breast pathology

Question 1

where is the tissue of highest density in breast?

Answer 1

upper outer quadrant

Question 2

milk production occurs in the….

Answer 2

terminal duct lobular unit

all are drained by collecting duct

Question 3

all ducts and lobules in breast tissue have two epithelial layers…..

Answer 3

luminal cells (outer layer) - milk production

myoepithelial layer (inner layer) - contractile function

Question 4

galactorrhea

Answer 4

production of milk NOT during lactation

caused by nipple stimulation, prolactinoma of anterior pituitary, and drugs

is NOT a symptom of breast cancer!

Question 5

acute mastitis

Answer 5

bacterial infection of the breast due to staph aureus

mechanism = due to stress fissures from breast feeding that allow entry for microbes

• Warm erythematous breast, with purulent nipple discharge

Question 6

how to treat acute mastitis?

Answer 6

drainage and dicloxacillin

Question 7

periductal mastitis

Answer 7

inflammation of subareolar ducts that causes subareolar mass with nipple retraction (fibrosis)

seen in smokers
• Smoking causes vitamin A deficiency –> specialized epithelium undergoes keratinizing squamous metaplasia and keratin blocks the duct

Question 8

mammary duct ectasia

Answer 8

inflammation and dilatation of subareolar duct

• Classically in multiparous(multiple births) post-menopausal women

• Periareolar mass with Green brown nipple discharge*** gives away that it isn’t cancer
• Biopsy shows chronic inflammation with plasma cells

Question 9

fat necrosis

Answer 9

necrosis of breast fat, usually due to trauma

Presents as a mass on exam or calcification (due to saponification) on mammography
• Biopsy shows necrotic fat with associated calcifications and giant cells

Question 10

Lymphocytic Mastopathy

Sclerosing Lymphocytic Lobulitis

Answer 10

• Single or multiple very hard masses made of collagenized stroma surrounding atrophic ducts and lobules with lymphocyte infiltrate
• Common in T1 Diabees and autoimmune thyroid disease

Question 11

granulomatous mastitis

Answer 11

Can be caused by granulomatous diseases (wegener, sarcoid) or infection

Question 12

fibrocystic changes

Answer 12

fibrosis, cysts, and adenosis, due to hormone imbalance; presents as irregular “lumpy breast” usually in upper outer quadrant

Occurs in most breasts between 20-40 years age

• Proliferative without atypia = Fibrosis, cysts, and apocrine metaplasia = no increased risk of cancer
• Calcifications are dark purple chunks

Question 13

sclerosing adenosis

Answer 13

benign, proliferation of terminal duct lobule = increased number of acini; multiple firm nodules/cysts; can have calcifications

2 cell layers are present so it is not carcinoma

Question 14

if two cell layers are present it is not ____

Answer 14

a carcinoma

Question 15

when fibrocystic changes show atypical hyperplasia –>

Answer 15

increased risk 5x of carcinoma

o Acquired loss of 16q and 17p; Clonal proliferation with some features of carcinoma in situ

Question 16

o Atypical ductal hyperplasia

Answer 16

monomorphic luminal cells, evenly spaced with peripheral slit like spaces

only partially involving ducts

Question 17

atypical lobular hyperplasia

Answer 17

small monomorphic round cells in lumens; like LCIS but do not fill >50% of acini in a lobule

Question 18

Intraductal Papilloma

Answer 18

papillary growth in large duct near nipple, seen as fibrovascular projections lined by luminal and myoepithelial cells
• Presents as bloody discharge in premenopausal women; usually small/cant feel mass

• **must distinguish from papillary carcinoma (doesnt have underlying myoepithelial cells) which can also present as bloody nipple discharge

Question 19

papillary carcinoma

Answer 19

fibrovascular projections lined by epithelial cells without underlying myoepithelial cells; common in older age

only 1 cell layer type

Question 20

fibroadenoma

Answer 20

benign, young women tumor of fibrous tissue and glands; multiple/bilateral

• well-circumscribed rubbery mobile mass that is estrogen sensitive (grows in pregnancy/painful during menses); no risk of carcinoma

Question 21

phyllodes tumor

Answer 21

fibroadenoma-like tumor; leaf-like projections; older women (60+); No skin change; Can be malignant; infiltrative borders
• increased stromal cellularity, pleomorphism, and mitoses; treat w wide excision

Question 22

which do you treat with wide excision: fibroadenoma or phyllodes tumor?

Answer 22

phyllodes tumor

Question 23

BOTH fibroadenoma and phyllodes tumor….

Answer 23

*both fibroadenoma and phyllodes are biphasic (both have epithelial and stromal overgrowth);
AND
arise INTRAlobular

Question 24

risk factors for breast cancer

Answer 24

• Risk factors: female, age, lifetime estrogen exposure (early menarche/late menopause), obesity, first degree family history

Question 25

most common mutation in sporadic breast cancer?

