Breast Flashcards
1
Q
What is the breast?
A
- present in males and females (rudimentary tissue only in males)
- subcutaneous gland
- (mammary gland)
2
Q
Describe the structure of the secretory tissue of the breast
A
- secretory tissue of the breast if made up of 15-25 lobes, each consisting of a compound tubulo-acinar gland which drains via a series of ducts leading to the nipple
- aggregating duct system that goes into a single lactiferous duct which then proceeds to the nipple
3
Q
What surrounds the secretory lobules?
A
- dense fibrous tissue
- which in turn is surrounded by adipose tissue
4
Q
Describe the basic structure of the non-lactating breast
A
- amongst the fibrous connective tissue are some larger condensations that extend from the dermis of the skin to the deep fascia overlying the muscle of the anterior chest wall
- forming essentially septa,
- these are referred to as suspensory ligaments
- often most pronounced in the upper breast and are thought to support the breast tissue
5
Q
Name the basic functional secretory unit of the breast?
A
The terminal duct lobular unit
6
Q
In the non-lactating breast, the terminal ductules lead where?
A
- into an intralobular collecting duct which leads into the lactiferous duct for that lobe
- the lactiferous duct leads to the nipple, passing through an expanded duct region near the nipple termed the lactiferous sinus
7
Q
What is the lactiferous sinus?
A
- expansion of the lactiferous duct
- believed to accumulate a small amount of milk for immediate release when baby latches
8
Q
Name features of the lobule
A
- both extralobular and intralobular ducts
- rudimentary secretory acini
- dense fibrocollagenous connective tissue surrounding the lobule
- looser connective tissue surrounding the acini within the lobule (this allows rapid expansion in pregnancy)
- adipose tissue between lobules
9
Q
Describe the histology of the lobule
A
- within the lobule the secretory epithelial cells line the acini and vary from cuboidal to columnar
- the secretory cells of the acinus are surrounded by myoepithelial cells (MEp)
- these are contractile epithelial cells which is turn are surrounded by the basal lamina
10
Q
Describe the histology of ducts
A
- larger ducts, such as a lactiferous duct are lined by an epithelium that varies from a thin stratified squamous to stratified cuboidal
- myoepithelial cells are present
11
Q
What is the nipple formed of?
A
- the nipple has a wrinkled surface and is covered by a thin, highly pigmented keratinised stratified squamous epithelium
- it has a core of dense irregular connective tissue mixed with bundles of smooth muscle
- smooth muscle presses on ducts to help deliver milk and plays a role in erectile function
12
Q
Describe the structure of the nipple
A
- several lactiferous ducts
(at apex of the nipple), each will serve one lobe of the breast - as the duct approaches the surface it becomes lined by stratified squamous epithelium, deeper it is lined by stratified cuboidal epithelium
- sebaceous glands are present and these open directly onto the surface of the skin
- secrete via holocrine secretion
13
Q
Describe the changes to the mammary gland during the menstrual cycle
A
During the luteal phase the epithelial cells increase in height, the lamina of the ducts become enlarged and small amounts of secretions appear in the ducts
14
Q
Describe the changes to the mammary gland in pregnancy
A
- in the first trimester there is elongation and branching of the smaller ducts, combined with proliferation of the epithelial cells of the glands and the myoepithelial cells
- in the second trimester glandular tissue continues to develop with differentiation of secretory alveoli. also, plasma cells and lymphocytes infiltrate the nearby connective tissue
- in the third trimester secretory alveoli continue to mature, with development of extensive rough endoplasmic reticulum
15
Q
What drives the mammary gland changes in pregnancy?
A
Oestrogen and progesterone
16
Q
What is the composition of human milk?
A
- 88% water
- 1.5% protein (mainly lactalbumin and casein)
- 7% carbohydrate (mainly lactose)
- 3.5% lipid
- with small quantities of; ions, vitamins and IgA antibodies
17
Q
How are the different components of milk secreted?
