Breast Pathology Flashcards
What imaging is used in the assessment of breast disease?
Mammography
US
MRI
What pathology testing is carried out in breast disease assessment?
Cytopathology
Histopathology
How are samples taken for breast cytopathology?
FNA
Fluid
Nipple discharge
Nipple scrape
What are the categories in breast FNA cytology?
C1- Unsatisfactory C2- Benign C3- Atypia, probably benign C4- Suspicious of malignancy C5- Malignant
What Ix are carried out in breast histopathology?
(Needle) core biopsy
Vacuum assisted biopsy (large volume, mammotome)
Skin biopsy
Incisional biopsy of mass
What therapeutic interventions are carried out in breast histopathology?
Excisional biopsy of mass
Resection of cancer- wide local excision/mastectomy
What are the categories in breast 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
What are some developmental anomalies in breast growth?
Hypoplasia
Juvenile hypertrophy
Accessory breast tissue
Accessory nipple
What are some non-neoplastic breast diseases?
Gynaecomastia Fibrocystic disease Hamartoma Fibroadenoma Sclerosing lesions- sclerosing adenosis, radial scar/complex sclerosing lesions
What are some inflammatory benign breast diseases?
Fat necrosis
Duct ectasia
Acute mastitis/abscess
What are some benign tumours of the breast?
Phyllodes tumour
Intraduct papilloma
What is gynaecomastia?
Breast developmental in the male
Ductal growth without lobular development
What are some causes of gynaecomastia?
Exogenous/endogenous hormones
Cannabis
Prescription drugs
Liver disease
When do fibrocystic changes usually occur?
20-50yo, majority 40-50
Very common
What are the clinical features of fibrocystic change?
Menstrual abnormalities
Early menarche
Late menopause
Often resolve or diminish after menopause
How do fibrocystic changes present?
Smooth discrete lumps Sudden pain Cyclical pain Lumpiness Incidental finding Screening
What is the usual appearance of cysts related to fibrocystic changes?
1mm to several cm
Blue domed with pale fluid
Usually multiple
Associated with other benign changes
How do cysts related to fibrocystic changes appear microscopically?
Thin walled, but may have fibrotic wall
Lined by apocrine epithelium
How are cysts managed?
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
How do fibroadenomas usually present?
Common- found through screening
Usually solitary (10% multiple)
Commoner in African women
When is the peak incidence of fibroadenomas?
3rd decade
How will fibroadenomas feel?
Painless Firm Descrete Mobile mass 'Breast mouse'
How will fibroadenomas appear on US?
Solid
How will fibroadenomas appear grossly and microscopically?
Circumscribed
Rubbery
Grey-white
Biphasic tumour/lesion- epithelium/stroma
How is fibroadenoma managed?
Diagnose
Reassure
Excise
Describe sclerosing lesions
Benign, disorderly proliferation of acini and stroma
Can cause a mass or calcification
May mimic carcinoma
How will sclerosing adenosis present?
Pain, tenderness of lumpiness/thickening
Asymptomatic
Usually 20-70yo
How will radial scar present?
Wide age range
Common- 67% multicentric, 43% bilateral
Incidental finding
Mammographically detected
How is a radial scar and complex sclerosing lesion differentiated?
RS 1-9mm
CSL >10mm
Describe the appearance of a radial scar
Stellate architecture
Central puckering
Radiating fibrosis
What are the histological characteristics of a radial scar?
Fibroelastotic core
Radiating fibrosis containing distorted ductules
Fibrocystic change
Epithelial proliferation
Are radial scars malignant?
Usually no
Mimic carcinoma radiologically
Likely not premalignant
In situ or invasive carcinoma may occur within lesion
What can cause fat necrosis?
Local trauma- seat belt trauma, frequently no Hx
Warfarin therapy
What occurs in fat necrosis?
Damage and disruption of adipocytes
Infiltration by acute inflammatory cells
Foamy macrophages
Subsequent fibrosis and scarring
How is fat necrosis managed?
Confirm diagnosis
Exclude malignancy
What are the clinical features of duct ectasia?
Affects sub-areolar ducts Pain Acute episodic inflammatory changes Bloody and/or purulent D/C Fistulation Nipple retraction and distortion
What is duct ectasia associated with?
Smoking
Does fibrosis occur in duct ectasia?
Yes- Periductal fibrosis
How is duct ectasia managed?
Treat acute infections
Exclude malignancy
Stop smoking
Excise ducts
What are the 2 main causes of acute mastitis/abscess?
Duct ectasia- mixed organisms, anaerobes
Lactation- staph aureus, strep pyogenes
How is acute mastitis/abscess managed?
Antibiotics
Percutaneous drainage
Incision & drainage
Treat underlying cause
What are the clinical features of phyllodes tumour?
40-50yo
Slow growing unilateral breast mass
Describe the growth of phyllodes tumour
Biphasic
Stromal overgrowth
Behaviour depends on stromal features
Benign, borderline, malignant (sarcomatous)
What is the behaviour of phyllodes tumour?
Pathology helps to predict
Prone to local recurrence if not adequately excised
Rarely metastasise
What are the papillary lesions of the breast?
Intraduct papilloma
Nipple adenoma
Encysted papillary carcinoma
What are the symptoms and signs of intraduct papilloma?
