1
Q
What level is the nipple at?
A
T4
2
Q
What are the common draining lymph nodes of the breast and why?
A
- apical axillary
- lateral axillary
- pectoral axillary
lesions are more common in the upper outer quadrant
3
Q
Outline breast anatomy
A
- modified sweat glands
- lobes and lobules of gland
- glands –> lactiferous ducts
- ducts enlarge beneath nipple to form lactiferous sinus –> individually open on nipple (6-10)
4
Q
Outline age changes in breast
A
Puberty
- less glands
- more fibrous tissue
Adult (lactating)
- plenty of glands (esp. during lactation)
- fibro-fatty
Menopause
- atrophy of glands
- fat
5
Q
What is congenital aplasia of the breast known as?
A
Turners
6
Q
Where are accessory/ectopic breasts seen?
A
along the milk line
7
Q
What is the most common breast disorder?
A
Inflammation
*mastitis –> acute lactational common (bacteria)
8
Q
What is the commonest proliferative condtion of the breast?
A
Fribrocystic disease/change
9
Q
What is the commonest benign and malignant neoplasm of the breast?
A
benign –> fibroadenoma
malignant –> carcinoma + DCIS
10
Q
Clinically, what is the commonest cause of breast lumps?
A
- **fibrocystic changes (hormone-induced) –> 40%
- no disease = 30%
- cancer = 10%
11
Q
What is likely Dx of a single mobile breast lump in young adult?
A
fibroadenoma
12
Q
What is likely Dx of an ill-defined lump(s) or cyclical pain?
A
fibrocystic change
13
Q
What is likely Dx of a firm lump +/- tethering (fixed)?
A
carcinoma
25-35yrs = familial
35-55yrs = sporadic
14
Q
What is the cause of clear/purulent discharge vs bloody discharge?
A
clear/pus –> inflammation (duct ectasia)
bloody –> duct papilloma
15
Q
What is the difference between non-lactational and lactational acute mastitis?
A
non-lactational –> central, periductal, rare
lactational –> periphery, common
16
Q
What is the etiology of acute lactational mastitis?
A
- first few weeks after delivery
- crack in nipple (entry point)
- S. aureus/Strep. pyogenes
- localised inflammation, swelling, erythema + pus (periphery)
- enlarged axillary LNs
17
Q
What are the causes of chronic mastitis?
A
- granulomatous (TB, silicone implants)
- traumatic fat necrosis (chronic granuloma, radial scar)
- diabetic mastopathy (DM1 lymphocytic inflamm)
18
Q
What is a multiparous woman?
A
having borne more than one child
19
Q
Who is affected more commonly by duct ectasia?
A
- chronic inflammatory condition
- later age >50yrs
- multiparous women
20
Q
What is the etiology of duct ectasia?
A
-inpissation of breast secretions (drying of milk) within ducts –> chronic inflammation
21
Q
What are the features of duct ectasia?
A
- duct obstruction/destruction, dilatation –> inflammation, fibrosis with fat globules (obstructed milk) + foamy macrophages in lumen
- periareolar mass with white, cheesy nipple discharge
- recurrent abscess/fistula
- scarring with nipple inversion may mimic carcinoma
*similar to bronchiectasis in lung (plenty of pus)
22
Q
What is microscopy of duct ectasia?
A
- dilated ducts
- plenty of surrounding inflammatory cells
23
Q
What is fat necrosis and what is the typical cause?
A
- uncommon, chronic scarring of breast
- usually following trauma, surgery, biopsy –> fat necrosis granulomatous inflammation –> scarring and calcification
- *mimics carcinoma**
24
Q
Why is there cyclical pain/discomfort in fibrocystic disease/change?
A
- hormone sensitive
- estrogen-induced hyperplasia of glands + stroma
25
What re the 2 major types of fibrocystic disease/change?
1. non-proliferative (low grade)
- cystic dilatation of ducts + fibrosis
2. proliferative (high grade)
- epithelial proliferation** --> higher chance of malignant transformation (DCIS --> carcinoma)
26
What are the gross and microscopic features of fibrocystic diasease/change?
Gross:
-grey, white scar tissue with cysts; multiple irregular nodules
Micro:
-fibrosis, cysts, hyperplastic/dilated glands
27
What is sclerosing adenosis?
- fibrocystic disease (proliferative type) --> epithelial proliferation
- sometimes epithelial proliferation forms multiple glandular structures with dense fibrous stroma
- clinical and biopsy findings mimic carcinoma
28
What is blue dome cyst?
when one of the cysts in fibrocystic disease becomes very large --> blue dome cyst
29
What is the pathogenesis of fibrocystic disease?
