Introduction

Sunday, November 8, 2015

11:40 AM
 
1. Describe the anatomy and histology of breast.
 Anatomy:
o Breast can develop anywhere along the milk line (a straight line from vulva to axilla)
o In females, lobules and ducts are present in highest density in upper lateral part of breast
o In males, lobules and ducts are present in highest density in subaerolar area
o Estrogen and progesterone cause hyperplasia of breast lobules
 Histology:
o Terminal duct and lobular unit is the functional unit of breast. Lobules make milk and
ducts drain them
o Lobules and ducts are lined by two cell layers:
 Luminal cell layer: columnar epithelial cell that makes milk in lobules
 Myoepithelial cell layer: Outer layer; contracts to expell milk outside
 
2. What is galactorrhea? What are its causes?
 Galactorrhea is milk production outside pregnancy
 Causes:
o Nipple stimulation
o Prolactinoma
o NOT A SIGN OF CANCER
 
 
Inflammatory conditions
Sunday, November 8, 2015
12:13 PM
 
1. Describe the following inflammatory conditions of the breast.
  Cause Presentation Treatment

Acute  Staph Aureus infection  Erythematous  Continue

mastitis  Associated with breast breast drainage
feeding (fissures develop in  Purulet nipple  Dicloxacillin
nipple and bacteria enter) discharge
 May have abscess

Periductal  Usually seen in smokers.  Subareolar mass  

mastitis Smoking causes relative Vit a with
decifiency. Vit A deficiency  nipple retraction -
causes squamous metaplasia due to inflammation
of periductal cells. Cells and fibrosis
produce keratin and block the
duct resulting inflammation

Mammary  Chronic inflammation that  Periareolar mass  

duct ectasia causes dilation (ectasia) of with green-brown
(dialation) subareolar duct nipple discharge
 Plasma cells on
biopsy
 Fat necrosis  Usually related to trauma  Mass on physical  
exam or abnormal
calcification on
mammography (due
to saponification)
 Calcification and
giant cells on biopsy
 
 
Benign tumor and fibrocystic changes
Sunday, November 8, 2015
12:23 PM
 
1. Describe the following benign tumor and fibrocystic changes in the breast.
  Epidemiology Presentation

Fibrocystic Most common change in premenopausal women (hormone  Presents as vague irregu
change mediated) - seen in 30-60% of women (lumpy breast) in upper
quardant
 Cyst look blue-dome on
exam

Fig: fibrocystic change presents as fibrosis of stromal cells and

cystically dilated ducts

Intraductal Classically seen in premenopausal women  Bloody or serous nipple

papilloma discharge
 Usually present in one o
 main lactiferous duct be
areola and may cause n
retraction

Fig: intraductal papilloma (mass has both epithelial and

myoepithelial layers)

Fibroadenom  Most common benign neoplasm of breast (classically seen in  Well circumscribed mob
a premenopausal woman) - hormone sensitive - mass grows marble like mass - move
during pregnancy and maybe painful in menstruation cycle freely (contrast to infiltr
 Growth of fibrous part squeezes the lumen of duct ductal carcinoma that's
immobile)
 Benign - 1.5-2x increase
of cancer (FA)

Fig: Fibroadenoma (growth of both lobular and stromal cells)

 Fig: gross speciman shows well demarked, capsulated tumor

Phyllodes Classically seen in postmenopausal woman  Fibroadenoma like tumo

tumor much larger with overgr
(phyllodes = of fibrous part
leaflike)  Leaf like projection on b
(tumor of stromal cell -
between lobules)
 Maybe malignant in som
cases
 Most common in 5th de

Fig: fingerlike projection of Phyllodes tumor (stromal tumor)

 Only phyllodes tumor is mainly seen in postmenopausal woman and maybe malignant. All
others are seen mainly in premenopausal woman and not usually malignant
 
2. What are the different types of fibrocystic changes and their associated breast cancer risk?
  Breast cancer risk Presentation

Fibrous, cysts and apocrine No increased risk  

metaplasia

Ductal hyperplasia and 2x increased risk in both Sclerosing = hard (fibrous); adenosis = too many gla
sclerosing adenosis breasts calcification maybe seen

Atypical hyperplasia 5x increased risk in both Hyperplasia maybe lobular or ductal

breasts
 
3. How do you distinguish intraductal papilloma from papillary carcinoma of breast?
Intraductal papilloma Papillary carcinoma

Both present as bloody nipple discharge  

More common in premenopausal women As it's cancer, its more common in postmenopausal
women

Papillary growth has both epithelial and myoepithelial Papillary growth has epithelial cells but lacks
cells myoepithelial cells
 
