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Quiz funtimes

  • What is correct?
    • They are polyclonal unlike malignancies which are monoclonal (NO - all neoplasms are monoclonal)
    • They lack stromal blood vessels to support their growth (NO - otherwise they couldn't survive)
    • They are always encapsulated (NO - e.g. bowel polyp)
    • They do not metastasise, but can still have fatal consequences ANSWER (intracranial; hormone excess (hypoglycemia in insuloma); bleeding due to leiomyoma of stomach)
  • What is not true of malignant?
    • Angiogenesis and metastasis
    • Decreased proliferative fraction (percentage of cells entering the cell cycle) (ANSWER; this should be high)
    • Invasion into tissue
    • growth independent of external signals
    • Failure to respond to inhibitory
  • Which is important for histo typing?
    • How widely the tumour has metastasised
    • The degree of differentiation of neoplastic
    • Extent of local invasion
    • Pathway of differentiation of tumour cells (ANSWER)
  • GRADE = degree of differentiation; STAGE = T, N, M; TYPE = name
  • Rare types of breast cancer have a better prognosis
  • Used for finding point of origin of mets, and for prognosis
  • Which is correct, which is most common
    • Carcinoma - malignant tumour showing epithelial diff TRUE Most common because 1) epithelial cells exposed to environment and 2) have stem cells so they have a greater capacity for self-renewal than other types
    • Sarcoma - benign tumour showing mesenchymal diff INCORRECT (these are malignant neoplasms)
    • Leukaemia - malignant neoplasm arising in bone marrow from haematopoietic cells CORRECT
    • Myeloma - malignancy of the spinal cord (B cell one) INCORRECT
    • Lymphoma - benign neoplasm of lymphocytes and their precursors INCORRECT
  • What's associated with breast cancer?
    • Western diet - high fat, low fibre TRUE
    • Long term HRT TRUE (but not much)
    • Early menarche, late menopause and nullparity TRUE (length of exposure of epithelium to oestrogen)
    • Age TRUE
    • Genetic predisposition e.g. BRCA1 and BRCA2 TRUE (5-10% correspondence)
  • By which of the following methods might a diagnosis of breast be confirmed
    • Clinical history/exam
    • Mammography; suggestive - not confirm
    • Cytological assessment of FNAB TRUE
    • Core needle TRUE
    • Open surgical biopsy TRUE
  • Core needle +/- cytological specimen are all that's needed
  • Microscopic appearances of carcinoma of breast
    • Histopathological typing has little influence on prognosis (60% 30 year survival compared to 20% with no type)
    • Histopathological grading provides assessment of degree of differentiation (YES)
    • Histo is most important factor in prognosis (NO Staging is more important)
    • Invasion of lymphatics or bvs by tumour is indicative of worse prognosis (YES; lymph node involvement)
  • Which is useful
    • Site of primary tumour
    • Local invasion
    • Axillary lymph node metastases
    • Oestrogen and/or progesterone receptors in tumour cells
    • Overexpression of Her2/neu
  • Answer: ABC; stage 0 - LCIS, 92%; 1 - CIS without nodes; 87%; 2- invasive with <3 N (75%; 3-invasive with >4, etc
  • Radionucleotide scan
    • Two ribs show increased uptake of radionuclide consistent with metastatic carcinoma
    • Clinically - pain on inspiration and tenderness over ribs
    • Metastases in axial skeleton are common because of presence of vascular red marrow
    • Woman was hypercalcaemic (FALSE)
    • Metastatic disease might also be found in lungs, liver and brain
  • All the rest are true; multiple rib lesions are commonly caused by carcioma
  • Pathological fractures = pain and tenderness
  • Mets in bone = highly vascular red marrow, brain bone, etc
  • Likely cause of death with metastatic disease? Explain underlying mechanism
    • Massive pulmonary embolism - cachexia and immobilisation --> DVT
    • Bronchopneumonia - cachexia -> weak cough -> inadrequate clearance of secretions. Immunosuppression, respiratory depression --> infection. Die from hypoxia and sepsis
    • Intracranial herniation syndromes; mass effect
    • Liver failure; due to metastasis
  • All are true

Group presentations from homework

  • BC: female: male = 150:1
  • 3 dates have a major impact on BV: first menarche; age at first full term pregnancy; menopause
  • Linear increase with age until menopause
  • Decrease after menopause

