Breast Flashcards
a large cyst with a thin smooth wall. Benign or malignant?
Likely to be benign
Pathophysiology of breast cysts
dilatation of the acini of the lobules and the terminal ducts
Who gets breast cysts?
They occur in the setting of fibrocystic change, particularly in women nearer the menopause.
What can you do to see if the cyst is malignant?
Cytological analysis of fluid aspirated from the cyst is helpful to exclude the presence of malignant cells. Disappearance of the palpable lump following aspiration offers further reassurance that it is most likely a benign breast cyst.
80% of patients with this pathology present with a nipple discharge, which is often blood-stained and may be associated with a lump. They occur more frequently in middle-aged females.
Intraductal/mammary duct papilloma
Close to the nipple the skin has been removed and deep to it a roughly spherical mass is visible, which appears to be pedunculated (on a stalk). The surface is convoluted / papillomatous.
A central mammary duct papilloma (intraductal papilloma), a benign tumour arising in a large duct near the nipple.
fibrovascular cores covered by benign breast glandular epithelium
Intraductal papilloma
Features of intraductal papillomas that occur at the periphery
Tend to be multiple and associated with other proliferative epithelial changes and therefore a mildly increase risk (2-fold) of subsequent invasive breast carcinoma. Nipple discharge is generally not associated with peripheral papillomas.
ANDI
Abnormalities of normal development and involution:
Fibrocystic change
Fibroadenoma
Papilloma
Infalmmatory breast lesions
Common:
- Fat necrosis
- Acute mastitis
- Periductal mastitis/duct ectasia
Uncommon:
- granulomatous mastitis
- Sclerosing lymphocytic lobulitis
Common site for extra nipples
Milk line, axilla
Ruptured duct, particularly during lactation, may have bacterial infection, usually staph, but not usually infected
Acute mastitis
Post traumatic lump/distortion, painless mass often with skin involvement, may calcify, mimics carcinoma clinically
Fat necrosis
Histology:
Haemorrhage, damaged adipocytes, foamy macrophages, foreign body giant cells, fibrosis, calcification
Fat necrosis
young, recurrent subareolar abcess, squamous metaplasia, 90% smokers, cheesy green discharge, often bilateral
Duct ectasia/ periductal mastitis
Histology:
Dilated duct, lumen: granular necrotic pink debris with lipid-laden macrophages, atrophic lining epithelium, periductal inflammation: plasma cells
Duct ectasia
stellate lesion, benign, central nidus: entrapped glands, elastotic and fibrotic stroma, peripheral glands with hyperplasia and cyst formation, myoepithelial cells present
Mimics carcinoma on mammogram, frequently seen in breast screening
Radial sclerosing lesion
- Larger ducts in premenopausal women
- Intraduct proliferation of epithelial and myoepithelial cells around fibrovascular cores
- Large duct papillomas present with nipple discharge which may be blood stained
- Multiple forms: associated with higher malignancy risk
Intraduct papilloma
What are the papillary lesions?
Not always a papilloma!
Benign
• Papilloma
In-situ:
• Micropapillary DCIS
• Intracystic papillary carcinoma
Invasive:
• Invasive papillary carcinoma
• Micropapillary carcinoma
What are the fibroepithelial lesions?
Mixed epithelial and stromal lesions:
• Fibroadenoma (benign, common)
• Phllodes tumour (spectrum from benign to high grade malignancy, uncommon), stromal layer becomes invasive
- Benign tumour with epithelial and stromal proliferation
- Reproductive age
- Smooth, oval well-defined, mobile (breast mouse)
- Hyalinisation, sclerosis and calcification with age
- Not pre-malignant and no association with carcinoma
- Not painful, 0.5-2cm
Fibroadenoma
- Mixed epithelial and stromal tumour (cf fibroadenoma)
- Stromal overgrowth and hypercellularity may progress towards malignancy of stroma
- Benign glandular elements
- Tendency to local recurrence
- May metastasize – haematogenously (rare)
Phyllodes tumour
- ‘Lumpy’ breasts
- Often cyclical variation in size and pain
- Usually symmetrical-ish
- Mammogram: dense breast tissue with cysts
- Slightly older reproductive age…30ish!
Fibrocystic changes
- Cysts
- Fibrosis
- Sclerosing adenosis- proliferation of glands with fibrosing
- Apocrine metaplasia
- Columnar cell change
- Epithelial hyperplasia
- Admixture of lesions
Fibrocystic changes
What’s the significance of fibrocystic change?
• Need to differentiate lesions from carcinoma
• Associated with risk of neoplasia
- related to degree of epithelial proliferation
What’s the link between epithelial proliferation and cancer?
- Many benign breast conditions involve epithelial proliferation
- Epithelial proliferation has many types with different (confusing) names
- Cytological atypia in epithelial proliferation increases the risk of invasive cancer
- Severe atypia and epithelial proliferation has a high risk of progression to invasive cancer, and is described as “in situ carcinoma”.
Degrees of epithelial hyperplasia and risk of progression to invasive carcinoma
- Usual type hyperplasia (UDH) 1.5 x ref pop
- Atypical ductal hyperplasia (ADH) 4-5 x
- Columnar cell change
- Columnar cell hyperplasia
- Columnar cell hyperplasia with cytological atypia
• Ductal carcinoma in-situ (DCIS) 8-11 x
- Intraduct epithelial proliferation with cellular atypia and an inherent but not necessarily obligate tendency for progression to invasive carcinoma.
- In situ (limited by basement membrane), therefore not invasive, therefore cannot metastasise
- ~10% associated with symptoms/signs: lump, nipple discharge, Paget’s disease
- Often associated with calcification - detected with mammography
- Progression to invasive carcinoma - unknown; estimated 30% at 10 years.