 
Breast cancer
Sunday, November 8, 2015
12:51 PM
 
 1. What are the risk factors for breast cancer?
 Risk factors are associated with estrogen exposure
o Female gender (female:male = 100:1 for breast cancer incidence)
o Age - cancer usually seen in postmenopausal woman with exception of hereditary breast
cancer
o Early menarche/late menopause (increases estrogen exposure)
o Obesity (fat cells converts testosterone to estrogen)
o Atypical hyperplasia
o First degree relative with breast cancer
o Race - AA at more risk
o BRACA +ve (BRACA 1 = risk of ovarian cancer and triple neg breast cancer; BRACA 2 =
breast cancer in males)
 
2. What are the characters of the following types of breast cancer?
 
  Histology Mass? Rema

Ductal carcinoma  Cell proliferate in duct without invading basement membrane  No mass
in situ  Histologic subtypes present:
 Comedo type: high grade cells with necrosis in duct with
calcification

Fig: DCIS m
Fig: DCIS - note cellular proliferation, necrosis and centrally located
calcification

Invasive ductal  MOST COMMON INVASIVE CARCINOMA OF BREAST - >80% of cases  Rock hard
carcinoma  Invasive cancer that produces duct like structure in desmoplastic stroma classic 'ste
 Subtypes:  Most com
 Tubular carcinoma:  Inflammat
o has well differentiated ducts without myoepithelial layer in have relati
desmoplastic stroma better pro
o Good prognosis
 Mucinous carcinoma:
o ducts in abundant extracellular mucin
o Good prognosis
 Medullary carcinoma:
o high grade ductal cells associated with lymphocytes and
plasma cells
o Increased incidence of BRCA1 carriers
o Good prognosis
  Inflammatory carcinoma -
o carcinoma in dermal lymphatics
o Poor prognosis (tumor already in lymph)
o Presents as inflamed, swollen breast due to blockage of
lymphatics - orange peel appearance; can be mistaken for
acute mastitis

Fig: 'stella
 
 
 
Fig: Tubular carcinoma (left); mucinous carcinoma (right)

Fig: Peau d
appearanc
Fig: medullary carcinoma (left); inflammatory carcinoma (right)

Lobular  Cells proliferate in lobules without invading basement membrane  No mass,

carcinoma in situ  Often multifocal and bilateral discovere
 Characterized by dyscohesive cells lacking E-cadherin adhesion protein  Often bila
 Treatment:  
 Tamoxifen (to reduce risk of carcinoma)
 Follow up closely because it can progress to invasive carcinoma

Invasive lobular  Cells characteristically grows in single file (aka Indian file) and may show  Often bila
carcinoma signet ring morphology - cells don't make duct because they lack E- same loca
cadherin  Better pro
 Usually bilateral carcinoma
 Associate
in 90% of
 Has diffus
difficult to
exam
 Fig: Small runs of invasive lobular carcinoma (arrows) with two adjacent
foci of LCIS.
 
3. What are the prognostic factors for breast cancer?
 TNM staging
o Metastasis is most important prognostic factor but pt present early so not very useful
o Spread of tumor to axillary lymph nodes (N) is most useful prognostic factor - Sentinel
lymph node biopsy used to assess axillary lymph nodes
 
4. What is sentinel lymph node biopsy?
 Many years before, doctors use to take out all lymph nodes in axilla to check for spread of
breast cancer. In many patients, there was no spread and they had to suffer upper extremity
edema due to lack of lymph nodes
 Then doctors started to inject dye in tumor and check which lymph nodes in axilla the dye
moved to. If the lymph nodes with dyes didn't had metastasis, the doctors didn't take out all
the lymph nodes. If the nodes had metastasis, they would then proceed to take out all lymph
nodes. This process is called sentinel lymph node biopsy.
 
5. What are the predictive values of breast cancer treatment?
 Imprtant predictive values of treatment are presence of absence of overexpression of estrogen
receptor (ER), progesterone receptor (PR), and HER2/neu receptor. (HER2/neu are receptors in
RAS/MAPK pathway).
Overexpression of ER, PR (nuclear receptor) Good response to anti
tamoxifen)

Overexpression of Her2/neu receptor (cell surface receptor) Good response to tra

receptor Ab)

Triple negative receptor (none of above overexpressed) - usually seen in African Poor pharmacologica
American women
 
6. What is Paget's disease of nipple?
 Extension of ductal carcinoma in situ to lactiferous ducts and skin of nipple producing rash.
Paget cells are present.
 Fig: Paget disease of nipple
Hereditary breast cancer
Epidemiology 10% of breast cancer cases

Presentation  Seen in premenopausal cancer

 Presence of multiple tumor
 Having multiple first degree relative with breast cancer

Mutations  BRCA1- breast (medullary carcinoma - type of invasive ductal carcino

(serous carcinoma)
 BRCA2 - breast carcinoma in males

Value of prophylatic bilateral  Decreases risk of carcinoma but not to zero

mastectomy
 
Male breast cancer
Epidemiology  1% of all breast cancers

Common type  Invasive ductal carcinoma

Presentation  Subareolar mall in older males (most breast tissue in males is in subareolar area - in fem
quadrant of breast)
 May have nipple discharge

Genetic  Klinefelter syndrome (XXY)

associations  BRCA2 mutations