Breast Pathology Flashcards
What is the gold standard assessment of a patient with breast disease?
Triple assessment;
Clinical - hx and exam
Imaging - MMG, USS, MRI
Path - cytopathology, histopathology
What can give a sample of breast cytopathology?
FNA
Fluid
Nipple discharge
Nipple scrape
What is the grading of breast FNA cytology?
C1 - unsatisfactory C2 - benign C3 - atypia but probs benign C4 - suspicious of malignancy C5 - malignant
What are diagnostic breast histopathology mechanisms?
Needle core biopsy
Vacuum assisted biopsy
Skin biopsy
Incisional biopsy of mass
What are the therapeutic breast histopathology mechanisms?
Vacuum assisted excision
Excisional biopsy of mass
Resection of cancer; wide local, mastectomy
What is the grading for a needle core biopsy?
B1; unsatisfactory B2; benign B3; atypical probs benign B4; suspicious of malignancy B5; malignant (B5a; CIS, B5b; invasive carcinoma)
What are developmental anomalies of benign breast disease?
Hypoplasia
Juvenile hypertrophy
Accessory breast tissue or nipple
What are the common non-neoplastic pathologies of benign breast disease?
Gynaecomastia Fibrocystic change Hamartoma Fibroadenoma Sclerosing lesions; sclerosing adenosis or radial scar
What are the benign inflammatory pathologies of the breast?
Fat necrosis
Duct ectasia
Acute mastitis/ abscess
What are the benign tumours of the breast?
Phyllodes tumour
Intraductal papilloma
What is gynaecomastia?
Breast development in the male
Ductal growth without lobular development
What can cause gynaecomastia?
Exogenous/ endogenous hormones
Cannabis
Prescription drugs
Liver disease - increase in oestrogenic hormones
What is the etiology of fibrocystic change of the breast?
Women aged 20-50; mostly 40-50
Very common
What are risk factors for fibrocystic change of the breast?
Menstrual abnormalities
Early menarche
Late menopause
What is the presentation of fibrocystic change of the breast?
Smooth discrete lumps Sudden pain Cyclical pain Lympiness Incidental finding Screening
What is seen in the gross pathology of fibrocystic change of the breast?
Cysts; 1mm to several cm Blue domed with pale fluid Usually multiple Assoc with other benign changes Intervening fibrosis
What is the microscopic pathology of fibrocystic change of the breast?
Cysts; thin walled
Apocrine epithelium
Intervening fibrosis
What is metaplasia?
Change from one fully differentiated cell type to another fully differentiated cell type
What is the management of fibrocystic change of the breast?
Exclude malignancy
Reassure
Excise if necessary
What is a hamartoma?
Circumscribed lesion composed of cell types normal to the breast but present in an abnormal proportion or distribution
What is a fibroadenoma?
Common
Usually solitary
Commoner in African Women
What is the clinical presentation of a fibroadenoma?
Painless, firm, discrete, mobile mass Solid on USS Circumscribed Rubbery Grey-white colour Biphasic tumour
What is a biphasic tumour?
Has epithelium and stroma
Tx for fibroadenoma?
Diagnose
Reassure
Excise if necessary
What is a sclerosing lesion?
Benign, disorderly proliferation of acini and stroma
Can cause mass or calcification
May mimic carcinoma
How will sclerosing adenosis present?
Pain
Tenderness
Lumpiness/ thickening
Can be asymptomatic
What is the pathology of a radial scar?
If 1-9mm = radial scar If >10mm = complex sclerosing lesion Stellate architecture Central puckering Radiating fibrosis
What is the histology of a radial scar?
Fibroelastic core
Radiating fibrosis containing distorted ductules
Fibrocystic change
Epithelial proliferation
What is the treatment for a radial scar?
Excise or sample extensively via vacuum biopsy
Is a radial scar premalignant?
No; but in situ or invasive carcinoma may occur within the lesion
Can mimic carcinoma radiologically
Shows epithelial proliferation
What can cause fat necrosis of the breast?
Local trauma; seat belt injury
Recently stared warfarin therapy
What is the pathology of fat necrosis?
Damage and disruption of adipocytes
Infiltration by acute inflammatory cells
Foamy macrophages
Subsequent fibrosis and scarring
Tx for fat necrosis of breast?
Confirm diagnosis
Exclude malignancy
What are the clinical features of duct ectasia?
