Chapter 23- The Breast Flashcards
What are the three components of the breast?
- Lobules
- Ducts
- Stroma
What are the two types of epithelial cells in breast?
- Luminal
2. Myoepithelial (contractile)
What are the two types of stroma found in breast?
- Interlobular (fat and fibrous tissue)
2. Intralobular (epithelial support)
Major ducts are lined by what kind of epithelium?
Keratinizing squamous
Remaining ducts (not major) are lined with what kind of epithelium?
Luminal and myoepithelial
What do ducts end in?
Terminal ductal lobular units (TDLU)
How do TDLU change during menstruation?
Cell proliferation
Intralobular stroma become edamatous
When do the breasts become completely mature and functional?
Pregnancy onset
What is the composition of completely mature and functional breasts?
Almost entirely lobules and scant stroma
What changes happen to breasts after lactation?
Epithelial cells undergo apoptosis
Lobules regress but there is a permanent increase in lobule number
What changes occur in breasts during the third decade?
Lobules and stroma involute
Composition changes from fibrous to adipose
What are the developmental disorders of the breast?
Milk line remnants (supernumerary nipples/breasts)
Accessory axillary breast tissue (ducts into chest wall/axillary fossa)
Congenital nipple inversion
What type of nipple inversion is most concerning?
Acquired
What are the clinical presentations of breast disease?
Pain/mastalgia/mastodynia
Palpable masses (>2cm)
Nipple discharge
Abnormal mammographic screening
Noncyclic breast pain differs from cyclic pain in what way?
Noncyclic pain is normally localized
What percentage of breast cancers present with pain?
10%
The likelihood that a palpable mass is malignant increases with what?
Age
When is nipple discharge worrisome for cancer?
When it’s unilateral and spontaneous
What can cause the two types of nipple discharge?
Bloody/serous- cysts or intraductal papillomas
Milky/galactorrhea- PRL producing pituitary adenomas, hypothyroidism, anovulatory cycles, meds
What findings constitute abnormal mammographic screenings?
Densities
Calcifiations
What breast cancer mimics inflammatory disorders of the breast?
Inflammatory breast cancer
What are the different inflammatory disorders of the breast?
Acute mastitis (first month of lactation)
Periductal mastitis- metaplasia causes keratin shedding and plugging of ducts (dilation and rupture)
Mammary duct ectasia- secretions plug ducts, cause dilation and inflammation
Fat necrosis
Lymphocytic mastopathy/sclerosing lymphocytic lobulitis- rock hard masses, lymphocytic infiltrate
Granulomatous mastitis- systemic disease, foreign bodies, infection (Tb)
Periductal mastitis is associated with what behaviour?
Smoking
Fat necrosis normally surrounds what malignancy?
Breast cancer
Half of fat necrosis cases of the breast have a history of what?
Trauma or prior surgery
What disorders is lymphocytic mastopathy associated with?
DMI
Autoimmune thyroid disease
What are the different types of benign epithelial lesions of the breast and what are their characteristics?
- Nonproliferative (fibrocystic) breast changes- cysts from lobular dilation and unfolding, fibrosis, adenosis
- Proliferative breast disease without atypia- epithelial or stromal proliferation without cytological or architectural changes
- Proliferative breast disease with atypia- clonal proliferation, some features of CIS
What are the cancer risks associated with each type of benign epithelial breast lesion?
Nonproliferative- no malignant potential
Proliferative without atypia- 1.5-2x increased risk in developing carcinoma
Proliferative with atypia- 4-5x increased risk in developing cancer
What are the different forms of proliferative breast disease without atypia and their characteristics?
- Epithelial hyperplasia- more than two cell layers surround ducts/lobules, epithelial cells fill and distend
- Sclerosing adenosis- increased number of acini/lobule with distortion and dilation
- Papillomas- epithelial growth with fibrovascular cores, grow within dilated duct
- Complex sclerosing lesion- all the above components, “radial scar”
What are the differences in large and small duct papillomas of the breast?
Large- lactiferous sinuses, solitary
Small- deeper within system, multiple
What are the two forms of proliferative breast disease with atypia and their characteristics?
Atypical ductal hyperplasia- similar to DCIS
Atypical lobular hyperplasia- similar to LCIS but affecting less than 50% of the lobule
Almost all breast carcinomas are what form?
Adenocarcinomas
What single gene mutations are most commonly associated with breast cancer?