NSW epidemiology

  • Most common cancer in women (28% of new cancer) in NSW
  • 17% of female cancer deaths (2nd after lung cancer)
  • 1/9 will develop breast cancer at age of 85
  • average age of first diagnosis in women in 60 years
  • indigenous women are less likely to be diagnosed than non indigenous
  • Risk factors: age; reproductive (nulliorous, having children ager 30, early menarche, late menopause, no or limited breast feeding); excessive alcohol consumption, obesity, family history, HRT
  • Prevention - regular physical activity, high vegetable consumption, breast feeding
  • BreastScreen every 2 years

Comparison to other cancers

  • Most common cancer in NSW
  • Leading cance cause of burden of disease = 61100 DALYs in Australia; 40600 years of life lost due to premature death
  • All people - breast cancer is 3rd most common
  • Women - breast cancer is leading cancer
  • Breast cancer incidence has stayed the same in the past 10 years
  • Breast cancer is 2nd leading cause of cancer death in females; in all people it is the 4th leading cause of cancer death
  • Survival rates are improving. Reduced 27% from 1994 to 2007. 5-year relative survival rate has increased from 72% to 88%. Due to earlier detection, changes in risk factors, improved treatments.

Asian BC rate

  • Asians have 1/3 the risk compared to Americans (27/100k vs 93/100k)
  • Asians have a trend of earlier parity and higher breast feeding rate
  • Less people on COCP, HRT, and lower post-menopause obesity
  • Diet - larger soy intake (linked to less BC; due to isoflavins in soy that protect it from carcinogens)
  • Other factors re: Asians = smaller heights, lower growth rate, less alcohol intake, lower reporting

Migration effecting boob cancer incidence

  • Higher in western countries
  • Asian migrants - risk increases esp with generations
  • Modifiable risk factors in America
  • Exposure to western lifestyle in early age gives risk

Factors contributing to these phenomena

  • Exposure to western diet + culture
  • Incidence of BC in asia with westernisation

Mammogram

  • The quality of the mammograms should be assessed, and if not optimal, repeat examinations may be ordered. Mammograms of the right and left breasts are first placed back to back (mirror images) for comparable projections. Lighting should be homogenous, and adequate viewing conditions should be maintained. *The mammograms are inspected carefully. The search is done systematically through similar areas in both breasts, comparing them all the times.
  • First, breast symmetry, size, general density, and glandular distribution are observed. Next, a search for masses, densities, calcifications, architectural distortions, and associated findings is performed. For masses, the shape, margins, and density are analyzed. Malignant lesions tend to have irregular and (usually) spiculated margins. Malignancies, especially scirrhous cancers, also tend to have density greater than that of the normal breast tissue. Very low density, such as that of fat, is seen in benign lesions (eg, oil cyst, lipomas, galactoceles, hamartomas).
  • Benign calcifications are usually larger than calcifications associated with malignancy. They are usually coarser, often round with smooth margins, and more easily seen. Benign calcifications tend to have specific shapes: eggshell calcifications in cyst walls, tramlike in arterial walls, popcorn type in fibroadenomas, large and rodlike with possible branching in ectatic ducts, and small calcifications with a lucent center in the skin.
  • Calcifications associated with malignancy are usually small (<0.5 mm) and often require the use of a magnifying glass to see them well. They tend to have a pleomorphic or heterogeneous shape or a fine granular, fine linear, or branching (casting) shape.
  • The distribution of the calcification should be specified as grouped (clustered), linear, segmental, regional, or diffuse.
  • Special findings, such a linear density that might represent a duct filled with secretions or reniform shape of intramammary lymph nodes (with a radiolucent center) may be encountered.
  • Associated findings are then taken into account. These include skin or nipple retraction, skin thickening (which may be focal or diffuse), trabecular thickening, skin lesions, axillary adenopathy, or architectural distortion.
  • The lesion seen is located by using the views to either of the inner or outer or the lower or upper quadrants. It may also be central or retroareolar. The lesion can be described in a clock position. The breast is viewed as the face of a clock with the patient facing the observer. The depth of the lesion is assigned to anterior, middle, or posterior third of the breast.
  • If previous examination results are available, their comparison is useful in assessing disease progress.
  • All of these findings are considered together, a final impression is formed, and a BI-RADS category is assigned.
    • Category 0 - Need additional imaging evaluation
    • Category 1 - Negative
    • Category 2 - Benign finding, noncancerous
    • Category 3 - Probably benign finding, short-interval follow-up suggested
    • Category 4 - Suspicious abnormality, biopsy considered
    • Category 5 - Highly suggestive of malignancy, appropriate action needed
  • Category 0 is a temporary category that means additional imaging is needed before assigning a permanent BI-RADS assessment category. Most category 0 findings are shown to be benign after additional imaging is completed.
  • 2. What is the sensitivity of mammographic screening for 50-69 year olds in Australia attending breast screening? What does this mean?

