Breast Flashcards
Classification of benign breast lumps
o Non proliferative breast lesions
▪ Simple cysts
▪ Papillary apocrine change
▪ Mild usual type hyperplasia
o Proliferative breast lesions
▪ Intraductal papilloma
▪ Usual type hyperplasia
▪ Sclerosing adenosis
▪ Radial scar
▪ Fibroadenoma
o Atypical hyperplasia
▪ ADH
▪ ALH
Indications of breast MRI
• Breast implants
• Recurrent disease where conventional imaging inadequate
• Risk of multifocality in lobular cancer or occult cancer on mammography
• Assess response after neoadjuvant chemotherapy
- high risk breast screening (<50)
Fibroadenoma
• Pathology
o Aberration of normal development
o Formed by a combination of connective tissue and proliferative epithelium
o Arises from hormone-dependent terminal duct lobular unit
o Influenced by hormones
• Classification
o Depends on stromal element
▪ Simple fibroadenoma – low cellularity stroma with regular cytology
▪ Phyllodes tumour
• Thought to arise from fibroadenoma • Marked cellularity and atypica with stroma
• Simple fibroadenoma
o Features
▪ Benign, mobile, discrete
▪ Rubbery masses
o Clinical
▪ Usually seen in late teens and early 20s
▪ Incidental finding on imaging or palpable lump
▪ Single or multiple
o Aetiology
▪ Unknown
▪ Links to OCP
▪ Links to EBV following immunosuppression
o Workup
▪ US guided core biopsy (patients >23)
o Pathology
▪ Rapid growth can occur in juvenile fibroadenoma or in perimenopausal group
▪ Tumours >5cm are considered ‘giant fibroadenoma’
▪ Macro
• Discrete, bosselated, white tumours that bulge when cut
• Management
o Core biopsy to confirm diagnosis
▪ If multiple, biopsy largest lesion
o <4cm with histological confirmation
▪ Reassurance and discharge
o Symptomatic, significant increase in size, distortion of breast
▪ Excision
o >4cm
▪ Excision
o Histological concern about stroma activity
▪ Excision
Phyllodes tumour
o Definition
o Fibroepithelial tumour with a diverse range of biologic behaviours
▪ From phyllodes – leaf-like
▪ Papillary projections on pathology
o Epidemiology
▪ Rare, 4% of all breast neoplasms
▪ Women 42-45y
▪ older more likely to be malignant
▪ Present 15-20 years later than fibroadenoma
o Can be related to P53 gene mutation
o Clinical
▪ Breast mass
▪ Smooth, multinodular, mobile, painless
▪ 1-41cm
▪ Mass effect rare but can change breast contour
▪ Can have rapid growth
▪ Can produce marked distension and cutaneous venous engorgement
▪ Can have ulceration
▪ Incidental finding on biopsy for fibroadenoma
▪ LN mets very rare (usually haematogenous spread)
• Workup
o Mammogram/ ultrasound / biopsy
▪ Core → stromal overgrowth, mitoses, stromal cellularity
o Pathology
▪ Cauliflower-like appearance
▪ Pseudocapsule with stromal tongues protruding into breast tissue
▪ Brownish colour with areas of necrosis
▪ Not fixed to skin or muscle
o Classify (SAMSOM)
benign vs borderline vs malignant
▪ Stromal cellularity and atypia
▪ Mitotic activity • <4, 4-9, >9/10hpf
▪ Infiltration or circumscribed margins
▪ Stromal overgrowth – most important
o Management
▪ Excision with 1cm surgical margin, clear macroscopic margin
▪ RTX for borderline or malignant
▪ CTX for high risk malignant
▪ No role for hormonal treatment
▪ Metastatic disease
• poor response to radiation, hormone, chemotherapy
• Follow up
o 6 monthly for 2 years
o Prognosis
▪ Local recurrence in 20%
▪ Lymph node metastases are rare (5%)
• Metastasis usually haematogenous like sarcomas → lung most common
▪ Metastasis • <5% phylloides tumours metastasise
o 25% if malignant
o 5YS for malignant phyllodes → 60-80%
Nipple discharge
• Epidemiology
o 5% of referrals of breast clinic
o 20% due to in situ or malignant disease
• Clinical assessment
o Single or multiple ducts
o Coloured or bloodstained
o Induced or spontaneous
o Unilateral or bilateral
o Frequency, colour, consistency of discharge
o Increased risk of cancer
▪ Blood stained (but sensitivity/specificity not high)
▪ Persistent discharge >2x/week
▪ Age
• 3% <40, 10% 40-60, 32% >60
▪ No blood, no mass, <1% cancer
• Aetiology
o Physiological discharge
▪ Coloured opalescent discharge from multiple ducts
o Galactorrhoea
▪ Bilateral, copious, pale milky discharge from multiple ducts