-excess estrogens and sensitivity to estrogens --> hormone-induced hyperplasia of glands/stroma
30
What are the differences between benign and malignant breast neoplasms?
Benign:
- round, smooth, soft/rubbery, mobile
- multiple (FCD)
- young <35y
- painful
- no lymph nodes/no wt. loss
* fibroadenoma (stromal)
* ductal papilloma (epithelial)
Malignant:
- irregular, rough, hard/gritty, fixed
- single
- old >35y
- painless
- lymph nodes/wt. loss
- radiating scar (characteristic); nipple retraction/oedema
* ductal carcinoma
31
What are the 2 types of fibroadenoma?
1. simple fibroadenoma
- solitary, few (<5/breast), multiple (>5/breast)
- <5cm round, well demarcated capsulated nodules
2. giant fibroadenoma (>5cm)
- juvenile (<20yrs, benign)
- adult --> phyllodes tumour (benign to malignant)
32
What are gross and microscopic features of simple fibroadenoma?
Gross:
-well demarcated, mobile, round/nodular, capsulated, <5cm
Micro:
- atrophic, compressed slit like flat glands in loose fibrous stroma
- capsule
33
What is the difference between simple and giant fibroadenoma?
simple:
- tumour of stroma
- <5cm (small/round), mobile
- compressed, flat slit-like glands
- atrophic glands
giant:
- tumour of gland and stroma
- >5cm (large/round), non mobile
- can be malignant (in adults - 15%)
- "leaf-like" clefts and slits
- hypercellular, branching glands + stroma
34
What are the gross and microscopic features of intraductal papilloma?
Gross:
- solitary, intraductal papillary proliferation
- sub areolar lump with bloody discharge
Micro:
- benign papillary proliferation of lactiferous duct epithelium
- stalk + papillae
35
What is the prognosis of intraductal papilloma?
-recurrent but v rare risk of metastases
36
What happens to fibroadenomas in pregnancy vs. menopause?
pregnancy --> increases due to hormones
menopause --> regresses/calcifies
37
True or False?
| OCP is a known risk factor for BrCa
True
38
What is the majority of malignant breast cancers?
ductal carcinomas
39
What is the etiology of breast carcinoma?
1. hormone
- increased estrogen/estrogen therapy (OCP)
- long duration between menarche and menopause
- decreased progesterone
2. environment
- obesity, high fat diet
- smoking, alcohol, radiation
- atypical hyperplasia
3. genetics
- FHx (familial in 12%)
- early menarche/late menopause
- increased HER2/NEU (20%) - bad
- increased RAS + MYC
- decreased BRCA1 (50%) + BRCA2 (30%)
40
What is the normal appearance of a duct?
- luminal cells - columnar epithelial
- myoepithelial contractile cells
- basement membrane
- stromal cells
41
What is the pathogenesis of breast cancer?
- proliferation of luminal epithelial cells in response to etiological factors (hormone, environment, genetics)
- loss of apotosis/genome instability/loss of growth inhibition --> atypical hyperplasia
- dysplasia occurs --> when it fills the while duct but BM still intact (carcinoma insitu)
- invasive carcinoma once it ruptures/spreads through BM
*RF's --> hyperplasia --> dysplasia --> DCIS --> ca.
42
What are the IDC genetic subtypes?
1. luminal A** commonest
- ER +, PR +, HER2 -
2. luminal B
- ER +, PR +, HER2, +
3. HER2+
- ER -, PR -, HER2 +
3. Basal like
- ER -, PR -, HER2 -
43
What is low grade vs high grade IDC?
low grade = luminal types = ER/PR +
high grade = basal-like = familial --> "triple negative"
44
How can we tell if there is invasion or just carcinoma in situ?
-immunohistochemistry special stain for myoepithelial cells will indicate intact myoepithelial cells, and thus intact BM --> therefore DCIS/LCIS
45
What are the different morphologies of DCIS?
1. cribiform --> multiple cavities
2. comedo --> central necrosis (high grade)
3. Paget's disease --> DCIS spreads to skin to form eczematous patches
46
Commonest genetic mutation causing familial breast cancer is?
BRCA1 gene loss (50%)
47
What can happen to nipple in breast carcinoma?
skin tethering/puckering due to radiating fibrous tissue--> pulls nipple inside (nipple retraction)
48
Why are malignant tumours of the breast fixed/immobile?
-scar tissue gets attached to muscles/bones/surrounding tissue
49
What is the mammographic appearance of breast carcinoma?
