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Study Robbins

Basics

  • Histopathalogical type = histiogenesis (pattern of differentiation) and anticipated behaviour (benign, malignant, Ca in situ)
  • Grade = degree of differentiation
  • Stage = extent of spread (TNM)
  • Diagnostic, Prognostic, and Predictive (response to treatment)
    • eg. of predictive = expression of oestrogen receptors in breast cancer, HER2 receptor status, etc

Pathological diagnosis of cancer

  • Clinical data + Appropriate specimen = Accurate diagnosis
    • Specimen should be adequate (enough), representative, and well preserved

Cytopathological Diagnosis of Cancer

  • Methods
    • Cells fall off (exfoliative cytology)
      • sputum, bronchoalveolar lavage, pleural fluid
    • Cells brushed or scraped off
      • Cervical cytology, bronchial brushing
    • Cells removed by fine needle aspiration
      • Breast/Thyroid/Lymph node FNA Breast/Thyroid/Lymph node FNA (fine needle aspiration biopsy)
        • Jiggle needle up and down to get cells, aspirate then look under microscope. Each time it moves past the tumour mass, it takes up some tissue

Gauge is the reciprocal of the diameter of the needle in inches. 18 gauge = drip, 21 gauge = taking blood (too small = too much pressure, lyses red cells)

Case 1

  • 53 male
  • Accountant, second marriage
  • Children 25, 21 and 15 years of age
  • Pneumonia 3/12 ago
  • Second episode of pneumonia 3/52 ago
  • CXR shows poorly defined opacity near hilum


  • Recurrent pneumonia = obstruction
    • Due to impaired drainage
  • Think about tumour: mass in the hilum and recurrent pneumonia. Do cytology to find out
  • Sputum culture = non-invasive
    • Dx = Squamous cell carcinoma of the lung
    • Increased N:C ratio
    • Coarse chromatin
    • Irregular membrane
    • Cytoplasm full of protein (cytokeratin – typical of squamous cells)
    • Non-small cell cancer
      • Behave differently
      • Predicatble spread
      • Can be treated more easily
  • Clusters of cells together - epithelial in origin therefore carcinoma
  • Most likely lung cancer = squamous cell carcinoma
    • To understand the differentiation of the cell, you must look at the cytoplasm = cytokeratin protein in cytoplasm
  • The two clinical types of lung cancer = small cell and non-small cell.
  • Nonsmall cell = spread to lymph nodes, predictable pathway
  • Histological diagnosis = guide treatment
  • Since it's nonsmall cell, you can resect it, potentially cure it

Case 2

  • 71 female
  • Widower, 4 children
  • P/S – haemoptysis
  • 90 pkt years
  • CXR – NAD


  • Sputum biopsy, bronchoscopy + take brushings
    • No cytoplasm visble
    • Irregular membrane
    • Clustered = epithelial
    • Poorly differentiated
    • Small cell lung cancer cells
      • Pattern of differentiation usually = neuroendocrine (well differentiated = carcinoid, poorly = small cell)
      • Poor prognosis, very aggressive, likely metastasised
      • Poorly differentiated
      • Essentially incurable
      • Responds well to chemo for a while, but in the end is only palliative


Case 3

  • 68 yo female
  • Non-smoker
  • Persistent cough
  • CXR - Poorly defined peripheral mass lesion
  • ciliated pseudostratified columnar epithelium (respiratory), one cell on the left. On the right, we have malignant cell (cytological features of malignancy
  • Cell sample obtained by bronchioalveolar lavage
    • Bronchoscope flood salt water in part of lung with lesion and then sucked back up (bronchoalveolar lavage)
    • Ciliated columnar epithelial cell (resp. epithelial cell) (Normal)
    • Signs of malignancy again
    • Large nuclei
    • Dx = adenocarcinoma
      • Cytoplasm – full bubbly, pale mucin. - full of mucus
      • Therefore glandular cells
    • Tx
    • Resect primary tumour if no metastatic spread

NB: large cell = diagnosis of exclusion, no glandular or squamous differentiation

Benefits of Cytopathology

  • Rapid
  • Cheap
  • Painless
  • Few false positives

Limitations of cytopathology

  • Skill and training of cytotechnocians and cytopathologists
  • Sampling error, causing false negatives
  • No information relevant to staging
  • Good at making a diagnosis, but not very good at excluding diagnosis. So if you find a lump, you're obliged to remove it.

Biopsy Diagnosis of Cancer

  • Incision biopsy (colorectal cancer)

(Frozen sections are a type of incisional biopsy that will be considered later)

  • Core biopsy (prostate cancer)
    • Gives architecture of cells unlike fine needle aspiration
    • Used in US-guided prostatic biopsy (can't biopsy across surgical barriers as cells may fall back out in biopsy tract)
  • Excision (breast cancer)
    • If palpable then usually excised in total
    • If mammogram shows, but not palpable, then excise with image assistance

The needle has a sheath around the outside of it, so that between the needle and the sheath, a tissue sample will be collected.

Excisional biopsy methods

  • Excision of visible mass
    • skin
    • endoscopic biopsy e.g. wire wrapped around pedunculated colonic polyp
  • Excision of palpable mass
  • Imaging-assisted excision
    • I.e. hookwires for poorly defined or non-palpable breast lesions
    • Use hookwire to label what to dig out

Special Procedures in Cancer Diagnosis

  • Intraoperative diagnosis = 'frozen sections'
    • Allows real tiem decision making e.g. know the extent of spread of the tumour during the operation.
    • Labour intensive and disruptive
    • Difficult to interpret technically
    • Possibility of communication error
    • No patient involvement in decision making
  • Flow cytometry
    • Used in haemotological malignancies
    • Cells from blood or disaggregated lymph tissue are used
  • Serum tumour markers
    • Proteins in blood released from tumours
    • Useful aid to diagnosis
    • Eg. PSA, carcinoembryonic antigen (colon, pancreas, stomach, other), beta-HCG, alphafetoprotein (liver)
  • Molecular diagnosis of cancer
    • Not generally used at present, diagnostic in certain uncommon tumours (t cell receptor clonality, Bcr/Abl)
    • Useful in specific treatment decisions
    • Useful to see clonality - for looking at distinctive genes in a population, and showing that all cells in a population are identical (clonal). Also drugs target particular genetic mutations in tumours. e.g. her2/neu for herceptin

Diagnosis in the setting of metastatic cancer, unknown primary

  • Sex
  • Location of lesions
  • Clinical features
  • Investigations
    • Imaging procedures
    • +/-Endoscopy
    • +/-Serum tumour markers
    • +/-Biopsy of metastasis +/- special stains

Case 4

  • 78 male
  • Worsening back and chest wall pain
  • X-ray showed multiple

sclerotic bony mets

  • Do PSA
  • Ddx
    • Prostate cancer
    • Multiple myeloma
    • Hodgkins
    • Lymphoma
  • Confirm diagnosis
    • PSA = 64
    • Very high therefore very specific
    • Could get tissue for immunochemistry
    • BPH would cause like 5-8, but not 64. Cutoff is 5.

Note that sclerotic is the same as blastic.

Goljan says DRE is better than PSA

Case 5

  • 69 female multiple hepatic mets
  • No primary identified clinically
  • Past history of breast cancer removed 12 years earlier
  • Liver mets
    • Lung, breast, colon
  • Do needle biopsy of liver
    • Lets us diagnose better
    • Adenocarcinoma
    • Look for oestrogen receptors (likely to be mets from breast, can compare tissue)
    • Treat with tamoxifen if oestrogen receptor positive

NB - Mammography is a screening thing to check for asymptomatic lesions