A
- lipid droplets are secreted surrounded by membrane and carrying a small amount of cytoplasm with it (apocrine secretion)
- proteins in milk are made in the rR, packaged in the golgi apparatus and secreted via vesicles which merge with the apical membrane to release only their contents into the duct system (merocrine / exocytosis)
18
Q
Describe the changes in the mammary gland following menopause
A
- the secretory cells of the TDLUs degenerate leaving only ducts
- in the connective tissue, there are fewer fibroblasts and reduced collagen and elastic fibres
19
Q
Describe the blood supply to the breast
A
- lateral mammary branches from lateral thoracic artery
- medial mammary branched form internal thoracic artery
- venous drainage by medial and lateral mammary veins
20
Q
Describe the lymphatics of the breast
A
- most lymph (>75%) to axillary nodes
- remainder to parasternal nodes (some may also drain to abdominal nodes)
- subareolar lymphatic plexus
21
Q
Describe the assessment of a patient with breast disease
A
- triple assessment
- clinical; history and examination
- imaging; mammography, ultrasound, MRI
- pathology; cytopathology, histopathology
22
Q
Describe the result classifications for breast FNA cytology
A
C1 - unsatisfactory C2 - benign C3 - atypia, probably benign C4 - suspicious of malignancy C5 - malignant
23
Q
Name diagnostic tests for breast histopathology
A
- needle core biopsy
- vacuum assisted biopsy (large volume)
- skin biopsy
- incisional biopsy of mass
24
Q
Name therapeutic interventions in breast histopathology
A
- vacuum assisted excision
- excisional biopsy of cancer
- resection of cancer; wide local excision, mastectomy
25
Describe the result classification for needle core biopsy
```
B1 - unsatisfactory / normal
B2 - benign
B3 - atypia, probably benign
B4 - suspicious of malignancy
B5 - malignant
B5a - carcinoma in situ
B5b - invasive carcinoma
```
26
Name developmental anomalies of the breast (benign breast disease)
- hypoplasia
- juvenile hypertrophy
- accessory breast tissue
- accessory nipple (tends to be present on the milk line)
27
Name non-neoplastic benign breast conditions
- gynaecomastia
- fibrocystic change
- hamartoma
- fibroadenoma
- sclerosing lesions; sclerosing adenosis, radial scar / complex sclerosing lesions
28
Name inflammatory benign breast conditions
- fat necrosis
- duct ectasia
- acute mastitis / abscess
29
Name tumours of benign breast disease
- phyllodes tumour
| - intraduct papilloma
30
What is gynaecomastia?
- breast development in the male
| - ductal growth without lobular development
31
Name causes of gynaeocmastia
- exogenous / endogenous hormones
- cannabis
- prescription drugs
- liver disease
32
Describe the epidemiology of fibrocystic change
- women aged 20-50 (majority 40-50)
- very common
- menstrual abnormalities
- early menarche
- late menopause
- often resolve or diminish after menopause
33
Describe the presentation of fibrocystic change
- smooth discrete lumps
- sudden pain
- cyclical pain
- lumpiness
- incidental finding
- screening
34
Describe the pathology of fibrocystic change
Gross pathology;
- cysts; 1mm-several cm, blue domed with pale fluid, usually multiple, associated with other benign changes
- intervening fibrosis
Microscopic pathology;
- cysts; thin walled but may have fibrotic wall, lined by apocrine epithelium
- intervening fibrosis
35
Describe management of fibrocystic change
- exclude malignancy
- reassure
- excise if necessary
36
What is a hamartoma?
Circumscribed lesion composed of cell types normal to the breast but present in an abnormal proportion or distribution
37
Describe the epidemiology of fibroadenomas
- common
- usually solitary (10% multiple)
- commoner in African women
- peak incidence in 3rd decade
38
Describe the clinical features of fibroadenomas
- painless, firm, discrete, mobile mass
- 'breast mouse'
- solid on ultrasound
39
Describe the pathology of fibroadenomas
- circumscribed
- rubbery
- grey white colour
- biphasic tumour / lesion' epithelium, stroma
- localised hyperplasia
- proliferation of intralobular stroma
40
Describe the treatment of fibroadenomas
- diagnose
- reassure
- excise
41
What are the two forms of sclerosing lesions?