- mammographic density (white areas)
- more white areas = more risk of malignancy
- >75% density = 4-fold increased risk
* dusty calcification
* radial scar
50
What are the gross and microscopic features of IDC?
Gross:
- hard, gritty
- dense fibrous tissue with radiating folds
Micro:
- pleomorphic cells forming irregular ducts
- collagen stroma
51
True or False?
| HER2 is good, ER/PR is bad
FALSE
| ER/PR is good, HER2 is bad
52
What are the features of lobular carcinoma?
- multifocal, bilateral, familial
- small cells, uniform cluster
- NO tubule/duct formation
- "indian file" (single cell lines between collagen bundles)
- LCIS = precancer stage
- typically ER/PR -, HER2/neu +
- E-cadherin neg. (unlike IDC)
53
What are the features of medullary carcinoma?
- <3% (rare)
- high grade, better prognosis (plenty of lymphocytes within tumour)
- expansile* (no skin tethering)
54
What are the features of inflammatory carcinoma?
- clinically erythematous breast (mistaken for mastitis)
| - dermal lymphatic obstruction --> inflammatory-like appearance, yet NO significant inflammation
55
Which breast cancer can males get?
- 1%
- ONLY ductal carcinoma
* males have NO lobules*
56
What is Paget's disease?
- spreading of cancer cells from DCIS along ducts --> peri areolar skin --> eczematous reaction
- micro --> clusters of malignant cells in superficial epidermis
57
What is peu-de Orange and how does it occur?
- orange-skin appearance in breast cancer lymphoedema
- tumor cells/emboli within lymphatic vessels --> obstruction --> lymphoedema
*exacerbated by radiation --> radiation kills malignant cells --> lymphangitis --> more obstruction
58
How can breast cancer spread?
direct:
-chest wall, muscles, bones
lymphatics:
-axillary
haematogenous:
-CNS/brain, liver, bone, lungs
59
What is gynecomastia and the causes of it?
- breast enlargement in men
- *estrogen excess --> klinefelter's, hyperthyroidism, pituitary/adrenal tumours, testicular failure, drugs
- liver failure/cirrhosis, lung cancer, testicular cancer
- diethylstilbestrol Tx. for prostate ca.
- drugs --> spironolactone, H2 antagonists (peptic ulcer), neuroactive agents
60
What is microscopy of gynecomastia?
- duct + stromal hyperplasia
- NO acini or lobules
*reason why male breast cancers are only DUCTAL carcinomas
61
How is a breast lump diagnosed?
* history first*
- mammography
- US
- fine needle aspiration biopsy (FNA)
- core/needle biopsy
- excision biopsy
- special molecular tests on biopsy --> immunoperoxidase (HER2, PR, ER); molecular techniques - gene detection (BRCA)
*TRIPLE ASSESSMENT*
62
What is triple assessment?
Diagnostic methods for BrCa:
1. clinical assessment
2. imaging
3. biopsy
63
What is a mammogram?
- low radiation x-ray of breast (0.4mSv c.f. 3-8 X-ray)
- light compression by plates to stabilise/spread interior structures
- detects v. fine fibrosis/calcification (<100microm)
- reveals a lump 1-2yrs before palpable
- more for those at risk or Sx.
64
Compare breast cytology for normal breast vs malignancy
normal:
-uniform cells, v few, regular, cohesive
malignancy:
-plenty cells, haemorrhagic, pleomorphic, necrotic
65
What Tx. is used for HER2+ breast cancer pts.?
herceptin (trastuzumab)
| *HER2+ BrCa grow quickly and spread more than others (poor prognosis)
66
Compare BRCA1 and BRCA2
BRCA1:
- 52% of genetic type
- young age
- high grade, necrosis
- triple negative***
- FHx ovarian, prostate, pancreas Ca.
- chromosome 17q
BRCA2:
- 32% of genetic type
- not specific
- low grade, NOS type, scarring (schirrous)
- ER+***
- FHx of male breast ca (ovary/prostate also)
- chromosome 13q
67
What contrast is used in PET scan and what does it show?
- radiolabelled glucose by IV
| - high metabolic rate cells (cancer cells) --> 3D view of cancer spread over body
68
Fibroadenoma is a tumour of..?
intralobular stroma
69
What is microscopy of DCIS?
- dilated ducts, epithelial proliferation --> CRIBIFORM = commonest type
- intact wall (myoepithelial cells)
- no infiltration
70
What is microscopy of IDC?
- pleomorphic cells forming irregular ducts
- dense fibrous stroma
- DCIS at periphery (if present suggests cancer has gone through DCIS stage)
- radiating scars of collagen tissue
Pathology Term 5
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