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Breast Pathology Lecture - 2013Presentation Transcript
Knowledge is a burden,
If it robs you of innocence,
If it makes you feel you are special,
If it gives you an idea you are wise,
If it is not integrated into life,
If it does not bring you joy,
If it does not set you free.
Sri Sri Ravi Shankar,
Humanitarian and founder of the Art of Living Foundation, India.
CPC 4.5 – 42y Woman, sore R. breast.
Mrs JM is a 45y old woman, primary school teacher, living in Weipa.
“odd change in my left breast when I was showering last week”
Noticed it 8 days ago
What? “My left breast feels a bit thicker – points to upper outer quad*
Pain No, Nipple discharge: No, Trauma to breast: No
Menstrual cycle: regular, Mastalgia: not usually
LMP: about 4/52 ago; K due now.
Age of menarche: 13 years*, Parity: none* (failed IVF / infertility*)
Appetite, Weight : stable*
was on COCP* ages 17yrs – 30 yrs.
Cervical smear: Never*
Menarche aged 13yrs*
Has never had mammogram/breast USS* ‘I check regularly’ *
CPC 4.5- Examination
Key .. ?
o R breast NAD, L breast firm thickening ? upper
outer axillary tail ?; no discrete mass ? no skin
tethering ? / changes; no nipple inversion ?; no
areola changes ?, no axillary or supracla. LN. No Cancer
nipple discharge(blood/pus) ?
Benign proliferations, Breast malignancy
What further investigations?
Mammogram, FNAB, CT Scan, PET Scan,
Biopsy + immunochemistry (HER2) ?
CPC 4.5- Examination
Mammogram – solid* non mobile* irregular* mass lying at
the 10 o’clock position of the L breast. Mass has prominent
radiating spicules*; 2 x small calcifications* within the mass.
Overall mass 1x 1.5x 1cm.
US guided FNAB: High grade infiltrating ductal carcinoma ?
CT scan: no sign metastatic disease in liver or lung
Bone scan: no sign of metastases.
Immunochemistry : ER: ++ PR: neg HER2: +++.. ? ? ?
(? Sub types, Luminal B)
CPC 4.5 – 42y Woman, sore R. breast.
2013 Term 4 CPC 5 Title: Breast Cancer
Aim: Clinical, Pathology & population study of patients breast
1. Demonstrate competency in history taking & the
clinical examination of patients with breast
2. Describe the first line investigation and
management of patients with breast disease or
The student will be 3. Describe the Pathophysiology of breast
disease (benign and malignant)
4. Outline the basic sciences relating to function of
5. Describe the Epidemiology and aetiology of breast
disease in Australia and world wide.
6. Illustrate the advantages and disadvantages of
the breast screening program in Australia
CPC 4.5- Core Learning Issues
Pathology Major CLI:
Pathology of Breast – overview, classification & common dis..
Breast Lumps - Differential diagnosis.
Trauma, infections & Inflam. – Mastitis, fat necrosis, abscess.
Hyperplasia – Fibrocystic disease
Tumours – Benign – Fibroadenoma, giant fibroadenoma.
Breast cancer – etiology, pathogenesis, morphology &
complications, Laboratory diagnosis, including markers.
Pathology Minor CLI:
Gynecomastia & male breast disorders.
22year female, noticed small mobile round
lump in her right breast, lower inner quadrant.
39year female, multiple small lumps, irregular,
firm, tender more during mid cycle.
41year female, two left axillary LN, no pain, no
breast mass. mild loss of weight.
34year female, diffuse firm left breast. FNAC
reports abnormal cells. No LN.
39year female, painful lump, chronic pus
discharge from nipple.
71year old female. Rough, red scaling pruritic
patch on left nipple and areola.
26y nurse, right breast lump 5m, firm irregular,
6cm firm, fixed lump.
• Fibrocystic dis
• Ca breast.
• Duct ectasia
• Paget’s dis
• BRCA Ca.
Clinical features of benign, malignant & reactive…
Breast cancer screening guidelines.
Hyperplasia / tumour features.
Familial vs Non familial breast Ca features.
Screening Mammogram – policy, procedure &
Fibrocystic disease, fibroadenoma & cancer.
Breast cancer common types & features (gross,
microscopy, complications etc.)
Duct carcinoma, lobular carcinoma, other types.
BRCA testing in familial breast ca.
“Strength does not come from winning,
Struggles & Hardship develop strength.
- - Arnold Schwarzenegger
Bodybuilder, Actor & Leader.
