breast disease histopathology

Question 1

What does normal breast tissue look like histologically

Answer 1

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•Modified sweat glands
•Non-functional except during lactation
•Lobules = acini and intralobular stroma

Question 2

What psysiological changes are seen in breast tissue prepubertally?

Answer 2

• Prepubertal breast –few lobules (before puberty male and female breasts are identical)
• Menarche –increase in number of lobules, increased volume of interlobular stroma

Question 3

What psysiological changes are seen in breast tissue in a woman of childbearing age?

Answer 3

•Menstrual cycle
–follicular phase lobules quiescent, after ovulation cell proliferation and stromal oedema, with menstruation see decrease in size of lobules
•Pregnancy
–increase in size and number of lobules, decrease in stroma, secretory changes

Question 4

What does breast tisssue look like in pregnancy?

Answer 4

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Question 5

What phsyiological changes are seen in breast tissue with increasing age?

Answer 5

Cessation of lactation
–atrophy of lobules but not to former levels
•Increasing age
–terminal duct lobular units (TDLUs) decrease in number and size, interlobular stroma replaced by adipose tissue (mammograms easier to interpret)

Question 6

How can breast conditions present?

Answer 6

• Pain
• Palpable mass
• Nipple discharge
• Skin changes
• Lumpiness
• Mammographic abnormalities

Question 7

Which breast conditions can cause pain?

Answer 7

•May be cyclical and diffuse, in which case often physiological
•Non-cyclical and focal
–ruptured cysts, injury, inflammation
•Occasionally presenting complaint in breast cancer

Question 8

Which breast conditions can cause a palpable mass?

Answer 8

•Causes include:
–Normal nodularity
–Invasive carcinomas
–Fibroadenomas
–Cysts
•Most worrying if hard, craggy and fixed
•No woman should be allowed to have a lump in the breast without a firm diagnosis

Question 9

Which breast conditions can cause nipple discharge

Answer 9

•Milky
–endocrine disorders e.g. pituitary adenoma; side effect of medication e.g., OCP
•Bloody or serous
–benign lesions e.g. papilloma, duct ectasia; occasionally malignant lesions
•Most concerning if spontaneous and unilateral

Question 10

Which breast conditions can cause mammographic abnormalities?

Answer 10

•Worrying findings include densities and calcifications
–Densities –invasive carcinomas, fibroadenomas, cysts
–Calcifications
–ductal carcinoma in situ (DCIS), benign changes
•Found during mammographic screening
•Women between 47-73 years invited every 3 years
•Easier to detect lesions in breasts of older women

Question 11

Are breast conditions common?

Answer 11

Breast symptoms and signs are common
•Most breast symptoms and signs will be benign
•Fibroadenoma most common benign tumour
•Breast cancer most common non-skin malignancy in women
•Mammographic screening increases detection of small invasive tumours and in situ carcinomas

Question 12

How common are fibroadenomas

Answer 12

•Fibroadenomas

–Can occur at any age during reproductive period–Often <30 years

Question 13

How common are Phyllodes tumours

Answer 13

Phyllodes tumours

–Most present in 6thdecad

Question 14

How common is breast cancer

Answer 14

•Breast cancer
–Rare before 25 years (except for some familial cases)
–Incidence rises with age
–77% occurs in women >50 years
–Average age at diagnosis is 64 years
–In UK:
•45,500 new female cases and 300 new male cases a year
•12,500 deaths per year

• Accounts for 20% of all malignancies in women
• 1 in 12 women will develop breast cancer at some time in their life
• Approximately 95% are adenocarcinomas
• Other malignant tumours of the breast are very rare, e.g., primary sarcomas such as angiosarcoma
• Most common in the upper outer quadrant (approximately 50% occur here)

Question 15

How do we classify pathological conditions of the rbeast

Answer 15

• Disorders of development
• Inflammatory conditions
• Benign epithelial lesions
• Stromal tumours
• Gynaecomastia
• Breast carcinoma

Question 16

What disorders of development can be seen

Answer 16

E.g., milk line remnants -polythelia, accessory axillary breast tissue

Question 17

What inflammtory conditions can be seen

Answer 17

•Acute mastitis–Almost always occurs during lactation–Usually Staphylococcus aureus infection from nipple cracks and fissures
–Erythematous painful breast, often pyrexia
–May produce breast abscesses
–Usually treated by expressing milk and antibiotics

•Fat necrosis
–Presents as a mass, skin changes or mammographic abnormality
–Often history of trauma or surgery
–Can mimic carcinoma clinically and mammographically

Question 18

What benign epithelial lesions can be seen?