- sclerosing adenosis
| - radial scar / complex sclerosing lesion
42
What are sclerosing lesions?
- benign, disorderly proliferation of acini and stroma
- can cause a mass or calcification
- may mimic carcinoma
43
Describe the features of sclerosing adenosis
- pain. tenderness or lumpiness / thickening
- asymptomatic
- age 20-70
- benign
- negligible risk of subsequent carcinoma
- often seen with other changes in the breast
44
Describe the epidemiology of radial scars
- wide age range
- common; 67% multicentric, 43% bilateral
- incidental finding
- mammographically detected
45
Describe the pathology of radial scars
- 1-9mm
- stellate architecture
- central puckering
- radiating fibrosis
- fibroelastic core
- radiating fibrosis containing distorted ductules
- fibrocystic change
- epithelial proliferation
Note; complex sclerosing lesion >10mm
46
Describe the treatment of radial scar
- mimic carcinoma radiologically
- in situ or invasive carcinoma may occur within these lesions
- excise or sample extensively by vacuum biopsy
47
How can fat necrosis occur?
- local trauma; seat belt injury
- frequently no history
- warfarin therapy
48
Describe pathophysiology of fat necrosis
- damage and disruption of adipocytes
- infiltration by acute inflammatory cells
- 'foamy' macrophages
- leakage of fat into tissue
- subsequent fibrosis and scarring
49
Describe management of fat necrosis
- confirm diagnosis
| - exclude malignancy
50
Describe clinical features of duct ectasia
- affects sub-areolar ducts
- pain
- acute episodic inflammatory changes
- bloody and or purulent discharge
- fistulation
- nipple retraction and distortion
51
What can duct ectasia go on to cause?
- sub-areolar duct dilatation
- periductal inflammation
- periductal fibrosis
- scarring and distortion
52
Describe management of duct ectasia
- treat acute infections
- exclude malignancy
- stop smoking
- excise ducts
53
What are the two main aetiologies for acute mastitis / asbcess?
- duct ectasia; mixed organisms, anaerobes
| - lactation; staph aureus, strep pyogenes
54
Describe management of acute mastitis / abscess
- antibiotics
- percutaneous drainage
- incision and drainage
- treat underlying cause
55
What is a phyllodes tumour?
- age 40-50
| - slow growing unilateral breast mass
56
Describe pathology of phyllodes tumour
- cystosarcoma phyllodes
- biphasic tumour
- stromal overgrowth
- behaviour depends on stromal features; benign, borderline, malignant (sarcomatous)
57
Name the different forms of papillary lesions
- intraduct papilloma
- nipple adenoma
- encapsulated papillary carcinoma
58
Describe the clinical features of intraduct papilloma
- age 35-60
- nipple discharge +/- blood
- asymptomatic at screening; nodules, calcification
59
Describe the pathology of intraduct papilloma
- sub-areolar ducts
- 2-20mm diameter
- papillary fronds containing a fibrovascular core
- covered by myoepithelium and epithelium
- epithelium may show proliferative activity (usual type hyperplasia, atypical ductal hyperplasia, ductal carcinoma in situ)
60
When do angiosarcomas arise?
Post radiotherapy
61
What tumours can metastasise to the breast?
- carcinoma; bronchial, ovarian serous or clear cell of the kidney
- malignant melanoma
- soft tissue tumours; leiomyosarcoma
62
Where does breast carcinoma arise?
In the glandular epithelium of the terminal duct lobular unit (TDLU)
63
Name precursor lesions of breast carcinoma
```
Ductal;
- epithelial hyperplasia of usual type
- columnar cell change (+/- atypia)
- atypical ductal hyperplasia (ADH)
- ductal carcinoma in situ (DCIS)
Lobular;
- lobular in situ neoplasia
- atypical lobular hyperplasia (ALH)
- lobular carcinoma in situ (LCIS)
```
64
Describe in situ carcinoma
- confined within basement membrane of acini and ducts
- cytologically malignant but non-invasive
- non-obligate precursor of invasive carcinoma
- classification; lobular, ductal
65
What are the two forms of lobular in situ neoplasia?
