Pathology of Breast Disease Flashcards by Chloe Mackle

Describe the normal structure of the breast

Epithelium - ducts and lobules (glandular)
Mesenchyme - fat and fibrous tissue
Hormone dependent - ER, PR
Physiological changes with age and pregnancy

Each breast has 8-10 sections (lobes) arranged like petals
Inside each lobe are many smaller structures called lobules
At the end of each lobule are tiny sacs (bulbs) that can produce milk

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What is the normal anatomy of the breast?

Before puberty - breasts in both sexes, contain ducts
Variable degrees of branching, lack lobules
15-25 lactiferous ducts, start in the nipple and branch out to terminal ductal lobular unit
Hormonally responsive

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What are the lymphatics of the breast?

Sentinel lymph node is the first draining node - involvement might indicate malignancy
Lymph ducts drain fluid that carries WBC from the breast tissues into the lymph nodes in the axilla and behind the sternum
Lymph nodes filter harmful bacteria and play a key role in fighting off infection

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What are some benign breast conditions?

Fibrocystic change - fibrosis, adenosine, cysts, apocrine metaplasia, ductal epithelial hyperplasia
Fibroadenoma - circumscribed mobile nodule in reproductive age
Intraductal papilloma - lactiferous ducts, nipple discharge
Fat necrosis - traumatic
Duct ectasia - nipple discharge

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What kind of pain might be associated with fibrocystic change?

Cyclical pain associated with menstruation

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What are the features of breast fibroadenoma?

Proliferation of epithelial and stromal elements
Most common breast tumour in adolescent and young adult women - peak age is third decade
Well-circumscribed, freely mobile, non-painful mass
May regress with age if left untreated
Ducts distorted and elongated
- slit-like structures, intracanalicular pattern
- ducts not compressed, pericanalicular growth pattern

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What are some other adenomas of the breast?

Tubular adenoma

far less common than fibroadenomas
young women, discrete, freely mobile mass
uniform size ducts

Lactating adenoma

enlarging masses during lactation or pregnancy
prominent secretory change

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What are the features of intraduct papilloma?

Usually middle aged women
Nipple discharge
Can show atypia

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What are the features of fat necrosis?

Can simulate carcinoma - clinically and mammographically
History of antecedent trauma or prior surgical intervention
Histiocytes with foamy cytoplasm
Lipid-filled cysts
Fibrosis, calcifications, egg shell appearance on mammography

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What is a Phyllodes tumour?

Fleshy tumour, leaf-like pattern and cysts on cut surface
Circumscribed
Connective tissue and epithelial elements - 1-15cm
Benign, borderline or malignant

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What percentage of breast tumours are Phyllodes tumours?

< 1%

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What is the mode of spread of metastases from Phyllodes tumours?

Haematogenous

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What is the treatment of Phyllodes tumours?

Complete excision

Lymph nodes not involved in management

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What percentage of female cancers are breast cancer?

22%

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How many women are affected by breast cancer?

1 in 8

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What is the commonest cause of female cancer death?

Breast cancer - 1/3 of affected women will die from disease

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What are the features of breast carcinoma on mammogram?

Soft tissue opacity, micro-calcification

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What is the macroscopic appearance of breast carcinoma?

Hard lump
Fixed mass
Tethering to skin
Peau d’orange dimpling of skin

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How many new cases of breast cancer worldwide were there in 2012?

1.7 million

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How much of the global burden in low and medium resourced countries is accounted for by breast cancer?

Half

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How many new female cases of breast cancer are there each year in the UK?

50,000

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How many new cases of male breast cancer are there each year in the UK?

350

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What are the risk factors for breast cancer?

Gender - F>M 
Age - risk increases with age
Menstrual history - early menarche and late menopause 
Age at first pregnancy 
Radiation 
Family history 
Personal history of breast cancer 
Hormonal treatment 
Genetic factors - BRCA1, BRCA2
Obesity. 
Lack of physical activity 
Excess alcohol

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What are the histological classifications of breast cancer?

Non invasive

ductal carcinoma in situ
lobular carcinoma in situ

Invasive

invasive ductal carcinoma, no special type (85%)
invasive lobular carcinoma (10%)
special type (5%)

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What are the features of in situ carcinoma?

Pre-invasive - does not form a palpable tumour Not detected clinically, only on x-ray in DCIS screening Multi-centricity and bilaterality No metastatic spread

What is the risk of progression of in situ carcinoma?

Low grade DCIS - 30% in 15 years High grade DCIS - 50% in 8 years LCIS - 19% in 25 years and bilaterality

What are the histological types of breast carcinoma?

Ductal (85%) or lobular ``` Special types Tubular carcinoma Mucinous carcinoma Medullary carcinoma Other ```

What are the diagnostic procedures for breast cancer?

``` Clinical examination Radiology - mammogram, ultrasound, MRI Fine needle aspiration cytology Needle core biopsy Wide local excision with adequate margins ```

What is the current screening for breast cancer?

Mammogram every 3 years for women aged 50-70 Uptake 80% Detect 5 cancers/1000 screened

What is the reduction in mortality caused by breast cancer screening?

30%

How many cases of screen-detected breast cancer were diagnosed in 2011-2012?

1700

What percentage of cancers detecting on breast cancer screening were invasive?

Over 80%

What are micro-calcifications?

Tiny deposits of calcium Can appear anywhere in the breast and often show up on mammogram Most women have one or more areas of various sizes Majority are harmless A small percentage may be precancerous or cancerous tissue

What are the two most important mammographic indicators of breast cancers?

Masses | Microcalcifications

What should be involved in the histology report of breast cancer?

``` Invasive or non-invasive Histological type - ductal or lobular Grade Size Margins Lymph nodes Oestrogen/progesterone receptor HER-2/neu ```

What are the modes of spread of breast cancer?

