ERS31 Pathology Of The Breast Flashcards
1
Q
Structure and function of normal breast
A
Breast:
- ***Modified sweat gland
—> develop into complete functional structure in female
—> remain rudimentary in male
- Respond to various physiological stimuli
- Go through stages of alteration through life:
—> Development + Puberty
—> Maturation + Differentiation (in fertile age)
—> Lactation
—> Involution, Senile atrophy - Sensitive to **Ovarian hormones, **Hormones of pregnancy, ***other growth factors in female breast
—> predispose to pathological conditions
3 major components:
- Skin
- SC adipose tissue
- ***Functional glandular tissue
Structure:
- Divided into 15-25 lobes
—> each based on a branching duct system —> lead to ***Terminal duct-lobular unit (最入): functional site of milk production
—> each lobe has 20-40 lobules
2
Q
Terminal duct-lobular unit
A
Ducts + Acini all lined by
- Epithelial cells (面)
- Myoepithelial cells (底)
(3. with Basement membrane, Intralobular CT)
Acinus —> ***Lobule (contain multiple acini) (***Hyperplasia, Carcinoma, Fibroadenoma, Cyst) —> Terminal duct —> Subsegmental duct (Papilloma) —> Segmental duct (Papilloma) —> ***Lactiferous duct (Papilloma) —> Lactiferous sinus —> ***Nipple (Paget’s disease of breast)
3
Q
***Clinical presentations of breast diseases
A
記: Pain, Lump, Discharge
- ***Pain
- ***Presence of dominant lump
- ***Abnormal nipple discharge
Benign breast condition mimic breast cancer
4
Q
Breast pathologies
A
- Inflammatory lesions
- Fibrocystic disease (40%, most common)
- Proliferative lesions of breast
- Tumours
- Benign tumours
- Phyllodes tumour
- Breast carcinoma (10%)
5
Q
- Inflammatory lesions
A
- Acute mastitis / Breast abscess
- uncommon except during lactation
- **abrasion / crack acquired from mouth of baby —> infection via nipple
- hot, swollen, red
- may mimic **Inflammatory breast cancer - Mammary duct ectasia (dilation)
- unclear etiology
- **Dilated ducts filled with cheesy material in area adjacent to areola
- Ulceration of ducts —> Liberation of lipids into CT stroma —> Chronic **Granulomatous inflammation —> **Fibrosis of CT —> **nipple retraction (mimic carcinoma) - Fat necrosis
- due to trauma
- most common in **obese, pendulous breast
- Localised **firm / hard mass occasionally ***adhered to skin —> easily mistaken for carcinoma
- Traumatic rupture of fat cells —> Foreign-body granulomatous reaction —> Fibrosis - Other granulomatous lesions
- Paraffin wax / Silicone fluid for breast augmentation —> strong **Foreign-body granulomatous reaction —> Epitheloid + **Foreign body giant cells
- TB: uncommon complication of pulmonary tuberculosis
- Idiopathic granulomatous mastitis (after excluding infection) —> Autoimmune base
6
Q
- Fibrocystic disease
A
Multi-patterned disease (∵ ***Cyclical hormonal influences during menstrual cycle do NOT affect all parts of breast equally in each cycle)
- Most common around 30 yo, rare after menopause
- ***Generalised (but localised area draw attention to disease e.g. fluid retention in a dominant cyst during Estrogen peaks —> comes and goes following menstrual cycle)
- ***Firmer / More nodular (but NOT hard / fixed to surrounding tissues like carcinoma)
Causes:
Hormonal imbalances e.g. Estrogens excess, Progesterone deficiency, Abnormal end-organ metabolism of hormones
Histology
- Cystic formation + Fibrosis
- ↑ Fibrous CT stroma
- ↑ Cysts formation of various sizes (microscopic / large)
- Cysts 2-10 mm diameter, frequently in clusters, fluid-filled, Large cysts occur - Apocrine metaplasia
- Ductal epithelium changes to pink cells (abundant eosinophilic cytoplasm, look like Apocrine cells) with budding of luminal aspect - Epithelial hyperplasia
- Proliferation of ductal lining epithelium —> more severe / atypia of hyperplasia —> ↑ risk of malignancy
7
Q
- Proliferative lesions of breast
A
- Ductal / Lobular epithelial hyperplasia
- Ductal: proliferation of epithelium in Ducts
- Lobular: proliferation of epithelium in Acini - Sclerosing adenosis
- Adenosis:
—> enlargement of lobules
—> increased acini
—> if near one another, collection may be large enough to be palpable
- Acini in enlarged lobules compressed / distorted by fibrous CT stroma —> simulate malignancy