- atypical lobular hyperplasia, <50% of lobule involved
| - lobular carcinoma in situ (LCIS), >50% of lobule involved
66
Describe the pathology of lobular in situ neoplasia
- intra lobular proliferation of characteristic cells
- small intermediate sized nuclei
- solid proliferation
- intra-cytoplasmic lumens / vacuoles
- ER positive
- E-cadherin negative (deletion and mutation of CDH1 gene on Chr 16q22.1)
67
Describe the clinical features of lobular in situ neoplasia
- frequently multifocal and bilateral
- incidence 0.5-4% in benign biopsies
- incidence decreases after menopause
- not palpable, not visible grossly
- may calcify; mammography
- usually an incidental finding
68
Describe the management of lobular in situ neoplasia
- L(is)N discovered on core biopsy; proceed to excision or vacuum biopsy to exclude higher grade lesion
- L(is)N discovered on vacuum or excision biopsy; follow up, clinical trials
69
What are the forms of intraductal proliferation?
- epithelial hyperplasia of usual type
- columnar cell change (lesion)
- columnar cell change with atypia
- atypical ductal hyperplasia
- ductal carcinoma in situ
70
Describe the clinical features of ductal carcinoma in situ
- 15-20% of breast malignancies are DCIS
- arises in TDLU
- characteristically unicentric (single duct system)
71
Describe the pathology of ductal carcinoma in situ
- cytologically malignant epithelial cells
- confined within basement membrane of duct
- may involve lobules (cancerisation)
- may involve nipple skin (pagets)
72
Describe pagets disease of the nipple
- high grade DCIS extending along ducts to reach the epidermis of the nipple
- still in situ carcinoma (i.e. non-invasive)
73
Describe management of ductal carcinoma in situ
- diagnosis
- surgery; trials of mammographic follow up in low risk DCIS
- adjuvant radiotherapy
- chemoprevention; endocrine therapy
74
Describe microinvasive carcinoma
- rare
- DCIS (high grade) with invasion <1mm
- treat as high grade DCIS
75
What is invasive breast carcinoma?
- malignant epithelial cells which have breached the BM
- infiltration of normal tissues
- risk of metastasis and death
76
Name risk factors for breast carcinoma
- age
- age at menarche
- age at first birth
- parity
- breastfeeding
- age at menopause
- hormones; endogenous, exogenous (OCP, HRT)
- previous breast disease
- high BMI
- alcohol consumption
- high fat intake
- smoking
- genetics
77
Name cancer syndromes associated with breast cancer
- BRCA1
- BRCA2
- li fraumeni syndrome (TP53)
- PTEN cowdens syndrome
- peutx-jeghers syndrome
- ataxia telangiectasia
78
Describe the histopathological classification of invasive breast carcinoma
- ductal 70%
- lobular 10%
- mucinous 2%
- medullary 3%
- tubular 2%
- cribiform 1%
- papillary <1%
- mixed 10%
79
What are the hormone receptors associated with invasive breast carcinoma?
- 80% ER positive
- 67% PgR positive
- 14% HER2 positive
80
HER2 overexpression and amplification predicts the response to which drug?
trastuxamab (herceptin), human mouse monoclonal antibody
81
Name imaging techniques used in breast radiology
Standard techniques;
-mammography, ultrasound
Advanced techniques;
- mammographic; tomosynthesis, contrast enhanced spectral mammography
- ultrasound; elastrography, contrast enhanced US, automated breast ultrasound
- MRI
82
Name different forms of benign micro-calcification
- vascular calcification
- oil cyst 'eggshell' calcification
- plasma cell mastitis; long, bilateral, pointing to nipple, rod shaped coarse
- dystrophic calcification in scar
83
Describe the radiological appearance of ductal carcinoma in situ
- shape; linear or branching
- distribution; cluster or segmental
- pleomorphic (varying) size and density
84
Name indications for mammography
- screening (50-70yrs)
- higher risk screening >40 years
- symptomatic assessment >40 years
- monitoring response to systemic treatment; NACT
- follow up after cancer treatment
- image guided (stereotactic) techniques, biopsy / VAE, localisation
85
Describe the appearance of benign masses on ultrasound
- 'wide'
- well defined
- anechoic (black)
- hyperechoic
86
Describe the appearance of malignant masses on ultrasound
- 'tall'
- ill defined
- hyperechoic and heterogeneous (dark/ mixed)
87
What is tomosynthesis?