Answer 18

•Fibrocystic change–Commonest breast lesion
–May present as a mass or mammographic abnormality
–Mass often disappears after fine needle aspiration (FNA)
–Histology
–cyst formation, fibrosis and apocrine metaplasia
–Can mimic carcinoma clinically and mammographically

Question 19

Describe the appearence of fibrocystic change

Answer 19

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Question 20

What stromal tumours can be seen?

Answer 20

•Stromal tumours –e.g., fibroadenoma, phyllodestumours, lipoma, leiomyoma, hamartoma
•Fibroadenomas
–Present with a mass, usually mobile, or mammographic abnormality
–‘Breast mouse’
–mobile and elusive
–Can be multiple and bilateral
–Can grow very large and replace most of the breast
–Macroscopically -well circumscribed, rubbery, greyish/white
–Histology -composed of a mixture of stromal and epithelial elements
–Can mimic carcinoma clinically and mammographically
–Localised hyperplasia rather than true neoplasm

Question 21

What do fibroadenomas look like?

Answer 21

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Question 22

What are phyllodes tumours?

Answer 22

–Rare before 40 years old–Present as masses or as mammographic abnormalities
–Benign, borderline and malignant types; most benign, less than 5% malignant
–Can be very large and involve entire breast
–Histology:
•Nodules of proliferating stroma covered by epithelium (phullon = leaf)
•Stroma more cellular and atypical than that in fibroadenomas
–Need to be excised with wide margin or may recur
–Malignant type behave aggressively, recur locally and metastasize by blood stream

Question 23

What do phyllodes tumours look like

Answer 23

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Question 24

How common is male breast cancer

Answer 24

•Male breast cancer
–1% of all cases of breast cancer
–Increased risk with Klinefelter’s syndrome, male to female transsexuals, men treated with oestrogen for prostate cancer

Question 25

What are the hormone related risk factors for breast cancer

Answer 25

•Major risk factors are related to hormone exposure
–Gender
–Uninterrupted menses
–Early menarche (< 11 years)
–Late menopause
–Reproductive history -parity and age at first full term pregnancy
–Breast-feeding
–Obesity and high fat diet
–Exogenous oestrogens –HRT slightly increases risk (1.2-1.7 times), long term users of OCP possibly have an increased risk

Question 26

What are other risk factors for breast cancer

Answer 26

•Geographic influence
–Higher incidence in US and Europe
–Possible explanations include diet, physical activity, breast-feeding, environmental factors
•Atypical changes on previous biopsy (4-5 times)
•Previous breast cancer (10 times)
•Radiation
–Increased risk with previous exposure to therapeutic radiation (especially in childhood or adolescence), e.g. mantle radiation for Hodgkin’s lymphoma

Genetic

Question 27

Describe herediaty breast cancer

Answer 27

Hereditary breast cancer
–10% of breast cancers
–3% of all breast cancers and 25% of familial cancers attributed to mutations in BRCA1 (BReastCAncerassociated gene 1) or BRCA2
•Both tumour suppressor genes –their proteins repair damaged DNA
•0.1% of population has BRCA1 germline mutations
•Lifetime breast cancer risk for female carriers is 60-85%
•Median age at diagnosis is approximately 20 years earlier than sporadic cases
•Carriers may undergo prophylactic mastectomies
–Another gene involved in hereditary breast cancer is p53 (Li-Fraumenisyndrome)

Question 28

How do we classify breast carcinoma

Answer 28

• Carcinomas divided into in situ and invasive

* Carcinomas can be ductal or lobular

Question 29

What is in situ carcinoma

Answer 29

• Neoplastic population of cells limited to ducts and lobules by basement membrane (BM), myoepithelial cells are preserved
• Does not invade into vessels and therefore cannot metastasise or kill the patien

Question 30

Why id DCIS a problem

Answer 30

• Non-obligate precursor of invasive carcinoma
• Most often presents as mammographic calcifications (clusters or linear and branching) but can present as a mass
• Can spread through ducts and lobules and be very extensive
• Histologically often shows central (comedo) necrosis with calcification

Question 31

What does DCIS look like

Answer 31

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Question 32

What is Paget’s disease

Answer 32

Cells can extend to nipple skin without crossing BM = Paget’s disease
–Unilateral red and crusting nipple
–Eczematous or inflammatory conditions of the nipple should be regarded as suspicious and biopsy performed to exclude Paget’s disease

Question 33

How does invasive carcinoma differ from DCIS

Answer 33

Neoplastic cells have invaded beyond BM into stroma
•Can invade into vessels and can therefore metastasize to lymph nodes and other sites
•Usually presents as a mass or as mammographic abnormality
•By the time a cancer is palpable more than half of the patients will have axillary lymph node metastases•Peaud’orange–involvmentof lymphatic drainage of skin