- may be found during childbearing / peri-menopausal years
- some risk of breast cancer - Radial scars (complex sclerosing lesions)
- only detected radiologically (look like stars)
- distortion of normal arrangement of breast tissue
—> epithelial hyperplasia look like spokes of wheel with central fibrosis
- can mimic ***Tubular carcinoma both clinically / radiologically
8
Q
- Benign tumours
A
- Fibroadenoma
- tumour composed of **Glandular breast tissue + **Stromal tissue
- Benign epithelium + Proliferation of CT —> compress ducts into slit-like spaces
- any age, **commonest cause of palpable lump up to 30 yo
- Well-circumscribed, firm, **mobile, ***painless lump (~ mouse in breast) (vs Cysts which are immobile and painful ∵ stretching of wall)
- Ultrasound: distinguish Solid (Hyperechoic) vs Cystic lesion (Hypoechoic) - Intraduct papilloma
- **Epithelial + **Myoepithelial hyperplasia grow **within ducts
- any age
- Solitary:
—> involve larger ducts near nipple (within 4cm)
—> unilateral **Bloody nipple discharge (most common cause, followed by carcinoma)
(if bilateral —> suggest hormonal / systemic problem)
- Multiple:
—> involve smaller ducts
—> associate with slight ↑ risk of breast cancer
9
Q
- Phyllodes tumour
A
- Resembles Fibroadenoma (**Glandular tissue + **Stromal tissue)
- In between Benign / Malignant (Variable clinical behaviour) (Benign: majority / Malignant: 3-12%)
- Simple excision of tumour —> high frequency of recurrence
- peak age 45
Differentiated from Fibroadenoma:
- Presence of **Overgrowth of **CT stroma (a lot more stroma)
- Frond-like arrangement of fibroepithelial element
Malignant form:
- Increased mitosis
- Cellular atypia
- Invasive edge
- Stromal overgrowth
Treatment:
- Wide excision with sufficient margin (for benign)
- Mastectomy (for malignant)
10
Q
- Breast carcinoma
A
- ***Leading female cancer in HK
- Incidence ↑ in HK
- Incidence ↑ with age, median age 57
- lifetime risk: 1 in 15 women
- lump in breast has ↑ chance of being carcinoma ***after menopause
- ↑ trend affecting 40-60 yo
Causes:
Remain unknown
Risk factors:
- Genetic predisposition / Positive family history (***10% of all breast cancers)
- Hormonal imbalance
- Environmental influences
11
Q
Genetic predisposition / Positive family history
A
BRCA-1 + BRCA-2:
- Major **Breast + **Ovarian cancer susceptibility genes
- ***Autosomal Dominant genes (Mendelian inheritance)
- Can be transmitted by either parent
- Account for majority of hereditary Breast + Ovarian cancer
-
**Very large genes with **absence of mutational hot-spots
—> difficulty in genetic testing for germ-line mutations in high risk families (i.e. need to sequence whole gene)
—> usually done on affected individuals first
—> only if mutation is identified in affected individual
—> can then other family members check to find out whether they have the mutation (i.e. not routinely done on public, not done on family members if affected person don’t have mutation)
—> -ve result from families where no mutation identified —> still cannot exclude possibility of other genes that is unknown but involved in the family —> ∴ tests may be unhelpful
Criteria for assessment of High risk:
1. **Number of affected relatives
2. Presence of **ovarian cancer in family
3. **Relationship of affected relatives (1st degree relative)
4. **Age at diagnosis of breast cancer (young onset has higher chance of carrying BRCA gene)
—> Families with ***>=3 related individuals with Breast / Ovarian cancer are at highest risk of carrying mutation in either of these genes
- BRCA mutation carrier are predisposed to
—> **Early onset breast cancer
—> **Bilateral / Multifocal breast cancer
—> Ovarian cancer / other associated cancer
—> 56-84% lifetime cancer risk
Genetic testing
- identify the exact mutation that predispose cancer
- in identified germ-line mutations in BRCA1/2 in a family —> greater accuracy of estimating breast cancer risk
Ethical issues:
- Problems of health insurance
- Disclosure of information
- Controversies in ***multiple options for management of women found to have mutations (i.e. Surveillance only? Prophylactic mastectomy?)