Answer 25

p53

Question 26

DCIS

Answer 26

Ductal Carcinoma In Situ – malignant proliferation in ducts with no invasion of BM; usually not a mass detected as calcification on mammography only THAT breast is at risk of carcinoma

Question 27

two types of DCIS

Answer 27

• Comedo subtype = high grade pleomorphic cells, ducts with central necrosis, and calcifications; necrotic cells can be extruded from ducts * Noncomedo – lack either high grade nuclei or necrosis; cribiform/cookie cutter, solid, micropapillary or papillary * **nuclear grade and necrosis are best indicators of recurrence and progression to invasion

Question 28

Paget disease of the breast

Answer 28

malignant large clear cells from underlying DCIS that extends up the ducts to involve the nipple – almost always invasive ``` unilateral scaly (eczema) nipple ulceration and erythema; associated with underlying carcinoma o ER (-); HER2 overexpressed ```

Question 29

LCIS

Answer 29

Lobular Carcinoma In Situ – malignant proliferation of cells in lobules with no BM invasion; DOESNT produce mass or calcification; always found incidentally * dyscohesive uniform round cells lacking E-cadherin adhesion protein (acquired loss); Mucin + signet ring cells * Often multifocal and bilateral risk; contralateral breast IS at risk * Treat: tamoxifen (reduces subsequent carcinoma risk) and watch close; low risk of progression to invasive carcinoma

Question 30

most useful factor to predict progression of in situ to invasive carcinoma?

Answer 30

metastasis to axillary lymph nodes

Question 31

presence of ER and PR in carcinoma is associated with...

Answer 31

response to antiestrogenic agents = response to TAMOXIFEN both receptors are in nucleus

Question 32

presence of HER2/neu in carcinoma is associated with

Answer 32

response to trastuzumab (antibody against HER2 receptor which is on cell surface)

Question 33

triple negative tumors

Answer 33

are negative for all: ER, PR, and HER2/neu VERY poor prognosis increased incidence in AA women unresponsive to drugs - must use chemo

Question 34

ER ___ HER2neu ____? 1) young women, nonwhite, tp53 mutation 2) young women, BRCA1 mutation, AA and hispanic 3) BRCA2 mutation, older men and women

Answer 34

1 ER+ or -, HER2neu + 2 ER-, HER2neu - 3 ER+, HER2neu -

Question 35

invasive ductal carcinoma

Answer 35

mass of duct structures; irregular borders IDC – NST (non special type) o High grade – poorly differentiated, few or no tubules, pleomorphism and mitoses o Low grade – well differentiated, lots of tubules still, no nuclear pleomorphism, low mitoses • Advanced tumors can cause dimpled skin or retracted nipple

Question 36

tubular carcinoma

Answer 36

well-differentiated tubules that lack myoepithelial cells; ER+/HER2neu- good prognosis

Question 37

types of invasive breast cancer associated with ER-/HER2-

Answer 37

medullary cystic secretory metaplastic

Question 38

types of invasive breast cancer associated with HER2+ (ER + or -)

Answer 38

apocrine

Question 39

types of invasive breast cancer associated with ER+/HER2-

Answer 39

lobular, tubular, and mucinous

Question 40

• Mucinous carcinoma

Answer 40

tumor cells floating in abundant mucus; usually older (70yo+); good prognosis (better than IDCNST)

Question 41

• Medullary carcinoma

Answer 41

– large, high grade cells growing in sheets with associated lymphocytes and plasma cells; well circumscribed mass that can mimic fibroadenoma on mammography; lack ER and PR; good prognosis; increased in BRCA1 carriers

Question 42

• Inflammatory carcinoma

Answer 42

carcinoma in dermal lymphatics; presents as inflamed swollen breast (blocked lymph drainage) with no discrete mass; can be mistaken for acute mastitis; poor prognosis

Question 43

IDC-NST, micropapillary and lobular order from best px to worst px

Answer 43

lobular > IDC-NST > micropapillary

Question 44

Invasive Lobular Carcinoma

Answer 44

grows in a single-file pattern; cells may display signet-ring morphology; No duct formation due to lack of E-cadherin

Question 45

hereditary breast cancer classic features? common mutations?

Answer 45

``` classic features: multiple first-degree relatives with breast cancer, tumor at early age (premenopausal), and multiple tumors • tP53 mutations common • BRCA1 (17q21)= breast and ovarian • BRCA2 (13q12)= male breast carcinoma • CHEK2 ```

Question 46

male breast cancer

Answer 46

Rare; presents as sub-areolar mass in older males; may make nipple discharge; usually subtype is invasive ductal carcinoma • Associated with bRCA2 mutation and klinefelter syndrome; and older age! (>70)

Question 47

what is a main cause of gynecomastia?

Answer 47

Chronic alcoholism can cause micronodular sclerosis and can lead to impaired estrogen metabolism and gynecomastia!