Affects subareolar ducts Pain Acute episodic inflammatory changes Bloody +/- purulent discharge Fistulation Nipple retraction and distortion Periductal inflammation and fibrosis
What environmental factor is assoc with duct ectasia?
Smoking
Tx for duct ectasia?
Treat acute infections
Exclude malignancy
Stop smoking
Excise ducts
What are the 2 main aetiologies for acute mastitis?
Duct ectasia; mixed organisms, anaerobes
Lactation; staph aureus, strep pyogenes
Mx for acute mastitis/ abscess?
Antibiotics
Percutaneous drainage
Incision and drainage
Treat underlying duct ectasia if present
What are the clinical features of a phyllodes tumour?
Slow growing unilateral breast mass
Biphasic tumour
Stromal overgrowth
What does the behaviour of a phyllodes tumour depend on?
Stromal features; benign, borderline, malignant (sarcomatous)
Does a phyllodes tumour tend to metastasize?
No
But, prone to local recurrence if not adequately excised
What are the different forms of papillary lesion seen in the breast?
Intraductal papilloma
Nipple adenoma
Encapsulated papillary carcinoma
What is the presentation of an intraductal papilloma?
Nipple discharge +/- blood
Asymptomatic at screening; nodules or calcification
What are the histological features of an intraductal papilloma?
Papillary fronds containing a fibrovascular core
Covered by myoepithelium and epithelium which may show proliferative activity
What are the miscellaneous malignant tumours of the breast (not carcinomatous)?
Malignant phyllodes; sarcomatous stromal Angiosarcoma; post XRT Lymphoma; breast +/- lymph nodes Metastatic tumours Malignant melanoma LEiomyosarcoma
What primary cancers can metastasize to the breast?
Bronchial
Ovarian serous
Clear cell carcinoma of kidney
What is the definition of a breast carcinoma?
A malignant tumour of breast epithelial cells
Where will a breast carcinoma arise from?
Glandular epithelium of the terminal duct lobular unit (TDLU)
What is the precursor lesion to ductal carcinoma of the breast?
Epithelial hyperplasia of usual type
Columnar cell change (+/- atypia)
Atypical ductal hyperplasia
Ductal carcinoma in situ
What is the precursor lesion to lobular carcinoma of the breast?
Atypical lobular hyperplasia
Lobular carcinoma in situ
Lobular in situ neoplasia
What is an in situ carcinoma of the breast?
Confined within the basement membrane of acini and ducts
Cytologically malignant but non-invasive
Will all in situ carcinomas transform into an invasive carcinoma?
No; they are non-obligate
What is the difference between atypical lobular hyperplasia and lobular carcinoma in situ?
ALH; <50% of lobule
LCIS; >50% of lobule
Describe the histopathology of lobular in situ neoplasia
Intralobular proliferation of characteristic cells Small intermediate sized nuclei Solid proliferation Intra-cytoplasmic lumens/ vacuoles ER positive E-cadherin neg
What is E-cadherin in terms of breast carcinoma?
Deletion and mutation of the CDH1 gene on chromosome 16
What are the clinical features of lobular in situ neoplasia?
Multifocal and bilateral Incidence decreases after menopause Not palpable, not visible grossly May calcify; seen on MMG Incidental finding
What is the significance of lobular in situ neoplasia?
Marker of subsequent risk
True precursor lesion
Mx for lobular in situ neoplasia?
Discovered on core biopsy; excision or vacuum biopsy to exclude higher grade lesion
Discovered on vacuum or excision biopsy; follow up
What is the follow up for lobular in situ neoplasia found on vacuum or excision biopsy?
Annual MMG for 5 years
Describe the natural history of intraductal proliferation
Epithelial hyperplasia of usual type Columnar cell change CCC with atypia Atypical ductal hyperplasia Ductal carcinoma in situ
What is the risk of progression to invasive carcinoma from DCIS (low grade)?
10x RR
25% over 10 years
How many breast malignancies are DCIS?
15-20%
Arises in TDLU
Characteristically unicentric
Describe the histopathology of DCIS?
Cytologically malignant epithelial cells
Confined within BM of duct
Can involve lobules (cancerisation)
Can involve nipple skin (Paget’s)
What is paget’s disease of the nipple?
High grade DCIS extended along ducts to reach the epidermis of nipple
Still in situ
How is DSCIS classified?
Cytological grade
Histological type
Presence of necrosis
Mx for DCIS?
Diagnosis
Surgery
Adjuvant radiotherapy
Chemoprevention; endocrine therapy
What is a microinvasive carcinoma of the breast?