Local - skin, pectoral muscles Lymphatic - axillary and internal mammary nodes Blood - bone, lungs, liver, brain

What ist he prognosis of breast cancer dependent on?

``` Node status Tumour size Type Grade Age Lymphovascular space invasion Oestrogen receptors Progesterone receptors HER-2 ```

What is the overall 5 year survival of breast cancer?

64%

What is the Nottingham Prognostic Index (NPI) based on?

Tumour size, grade and nodal status

What are the molecular markers for breast cancer?

ER/PR strong predictors of response to hormonal therapies ER/PR negative tumours do not respond HER2 - about 2-30% positive, predicts the response to trastuzumab (Herceptin)

What is involved in the molecular classification of breast cancer?

Gene expression technology Predictive gene signatures/potential to improve therapy Complements current clinicopathological features

What are the 5 subtypes of molecular classification of breast cancer?

``` ER and luminal A Luminal B Basal HER 2+ Normal breast-like ```

What are the features of Luminal A subtype of breast cancer?

ER positive and/or PR positive HER 2 negative Low Ki67

What is the prevalence of luminal A subtype of breast cancer?

30-70%

What are the features of luminal B subtype of breast cancer?

ER positive and/or PR positive | HER2 positive or HER2 negative with high Ki67

What are the features of basal like subtype of breast cancer?

ER negative PR negative HER2 negative

What is the prevalence of luminal B subtype?

10-20%

What is the prevalence of basal-like subtype?

15-20%

What are the features of HER2 type subtype of breast cancer?

ER negative PR negative HER 2 positive

What is the prevalence of HER2 subtype?

5-15%

What is involved in management of breast cancer?

``` Staging Surgery Radiotherapy Anti-hormonal therapy Chemotherapy ```

What is Paget's disease of the nipple? What are its features?

Result of intraepithelial spread of intraductal carcinoma Large pale-staining cells within the epidermis of the nipple Limited to the nipple or extending to the areola Pain or itching, scaling and redness, may be mistaken for eczema Ulceration, crusting and serous of bloody discharge

What are the pathologies of the male breast?

Gynaecomastia | Breast carcinoma

What is gynaecomastia?

Most common clinical and pathological abnormality of the male breast Increase in sub-areolar tissue

What percentage of adult males have gynaecomastia?

30-40%, both breasts affected in many cases

What is gynaecomastia associated with?

``` Hyperthryoidism Cirrhosis of the liver Chronic renal failure Chronic pulmonary disease Hypogonadism Use of hormones and other drugs ```

What percentage of all breast cancers are accounted for by male breast cancer?

< 1%

What are the signs of breast disease?

``` Dominant mass Asymmetry Architectural distortion Parenchymal contour Calcifications ```

What are the signs of a malignant soft tissue breast mass?

Irregular, ill-defined Speculated Dense Distortion of architecture

What are the signs of a benign soft tissue breast mass?

Smooth or lobulated Normal density Halo

What are the modes of breast imaging?

``` Mammography Ultrasound Image-guided techniques MRI Nuclear medicine/PET Breast screening programme ```

What views can be obtained by mammography?

ML oblique view and craniocaudal view Additional; - coned view - magnification view - true lateral - extended CC

When is mammography usually performed?

Usually only in > 40s | Only performed in < 40s if there is a strong suspicion of cancer or family history risk is greater than 40%

When is ultrasound useful in breast disease?

Useful for differentiating between solid and cystic mass Distinguishes between solid benign and solid malignant Under 40 age group Improves specificity of imaging No ionising radiation

What are the features of a solid benign mass on US?

Smooth outline Oval shape Acoustic enhancement

What are the features of malignant mass on US?

Irregular outline Interrupting breast architecture Acoustic shadowing and anterior halo

What is the triple assessment of a breast lump?

Clinical examination - usually by surgeon Imaging FNA cytology of lump Imaging and cytology shown to be most reliable components

What is the sensitivity of triple assessment for detection of breast cancer?

97-100%

What is the specificity of triple assessment for detection of breast cancer?

98-100%

What are the modes of image guided needly biopsy?

Stereotactic - upright or prone table, digital or analogue image Ultrasound - guided or free-hand

What are the basic types of biopsy?

FNA and core biopsy Biopsy samples are x-rayed for calcification and then sent to pathology

What are the indications for MRI of the breast?

``` Recurrent disease Implants Indeterminate lesion following triple assessment Screening high risk women Dense breast Lobular malignancy for multifocality ```

What is the sensitivity of MRI for all breast densities?

94-98%

What are the disadvantages of MRI of breast?

``` Specificity poor Claustrophobic Noisy Lengthy IV contrast Expensive ```

What are the nuclear medicine techniques used in breast imaging?

Sesta-MIBI and thallium can identify breast cancers more than 2cm in size but are not very useful clinically Can be useful in sentinel node sampling

What is the process of sentinel node sampling?

``` Peri-tumoral injection of 99m Tc sulphur colloid +/- isosulphan blue dye Lymphoscintigraphy Intraoperative gamma probe Single lymph node removed Sent to pathology ```

How accurate is sentinel node sampling in identifying sentinel node?

97%

What is the PET tracer used in breast imaging?

18F-fluorodeoxyglucose

What is the specificity and sensitivity of PET scan in breast imaging?

Specificity 66-100% | Sensitivity 67-100%

What is the negative predictive value of PET in breast imaging?

93-95%

What are the disadvantages of PET scanning in breast imaging?

Poor resolution | Limitations with cost/availability

What is the recall for further investigations following breast screening?

7-10%

What is the uptake of the breast screening programme?

80%

What is the aim of breast cancer screening?

To detect cancers at DCIS stage or < 15mm in size (impalpable)