▪ Usually develops after ceasing breast feeding
▪ Causes
• Prolactin secreting pituitary adenoma
• Medications that influence esotrogen/progesterone/prolactin pathway
• Hypothyroidism
• Marijuana
▪ Workup
• Check prolactin level (if >1000mIU/L = elevated)
o Cause – pituitary tumour secondary to medication
o Duct ectasia
▪ Older women with thick yellow discharge
▪ Tortuous and dilated ducts predispose to fluid accumulation
• Results in multiduct discharge
o Benign breast changes (ANDI)
o Papilloma (80% of bloody discharge), cancer, epithelial hyperplasia, DCIS
▪ Serosanguineous, bloody discharge from a single duct
o Inflammatory cause
▪ Periductal mastitis/ abscess
• Examination
o Breast examination for mass
o Pressure around areola to identify any dilated duct (will produce discharge)
o Testing of discharge
▪ Haemoglobin
Investigations
o Ductoscopy
▪ Microendoscope passed into offending duct to directly visualize lumen
▪ Can assist in directing duct excision at surgery and detecting deeper lesions missed by blint centlra excision
o Ductal lavage
▪ Cannulation of duct then irrigation and cytology on subsequent discharge
▪ Role has been questioned due to low sensitivity/specificity
o Ductography
▪ Can identify intraductal lesions
• Filling defect or duct cut off has high PPV for papilloma or carcinoma
▪ Painful therefore limited use
▪ Not widely practiced
o Cytology
▪ Poor sensitivity, limited use
o Mammogram
▪ If patient >35
o Ultrasound
▪ Can occasionally identify papillomas and malignant lesions in ducts close to nipple
• Next steps
o Single duct spontaneous discharge
▪ → surgery to determine cause if
• Blood stained discharge
• Persistent >2x/week
• Associated with a mass
• New serosanguineous discharge in postmenopausal women
Mastalgia
• Symptoms
o Main consideration is referred pain vs breast pain
▪ Referred pain is unilateral, associated with activity, reproduced with pressure on chest wall
• NSAIDs relieve symptoms
o True mastalgia is associated with swelling and nodularity of breasts
▪ Resolves spontaneously in 20-40%, but can recur
▪ Worse before and relieved after menstruation
▪ Exacerbated by perimenopausal state, exogenous hormones (HRT, OCP)
• Aetiology
o Cyclical mastalgia thought to be related to excess prolactin, excess estrogen or lack of progesterone, or increased sensitivity of receptors in breast tissue
• Workup
o History as above
o Examine chest wall
▪ Roll patient and palpate chest wall
o Mammography if patient >40 years
▪ 5% of women with breast cancer complain of pain
▪ 2.7% women complaining of pain are diagnosed with cancer
• Management
o Exclude worrisome diagnoses
o Reassurance
o Analgesia
o Firm bra 24h/day
o Gentle stretching exercises, swimming
o Evening primrose oil not shown to be of benefit in RCA
o Phytoestrogens (soy milk, agnus castus – a fruit extract) – have been shown to have a mild benefit
o Reducing dietary fat intake (<15% dietary calories) – some benefit
o Severe symptoms
▪ Tamoxifen 10mg daily or danazol during luteal phase
Sclerosing adenosis
o Present with palpable mass and breast pain
o Mammogram
▪ Microcalcifications
o Histology
▪ Fibrosis with excessive myoepithelial proliferation
Management
Excisional biopsy
Radial scar and complex sclerosing lesions
o Radial scar <1cm, CSL>1cm
o Usually asymptomatic, found on mammogram
▪ Occasionally present as palpable mass
o Pathology
▪ Can serve as background for formation of ADH, CIS
o Can appear like malignancy mammographically, macro/histo
• Management
o High volume core biopsy or excision biopsy to exclude malignancy
Pseudoangiomatous stromal hyperplasia of the breast
• Benign myofibroblastic proliferation of non-specialised mammary stroma
o Often incidental finding on biopsies
o Can be confused histologically with mammary angiosarcoma – needs IHC to distinguish
• Management
o Excision biopsy
Fibromatosis
• Aka desmoid tumour of breast
• Features
o Infiltrative fibroblastic and myofibroblastic proliferation
o Risk of local recurrence but not metastases
o Rare, <0.2% all primary breast lesions
o Most likely arises from chest wall muscles
• Workup
o Biopsy – often core or vacuum assisted needle biopsies required