DCIS (high grade) with invasion of <1mm beyond BM
Treat as high grade DCIS
What is the commonest cancer for women?
Breast
What is the peak incidence for breast cancer in women?
50-70
What are risk factors for carcinoma of the breast?
Age
Repro hx; age at menarche, age at first birth, parity, breastfeeding, age at menopause
Hormones; endogenous, exogenous (OCP, HRT)
Previous breast dx (esp malignant)
Geography
Lifestyle; BMI, physical activity, alcohol, diet, NSAIDs (lowers risk), smoking
Genetics; BRCA
Which genetic anomalies increase the risk for breast cancer?
BRCA 1 and 2 Tp53 PTEN STK11/ LKB1 ATM
What cancer syndrome and associated tumours will the BRCA mutations cause?
BRCA1 = breast, ovarian, bowel, prostate
BRCA 2 = breast (inc male), ovarian, prostate, pancreatic
What cancer syndrome and assoc tumours will the Tp53 mutation cause?
Li Fraumeni Syndrome
Childhood sarcoma, brain, leukaemia, adrenocortical carcinoma, early-onset breast
What cancer syndrome and assoc tumours will the pTEN mutation cause?
Cowden’s syndrome
Breast, GI, thyroid
What cancer syndrome and assoc tumours will the STK11/LKB1 mutation cause?
Peutz-Jeghers Syndrome
Breast, GI, pancreatic, ovarian
What cancer syndrome and assoc tumours will the ATM mutation cause?
Ataxia Telangiectasia
Non-hodgkin’s lymphoma
Ovarian
Breast (in heterozygous carriers)
What percentage of breast cancers are caused by BRCA mutations?
2%
Present in 0.1% of population; 1 in 450 is a carrier
What is the lifetime risk for breast ca with BRCA mutations?
45-64% life-time risk
What is the net survival for women with breast cancer; age standardised?
1 yr; 96%
5 yr; 87%
10 yr; 78%
How many women will develop breast ca?
1 in 8
Describe the natural history of invasive breast ca
Local invasion (T); stroma of breast, skin, muscles of chest wall Lymphatics (N); regional draining lymph nodes Bloodborne (M); bone, liver, brain, lungs, abdominal viscera, female genital tract
Where does the majority of lymph from the breast drain to?
Axillary nodes
What are the routes for drainage of the breast?
Internal mammary
Intramammary
Axillary
What are the sentinel lymph nodes of the breast?
Apical nodes
Infraclavicular nodes
Supraclavicular nodes
How is invasive breast cancer classified?
Morphological; type, grade
Gene expression profiling
Hormone receptor; ER, PR, HER2
What is the most common histopathological type of breast ca?
Ductal (NST); 70%
Lobular; 10%
What is the grade of a tumour?
Measure of tumour differentation
How is breast carcinoma graded?
Tubular differentiation (1-3) Nuclear pleomorphism (1-3) Mitotic activity (1-3) Score of 3-5 = grade 1 Score 6-7 = grade 2 Score 8-9 = grade 3
What is a basal like intrinsic breast cancer sub-type?
ER -ve
HER2 -ve
Basal CK +
What is a HER2 intrinsic breast cancer sub-type?`
ER -ve
HER2 +ve
What is a luminal A intrinsic breast cancer sub-type?
ER +ve
Low proliferation
What are luminal B and C intrinsic breast cancer sub-type?
ER +ve
High proliferation
In terms of ER, PgR and HER2 hormone receptors, what percentage of breast ca are positive for them?
80% ER +ve
67% PgR +ve
14% HER2 +ve
What will ER positive breast ca respond to in terms of hormonal therapy?
Oophorectomy (don't really do anymore) Tamoxifen Aromatase inhibitors ( letrozole) GnRh antagonists (goserelin) - only in pre-menopausal women
What will HER2 +ve breast ca respond to in terms of hormonal tx?
Trastuzumab (herceptin)
In terms of hormone receptors, which subtype of breast cancers have the best outcome?
ER +ve
PR +ve
HER2 -ve
In terms of hormone receptors, which subtype of breast ca have worst outcome?
HER 2 +ve
THEN
Triple neg is worst
What prognostic indices are used for breast ca?
Nottingham Prognostic Index
NHS PREDICT
How is Nottingham Prognostic Index calculated?
0.2 x tumour diameter (cm)
Tumour grade (1-3)
Lymph node status (1-3)