Pathology of Breast
Dr. Venkatesh M. Shashidhar
Associate Prof. & Head of Pathology
CPC- 44 – Core learning Issues
Pathology of breast diseases – over view
Congenital, Inflammatory & Neoplastic disorders.
Breast Lumps – Hyperplasia – Fibrocystic disease.
Benign neoplasms: Fibroadenoma, Duct papilloma &
Breast cancer – Ductal Carcinoma & DCIS.
Hypertrophy, atrophy, accessory, supernumerary..
Mastitis (acute/chronic), Breast trauma, fat necrosis.
Phyllodes tumor, other carcinoma (Lobular etc)
Lobes and lobules of gland
in fat tissue stroma.
Ducts emerge from acini of glands
Smaller ducts join to form
Lactiferous ducts merge just
beneath the nipple to form a
Then individually open on nipple
Normal Breast – glands & stroma
Normal Breast – glands & stroma
Breast – Acini (SEM)
Age changes in breast:
Breast enlargement in men.
Estrogen excess –
Klinefelter’s, Hyperthyroidism, pitu
itary & adrenal tumors, testicular
Liver failure, cirrhosis
Lung, Testicular Cancer
diethylstilbestrol therapy for
Drugs (Spironolactone, H2
antagonists, Neuroactive agents).
Microscopy – only duct & stromal
hyperplasia. (no acini)
(central, periductal, rare)
Lactational (periphery, common)
First few weeks after delivery.
Crack in the nipple – entry point.
Staph. aureus, Strep. pyogenes.
Localized inflammation, Swelling erythema
Granulomatous (TB, Fungal, Silicone
Traumatic fat necrosis: Chronic
granuloma, foam macrophages, radial
scar – dd Ca.
Diabetic mastopathy: DM1, rubbery
>50y, multiparous. Periareolar mass
with white, cheesy nipple discharge.
inflammation, dilation, fibrosis with fat
globules & foamy macrophages in
Recurrent abscess / fistula.
Scarring with nipple inversion may
Lump in Breast: Diagnosis & Features
Mobile lump (single)
ill-defined lump/s or lumpy
areas – cyclic pain.
Firm lump tethering
Nipple ulceration, eczema
Pathology: Harmone induced acinar
Clinical: Commonest (40%) cause of
lumps in 20-40y. Irregular induration/
lumps. Cyclic pain/discomfort.
Gross: Grey white scar tissue with
Micro: Fibrosis, cysts, hyperplastic
Pathogenesis: Hyperplasia of glands
and stroma DCIS Carcinoma.
FibroCystic Disease: types
Non prol. / low grade
Prol. / High grade
A. Simple Fibrocystic change.
B. Lobular hyperplaisa without atypica (adenosis)
C,D - Ductal hyperplasia without atypia (E. with atypia - cribriform)
F. Lobular hyperplasia.
FCD: Cysts, Fibrosis & Proliferation
FCD + Ductal Hyperplasia*
Hyperplasia may progress to DCIS
(Duct Carcinoma In-Situ).
Progress to duct carcinoma.
Few (< 5 / breast )
Multiple (> 5 / breast )
Giant (> 4 / 5 cms) & Juvenile
Majority remain small & static
50% involute spontaneously
No future risk of malignancy
Pathology: Benign tumor of acini tissue (gland & stroma)
Clinical: Well demarcated, mobile, round/nod (mouse)
Gross: Capsulated, firm grey, nodular tumour, cysts+/-.
Micro: Compressed slit like ducts/glands in cellular stroma.
Mammogram - Benign
Note: well demarcated, capsulated, nodular tumour
C = capsule; In = intracanicular pattern; P = pericanicular pattern
Small discrete mobile.
Stromal neoplasm with
No malignant potential.
Regress / calcify in
Increase in pregnancy.
Pathology: Benign(young) to malignant(adult) tumor of acinii.
Clinical: young (Low grade) /adult (high grade)*, unilateral
macromastia, recurrent, metastasis 15%.
Gross: Large 10-15cm . Giant. With linear “leaf-like” clefts and slits –
Giant/Juvenile in young - Phyllodes tumor in adult.
Micro: Both stroma & glands are hypercellular & pleomorphic. glands
Clinical: Middle age, Bloody
discharge, sub areolar lump.
Gross: Solitary, Intra-ductal
Micro/Path: Benign papillary
proliferation of lactiferous duct
Stalk & papillae
Prognosis: recurrent, but no risk of
Education has two important
characteristics. One is learning of a
subject & skill. The other is the
personality to apply this knowledge to
the benefit of community.
One without the other is either useless or dangerous…. !
