6) Laboratory Diagnosis of Cancer

Question 1

Why is histology important in cancer diagnosis?

Answer 1

It is the gold standard

Question 2

How can tissue samples be taken for diagnosis?

Answer 2

Diagnostic biopsy - needle, core or incisional

Excisional specimen - whole lesion removed

Question 3

What are the types of cytology? (give examples of cells obtained this way)

Answer 3

Shed cells - sputum, urine, pleural and ascitic fluids
Scrape cells from surface - cervical smear, bronchial brushings
Fine needle aspiration (+ US guidance) - lump, breast, lymph node, liver, pancreas

Question 4

Why do shed cells provide a low pick up rate compared with scraped cells?

Answer 4

Cells usually degenerate whereas scraped cells are intact and viable

Question 5

How are excised specimens first analysed?

Answer 5

Macro-description of tumour e.g. size and appearance (useful for staging)
Excision margin - if cancer extends near margin may still be some in body

Question 6

How are excised specimens transferred to a slide?

Answer 6

Impregnated with wax, mounted on a glass slide and stained (H&E)

Question 7

What are some histological tissue changes suggesting malignancy?

Answer 7

Dysplasia, invasion, infiltrative margin

Question 8

What are some histological cytology changes suggesting malignancy?

Answer 8

Pleomorphism, increased proliferation and abnormal mitotic figures

Question 9

What are some histogenic classifications of tumours?

Answer 9

Squamous, glandular, lymphoid, melanocytic

Question 10

What histological factors can allow classification of the malignancy?

Answer 10

Architectural arrangement e.g. glands

Morphology and protein expression (markers)

Question 11

Explain what grading is and its function:

Answer 11

Assessing the degree of differentiation

Used for prognosis and management

Question 12

Explain the grading used in breast cancer:

Answer 12

Assessing tubule formation, pleomorphism and mitotic counts and marking each out of 3 to come up with an overall score from 3-9

Question 13

How do carcinomas and sarcomas differ in their spread?

Answer 13

Carcinomas to LNs

Sarcomas via blood

Question 14

What is a sentinel lymph node biopsy?

Answer 14

Inject dye and short half life isotope to find first LN in draining system, assess to see if cancer has spread here

Question 15

How can it be confirmed that all the tumour has been removed?

Answer 15

Clearance at surgical excision margins
Intra-operative frozen section
Moh’s micrographic surgery - lots of frozen sections

Question 16

What ancillary techniques can be used when investigating cancer diagnosis?

Answer 16

Histochemical stains 
Electron microscopy 
Immunohistochemistry
PCR
In situ hybridisation
Cytogenetics - translocations

Question 17

Explain the process of immunohistochemistry:

Answer 17

Antibodies bind to specific proteins in tissues and detected via colour producing perioxidase reaction

Question 18

Explain how PCR can be used in cancer diagnosis:

Answer 18

Assessment of clonality in lymphoid infiltrates by analysing T cell receptor arrangement (will be same in neoplastic growth)
Identify HHV8 infection in Kaposi’s sarcoma

Question 19

Explain how in situ hybridisation can be used in cancer diagnosis:

Answer 19

Assessment of clonality in B cell lymphoid neoplasms
Detection of EBV in Epstein-Barr encoded RNA
Tumour specific translocations

Question 20

How does HPV affect outcome in oropharyngeal carcinomas?

Answer 20

If HPV positive, p16 is upregulated and there is improved outcome

Question 21

Give examples of targeted treatments to markers:

Answer 21

Oestrogen receptors (breast) - tamoxifen
Her2 - Herceptin
C-kit expression (CML and gastric stromal) - imatininb
CD20 (B cell lymphoma) - rituximab

Question 22

How are cancer diagnoses discussed?

Answer 22

With MDT consisting of surgeon, radiologist, histopathologist and oncologist