Breast Flashcards
In terms of pathology, where do most of the breast diseases arise?
The terminal duct lobular unit (TDLU)
The entire ductal-lobular system of the breast is lined by two cell types, what are they?
The inner epithelial cells and outer myoepithelial cells
Why are the myoepithelial cells important in pathology?
Normal function of myoepithelial cells = to contract and propel the secretion forwards, but in pathology it is used as a surrogate marker of differentiating between in-situ and invasive disease. Remember that it is invasive disease once it has invaded the basement membrane, however this can be difficult because invasive tumours can produce their own basement membrane after invasion, so if you stain them for basement membrane material (collagen and laminin), you might be able to find it, so we stain the cells for myoepithelial markers.
What do the markers mean?
If there is in-situ disease, there will not only still be a basement membrane, but the myoepithelial cell layer as well. But if it is an invasive tumour, to invade the basement membrane they have to destroy the myoepithelial cells too.
Name some commonly used markers for myoepithelial cells
Cytokeratin ck5/6, p63 and smooth muscle myosin (SMM)
Give examples of inflammatory diseases of the breast
Acute mastitis
Chronic mastitis
Mammary duct ectasia
Fat necrosis
Tell me about acute mastitis
Usually occurs during the lactation period if the nipple is not looked after very well, because it develops some cracks, allowing bacteria to gain access to the breast, causing it to become acutely inflamed. Advise to breastfeed 8-12 times per day to allow effective milk removal. You can treat with antibiotics if severe. Complications include abscess formation and chronic mastitis.
And chronic mastitis…? What are the two types?
There are two specific types of chronic mastitis. Clinically are not very common but may mimic cancer. 1. Chronic lymphocytic lobulitis. 2. Idiopathic granulomatous mastitis
Tell me about chronic lymphocytic lobultiis
You can see lymphocytes infiltrated within the lobule and the stroma is densely fibrotic. Clinically, produces a very hard lump like a cancer, and can look like a cancer on a radiograph, so we confirm the diagnosis through biopsy, looking for the features described above. Clues in the history: often a history of diabetes, patient >40 yrs
Tell me about idiopathic granulomatous mastitis
Called granulomatous because granulation tissue formation (which is a collection of modified macrophages). We don’t know the cause. ? Some kind of immune response to the antigens in the breast, producing a granuloma. After excluding other causes of granulomas e.g. infective aetiology, when you label as ‘idiopathic granulomatous mastitis’, they need to be treated conservatively. If you perform surgery, you will cause it to further flare up and may end up having to do mastectomy.
What is fat necrosis of the breast?
Can occur because of trauma or because of rupture of a cyst. Clinically can look like cancer because it produces a hard mass. Whenever there is a fat necrosis there will be suppurative dystrophic calcification. One of the features we look for radiologically in cancer is calcification and density, and lesions of fat necrosis produce both calcification and density. However, when you take a biopsy and look under a microscope, you can prove there are macrophages etc, and that it is indeed fat necrosis.
What is mammary duct ectasia?
Duct ectasia means dilatation of the duct. This usually produces periductal inflammation and because of the inflammation, patients can sometimes get a bloody nipple discharge. But bloody nipple discharge is another potential feature of breast cancer. Investigations may include a nipple smear, or biopsy of the area
In terms of proliferative disease, what is a radial scar?
A scar is a dense fibrous tissue that occurs at the end of healing. Radial scars are not related to trauma, but mostly a condition called sclerosing adenosis. It is ‘radial’ because the fibrous tissue pokes out in spikes. This produces a soft tissue density with irregular borders and can hence mimic malignant neoplasm. Even though it is benign, in <1% of cases it is associated with malignancy- so they need to be excised.
Tell me about fibrocystic change
It is a proliferative change of the breast that is age-related and not technically a disease. It is common in 25-45 year olds. Occurs due to the hormonal cycling of oestrogen and progesterone. Cysts slowly grow each cycle under the influence of these hormones. These cysts can cause inflammation and calcium deposition (so can look like cancer on mammography).
What is the difference between hyperplasia and neoplasia?
Both are proliferation of cells, but hyperplasia is when growth is under physiological control, whereas neoplasia is when the cells proliferate without physiological control.
What is the difference between adenoma and papilloma?
Both are benign epithelial tumours. Adenomas form gland structures, whereas papillomas form finger-like structures.
What is the difference between carcinoma and sarcoma?
Both are malignant. Carcinoma is a malignant tumour of epithelial differentiation, and sarcoma is a malignant tumour of mesenchymal differentiation (bone, cartilage, connective tissue etc).
Name some benign neoplastic diseases of the breast
Adenoma
Fibroadenoma
Papilloma
Which is the most common benign tumour of the breast?
