Lab Diagnosis of Cancer Flashcards
What is the gold standard for cancer diagnosis?
Histology
What proportion of cases show histological features at either end of the benign-malignant spectrum?
The majority
What produces problems of diagnosis and management?
The small number of cases that sit in the middle of the spectrum that are difficult to classify
What types of tissue samples are sent for cancer diagnosis?
- Diagnostic biopsy (incisional/needle core)
- Excisional specimen (can be done with curative intent)
What types of cytology samples are sent for cancer diagnosis?
- Exfoliative (scraped or shed cells)
- Fine needle aspiration +/- US guidance
What samples can be taken of shed cells?
- Sputum
- Urine
- Pleural fluid
- Ascites
What is the issue with samples of shed cells?
Cells degenerate quickly so cancer pick-up rate is low
What samples can be taken of scraped cells?
- Cervical smear
- Bronchial brushings
Why are scraped cells better than shed cells?
Cells are intact and viable so cancer pick-up rate higher
When do you take an aspirate?
When no surface is available:
- Accessible lump
- Breast tissue
- Lymph node
When is US guidance needed?
For an aspirate of an inaccessible lump, the liver or pancreas
How are tissue samples processed?
Tissue blocks are impregnated with wax to support the tissue while 4µm sections are cut.
These sections are mounted on a glass slide and stained.
What is the major stain used in histology?
H&E (Haemotoxylin and Eosin)
What will a histology report consider? (6)
- Is there a lesion (sampling error)?
- Is it malignant?
- What kind of malignancy is it?
- Grade?
- Stage?
- Has it all been removed?
What 2 criteria are taken into consideration when judging if a lesion is malignant?
- Tissue changes
- Cytological changes
What tissue changes are considered when judging malignancy?
- Dysplasia
- Invasion
- Infiltrative margin
What cytological changes are considered when judging malignancy?
- Nuclear pleomorphism, size, shape and staining
- Increased proliferation, number mitotic figures
- Abnormal mitotic figures
What is judged when classifying the type of malignancy?
- Identifying differentiation (histogenic classification)
- Molecular classification (esp. with HPV)
- Architectural arrangement
- Cytological differentiation
What are the classes of tissues that can be distinguished in histogenic classification?
- Squamous
- Glandular
- Lymphoid
- Melanocytic etc
What can be looked at in cytological differentiation to judge what sort of malignancy is present?
- Morphology
- Protein expression
What is the grade of a tumour?
How well differentiated it is from the original tissue
What does grade indicate?
Management and sometimes prognostication
What does well differentiated mean?
The tumour cells closely resemble the original tissue. Likely to be indolent/less agressive than a poorly differentiated tumour.
How is grade assessed?
- Proliferation
- Architectural differentiation
- Pleomorphism
How is breast cancer graded?
Scoring of these categories then add scores up to get a number 3-9: -Tubule formation -Pleomorphism -Mitotic counts 3,4,5=Grade 1 6,7=Grade 2 8,9=Grade 3
How is tubule formation graded in breast cancer?
1= over 75% tubules
2= 10-75% tubules
3=less than 10% tubules
How is pleomorphism graded in breast cancer?
1=nuclear size similar to benign
2=large nuclei with open chromatin
3=marked variation in shape and size
What is the stage of a cancer?
The extent of the tumour’s spread
What is staging used for in most cancers?
Prognostication mainly and management
Where do carcinomas spread to?
Lymph nodes
Where do sarcomas spread via?
The blood stream
What is the most common staging system?
TNM
Tumour, Nodes, Metastasis
What staging system is used for Colorectal cancer?
Dukes
What staging system is used for Hodgkins lymphoma?
Ann Arbor
What happens in lymph node sampling?
- Involved nodes found are cleared
- If no nodes found on examination/imaging, targeted sampling occurs
What is a sentinel lymph node?
The first node or group of nodes that drain a cancer
How can the sentinel node be found?
Contrast (dye and short half life isotope) injected into tumour site, then imaging to show where the contrast drains to
What are sentinel lymph node biopsies used for routinely?
- Breast cancer
- Melanoma
- Penile SCC
- Head and neck SCC
What does lymphoedema mean in breast cancer?
Associated with significant morbidity. Occurs after axillary clearance (traditional treatment in breast cancer)
How does immunohistochemistry work in diagnosing cancer?
- Antibodies bind to specific proteins in tissues
- Abs applied to tissue sections and detected via peroxidase reaction (fluorescent staining tag)
How is PCR used in cancer diagnosis?
- For assessment of clonality in lymphoid infiltrates - look for TCR or Ig heavy chain gene
- Identifying HHV8 infection in Kaposi’s sarcoma
What can In situ hybridisation be used for in cancer diagnosis?
- Assess clonality in B cell lymphoid neoplasms
- Detection of EBV via EBER (EB encoded RNA)
- ID of tumour specific translocations
How does HPV presence help predict the outcome of oropharyngeal cancers?
HPV-positive have a much better outcome compared to HPV-negative
What can help determine therapy?
Presence of biological markers
Give example of biological markers determining therapy
- Steroid receptors and tamoxifen
- Her-2 and Herceptin
- C-kit expression and imatinib
- CD20 expression and rituximab
How frequently is HER-2 overexpressed in breast carcinoma?
20-30% of the time
What is routine in breast tumours?
Screening for Her-2 expression
What does herceptin treatment of Her-2 positive tumours lead to?
Improvement in survival