89% sensitivity (first round screening), less for subsequent screening rounds (84%) (for invasive breast cancer, from page 27 of the AIHW (2006) report- ref below). This means that nearly nine out of ten women aged 50-60 years old attending this screening who have breast cancer are detected on their first mammogram. Sensitivity falls off after first screening as less women have cancer to be detected in the second and subsequent rounds, despite the ageing effect. *Density of breast tissue also affects sensitivity: lower sensitivity for denser breasts.

  • Specificity is the % of correctly identified screened patients who have no cancer. Harder to get evidence on this: around 90% in general for screened women and this is lower if symptomatic (nearer 70%) and higher if asymptomatic (over 90%).This means that a lot of women (10% false positive rate, which in this condition is 10% of most of the women screened) will be sent for additional tests with the thought that they may have cancer when they actually haven’t.
  • Interval cancer is the diagnosis of cancer between screening rounds. (The interval cancer rate is the rate of invasive breast cancers detected during an interval between two screening rounds per 10,000 women-years).
  • 3. Does the sensitivity of mammography alter for the various age groups of women who are screened (e.g. those under 50 who request screening versus those aged 50-69 years)? Use examples to show what you find.
  • The following paper (and others that the students may find) show that sensitivity increases with age. This is probably due to combined effect of decreasing density of breast tissue, those reading the mammograms knowing that cancer is more likely in older subjects and therefore taking more care or being more ready to call a lesion ‘cancer’, and an increase in prevalence of the disease with age. Students might attempt to illustrate this with a hypothetical or real patient from the literature if possible.
  • Rosenberg RD. Hunt WC. Williamson MR. Gilliland FD. Wiest PW. Kelsey CA. Key CR. Linver MN. Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico. [Journal Article. Research Support, U.S. Gov't, P.H.S.] Radiology. 209(2):511-8, 1998 Nov.
  • 4. Is the sensitivity of mammography different if there is already a lump compared to a screening mammogram of someone with no symptoms or signs who attends a population screening program? Use examples to show what you find.
  • Mammography has 90% sensitivity and 70% specificity (for symptomatic patients) (from Segelov (2000) below). This is slightly higher than for screening as would be expected, because with the suspicion already there, perhaps more care is taken when viewing the mammogram. Thus, 30% of women without invasive breast cancer will be incorrectly be given a positive result with this test (false positives) and 10% of women who actually have invasive breast cancer will have their cancer missed by this particular method (false negatives). The Moss et al (1999) study shows less favourable figures overall and suggests that ultrasound increases the accuracy of diagnosis. (This is just one paper though, rather than an evidence-based review). Ultrasound should definitely be used in younger women (<35 years) and in those whose mammograms are difficult to interpret. A diagram in Segelov (2000, p. 99) shows a suggested route for diagnosis that yields the most accurate results.
  • 5. What role does ultrasound of the breast have in breast cancer diagnosis and/or staging?
    • Ultrasound is an imaging test that sends high-frequency sound waves through your breast and converts them into images on a viewing screen. The ultrasound technician places a sound-emitting probe on the breast to conduct the test. There is no radiation involved.
    • Ultrasound is not used on its own as a screening test for breast cancer. Rather, it is used to complement other screening tests. If an abnormality is seen on mammography or felt by physical exam, ultrasound is the best way to find out if the abnormality is solid (such as a benign fibroadenoma or cancer) or fluid-filled (such as a benign cyst). It cannot determine whether a solid lump is cancerous, nor can it detect calcifications.
    • If you’re under age 30, your doctor may recommend ultrasound before mammography to evaluate a palpable breast lump (a breast lump that can be felt through the skin). Mammograms can be difficult to interpret in young women because their breasts tend to be dense and full of milk glands. (Older women’s breasts tend to be more fatty and are easier to evaluate.) In mammograms, this glandular tissue looks dense and white — much like a cancerous tumor. Some doctors say that locating an abnormality in the midst of dense gland tissue can be like finding a polar bear in a snowstorm. Most breast lumps in young women are benign cysts, or clumps of normal glandular tissue.
    • Doctors also can use ultrasound to guide biopsy needles precisely to suspicious areas in the breast.
    • Ultrasounds can't detect tiny calcifications that mammograms can
  • 1. Describe what happens when someone has a fine needle biopsy.
  • Specimen
    • Aspiration of material for cytological examination through a fine bore needle (approximately 23-25 gauge) can be performed from virtually any site.
    • The technique is best performed by a trained cytopathologist who will also evaluate the smears. Other clinicians, such as surgeons and radiologists, frequently perform the technique after appropriate training and supervised experience, and may request attendance of laboratory staff to aid in smear preparation and indicate adequacy of material (especially during X-ray, **CT or ultrasound guided aspiration).
    • Clinical information is essential.
  • Method
    • Tissue is obtained following puncture of the lesion and careful movement of the tip of the needle within the lesion; gentle suction may be applied.
    • For superficial palpable lesions the needle may be moved back and forth with a fanning action providing wider sampling and cell dislodgement.
    • In most cases, the aspirated material remains in the needle (unless cyst fluid present), and is then expressed onto pre-labelled slides and smeared out rapidly.
    • Care needs to be followed when expressing material onto slides in patients with suspected infection e.g. tuberculosis.
    • Ideally this should be undertaken in a controlled biohazard cabinet.
    • Both air-dried and 70-95% ethanol or commercial spray wet fixed smears are preferred, but may depend on the tissue being sampled and on the preference of the reporting pathologist.
    • Tissue remaining within the needle, or a repeat aspirate, may be washed out in a non-fixative solution and used for microbiological examination, cytocentrifuge preparations, hormone receptor evaluation, cell block preparation, immunohistochemistry, cytogenetics, molecular genetics, or EM (special fixative).