Nipple discharge +- blood
Asymptomatic at screening- nodules, calcification
What age group is effected by intraduct papilloma?
35-60yo
What are the pathological and clinical features of intraduct papilloma?
Sub-areolar ducts
2-20mm diameter
Papillary fronds contained a fibrovascular core, covered by myoepithelium and epithelium
Epithelium may show proliferate activity
What are the categories of epithelial proliferation in intraduct papilloma?
None-benign
Usual type hyperplasia-benign
Atypical ductal hyperplasia
Ductal carcinoma in situ
What tumours often metastasise to the breast?
Carcinoma- bronchial, ovarian serous carcinoma, clear cell carcinoma of kidney
Malignant melanoma
Soft tissue tumours- leiomysarcoma
Where does breast carcinoma arise from?
Glandular epithelium of the terminal duct lobular unit (TDLU)
Technically adenocarcinoma
What are some ductal precursor lesions of breast carcinoma?
Epithelial hyperplasia of usual type
Columnar cell change
Atypical ductal hyperplasia
Ductal carcinoma in situ
What are some lobular precursor lesions of breast carcinoma?
Lobular in situ neoplasia- atypical lobular hyperplasia, lobular carcinoma in situ
Where is in situ carcinoma confined within?
Basement membrane of acini and ducts
What is in situ carcinoma on cytologically?
Malignant but non-invasive
What is the difference between atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS?
ALH <50% of lobule involved
LCIS >50% of lobule involved
What are the pathological findings in lobular in situ neoplasia?
Small-intermediate sized nuclei Solid proliferation Intra-cytoplasmic lumens/vacuoles ER +ve E-cadherin -ve (deletion & mutation of CDH1 on Ch 16)
What are 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
What is the management of lobular in situ neoplasia?
LN on core biopsy- proceed to excision or vacuum biopsy to exclude higher grade lesion
LN on vacuum or excision biopsy- follow up, clinical trials
What is the risk of progression to invasive carcinoma of epithelial hyperplasia of usual type?
2x RR
What is the risk of progression to invasive carcinoma of atypical ductal hyperplasia?
4x RR
What is the risk of progression to invasive carcinoma of ductal carcinoma in situ (low grade)?
10x RR (25% over following 10y)
What % of breast malignancies are DCIS?
15-20%
Where does DCIS arise?
TDLU
What is characteristic about DCIS?
Unicentric (single duct system)
What are the pathological features of DCIS?
Cytologically malignant epithelial cells
Confined within basement membrane of duct
May involve lobules (cancerisation)
May involve nipple skin (Paget’s)
What is Paget’s disease of the nipple?
High grade DCIS extending along ducts to reach epidermis of nipple
Still in situ carcinoma (non invasive)
What is used to classify DCIS?
Cytological grade
Histological type
Presence of necrosis (comedo)
Describe microinvasive carcinoma
Rare
DCIS (high grade) with invasion of <1mm
Treat as high grade DCIS
Why is DCIS significant?
RF for development of invasive carcinoma
True precursor lesion
75% progress to invasion following incisional biopsy only
How is DCIS managed?
Diagnosis
Surgery- trials of mammographic follow-up in low risk DCIS
Radiotherapy
Chemoprevention (trial)
What is the definition of an invasive carcinoma?
Malignant epithelial cells which have breached the BM
What are the RFs for breast carcinoma?
Age
Reproductive history- age at menarche/first birth/menopause, parity, breast feeding
Hormones- endogenous, exogenous- OCP, HRT
Oral contraception
Previous breast Hx
Geography
Lifestyle- bodyweight, physical activity, alcohol, diet, NSAID (lower risk), smoking
Genetics
By how much is the RR increased if a first degree relative is affected by breast cancer?
2x
Describe the incidence and risk of BRCA 1/2
Each present in 0.1% of population (approx 1 in 450 carry mutation in one of these genes)
2% of all breast cancers
45-64% lifetime risk
What is the 1,5,10,20y survival rate for breast cancer?
- 8%
- 1%
- 0%
- 5%
How can invasive breast carcinoma be classified histologically?
Ductal (NST) Lobular Mucinous Medullary Tubular Cribriform Papillary Mixed
What is tumour grade a measure of?
Differentiation
If a tumour is very similar to the parent tissue, is it well or poorly differentiated, and thus a good or poor prognosis?
Well differentiated, therefore good prognosis
What is assessed in breast carcinoma grading?
Tubular differentiation (1-3) Nuclear pleomorphism (1-3) Mitotic activity (1-3)
How is tumour grade scored from it’s assessment?
Score 3,4,5= Grade 1
6 or 7= Grade 2
8 or 9= Grade 3
What does ER expression in invasive carcinoma predict?
Response to anti-oestrogen therapy: oophorectomy, tamoxifen, aromatase inhibitors, GnRG antagonists
What does HER2 overexpression or amplification in invasive carcinoma predict?
Response to trastuzamad (Herceptin)
Seen in ~15%
What hormone receptors will usually be +ve in invasive carcinoma?
80% ER
67% PgR
14% HER2
What is the Nottingham Prognostic Index?
Histopathology based (grade and stage)
How is the NPI calculated?
0.2 x tumour diameter (cm) Tumour grade (1-3) LN status (1-3)