Benefits and limitations:
- Potential benefit of knowing one not inherited a predisposition must weigh against possible harm that may result from finding one at risk
- Test may be unhelpful / give uncertain results
- Benefits and limitations of tests + Potential complexities of genetic counselling should be explained clearly to families beforehand
12
Q
BRCA1 vs BRCA2
A
BRCA1:
- 85% Breast cancer
- 35-60% Ovarian cancer, Fallopian tube, Primary peritoneal cancer
BRCA2:
- 85% Breast cancer
- 10-27% Ovarian cancer, Fallopian tube, Primary peritoneal cancer
- 6% Male Breast cancer
13
Q
Hormonal imbalance
A
- Significant role in development of Breast carcinoma
- Early menarche (<12 yo), Late menopause (>54 yo), Nulliparity (∵ lactation results in full maturation of breast epithelium), Late age at first child
—> longer duration of reproductive life
—> imply ***↑ exposure to Estrogen peaks during menstrual cycle over lifetime
—> ↑ risk of cancer (∵ Estrogen stimulate proliferation of epithelial cells) - Functioning ovarian tumours —> secrete Estrogen —> associated with Breast carcinoma in postmenopausal women
- Risk of breast cancer by using ***oral contraceptives / HRT is controversial
14
Q
Environmental influences
A
- Dietary fats, ***Obesity associated with carcinoma (esp. after 50 yo)
- ∵ associated with endogenous hormonal modification (∵ more Estrogen produced) - ***Ionising radiation
- higher incidence in patients receiving multiple chest X-rays during treatment of TB / other diseases
15
Q
Breast cancer screening
A
Early detection + Treatment
- better prognostic features —> more amenable to treatment
- Breast self examination (not particularly useful)
- Clinical examination (not particularly useful)
- Mammography:
- detect impalpable cancer / characterise/delineate palpable lesions
- check for bi-laterality (whether the other breast has lesions)
- 10-20% carcinoma may still be undetectable
- use in symptomatic (palpable) cases:
—> baseline for follow up
—> **size and extent of lesion
—> **presence of Ductal carcinoma in situ (DCIS)
—> **detection of multifocal disease (i.e. other sites)
—> **other non-palpable abnormalities
—> ***opposite breast - Other radiological detection:
- Ultrasonography (distinguish between solid lesion and cysts)
- MRI - Fine needle aspiration cytology (FNAC) —> Cytology / Core-cut biopsies (cut out a piece of tissue) —> Histology
- routinely used for ***pre-operative diagnosis
- used for both clinically palpable + screen-detected/non-palpable lesions (need image guidance)
- Core biopsy —> able to provide histologic confirmation (Definitive diagnosis), predictive markers to plan therapy (e.g. neoadjuvant therapy)
Triple approach to pre-operative diagnosis:
1. Clinical examination
2. Imaging: Mammography / Ultrasound
3. FNAC
—> if only cytology suggest malignancy but other 2 don’t —> cytology still ***should not taken as authority for therapeutic surgery
Multidisciplinary approach: - Surgeon - Radiologist - Pathologist —> Diagnosis, Management, Treatment, Follow-up
