Breast Pathology

Question 1

Embryology of Breast

Answer 1

modified sweat gland, derived form the skin

breast tissue can develop anywhere along the milk line, which runs from axilla to vulva

Question 2

lubules and ducts are lined by how many laters of epithelium?

Answer 2

Two layers:

Luminal cell layer - inner cell layer lining the ducts and lobules; responsible for milk production in the lobules

myoepithelial cell layer - outer cell layer lining ducts and lobules; contractile function propels milk towards the nipple.

Question 3

During pregnancy, what promotes the breast lobules to undergo hyperplasia?

Answer 3

Hyperplasia is driven by estrogen and progesterone produced by the corpus luteum (early first trimester), fetus, and placenta (later in pregnancy)

Question 4

galactorrhea

Answer 4

milk production outside of lactation

not a symptom of breast cancer

causes include nipple stimulation (common physiologic cause), prolactinoma of the anterior pituitary (common pathologic cause), and drugs

Question 5

acute mastitis

Answer 5

bacterial infection of the breast, usually due to Staph aureus

associated with breast-feeding; fissures develop - route of entry for microbe

present as erythematous breast with purulent nipple discharge; may progress to abscess formation

Question 6

periductal mastitis

Answer 6

inflammation of the subareolar ducts

seen in smokers

vitamin A deficiency results in squamous metaplasia of lactiferous ducts, producing duct blockage and inflammation

clinically presents as a subareolar mass with nipple retraction

Question 7

mammary duct ectasia

Answer 7

inflammation with dilation (ectasia) of the aubareolar ducts

RARE, arises in multiparous postmenopausal women

Presents as a periareolar mass with green-brown nipple discharge (inflammatory debris)

chronic inflammation with plasma cells seen on biopsy

Question 8

Fat necrosis

Answer 8

necrosis of breast fat

related to trauma

presents as a mass on physical exam or abnormal calcification on mammography (due to saponification)

biopsy shows necrotic fat with associated calcifications and giant cells

Question 9

What is the gross appearance of breast cysts?

Answer 9

blue-dome

Question 10

What is the risk for invasive carcinoma when there is a presence of fibrosis, cysts, and apocrine metaplasia?

Answer 10

no increased risk

Question 11

What is the risk for invasive carcinoma when there is a presence of ductal hyperplasia and sclerosing adenosis?

Answer 11

2x increased risk

Question 12

What is the risk for invasive carcinoma when there is a presence of atypical hyperplasia?

Answer 12

5x increased risk

Question 13

Intraductal papilloma

Answer 13

papillary growth into large duct

fibrovascular projections lined by epithelial (luminal) and myoepithelial cells

Presents as bloody nipple discharge in premenopausal women

Question 14

Papillary carcinoma

Answer 14

fibrovascular projections lined by epithelial cells without underlying myoepithelial cells

presents as bloody nipple discharge

risk of papillary carcinoma increases with age thus, more commonly seen in postmenopausal women

Question 15

Fibroadenoma

Answer 15

tumor of fibrous tissue and glands

presents as a well-circumscribed, mobile marble-like mass

estrogen sensitive-grows during pregnancy and may be painful during the menstrual cycle

benign, with no increased risk of carcinoma

Question 16

Phyllodes tumor

Answer 16

fibroadenoma-like tumor with overgrowth of the fibrous component; characteristic ‘leaf-like’ projections are seen on biopsy

commonly seen in postmenopausal women

malignant in some cases

Question 17

What are risk factors for breast cancer?

Answer 17

estrogen exposure:

age- cancer usually arises in postmenopausal women

early menarche/late menopause

obesity

atypical hyperplasia

first-degree relative (mother, sister, or daughter) with breast cancer

Question 18

Ductal carcinoma in situ

Answer 18

malignant proliferation of cells in ducts with no invasion of the basement membrane

often detected as calcification on mammography; DCIS does not usually produce a mass

histologic subtypes are based on architecture; comedo type is characterized by high-grade cells with necrosis and dystrophic calcification in the center of ducts

Question 19

Paget disease

Answer 19

DCIS that extends up the ducts to involve the skin of the nipple

Presents as nipple ulceration and erythema

Almost always associated with an underlying carcinoma

Question 20

invasive ductal carcinoma

Answer 20

classically forms duct-like structures

most common type of invasive carcinoma in the breast, accounting for >80% of cases

presents as a mass detected by physical exam or by mammography - advanced tumors may result in dimpling of the skin or retraction of the nipple.

Biopsy usually shows duct-like structures in a desmoplastic stroma

Question 21

Special subtype of invasive ductal carcinoma:

Tubular carcinoma

Answer 21

characterized by well-differentiated tubules that lack myoepithelial cells; relatively good prognosis

Question 22

Special subtype of invasive ductal carcinoma: Mucinous carcinoma

Answer 22

characterized by carcinoma with abundant extracellular mucin (‘tumor cells floating in a mucus pool’)

tend to occur in older women

relatively good prognosis

Question 23

Special subtype of invasive ductal carcinoma:

Medullary carcinoma

Answer 23

characterized by large, high-grade cells growing in sheet with associated lymphocytes and plasma cells

grows as well-circumscribed mass that can mimic fibroadenoma on mammography

relatively good prognosis

increased incidence in BRCA1 carriers

Question 24

Special subtype of invasive ductal carcinoma: Inflammatory carcinoma

Answer 24

Carcinoma in dermal lymphatics

presents classically as an inflamed, swollen breast (tumor cells block drainage of lymphatics) with no discrete mass; can be mistaken for acute mastitis

poor prognosis

Question 25

Lobular carcinoma in situ

Answer 25

malignant proliferation of cells in lobules with no invasion of the basement membrane

does not produce a mass or calcifications and is usually discovered incidentally on biopsy

dyscohesive cells lacking E-cadherin adhesion protein

Often multifocal and bilateral

Treatment is tamoxifen (to reduce risk of subsequent carcinoma) and close follow-up; low risk of progression to invasive carcinoma

Question 26

Invasive lobular carcinoma

Answer 26

invasive carcinoma that characteristically grows in a single-file pattern cells may exhibit signet-ring morphology

no duct formation due to lack of E-cadherin

Question 27

What are the most important factors predicting the response to treatment?

Answer 27

Estrogen receptor
Progesterone receptor
HER2/neu gene amplification

The presence of ER and PR is associated with response to antiestrogenic agents (e.g., tamoxifen); both receptors are located in the nucleus

HER2/ neu amplification is associated with response to trastuzumab (Herceptin), a designer antibody directed against the HER2 receptor; HER2/neu is a growth factor receptor present on the cell surface

Triple negative tumors are negative for ER, PR, and HER2/neu and have a poor prognosis; african american women have an increased propensity to develop triple-neg carcinoma

Question 28

hereditary breast cancer

Answer 28

10% of breast cancer cases

multiple first-degree relatives with brease cancer, tumor at an early age (postmenopausal), and multiple tumors in a single patient

BRCA1 and BRCA2 = most important single gene mutations associated with hereditary breast cancer

Question 29

BRCA1

Answer 29

breast and ovarian carcinoma

Question 30

BRCA2

Answer 30

breast carcinoma in males

Question 31

Male breast cancer

Answer 31

rare
usually present as subareolar mass in older males

highest density of breast tissue in males is underneath the nipple

may produce nipple discharge

most common histological subtype = invasive ductal carcinoma - lobular carcinoma is rare (the male breast develops very few lobules)

associated with BRCA2 mutation and klinefelter syndrome