- '3D' technique
- images taken at different angles in an arc
- reconstruction into multiple slices; removes overlap, shows margins better
88
Name indications for tomosynthesis
- assessment of mammographic abnormalities
| - screening; may increase sensitivity in denser breasts (not very dense)
89
What is contrast enhanced spectral mammography?
- mammogram technique
- IV contrast agent (same as for CT)
- two clinical images for each breast view
- low energy image; equivalent to a standard mammogram
- subtracted image; enhancing lesions only, cancer have increased vascularity so enhance
90
What is elastography?
- a measure of tissue 'stiffness'
| - cancer tends to be stiffer than normal breast tissue / benign lesion
91
Describe strain elastography
- produced by palpation with ultrasound probe
- colour map of stiffness superimposed on grey scale image
- area of stiffness often bigger than greyscale abnormality
92
Describe shear wave elastography
- strain produced by the ultrasound probe (shear wave)
| - ultrafast sequence catches in real time the propagation of shear waves
93
Name indications for shear wave elastography
- adjuvant to grey scale ultrasound
- diagnosis of fibroadenomas (24-40 years)
- monitoring of treatment response
94
Describe malignant features on contrast-enhanced ultrasound
- hyper-enhancement with enlarged range / irregular margin
- hyper centri-petal enhancement with persfusion defect
- rapid / iso-enhancement with penetrating vessels
95
Name red flag symptoms for breast cancer
- solitary breast lump
- altered shape or contour or skin change
- breast lumpiness or nodularity
- breast pain
- non blood stained nipple discharge
96
Describe the neoadjuvant treatment that can be used to achieve breast conservation
- chemotherapy (standard FEC and taxane) +/- herceptin
- endocrine; aromatase inhibitors more effective than tamoxifen, so usually reserved for postmenopausal women
- both methods shown to reduce mastectomy rates
97
What are the types of breast surgery?
- breast conservation; wide local excision, image guided local excision, oncoplastic breast conservation including therapeutic mammopladty
- mastectomy; traditional transverse, skin sparing with immediate reconstruction
98
Describe the reconstruction options for mastectomy
- external prosthesis
- implant only (+/- autologous cellular matrix)
- latissimus dorsi pedicled flap +/- implant
- deep inferior epigastric artery perforator free flap
- inferior gluteal artery perforator free flap
- superior gluteal artery perforator
- transverse upper gracilis free flap
- profunda artery perforator free flap
99
Name genomic tests used for staging cancer
- mammaprint test; analyses the activity of certain genes in early bc
- breast cancer index test; used to predict risk of node negative, hormone receptor positive breast cancer combing back in 5-10 years
- endopredict test; used to predict risk of distant recurrence
- mammostrat; predict risk of recurrence
- oncotype DX; how likely the benefit of chemo / radio
100
Name acute side effects of chemotherapy
- fatigue
- myelosuppression and risk of infection, anaemia, thrombocytopenia
- nausea / vomiting
- alopecia
- mucositis
- diarrhoea
- constipation
- renal probloems
- neurotoxicity
- infertility
101
Name late side effects of chemotherapy
- cardiac
- infertility; premature menopause
- neuropathy
- renal impairment
- osteoporosis
- carcinogenesis
102
Describe the neo-adjuvant endocrine therapies
Pre or perimenopausal
- tamoxifen 20mg daily for up to 12 months +/- goserelin 3.6 mg by monthly subcutaneous implant
- letrozole 2.5mg daily for up to 12 months + goserelin 3.6mg by monthly s/c injectio
Post menopausal
- letrozole 2.5mg daily for up to 12 months
103
Adjuvant bisphosphonates are used whe?
- for women with a diagnosis of early invasive breast cancer who are;
- post menopausal and considered of sufficient clinical risk for treatment with an adjuvant AI or HER2 positive or ER low /negative or
- pre menopausal with ovarian suppression