Knowledge, Skill & Attitude
* JCU graduate attributes..
Breast Carcinoma – Aus. stat.
The most common cancer among Australian women (also
in aboriginals). (20%)
UK 1 in 10 women, 1 in 8 in US, 1 in 9 Aus.
One in nine women before the age of 85.
28% of all cancer diagnoses in 2006.
Increased from 5,289 in 1982 to 12,614 in 2006
Commonest cause of death in young < 55y
Rare before age 30. (30-50 genetic, >50 sporadic)
Much less incidence in Asia, Japan.
Majority of cancers arise in the ducts.
Survival is improving with therapy. (96% 5y – 2006)
Etiology of Breast Carcinoma:
• RAS & MYC
• BRC A1, A2.
• Family history – First degree relative.
• Premenopausal & bilateral.
• Early menarche/Late menopause.
• Estrogen therapy.
• Alcohol, Smoking.
• High fat diet, Obesity.
Overexposure to oestrogens and underexposure to progesterone
No definite relationship to oral contraceptives
Some tumours contain hormone receptors and respond to hormone manipulation
No good evidence for viral involvement
Pathogenesis of Breast Cancer.
Duct Ca. in-Situ
Hyperplasia Dysplasia DCIS Carcinoma
Fibrocystic change Cancer
Ductal Carcinoma in Situ (DCIS)
Dysplastic cells filling ducts with
Ca+, no invasion. Pre-cancer state.
Increasing incidence of DCIS due to
mammographic screening. (diffuse
irregular firm/lumpy areas)
Spreads throughout ductal system to
produce extensive lesions.
Many types: solid
cribriform, papillary, and
micropapilary, comedo type or mixed
pattern. (dysplasia: low – high grade)
Progress to invasive carcinoma.
Ductal Carcinoma in Situ, DCIS
DCIS – Comedo type (high grade)
Central necrosis (comedo)
Myoepithelial Cells in DCIS
(imunoperoxidase stain note intact BM & ME cells)
All ducts, ductules and acini are separated from the interlobular and intralobular
connective tissue (stroma) by a basement membrane & Myoepithelial cells.
DCIS- High grade
Ca Breast: Histological Types
InfiltratingDuctal & Lobular Ca
Mucinous (colloid) Carcinoma
Prognostic / Genetic Classification: (new)
1. Luminal A – 50% of NST. ER+, HER2 –ve. Low grade, slow
growing, post menopausal, respond to harmone therapy. –
2. Luminal B – 20% of NST. ER+, HER2/neu +ve. (triple
positive ca.) high grade, respond to chemo.
3. Basal like – (Triple neg) 15% of NST. ER-, HER2/neu –
ve, BRCA1+, young. Poor prog.
4. HER2 positive – 10% ER- HER2 +, high grade, poor
prognosis, early brain mets. (Trastuzumab)
HER - Human Epidermal Growth factor Receptor Growth.
ER - Estrogen receptor function.
ER is good & HER is bad…!
Irregular, hard, grit
Infiltrating Duct Carcinoma: Breast Ca.
(NOS or Classic or typical “Schirrhous carcinoma”)
Note: Fibrotic tumor, radiating fibrous scar around
resulting in nipple retraction & skin pulling (puckering)
Mammogram - Ca
Breast Carcinoma Inflammatory / medullary
Inflamed, bulging without
High grade / medullary type
(HER2 & BCRA1)
Breast Ca. Lymphedema
Pathogenesis of Peu-de Orange in High grade Ca.
Tumor in lymph Vessel
Tumour emboli within lymphatic vessels obstruction Lymphedema
(also radiation induced lymphangitis can cause peu-de orange)
Medullary type (high grade): * note lymphocytes, no collagen/scar
Small cells, uniform, no tubules.
Target like growth around
‘Indian file (single cell lines)
between collagen bundles. No
E-cadherin –ve (unlike IDC)
ER/PR neg, HER2/neu pos.
Spread of Breast
Spread of Breast cancer
cells to skin (areola) &
resulting in Eczematous
Diagnosis: History First….!
Fine Needle Aspiration Biopsy
Special molecular tests on Biopsy:
Immunoperoxidase – HER2, ER & PR.
Molecular techniques – Gene detection (BRCA).
Triple Assessment Clinical,
Imaging & Biopsy
Breast clinic: incidence
Breast clinic: incidence
• Light compression by plates to stabilize
and spread its interior structures.
• Detect Fibrosis & Calcifications <100 µm
• Reveals a lump 1-2y before BSE.
• Women >40y should have yearly* mammogram.