▪ If this insufficient, open excision biopsy required
• Management
o Observation only if confirmed diagnosis
o If becomes symptomatic (by invading chest wall and intercostal nerves) → pain → excision
o If recurs after excision, consider excision with 1cm margins
Periductal mastitis
▪ Young women
▪ associated with smoking – toxic metabolites (lipid peroxidase, epoxides, nicotine, cotinine) accumulate
• Gram negative bacteria (smoking inhibits gram positive bacteria) or anaerobes/mixed
• Local ischaemia contributes due to microvascular changes from smoking
▪ May present with mass or abscess
• Often anaerobes
• High rate of recurrence
Treatment
o As for other abscesses (aspiration)
30% get mammary duct fistula after incision & drainage
o Aim for excision 6 weeks after resolution of infection
Mammary duct fistula
• Fistula between damaged / infected duct and skin
• Occurs in 1/3 patients after I+D periareolar abscess
• Management
o Fistulotomy – cut onto a probe into fistula and allow healing by secondary intention
▪ Painful, scarring is worse
o OR Fistula excision and primary closure
▪ Use circumareolar incision if possible for best cosmetic outcome
▪ Need to completely excise granulation tissue-lined tract and affected ducts under nipple
Granulomatous mastitis
o Noncaseating granulomas and microabscesses within a breast lobule
o Epidemiology
▪ Rare
▪ Usually young women, not associated with smoking
o Presentation
▪ Firm irregular mass (may be suspicious for cancer)
▪ Multiple recurrent abscesses
o Aetiology
▪ Thought to be related to Corynebacterium but treatment of these infections does not seem to resolve infection
o Management
▪ Confirm diagnosis on biopsy
▪ Avoid excision of mass
• Usually has persistent wound discharge and failure of wound healing
▪ Steroids and immunosuppressants have variable efficacy
• Does improve symptoms but does not alter course of condition
• Controversial whether useful
▪ Treat superimposed infections as they appear and supportive therapy only
• Usually resolves spontaneously after 6-18 months
Mondor’s disease
o Spontaneous superficial thrombophlebitis of a breast vein
▪ Thoracoepigastric vein
▪ Lateral thoracic vein
▪ Superior epigastric vein
o Thickened palpable cord with surrounding erythema
▪ Never involves upper inner part of breast
o Resolves spontaneously with NSAIDs and massage
Gynaecomastia
• Definitions and epidemiology
o Hyperplasia of stromal and ductal tissue of male breast
▪ Pseudogynaecomastia → similar appearance but is related to excess adipose tissue not hyperplasia or stromal or ductal tissue
o Any age
o Common – 35% men
o Painful concentric swelling
o Benign and reversible
o Differential diagnosis is primary breast cancer
▪ Usually painless eccentric masses
• Aetiology
o Associated with Klinefelter syndrome
▪ Increased risk of male breast cancer
o Relative hyperestrogenism
▪ Decreased androgen production, increased estrogen production
▪ increased peripheral aromatization, reduced androgen receptors
o cause
▪ physiological
• neonatal, puberty, elderly
o usually self-limiting
▪ pathological
• → Klinfelter’s syndrome, hyperprolactinaemia, bilateral cryptochidism, testicular tumour, lung Ca, chronic liver disease, thyrotoxicosis, adrenal disease
▪ pharmacological
• increased beer or cannabis intake – phytoestrogens present in beer
• antiandrogens (spironolactone), gonadotrophin disturbance (H2 antagonists (cimetidine), antipsychotics, methyldopa), estrogen receptor competitors (digoxin, cannabis, griseofulvin), anabolic steroids
• antiretrovirals for HIV
▪ idiopathic
Clinical
o History to identify cause as above
o Examination of breast, axilla, testis, abdomen
o Investigations – aim to identify pathological cause or and exclude primary breast cancer
▪ Bloods – if rapidly growing gynaecomastia
• LFTs, renal function
• Prolactin, AFP, bHCG, total testosterone, TFTs
▪ Imaging – if indeterminate cause, suspicious for cancer or considering surgery
• Mammography / US +/- FNA or core needle biopsy
• US testis/abdo
• Treatment
o Reassurance
▪ 80% resolve in 2 years without treatment
o Stop drug if drug related
o Address underlying cause if pathological
