12 - Breast Pathology Flashcards
What does normal breast tissue look like histologically and what are some physiological changes?
- Dual layer of epithelium: cuboidal and myoepithelial
- Menarche causes increase number of lobules and increased interlobular stroma
- After ovulation cell proliferation and stromal oedema
- Pregnancy causes increase in size and number of lobules, decrease in stroma
What happens to breast tissue as we get older?
- Terminal duct lobular units decrease in number and size: cessation of lactation
- Interlobular stroma replaced by adipose tissue so mammograms are easier to interpret as less dense and palpation easier
what is the most common benign breast cancer
fibroadenoma
what does mammography screening achieve
detection of small invasive tumours and in situ carcinomas
What breast conditions cause a palpable mass and when is this worrying?
- Normal nodularity before menstruation
- Invasive carcinomas
- Fibroadenomas
- Cysts
Worry if hard, craggy, fixed or rapidly increasing in size
What breast conditions cause mammographic abnormalities?
- Densities: invasive carcinomas, fibroadenomas, cysts
- Calcifications: ductal carcinoma in situ (DCIS) and benign tissues
mainly detects small invasive tumours and in situ carcinomas, impalpable
Who is eligible for the breast screening programme in the UK and what are the challenges with this programme?
- Women between 47 and 73 every 3 years
- Very high risk (gene carriers) have annual MRIs and mammograms
- Moderate risk (FH) start screening 40-50
- Many women decline first invite
- Breast screening team are quite old so retiring soon
What are some common lumps in the breast and what age groups do these occur in?
- Fibroadenomas: usually in reproductive age <30 years
- Phyllodes Tumour: in 60’s, can be benign or malignant
- Breast cancer: rare before 25, most people diagnosed at 64. Men are 1% of breast cancer cases
Apart from acute mastitis, what are some other inflammatory conditions that can occur in the breast?
Fat Necrosis
- Can present as mass, skin change or mammographic density
- Can mimic carcinoma clinically and mammographically but usually history of trauma or surgery
What are the histological features of fibrocystic change?
- Cyst formation
- Fibrosis
- Apocrine metaplasia
What are some stromal tumours of the breast?
- Fibroadenoma
- Phyllodes tumour
- Lipoma
- Leiomyoma
- Hamartoma
What are the histological and macroscopic feaures of a fibroadenoma?
- Macroscopically: rubbery, greyish white, mobile
- Histology: mix of stromal and epithelial cells hyperplasia
- mobile mass, bilateral
Can look like carcinoma clinically and mammographically
What is gynaecomastia and what is the general reason for it’s occurence?
- Enlargement of the male breast
– unilateral and bilateral
– often seen in puberty and elderly
- Often seen in puberty and elderly
- Cause by relative decrease in androgen and increase in oestrogen
- No increased risk of cancer but can mimic carcinoma, especially if unilateral
What are some causes of gynaecomastia?
- Neonates due to maternal oestrogen
- Transient puberty (oestrogen peaks earlier than testosterone)
- Klinefelter’s syndrome (born with an extra X chromosome)
- Gonatrophin excess e.g leydig tumours
- Cirrhosis of liver causing oestrogen to not be metabolised
- Drugs: spironolactone, chlorpromazine, alcohol, marijuna, cimetidine, heroin, anabolic steroids
What is the most common type of breast cancer?
- 95% are adenocarcinomas
– 1/7 women will develop
- 50% occur in the upper outer quadrant
- Other tumours like angiosarcomas are rare
What are some risk factors for breast cancer?
- Geographic influence: higher incidence in US and UK though to be linked to diet, alchol consumption etc
- Previous breast cancer
- Previous radiation exposure, especially as a kid
– early menarche (< 11)
– breast feeding
– obesity and high fat diet
- Genetics
What are the genes associated with breast cancer?
- BRCA1 and BRCA2: tumour suppressor genes
- Li-Fraumeni Syndrome: p53
- 60-85% lifetime breast cancer risk with this gene and diagnosis 20 years earlier than sporadic cases
- Carriers may undergo prophylatic mastectomy and hysterectomy
How do we classify breast carcinomas?
- Lobular or Ductal
- Invasive or In Situ (breaking through basement membrane)
What is in situ breast carcinoma and why is DCIS a problem?
- Neoplastic cells limited by basement membrane, myoepithelial cells in tact so cannot metastasise or invade as no entrance into vessels
- DCIS can show us as calcifications and can spread through ducts and lobules to be very extensive when it breaks through. It is a precursor for invasive carcinoma
What does DCIS look like histologically?
→ Ductal carcinoma in situ
Often central comedo necrosis with calcification
What is Paget’s disease of the nipple?
- Unilateral eczematous nipple that can be retracted, associated with DCIS
- Often a sign of invasive breast cancer behind the nipple
What visible changes can occur to the breast with breast cancer?
- Often axillary lymph node metastases when palpable breast lump (this is the difference between DCIS and cancer)
How can invasive breast carcinoma be classfied?
- Invasive ductal carcinoma, no special type: 70-80% of cases with 35-50% 10 year survival
- Invasive lobular carcinoma: 5-15% of cases, similar prognosis
- Other: tubular and mucinous (good prognoses)
What does invasive breast carcinoma look like histologically?