BRCA1 and 2
What are the chromosome locations of BRCA1 and 2?
1- 17q21
2- 13q12.3
Which BRCA mutation is more often ER pos?
BRCA2
Why is the major risk factor for developing sporadic breast cancer?
Hormone exposure
What are the three genetic pathways for carcinogenesis of the breast?
- ER+HER-/luminal- BRCA2, dominant pathway of breast cancer development
- HER2+/HER2 enriched- pathway strongly associated with HER2 gene amplification
- HER2-/basal-like- pathway independent of ER mediated genetic changes and HER2 gene amplification, BRCA1
What are the different morphologies of DCIS?
- Comedocarcinoma- dilated ducts and lobules due to sheets of pleomorphic cells with central necrosis
- Noncomedo- monomorphic cell population, varying nuclear grades and patterns
- Paget disease- extension into nipple, cells move up duct and embed in epidermis, poorly differentiated
- Microinvasion
What is the prognosis of DCIS?
Progresses to invasive cancer at 1% per year
Mastectomy curative in 95%
<2% of patients die with or without treatment
What are the characteristics of LCIS?
Clonal proliferation of cells within ducts and lobules that grow in a discohesive fashion (E cadherin loss)
What is the molecular subtype of most LCIS?
ER+/PR+
What are the different types of breast carcinomas?
Invasive/ductal carcinoma- 80-90%
Lobular carcinoma- E cadherin loss, metastatic spread is characteristic
Medullary carcinoma- soft, fleshy with pushing border, solid sheets of cells with lymphocytic infiltrate
Mucinous/colloid carcinoma- well differentiated, gel/mucoid
Tubular carcinoma- well formed tubules
Inflammatory carcinoma- invasion and proliferation in lymphatic channels (swelling and dimpling)
What are the different types of invasive/ductal carcinomas and their characteristics?
ER+HER2-/luminal A- 40-55%
ER+HER2+/luminal B- higher grade, nodal mets common
ER+HER2-/normal breast like- most like normal tissue
ER-HER2-PR-/basal like/triple neg- high grade and aggressive
HER2+ER- poorly differentiated, metastatic
What is the characteristic metastatic spread of lobular carcinoma?
Involves peritoneum and retroperitoneum, leptomeninges, GI tract, ovaries and uterus
What morphologies are tubual carcinomas associated with?
Flat epithelial atypia
Atypical lobular hyperplasia
LCIS
Low grade DCIS
What are some prognostic factors related to the extent of breast cancer?
Invasive vs in situ
Distant mets
Lymph node mets
Size (<1cm = 90% 10yr vs >2cm = 77% 10yr)
Locally advanced disease
Inflammatory carcinoma
Lymphovascular invasion
What prognostic factors are related to tumour biology?
Molecular subtype (ER/HER2)
Special histological types
Histological grade
Proliferative rate (measured by mitotic counts)
ER and PR pos tumours (respond to hormone therapy)
HER2 overexpression- poorer survival and therapy response
What are the stages of breast cancer?
0- DCIS or LCIS, no mets
I- invasive microcarcinoma <2cm, no/micro mets
II- invasive 2-5cm, 0-3 positive lymph nodes without distant mets
III- invasive >5cm/any size, neg or pos lymph nodes/more than 4 pos, without distant mets
IV- any invasive carcinoma (distant mets)
What are the different types of stromal breast tumours and what are their characteristics?
Fibroadenomas- intralobular, circumscribed, rubbery, grey-white nodules with slit-like spaces, whorled
Phyllodes- intralobular, more stromal overgrowth, infiltrative borders
Interlobular- stromal cells without epithelial component
What is the most common benign breast cancer?
Fibroadenomas
What are the different types of interlobular tumours?
Myofibroblastomas
Lipomas
Fibromatosus- proliferation of fibroblasts and myofibroblasts
Angiosarcoma
Any mesenchymal tumour is possible
What is the most common interlobular tumour?
Angiosarcoma
What interlobular tumour is equally common in men?
Myofibroblastoma
What is a risk factor of developing angiosarcoma?
Radiation
What is the composition of the male breast?
Almost entirely fat with little fibrous tissue
What is gynecomastia?
Button-like subareolar enlargement
What does gynecomastia indicate?
Estrogen and androgen imbalance
Breast cancer in males is strongly associated with what mutation?
BRCA2