Fibroadenoma
Tell me about fibroadenomas
A fibroadenoma is when the benign tumour has both glandular and fibroblastic proliferative changes (so it’s a mixed tumour with both epithelial and mesenchymal differentiation i.e. composed of both proliferating ducts and connective tissue stroma). Often occurs between the ages of 20-35. Get bigger in size in pregnancy but become small and fibrotic after menopause so no need to excise them. No malignant potential. Microscopically, (like any benign tumour), there is a circumscribed border, and in the case of fibroadenoma you will see proliferation of both epithelial and mesenchymal elements.
Name some malignant neoplastic diseases of the breast
Carcinoma
Sarcoma
Paget’s disease
Phylloides tumour
What signs and symptoms might you find regarding a breast lump and what would they make you think about?
Diffuse- fibrosis, fibrocystic change
Discrete- neoplasm, cyst, abscess, hamartoma
Mobile- benign neoplasm
Tethered- Carcinoma
What is a cyst?
A cavity lined by epithelial cells which secrete fluid.
How commonly are the various diseases diagnosed after someone presents with a breast lump?
No disease (30%) Fibrocystic change (40%)- remember is not technically a disease Cancer (malignant) (10%) Fibroadenoma (7%) Miscellaneous benign (13%)
Consider other presentations of the nipple and what they might mean
Milky discharge- pregnancy?
Bloody discharge- duct papilloma/ carcinoma?
Retraction- invasive carcinoma
Erythema/scaling- Paget’s or eczema
What is Paget’s disease of the breast?
A type of cancer (in-situ malignancy involving the epidermis) that has the outward appearance of eczema, often involving the nipple. Associated with underlying (2%) ductal carcinomas. There is involvement of epidermis by malignant ductal carcinoma cells. Clinically there is roughening, reddening and slight ulceration of skin.
What is a phylloides tumour?
Phylloides= Greek for ‘leaf-like’
A mixed tumour of epithelial and mesenchymal elements- must be considered as a differential when diagnosing fibroadenoma (which is a benign mixed tumour). If a phylloides tumour is malignant, it is the mesenchymal component (so if any malignancy occurs it is a sarcoma and not a carcinoma). Treatment is wide local excision. Recurrence is common. Usually occurs in the 4th and 5th decades of life.
How do carcinomas vs sarcomas like to metastasise?
Carcinomas prefer to spread via the lymph nodes, however sarcomas prefer to go via the blood to distant organs.
What is the skin feature of peau d’orange usually indicative of?
Stands for skin of an orange. Many conditions can cause it. Appearance is usually due to oedema. May be a symptom of inflammatory breast cancer, which is where rather than forming a tumour, the cancer cells block the lymphatic vessels.
Give some statistics on carcinoma of the breast
20% of all cancers in women. In the UK 1 in 8 women will develop breast cancer. It is the commonest cause of death in women aged 35-55 years.
Give some risk factors for breast cancer
Family history I.e. Genetic factors (BRCA1- Chr 17, ovary and breast. BRCA2 - Chr 13). FHx particularly important in 1st degree relatives. 1.5–2 times if 1 relative. 4-6 times if two affected relatives.
Increased oestrogen exposure: female sex and age. Reproductive history: early menarche, late menopause, nulliparous women, 1st pregnancy after 30 years of age.
Obesity
How can carcinoma of the breast be classified?
Into in-situ vs invasive. And in terms of morphology: ductal vs lobular.
Therefore give the names of the in-situ and invasive types of carcinoma
In-situ carcinoma:
Ductal carcinoma in-situ
Lobular carcinoma in-situ
Invasive carcinoma:
Invasive ductal carcinoma (75-85%)
Invasive lobular carcinoma (10%)
Others (5%)
Tell me a bit more about each of the 4 types of breast carcinoma I need to know about
Ductal carcinoma in-situ (DCIS)- looks like a large duct filled with neoplastic cells. Can produce a Chinese letter appearance on a mammogram.
Lobular carcinoma in-situ (LCIS)- looks like a lobule, but is filled with neoplastic cells. Proliferation is confined within lobule and is lined by double layers of cells (epi + myoepithelial)
Invasive ductal carcinoma- same as DCIS but you see single cell layers (no myoepithelial cell layer).
Invasive lobular carcinoma- same as LCIS but you see cells that have invaded into the stroma. These cells aggregate in single-file lines.
Give some examples of treatments for breast cancer
Surgical excision (main treatment)
Chemotherapy (sometimes given before surgery to shrink the tumour- called neo-adjuvant treatment).
Radiotherapy
Hormonal therapy (tamoxifen in ER positive, Herceptin in HER2 positive)
What does carcinoma prognosis depend on?
Size of tumour Grade of tumour Histological type of tumour Vascular invasion Stage of tumour - nodal status Receptor status of the tumour
What is the aim of the breast cancer screening programme? And how does it work?
To detect breast cancer early, thereby reducing mortality. All women aged 50-70 years old are invited for mammographic examination every 3 years. Now ages 47-73 invited for mammogram.
