Role of the Lab in the Diagnosis and Management of Tumours Flashcards
What is the gold standard in the diagnosis of cancer?
Histology
What % of the work of a histology lab is convered with the diagnosis and treatment of cancer?
70%
Why is it important that cancer diagnoses are made correctly?
False positives and negatives are potentially disastarous and expensive
Why might false positive cancer results be disasterous?
A diagnosis of cancer can lead to radical treatment that is disfiguring or harmful
Why can false negative cancer results be potentially disastrous?
Because the patient will come back with more advanced tumours with a worse prognosis
Why are most cancers easily diagnosed histologically?
Because most cases show histological features that are at either end of the benign-malignant spectrum
What happens when cases are in the middle of the benign-malignant spectum histologically?
It produces problems of diagnosis, and therefore management
What are the categories of samples sent for cancer diagnosis?
- Tissue
- Cytology
What forms of tissue sample might be received for histological testing?
- Diagnostic biopsy
- Excisional specimen
What is the main purpose of diagnostic biopsies?
Diagnosis
Give two examples of methods of obtaining diagnostic biopsies
- Incisional
- Needle core
What is the main purpose of obtaining excisional specimens
Done with curative intent
What tissues are amenable to histological evaluation?
All
What is evaluated in cytology?
Cells suspended in fluid
What are the ways of obtaining cytology samples?
- Exfoliation
- Aspiration
How can cells be exfoliated?
- Can be shed - cells fall off a surface
- Can be scraped off a surface
Give 4 examples of fluids that cells are shed into
- Sputum
- Urine
- Pleural
- Ascitic
What is the problem with using cells that have been shed in diagnosis?
Cells usually degenerate, so cancer pick-up rate is low
How does the pick-up rate of cancer differ between shed cells and scraped cells?
The scraped cells are intact and viable, so the pick-up rate is higher
When is an aspirate sample taken?
When no surface is available for exfoliation
Give 3 locations that an aspirate sample would be taken from
- Accessible lump
- Breast
- Lymph node
How is an aspirate sample collected? al
With a needle into a lump, free hand - without guidance
How is an aspirate sample collected?
Under imaging guidance
Give three locations where an aspirate sample would be obtained
- Inaccessible lump
- Liver
- Pancreas
What is initially reported on when a histologist obtains a specimen?
A macroscopic description of;
- Tumour
- Apperance
- Size
- Spread
Why is tissue resected during cancer surgery inked?
To demonstrate the excision margin when you look at it down the microscope
What happens if a cancer extends to the excision margin?
Probably need further treatment
How is the tumour specimen further divided from its original form?
Blocks are taken from areas of interest
What happens to the tissue blocks cut from the specimen?
They are impregnanted with wax to support tissue, and 4μm sections are cut
How are the 4μm sections prepared for microscope visualisation?
They are mounted on a glass slide and stained
What factors will the histology report consider?
- 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?
What are the categories in the histological criteria of malignancy?
- Tissue changes
- Cytological changes
What are the tissue changes in the histological criteria of malignancy?
- Dysplasia
- Invasion
- Infiltrative margin
What are the cytological changes in the histological criteria of malignancy?
- Nuclear pleomorphism
- Nuclear size
- Nuclear shape
- Nuclear staining
- Increased proliferation
- Increased number of mitotic figures
- Abnormal mitotic figures
What are tumours named from?
The tissue in which they are derived
What are the potential histogenic classifications of tumours?
- Squamous
- Glandular
- Lymphoid
- Melanocytic
What kind of classification may be more useful than histogenic classification in the future?
Molecular classification, e.g. Braf +ve, HPV associated etc
Histologically, what can help determine what sort of malignancy it is?
- Architectural arrangement
- Cytological differentiation
What features are considered in cytological differentiation?
- Morphology
- Protein expression
What may be found when looking at morphology of malignant cells?
- Desmosomes
- Mucin
- Melanin
What may be found when looking at protein expression in malignant cells?
- Filaments
- Low or high molecular weight cytokeratins
- Specific protein products
- Thyroglobulin
- Enzyme production
What is the importance of the cancers grade?
It provides important prognostic information about some cancers
What is a cancer grade based on?
Degree of differentiation
How is a cancer grade determined?
Mixture of score and subjective assessment, considering;
- Proliferation
- Architectural differentiation
- Pleomorphism
What is the best predictor of prognosis in most cancers?
Stage
What does stage consider?
The extent of the spread
What is the importance of knowing the cancer stage?
It provides vital information for making management decisions
Where to carcinomas spread to first?
Lymph nodes
Where do sarcomas spread to first?
Blood stream
How do sarcomas spread?
Via the blood stream
What needs to be assessed in order to determine the cancer stage?
- Primary tumour
- Draining lymph nodes
- Distant spread
What happens when you cannot assess the primary tumour?
It is considered to be Tx
What happens if lymph nodes are found to be involved in cancer?
Clearance
What happens if no involved nodes are found on examination or imaging?
Targeted lymph node sampling
What is typically done to lymph nodes in breast cancer?
Axillary clearance
What is the problem of axillary clearance treatment in breast cancer?
There is significant morbidity from lymphoedema
When is sentinal lymph node biopsy conducted in breast cancer?
In clinical and USS negative cases
What cancers is sentinal lymph node biopsy routinely used for?
- Breast
- Melanoma
- Penile SCC
- Head and neck SCC
What happens in a sentinal lymph node biopsy?
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
What should be reported on when considering the margins in cancers?
How big the margins are, and if the margins are cleared, close, or involved
When might the margins in cancer exicision be left intentionally small?
When there is intent for plastic surgery - have to balance getting clearance with serious deformity
Give an example of a technique that can be employed when trying to make margins as small as possible
Moh’s micrographic surgery
What happens when the margins are involved?
Further excision or radiotherapy
Other than light microscopy, what other lab techniques can be used to investigate a tumour?
- Histochemical stains
- Electron microscopy
- Immunohistochemistry
- PCR
- In situ hydridisation
- Cytogenetics
How can histochemical stains be useful in the diagnosis of cancer?
- Can help characterise the tissue components, e.g. collagen, melanin
- Can detect infection
How can PCR be useful in the diagnosis of cancer?
- Can detect monoclonality
- Can detect some infections
How can in situ hybridisation be useful in diagnosing cancer?
Can use specific probes for RNA or DNA to detect clonality
What can be looked for using cytogenetics?
Translocations
How is immunohistochemistry conducted?
- Antibodies bind to specific proteins in tissues, and so can be applied to tissue sections and detected via colour producing peroxidase reaction
- Antigens of interest are injected into animals to stimulate the immune response
What can biological markers be used to determine?
Therapy
How can protein expression be characterised in the lab?
Using immunohistochemistry
Give an example of where steroid receptor status might be important
Breast cancer - oestrogen receptor expression predicts response to hormone therapy
Why does oestrogen receptor expression predict the response to hormone therapy?
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
What is HER-2?
A member of the ECG receptor family. It is a tyrosine kinase which promotes cell growth
What % of breast cancers have HER-2 gene amplification?
20-30%
What does gene amplification of HER-2 lead to?
Uncontrolled cell growth
Why is it important to know HER-2 status in breast cancer?
- 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