How does breast cancer metastasise and what are the most common sites of metastases?
- Via lymphatics, usually to ipsilateral axillary nodes
- Distant metastases via blood vessels: bones (most common site), lungs, liver, brain
- Invasive lobular carcinoma: odd sites like peritoneum, retroperitoneum, leptomeninges, GI tract, overies, uterus
What factors determine the prognosis of breast cancer?
- In Situ or Invasive
- Tumour grade
- TNM stage
- Histologic subtype (IDC NST has poorer prognosis)
- Molecular classifcation (HER2)
- Gene expression profile
In regards of the receptors present on breast cancers, what receptors indicate a better prognosis?
- 1st test is for oestrogen receptors and if present better prognosis
- Then test for HER2 gene so can use herceptin
- Triple Negative (PR, ER and HER2) is poorest prognosis
How do we investigate and diagnose suspected breast cancer?
Triple Approach
- Clinical: history, family history, examination
- Radiographic imaging: mammogram and ultrasound scan
- Pathology: core biopsy and fine needle aspiration cytology
What are some of the treatments for confirmed breast diagnosis?
- Breast surgery: mastectomy or lumpectomy depending on patient choice, size and site of tumour and size of breast
- Axillary surgery: sentinel node sampling or axillary dissection
- Post operative radiotherapy to chest and axilla
- Chemotherapy
- Hormonal treatment
What is sentinel lymph node biopsy?
- Done to reduce risk of post op morbidity
- Inject dye into tumour, first node that drains this remove and biopsy, if cancer present do axilla dissection, if not don’t
→ reduces risk of post operative morbidity
→ mapping of breast cancer
→ if it comes out negative then auxiliary dissection can be avoided
invasive breast carcinoma classification
invasive ductal carcinoma:
→ 70-80%
→ well differentiated: tubules lined by atypical, cells
→ poorly differentiated: sheets of pleomorphic cells
Invasive lobular carcinoma:
→ infiltrating cells in single file, lack cohesion
What are some hormonal treatments for breast cancer?
- Tamoxifen if ER+
- Herceptin if HER2 positive (humanised monoclonal antibodies against HER receptor)
How can we improve survival from breast cancer?
- Early detection: encourage screening and self examination
- Neoadjuvant chemotherapy to prevent metastases
- Gene expression profiles
- Prevention in familial cases e.g prophylatic mastectomy
What is a genetic expression profile and what is the relevance of this to breast cancer?
Using a DNA microarray in breast cancer patients to see that 17 marker genes are present that can tell you which women would develop metastases
What are the challenges patients may face when they are diagnosed with DCIS?
- Classed as pre-invasive cancer so could spread or could stay the same and never cause issues
- Offered mastectomy so have to weigh up benefit v risk
- Therefore could be having unnecessary cancer treatment
What is the Angelina Jolie effect?
- Rise in internet searches of BRCA genes
- Rise in prophylatic mastectomies
What is the likely pathway of investigation for a patient with suspected DCIS?
- Ultrasound of axilla then ultrasound guided needle biopsy if abnormal lymph nodes present
- Only offer MRI and triple therapy screening if suspect invasive
What are the benefits of a drastic mastectomy operation for DCIS vs a lumpectomy?
- Lumpectomy followed by radiation is likely to be equally as effective as mastectomy for people with only one site of cancer in the breast and a tumor under 4 centimeters
- Ask patient how anxious they are about cancer coming back as higher reoccurence with this
- Need more radiotherapy which can interrupt reconstruction time
- Breast cannot tolerate radiation if reocurrence of cancer in same breast
what are some treatment options for people with a local cancer
→ breast surgery: mastectomy or breast conserving surgery
→auxiliary surgery
→ post operative radiotherapy to chest and axilla
- chemo, tamoxifen (hormones) Herceptin treatment
what does a pre pubertal breast appear like
few lobules
what does breast tissue look like in menarche
more lobules and interlobular stroma
what does breast tissue look like during the menstrual cycle
follicular phase lobules quiescent, after ovulation: cell proliferation and stromal oedema
decreased size of lobules
what does breast cancer look like in pregnancy
increased size and number of lobules, decrease in stroma and secretory changes
if the pain is cyclical and diffuse what does this suggest
it is physiological
If the pain is non-cyclical and focal what pathology does this suggest
→ ruptured cyst, injury and inflammation
how do we classify pathological conditions of the breast
→ disorders od development
→ inflammatory conditions
→ benign epithelial lesions
→ stromal tumours
→ gynaecomastia
→ breast carcinoma
what is acute mastitis
→ almost always occurs during lactation
→ stap aureus infection from nipple cracks and fissures
→ eryhtmatous and painful breasts = pyrexia
→ can produce breast abscess
→ antibiotics
what is fibrocystic change
→ most common breast lesion
→ mass/mammographic abnormality
→ disappears after fine needle aspiration
→ cyst, fibrosis and apocrine metaplasia
→ can mimic carcinoma
what is cyclical mastalgia
→ cyclical pain in the breast that occurs 2 weeks before period