What is the marker for breast cancer on imaging?
Microcalcification
Where do we see this microcalcification histologically?
It is usually associated with DCIS, mostly high grade with central necrosis.
Is microcalcification always malignant?
No, it can associated with fat necrosis and fibrocystic change.
Do all breast cancers have microcalcification? And what other mammographic appearances can you get with breast cancer?
NO.
Can also get:
Circumscribed soft tissue density/ mass lesion
Stellate lesion (a form of architectural distortion where spicules radiate from a central point or mass)
BUT remember these are not specific for breast cancer
What is involved in the triple assessment of the breast?
- Clinical examination
- Radiological imaging: mammography (>40), ultrasound (<40)
- Pathology: Fine needle aspiration (FNA), Core biopsy
What is the peak age for diagnosis of breast cancer?
70-74 years
Tell me about the drug Tamoxifen
Tamoxifen is a SERM (Selective oestrogen receptor modulator).
Mainly used in the treatment of breast cancer. Remember that oestrogen causes breast and uterus proliferation. A selective oestrogen receptor modulator, means it does different things in different tissues. In breast blocks ER (partial agonist) therefore decreases breast proliferation and protects against cancer. In the uterus it is an agonist of ER, therefore increased risk of uterine cancer. In the bone, agonist of ER, therefore increased bone protection.
Indications for use: ER positive breast cancer. Infertility due to anovulation (disinhibits HPA axis, increasing LH and FSH). Gynaecomastia.
Side effects:
Major: increased risk of uterine cancer, stroke, vision problems and PE
Minor: irregular periods, weight loss and hot flushes
Administration: orally for 5 years
Tell me about Anastrozole
It is an aromatase inhibitor drug used in ER positive and PR (progesterone receptor) positive breast cancer. (Another example = letrozole).
Target physiology: testosterone is synthesised from cholesterol in the hormone pathway. Testosterone -> oestradiol via the aromatase enzyme.
Mechanism of action: reversible competitive inhibition of aromatase enzyme. This decreases the amount of oestrogen in the body. In the breast, this reduces proliferation and treats breast cancer. However in the bone, this blocks oestrogen’s protective effects -> bone loss.
Indications: ER positive and PR positive breast cancer.
Side effects: Hot flushes, altered mood, increased risk of osteoporosis and heart disease
Contraindications: none, but beware of osteoporosis
Dosage: orally for 5 years
Tell me about Herceptin (aka.Trastuzumab)
Used in the treatment of HER2 receptor positive breast cancer.
Target physiology: The HER2 pathway promotes cell growth and division when functioning normally. This is achieved because HER2 is an EGFR which when activated -> MAPK pathway -> gene upregulation. In some cancers, it is over-expressed, leading to uncontrolled and unregulated cell growth and division.
Mechanism of action: monoclonal antibody targeting HER2 receptor. The cell therefore arrests in the G1 phase of growth.
Side effects: flu-like symptoms, nausea and diarrhoea
contraindications: pregnancy, underlying heart conditions
Route of administration: slow IV injection, s/c
What is the triple assessment of the breast?
History and examination, imaging (USS, mammogram) and sampling (FNAC and core biopsy)
What is Tietze syndrome?
Inflammation of the joints between the sternum and the ribs. Often worse on pressing on the joints. Can present as ‘Breast pain’.
Which breast condition can present with bloody/clear nipple discharge from a single duct.
Intraductal papilloma
How does duct ectasia tend to present?
Multi duct discharge which can be classically green in colour. May also have transverse slit-like nipple retraction bilaterally
Roughly what % of breast cancers are due to BRCA1 and BRCA2 mutations?
~5%
Tell me about mammography
Uses low dose x-rays. Each breast compressed between 2 plates. 2 views are taken. Detects an abnormality requiring some form of further investigation in approximately 5% of women between 50 and 70 in the UK.
Tell me about ultrasound scanning for the breast
Uses high frequency sound waves (so no radiation). More comfortable than mammography. Very good for detecting cysts. Tends to be used for women <35 years of age.
Tell me about FNAC (fine needle aspiration cytometry) of the breast
(Note that both FNAC and core biopsy require imaging guidance with ultrasound scanning). A fine needle is used to biopsy the breast lump. This does not require local anaesthetic. Material aspirated is placed on a slide and immediately fixed. In some circumstances the aspirate doesn’t need to be sent for cytological analysis e.g. clear or yellow fluid from a suspected breast cyst.
Tell me about core biopsy of the breast
A core of tissue from the breast lump is extracted using a large bore needle. Unlike FNAC, this does require local anaesthetic. Imaging guidance improves overall diagnostic accuracy e.g. with USS. The sample is sent for histological analysis to determine the tissue type.
Is DCIS or LCIS more common?
DCIS is more common (comprises 85%) and LCIS comprises 15% of in situ carcinomas
