some infections

Question 67

How can in situ hybridisation be useful in diagnosing cancer?

Answer 67

Can use specific probes for RNA or DNA to detect clonality

Question 68

What can be looked for using cytogenetics?

Answer 68

Translocations

Question 69

How is immunohistochemistry conducted?

Answer 69

1. Antibodies bind to specific proteins in tissues, and so can be applied to tissue sections and detected via colour producing peroxidase reaction 2. Antigens of interest are injected into animals to stimulate the immune response

Question 70

What can biological markers be used to determine?

Answer 70

Therapy

Question 71

How can protein expression be characterised in the lab?

Answer 71

Using immunohistochemistry

Question 72

Give an example of where steroid receptor status might be important

Answer 72

Breast cancer - *oestrogen receptor expression predicts response to hormone therapy*

Question 73

Why does oestrogen receptor expression predict the response to hormone therapy?

Answer 73

Because some tumours are dependant on oestrogen for growth *(oestrogen regulates genes that promote growth)*, and detection of nuclear receptor indicates oestrogend dependance. If the tumour is dependant on oestrogen, blocking it will cause its death

Question 74

What is HER-2?

Answer 74

A member of the ECG receptor family. It is a tyrosine kinase which promotes cell growth

Question 75

What % of breast cancers have HER-2 gene amplification?

Answer 75

20-30%

Question 76

What does gene amplification of HER-2 lead to?

Answer 76

Uncontrolled cell growth

Question 77

Why is it important to know HER-2 status in breast cancer?

Answer 77

* HER-2 overexpression is a poor prognostic marker * Monoclonal antibodies to Her 2 inhibits Her 2 activity, and this treatment (herceptin) leads to a dramatic improvement in survival