o Medical management
▪ Tamoxifen 10mg daily or danazol 100mg BD for 1 week, TDS for 5 weeks
o Surgical management
▪ If medical failure or if large (class IIa/III)
▪ Technical aspects
• Periareolar incision
• Leave disc of breast tissue behind nipple with intact pectoral fascia and overlying fat to prevent retraction and fixation to muscle (saucer deformity)
• Keep thick skin flaps thick to reduce risk of skin necrosis
• If large consider free nipple grafts , excision of excess skin
▪ Risks
• Nipple necrosis, sensory changes, cosmesis
FNA vs core biopsy
• FNA previous standard of care
o Easy to perform, rapid diagnosis
o No architectural information
o ER but no PR/HER2
• Core biopsy
o Improved sens and spec
o Architectural information
o ER/PR/HER2 receptor status
• FNA still useful for assessment of suspicious lymph nodes
ADH
• Indicator of risk rather than a precursor lesion
• Diagnosis
o Found on core needle biopsy of mammographic microcalcifications
• Histology
o Proliferation of uniform epithelial cells with monomorphic round nuclei
▪ Fill part but not all of duct
o Similar to low grade DCIS but only involves <2mm
• Management
o Wire-localised excision biopsy to exclude associated malignant lesion
▪ 10-20% get upgraded to DCIS or cancer
o No need for re-excision if positive margins
▪ Unless positive only at margins which suggests missed lesion
ALH
• Diagnosis
o Incidental finding on breast biopsy
• Histology
o Proliferation of monomorphic, evenly spaced dyshesive cells that fill but don’t expand a lobule
▪ Can also involve ducts
o Has same cytological and architectural features of LCIS, but is less quantitatively
• Management
o Concordant lesion, incidental ALH → no further treatment
▪ Upgrade to DCIS or cancer is <3% after biopsy
DCIS
• Definition
o Clonal proliferation of malignant epithelial cells confined within basement membrane of mammary ducts, precursor lesion for invasive Ca
• Classification
o Subtype
▪ Comedo
• Central necrosis, multiple mitotic figures, large pleomorphic nuclei
▪ Non-comedo
• Absence of necrosis, no mitotic figures
• Solid, papillary, micropapillary or cibriform, flat (clinging) architecture
o Grade
▪ Low/intermediate/high
• Nuclear morphology
• Mitotic index
▪ High grade
• Necrosis, aggressive biologic characteristics
• High local recurrence rates
▪ I: irregular nuclei, small, no necrosis
▪ II: some necrosis, small nuclei
▪ III: pleomorphic nuclei, commedo necrosis
• Scoring system Van Nuys (Size, Margin, Age, Pathology) – for risk of local recurrence
o Lumpectomy alone for scores 4, 5, 6, lumpectomy and radiation for scores 7, 8, 9. Mastectomy for 10, 11, 12
• Clinical
o 90% asymptomatic
▪ Detected as pleomorphic or linear microcalcifications on mammogram
• Indeterminant calcifications can be examined using magnification views
▪ Incidental calcifications on mammogram that end up being malignant → • 65% pure DCIS • 32% DCIS with cancer • 4% breast cancer
▪ Sterotactic core needle biopsy shows diagnosis
o 10%
▪ Palpable mass
▪ Pagets
▪ Nipple discharge
Indication of mastectomy in DCIS
• Preferred if:
o Multicentric DCIs
o Large lesions
o Centrally located disease
o Inadequate margins after re-excision after BCS
o Patient preference
o Adjuvant radiotherapy contraindicated
• Should have immediate breast reconstruction
Margins for DCIS
2mm margin
SLNB in DCIS
• Nodal metastasis in DCIS <3%
• Consider SLNB if
o Large DCIS >4cm
o Palpable breast lesion, ie mass forming DCIS
o High grade disease
o Microinvasive disease
o Suspicious nodes on examination of ultrasound o → these high risk features increase risk of invasive cancer to 20%)
o Mastectomy
Indication of adjuvant radiotherapy for DCIS
• Indicated after BCS – reduces local recurrence (50%) but does not improve survival
• To chest wall if re-excision for local recurrence or positive margins
• 45-50G over 5 weeks
Indication of hormonal therapy after DCIS surgery
Hormonal therapy (tamoxifen – NSABP-B24 trial)
• Recommended in patients with high risk of developing breast cancer, especially ER+ DCIS
• ER neg – no role
LCIS
• Epidemiology
o Usually presents in 40s
▪ Median age 44-46 (10 years younger than DCIS)
▪ 10% post menopausal