If there is clinical suspicion of lymphoma or reactive lymph node, material may also be sent for cell surface markers.

  • Application
    • Fine needle aspiration biopsy is valuable in the diagnosis of superficial and readily accessible lesions e.g., skin and breast.
    • With organ imaging techniques, deeply situated organs can be sampled.
    • The technique is used mainly in the primary diagnosis of neoplasia and for the assessment of disease recurrence. Infections and benign lesions are also readily evaluated.
    • Some neoplasms and well differentiated lesions may result in an abnormal but equivocal diagnosis requiring histological confirmation (eg, follicular neoplasms of thyroid, well differentiated hepatocellular carcinoma).
  • Interpretation
    • Report by pathologist identifies the nature of the lesion sampled.
  • 2. What is the sensitivity and specificity of this diagnostic test? What does this tell you about this test?
    • These figures vary with skill of operator and histopathologist and whether ultrasound is used to target the sample. Sensitivity around 92% and specificity nearer 100%. Basically this is better than mammography and ultrasound alone but surgical biopsy is still recommended if malignancy is suspected from the other tests and FNAC is negative. This is because nearly 10% of women with an invasive cancer are still missed by this test (these are the false negatives).
  • 3. Describe what happens when someone has a core biopsy.
    • A wide bore needle is used to remove a small piece of tissue, called a core, from the lump or abnormal area in the breast. It is usually done under a local anaesthetic. An ultrasound or mammogram is used to help guide the needle. A core biopsy may be uncomfortable and the woman may experience some pain.
    • Core biopsy is more invasive than fine needle aspirate
  • 4. Does a negative biopsy mean there is no cancer?
    • As discussed above a fine needle biopsy alone may not detect a cancer. Surgical or core biopsy might miss a very few also despite their sensitivities being nearer 100%. Using clinical examination, diagnostic mammography and fine needle aspiration together is recommended by Segelov (2000) with a high combined sensitivity.