• More for those at risk or symptoms.
Normal – 18y
Breast Ca. screening: new research
Research involving 600,000 women, results showed “for
every 2000 women screened
one will avoid dying of breast cancer
10 healthy women will be treated unnecessarily.
>200 experience distress due to false positive findings.
Breast Cytology - FNAB
in Breast Ca.
ER: Estrogen Receptors.
PR: Progesterone Receptors.
HER2/neu: Human Epidermal growth factor
E-Cadherin: Cell adhesion protein.
BRCA: Breast Carcinoma Antigen.
portraits of breast
Identify new breast
positive,” & “basallike”).
HER2 (Human Epidermal growth factor Receptor 2)
The HER2 proto-oncogene encodes a cell surface
receptor that is over expressed in approximately 25%30% of breast cancers. (normally 2 copies).
HER2 positive breast cancers grow quickly and spread
more than others. (poor prognosis)
HER2 testing (Immunohistochemistry/FISH) results are
critical to ensuring that patients who may benefit from the
anti-HER2 antibody therapy.
Trastuzumab (Herceptin®) is the first monoclonal antibody
that targets the extra cellular domain of the HER2
protein, and inhibits growth of breast cancer cells that over
express this protein.
52% of genetic type (2%
Risk of Ca – 40-90%
grade, necrosis, inflam (..
Triple –ve (ER,PR, HER2)
ovarian, prostate, pancre
32% of genetic type (1%
Risk of Ca 30-90%
Low grade, NOS type.
F/H of male breast ca
(ovary, prostate also)
Progression of Breast Ca: (new)
Common Ca. Breast: NST / NOS / Schirrhous Ca / Infiltrating duct Ca.
Mammogram: Stellate Lesion on Mammogram
Gross: Hard irregular - Schirrhous
Micro: Pleomorphic cells forming tubules in dense fibrous stroma.
Sign or symptom
Fibrosis, epithelial hyperplasia and cysts in fibrocystic change
Neoplasm or solitary cyst
Benign neoplasm (usually fibroadenoma)
Invasive neoplasm (carcinoma)
Impaired lymphatic drainage due to carcinoma
Invasion of skin by carcinoma
Increased blood flow due to inflammation or tumour
Milky-pregnancy or prolactinoma
Bloody-duct papilloma or carcinoma (rare)
Tethering by invasive carcinoma
ERYTHEMA AND SCALING
Paget's disease of nipple (cancer) or eczema
Benign breast changes – fibrocystic change
Inflammatory lesion (e.g. mastitis)
invasive carcinoma (also in cysts, benign changes, DCIS)
BONE PAIN OR FRACTURE
Possibly due to metastatic breast carcinoma or associated with hypercalcemia
Distinction and explanation
Fibroadenoma is a localized circumscribed benign neoplasm comprising
epithelial cells and specialised fibrous tissue. Fibroadenosis is an obsolete
name for fibrocystic change, a diffuse hyperplastic lesion.
both comprise neoplastic epithelial and fibrous tissue components. However,
in phyllodes tumours the fibrous tissue component is more cellular and
abundant, and the lesion has less well defined margins; borderline and
malignant variants occur.
Ductal epithelial hyperplasia is a benign proliferation of duct epithelium,
whereas ductal carcinoma in situ has undergone neoplastic transformation,
although it is not yet invasive. These lesions can have morphological
similarities. A proportion share genetic alterations.
Radial scar &
Radial scars and complex sclerosing lesions differ only in size: the latter are
>10 mm diameter. Both mimic carcinomas radiologically and histologically,
but they are benign non-neoplastic lesions.
carcinoma of the
breast & of the
The term medullary refers only to the soft consistency (resembling the
medulla of the brain). There is no other relationship between these lesions.
Paget's disease of
the nipple & of
Both lesions were described by Sir James Paget (1814-1899). There is no
other relationship between these lesions.
No weight loss.
What is this?
What is PET Scan?
What contrast is used?
What does it show?
What are its Indications ?
Positron Emission Tomography.
Radiolabelled glucose by IV.
High metabolic rate cells (cancer cells)
3D view of cancer spread over body.
2. NonLactational infections : Central
Usually due to Periductal mastitis
Affects younger women. Often smokers
in the West
May present as : inflammation +/mass, abscess, mammary duct fistula
Aerobic + anaerobic organisms may
Antibiotics (E.G. Co amoxyclav etc)
before pus formation
Abscess : Repeated aspiration / mini
incision with topical anaesthetic cream
( I& D under GA occasionally)
MDF : Excision fistula + Total duct