o Increased risk of IBC (7-18x)
▪ 0.5-1% / year
▪ Cumulative risk 7.1% at 10 years = lifetime risk 30-40%
▪ 3x more likely in ipsilateral breast than contralateral breast
• Pathology
o LCIS subtypes
▪ Classic
• Monomorphic population of small, round, polygonal/cuboidal cells
• Thin rim of cytoplasm
• High N:C ratio
• Regular spaced, loosely cohesive
• Fill and distend acini
• Small nucleoli and a few mitotic figures
• Pagetoid spread – neoplastic cells spread along adjacent ducts
▪ Pleomorphic (treat like DCIS as high risk)
• Larger nuclei with prominent nucleoli and mitotic figures
• Central necrosis, calcification within lobules
o Diagnosis pathologically
▪ LCIS → 50% of acini in an involved lobular unit is filled and distended by LCIS cells
• Therefore no central lumina
▪ ALH → cells fill <50% acini or no distension of lobule
• Lumina visible 0.5-3.8% of otherwise benign breast biopsies
• Clinical
o Usually incidental finding after breast biopsy
▪ No specific symptoms, incidence in population therefore unknown
o Often multifocal and bilateral
▪ 50% have multiple foci in same breast
▪ 30% have LCIS in contralateral breast
• Management
o Treat as risk factor for invasive breast cancer
o Excision biopsy recommended to rule out malignancy
▪ Further resection required if pathology/imaging are discordant
o Risk reduction
▪ BRCA1/2 – bilateral mastectomy
▪ Tamoxifen in high risk patients
o Surveillance
▪ 6-12 monthly breast examination
▪ Annual mammogram
Genes involved in breast cancer.
BRCA 1, BRCA 2, p53, STK 11, CDH1, PALB2, PTEN, ATM
Pathophysiology of breast cancer.
o 95% sporadic, 5% hereditary
o Sporadic tumours are related to estrogen exposure
- early menarche
- late menopause
- nulliparity
- COCP/HRT
o Cyclical proliferation of glandular cells within breast related to oestrogen result in increased risk of DNA damage
Morphology of breast cancer.
- ductal carcinoma - 80%
- lobular carcinoma - 10%
- tubular/cribriform - 5%
- mucinous, medullary, micropapillary, metaplastic (5%)
Features of invasive lobular cancer
- 5-10%
Presentation
o often presents as an ill-defined thickening.
o Calcification uncommon, mammogram may be normal or show asymmetry
o FNA error-prone - ~50% false -ve
o Tend to be larger at Dx, but biochemical/genetic features more favourable
o If multicentric in 1 breast, 24% have +ve contralateral biopsy
Pathology
o small cells, “Indian filing”, multicentric. May have co-existing ductal component o Other pathological types - solid, alveolar, mixed
o Cells are monotonous, -> grading is difficult
o Pleomorphic type has nuclear pleomorphism and has poorer prognosis
o Most show loss of expression of CDH1 which encodes E-cadherin
- ER/PR positive, HER 2 negative
Prognosis
o As larger and can be multicentric, more often need mastectomy compared with IDC
o patients with ILC tended to be older and have lower grade tumours, hormone-receptor positive, of larger size and with absence of vascular invasion.
ILC showed indolent but progressive characteristics with nearly linear survival curves that crossed those of IDC after approximately 10 years of follow-up, thus eventually exhibiting a worse long-term outcome.
Secondaries to meninges, serosa, GIT, genital tract, adrenal, other unusual sites
Grading of breast cancer.
- Bloom-Richardson grade (TNM).
- Tubule formation (majority, moderate, little or none)
- Nuclear size/pleomorphism (small, moderate, marked variation)
- Mitotic rate ( 0-5, 6-10, >11)
Grade 1 - 3-5
Grade 2 - 6-7
Grade 3 - 8-9
ER/PR
- Both ER & PR are steroid receptors located in the cell nucleus
Measured using IHC (immunohistochemistry) - recognition of receptor by Ab
Only nuclear (not cytoplasmic) staining indicates a +ve result
Include in report:
o an estimate of the % of nuclei stained
o the predominant intensity of staining (low, intermediate or high)
o a conclusion as to whether the assay is positive or negative
e.g. ≥1% nuclei staining at any intensity (low, intermediate or high)
What percentage of patients respond to hormonal treatment?
o 30% of all comers
o 50-60% of oestrogen receptor positive tumours
o up to 80% of oestrogen/ progesterone receptor positive tumours