Ductal Carcinoma In Situ DCIS
Is UDH similar to ADH, DCIS or IDC with immunophenotyping and molecular studies?
No, different mutations
Is ADH similar to low grade DCIS with immunophenotyping and molecular studies?
Yes
Is low grade DCIS similar to high grade DCIS with immunophenotyping and molecular studies?
No
What’s Paget’s disease of the nipple?
- Eczematous looking rash / bleeding / scaly surface
- Spread of DCIS through ductal system to directly involve epidermis of nipple
- May be associated with underlying invasive carcinoma
- Usually in an old person
- Usually bilateral
Risk factors for invasive breast carcinoma
- Diet: increased weight, increased height, ‘Westernized’ diet
- Hormones: young menarche, older age at first birth, nulliparity, older menopause, OCP, HRT
- Amount of life spent breast feeding is protective.
- Benign breast changes with epithelial proliferation
- Family history
- BRCA mutations
What’s BRCA and association with cancer?
- Autosomal dominant
- Involved in repair of double stranded DNA breaks
BRCA1:
• susceptibility to breast and ovarian tumours, also colon, liver, endometrium, cervix, fallopian tube and peritoneum
• 1 in 883 caucasians
BRCA2:
• Susceptibility to breast cancer (male breast cancer) also pancreatic, ovarian (melanoma,
cholangiocarcinoma, fallopian tube)
• 1 in 1000 individuals
Lifetime risk for breast carcinoma if you have a BRCA mutation
85%
Lifetime risk of ovarian carcinoma if you have a BRCA mutation
60%
What’s offered to women who have BRCA mutations
Prophylactic masectomy
- Breast lump
- Nipple deformity: retraction, inversion
- Nipple discharge
- Skin changes: Peau d’orange, tethering
Carcinoma
Location of breast carcinomas
50% upper outer quadrant 17% nipple 15% upper inner quadrant 10% lower outer quadrant 5% lower inner quadrant 3% multi focal
Types of in-situ carcinoma
Ductal: low grade, high grade
Lobular (in situ lobular neoplasia)
Lobular vs ductal carcinoma
• Higher rate of multicentric & bilateral tumours
• Higher rate of positive oestrogen receptor status
• Lower frequency of nodal metastases: 3-10%
• Higher frequency of metastases to bone, uterus,
ovary, GIT, meninges and diffuse serosal involvement
• Less likely to metastasise to lung
• Overall probably same prognosis
• Therefore, treatment same as IDC
Prognosis of carcinoma depends on
- Grade
- Stage (TNM)
- Oestrogen receptor status
- Her2 status
Where does breast cancer spread to?
Direct spread: skin, pectoralis muscle
Lymphatic spread:
• lymph nodes: axillary, supraclavicular, internal thoracic
• other breast
Haematogenous: • Lungs • Bones • Liver • Adrenal • Brain
What’s Her2, how is it detected and how can it be treated?
Her2/neu (c-erbB-2)
• 17q12
• Human epidermal growth factor receptor-2 (erbB2)
• Gene amplified in 20-30% of breast cancers
• Signals cells to proliferate
• Can be assessed by IHC and FISH
• Monoclonal antibody (trastuzumab) that targets receptor
Who gets male breast cancer?
Males with gynaecomastia with increased oestrogen exposure (body builders, treatment of prostate cancer)
Why bother breast screening?
- Breast cancer survival is linked to stage
- 71% of DCIS is detected by mammogram
- Therefore, early detection of carcinoma should improve survival
What is picked up using mammography?
- Detects small & impalpable cancers
- Calcification pattern
- Tissue shadowing pattern
Diagnosis of breast cancer
The triple test
• No single test alone can detect all carcinomas
• Clinical + Radiology (ultrasound and / or mammography) + FNA or core biopsy
• Accuracy approaches 100%
• Radiology guided core biopsy for impalpable lesions
Mammogram shows an opaque lesion with an irregular margin. What do you suspect?
highly suspicious for malignancy
Benign or malignant
Macroscopically, there is an irregular white area (fibrous tissue / scirrhous reaction) which infiltrates the surrounding fatty tissue. The lesion appears to lie close to one of the inked excision margins.
Histological sections show the normal glandular morphology of the breast is lost, replaced by sheets of highly pleomorphic atypical cells embedded in a desmoplastic stroma. There is infiltration of the surrounding adipose tissue
Malignant
What clinical signs might be present with Invasive ductal carcinoma of breast (adenocarcinoma)?
Nipple changes, e.g. nipple retraction, discharge or eczematous changes as a result of Paget’s disease.
Skin changes (e.g. peau d’orange).
Axillary lymphadenopathy.
Effects of distant metastasis, e.g. to lungs, bone, liver or brain.
What are the major histological prognostic factors for Invasive ductal carcinoma of breast (adenocarcinoma)?
- major factor is lymph node status (axillary node)
- tumour stage (T size NM)
- tumour grade (the higher the grade the worse the prognosis)
- type (mucinous carcinoma better prognosis)
- the oestrogen and progesterone receptor status, and HER2 expression.
Breast cancers are amenable for screening. What age range of women are offered screening and what does the mammogram look for?
Women aged 50-70 are invited at three yearly intervals to attend for a mammogram, which is a low-dose X-ray of the breast. The mammogram detects micro-calcification (associated with DCIS and invasive carcinoma) and changes in tissue density.
What makes a good screening test?
A good screening test requires high sensitivity, specificity, patient acceptability and low cost. It should aim to detect a condition which is amenable to more effective treatment when discovered early
Monotonous ductal epithelial cells with background stromal cells
Fibroadenoma