Question 34

What are skin changes in breast cancer

Answer 34

Pulling in, peau d’orange

Question 35

How is invasive breast cancer classified

Answer 35

•Invasive ductal carcinoma, no special type (IDC NST)
–70-80%
–Well-differentiated type –tubules lined by atypical cells
–Poorly differentiated type –sheets of pleomorphic cells
–35-50% 10 year survival

•Invasive lobular carcinoma
–5-15%
–Infiltrating cells in a single file, cells lack cohesion
–Similar prognosis to IDC NST
•Other types, e.g. tubular (1-2%, excellent prognosis), mucinous (1-6%, excellent prognosis, often older women)

Question 36

What does invasive breast carcinoma look like?

Answer 36

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Question 37

What does mucinous carcinoma look like

Answer 37

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Question 38

How does breast cancer spread

Answer 38

• Lymph nodes via lymphatics–usually in the ipsilateralaxilla
• Distant metastases via blood vessels –bones (most frequent site), lungs, liver, brain
• Invasive lobular carcinoma can spread to odd sites –peritoneum, retroperitoneum, leptomeninges, gastrointestinal tract, ovaries, uterus

Question 39

What does vascular invasion look liek

Answer 39

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Question 40

What factors determine prognosis in breast canecr

Answer 40

In situ disease or invasive carcinoma
•Tumour stage:
–Tumour size and locally advanced disease –invading into skin or skeletal muscle 
–Lymph Node metastases
–Distant Metastases

• Tumour grade
• Histologic subtype –IDC NST has poorer prognosis
• Molecular classification and gene expression profile

Question 41

How does tumour grade affect survuval

Answer 41

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Question 42

What is molecular classification in breast cancer?

Answer 42

Oestogen receptor positive vs oestrogen receptor negative
Each split into her2 pos or neg
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Question 43

What is a gene expression profile and why is it important in breast cancer?

Answer 43

• Microarrays have been used to examine the expression patterns of some 25,000 genes in tissues from breast cancer patients.
• Computer cluster analysis of the patterns led to the identification of about 17 marker genes that can correctly identify about 90% of women who would eventually develop metastases.

Question 44

How do we investigate and diagnose breast cancer?

Answer 44

•Triple approach
–Clinical –history, family history, examination
–Radiographic imaging –mammogram and ultrasound scan
–Pathology –core biopsy and fine needle aspiration cytology (FNAC)

Question 45

What is mammographic screening

Answer 45

• Started in the UK in the late 1980s
• Women 47–73 years
• 2 view mammograms every 3 years
• Aim is to detect small impalpable cancers and pre-invasive cancer (incidence of DCIS has increased from 5% of breast cancers to 25% in screened populations)
• Look for asymmetric densities, parenchymal deformities, calcifications
• Assess abnormalities using further imaging, core biopsy and FNAC

Question 46

What is local/regional control?

Answer 46

•Local and regional control
–Breast surgery –mastectomy or breast conserving surgery –decision depends on patient choice, size and site of tumour, number of tumours, size of breast
–Axillary surgery –extent depending on whether there are involved nodes (sentinel node sampling or axillary dissection)
–Post-operative radiotherapy to chest and axilla

Question 47

What is sentinel lymph node biopsy

Answer 47

• Reduces the risk of postoperative morbidity
• Intraoperative lymphatic mapping with dye and/or radioactivity of the draining or ‘sentinel’ lymph node(s) –the one most likely to contain breast cancer metastases
• If the sentinel node(s) is negative axillary dissection can be avoided

Question 48

What are the therapeutic approaches in breast canecr

Answer 48

•Systemic control
–Chemotherapy –if benefits thought to outweigh the risks; if given before surgery = neoadjuvant
–Hormonal treatment, e.g. tamoxifen –depending on oestrogen receptor status (approximately 80% of cancers are ER positive)
–Herceptin treatment –depending on Her2 receptor status (approximately 20% of cancers are Her2 positive)
•Her2 is a member of the human epidermal growth factor receptor family
•Encodes a transmembrane tyrosine kinase receptor
•Herceptin = trastuzumab= humanised monoclonal antibodies against the Her2 protein

Question 49

Jow do we improve survival from breast cancer

Answer 49

Early detection –awareness of disease, importance of family history, self-examination, mammographic screening
•Neoadjuvant chemotherapy –early treatment of metastatic disease
•Use of newer therapies –e.g. Herceptin
•Gene expression profiles
•Prevention in familial cases –genetic screening, prophylactic mastectomies