Breast Pathology

Question 1

What do we associate with milk line remnants?

Answer 1

So breast tissue is just modified sweat glands derived from skin. Remnants of tissue can develop anywhere along the “milk line” from axilla to vulva

Question 2

What is galactorrhea?

Answer 2

Milk production outside of lactation. It is caused by nipple stimulation, prolactinoma of the anterior pituitary and drugs.

Question 3

What causes acute mastitis and how does it present?

Answer 3

Bacterial infection by Staph Aureus caused from breast feeding (fissures form, route for entry).

Presents with erythema with purulent discharge and possible abscess formation.

Treat it with draining that sucker or giving some dicloxicillin

Question 4

What risks and presentation do we see for someone with periductal mastitis?

Answer 4

This is inflammation of the subareolar ducts from blockage secondary to keratinizing squamos metaplasia of lactiferous ducts (seen in smokers)

Presents with subareolar mass and a nipple retraction.

Question 5

What is mammary duct ectasia, how does it present clinically and histologically?

Answer 5

dilation of subareolar ducts 2* inflammation

sx: poorly defined periareolar mass w/green-brown nipple discharge (inflammatory debris)
risk: multiparous postmenopausal women
histo: Chronic inflammation w/plasma cells

Question 6

What causes a fat necrosis and how does it present?

Answer 6

cause: Usually related to trauma;
sx: mass on physical exam or abnormal calcification on mammography (saponification)
histo: necrotic fat w/ calcifications & giant cells

Question 7

How does lymphocytic mastopathy present and who is at risk for it?

Answer 7

sx: Single or multiple very hard masses
histo: Collagenized stroma surrounding atrophic ducts & lobules w/lymphocyte infiltrate
risk: type 1 DM; autoimmune thyroid dz

Question 8

What is the most common change in the post menopausal breast?

Answer 8

Fibrosis with cysts in the breast

Question 9

How do fibrocystic changes present on mammography and histology? What’s the cancer risk?

Answer 9

No increased cancer risk.

mammo: dense, cysts, calcifications

Histology: metaplasia, benign.

Question 10

There are three nonproliferative, non cancer causing fibrocystic changes to know about. Compare the three of them.

Answer 10

Simple/apocrine cysts: Cysts contain turbid, semi-translucent fluid of a brown or blue color: “Blue dome cysts” that bleed into themselves due to calcium

Adenosis: inc number of acini per lobule and is a normal feature of pregnancy. This is the earliest recognizable precursor of epithelial neoplasia

Fibrosis:cause: Cysts rupture–> releasing secretory material into the adjacent stroma–> chronic inflammation and fibrosis –> palpable nodularity of the breast

Question 11

What types of proliferative breast diseases without atypia do we have? What increased risk of cancer is associated for them?

Answer 11

1.5-2x risk

• Gynecomastia
• Epithelial hyperplasia
• Sclerosing Adenosis
• Radial Scar (Complex Sclerosing lesion)
• Intraductal papilloma

Question 12

What causes gynecomastia and how does it present?

Answer 12

swelling of the breast tissue in boys or men

Histo: inc stromal & ductal tissue , lobules do not form

Causes: imbalance of the hormones estrogen and testosterone, Liver failure, hyperthyroid, adrenal tumors, drugs (marijuana, steroids, estrogens, digitalis, cimetidine), Klinefelter, old age

Question 13

What will epithelial hyperplasia look like?

Answer 13

> 2 cell layers; usually incidental finding. Duct will be distended with heterogenous-appearing luminal cells

Question 14

What does sclerosing adenosis look like?

Answer 14

acini/terminal duct > 2

Adenosis -inc number of acini per lobule; earliest recognizable precursor of epithelial neoplasia (more grapes on the vine)

histo: Acini compressed & distorted, many myoepithelial cells. Mimics invasive carcinoma.

Question 15

What is a radial scar and how does it present?

Answer 15

Commonly occurring benign lesion that forms irregular borders on a solid mass
can mimic invasive carcinoma

histo: Central nidus of entrapped glands in hyalinized stroma w/long radiating projections (“spicules”)

Question 16

What is an intraductal papilloma and how does it present?

Answer 16

Papillary growth, usually into a large lactiferous duct near the nipple

histo: fibrovascular core, multiple branches lined by epithelial (luminal) & myoepithelial cells

Clinical: bloody nipple discharge in a premenopausal woman

Question 17

How do we distinguish intraductal papilloma from papilloma carcinoma?

Answer 17

Both present with bloody nipple discharge, but for carcinoma on histo, it lacks underlying myoepithelial cells and is more common in postmenopausal women

Question 18

When we DO have atypia with proliferative disease, things get a little more dangerous. What genetic change is linked to these two conditions and what increase in risk do we see?

Answer 18

4-5x increased risk for cancer

Aquired loss of 16q and 17p

Question 19

Discuss the general appearence of atypical duct hyerplasia

Answer 19

Very monomorphic cells, cookie cutter, slit-like fenestrations

resembles DCIS, but only partially fills ducts

Question 20

Discuss the general appearence of atypical lobular hyperplasia

Answer 20

atypical lobular cells lie between the ductal basement membrane and overlying normal luminal cells.
Identical to LCIS, but cells do not fill more than 50% of acini w/in lobule

Question 21

How common is carcinoma of the breast and how lethal is it? What risk factors are associated with it?

Answer 21

2nd Most common carcinoma in women by incidence, following skin cancer

2nd most common cause of cancer mortality in women, following lung

Risk factors (mostly related to estrogen exposure): female, older, Early menarche/late menopause, Obesity, Atypical hyperplasia, 1 relative w/breast cance

Question 22

Discuss the three major molecular subtypes of breast carcinoma

Answer 22

3 major molecular subtypes: estrogen receptor (ER), progesterone receptor (PR), & HER2/neu gene amplification (overexpression) status.

65%= Luminal- ER (+) and HER2 (-); high or low proliferations

20%= HER2 enriched- germline mutations in TP53

15%= Basal-like (“triple negative”): (-)ER, PR, and HER2/neu

Question 23

What is the precursor carcinoma sequence of events with a BRCA2 mutation?

Answer 23

BRCA2 mutation (germline) - 1q gain, 16q loss, gives us flat epithelial atypia. With a PIK3CA mutation we turn our flat epithelial atypia to an atypical ductal hyperplasia, which develops into DCIS, which develops into ER positive, HER2 negative invasive luminal cancers (65% of cancers)

Question 24

What is the precursor carcinoma sequence of events with a Tp53 mutation?

Answer 24

Tp53 mutation leading to HER2 amplification, leading to atypical apocrine adenosis. This also leads to DCIS and HER2 invasive cancer (20% of cancers)

Question 25

What is the precursor carcinoma sequence of events with a BRCA1 mutation?

Answer 25

BRCA1 germline mutation - This is the ER negative pathway that leads to a TP53 mutation and inactivation of BRCA1. This leads to DCIS, and we get an invading ER and HER2 negative “basal-like” cancer.

Question 26

How do we treat the different cancer subtypes?

Answer 26

ER & PR: antiestrogenic agents (tamoxifen); receptors are in nucleus

HER2/neu: trastuzumab (Herceptin), a designer antibody directed against the HER2 receptor on the cell surface

‘Triple-negative’ tumors: poor prognosis, chemotherapy

Question 27

Discuss the 4 mutations that predispose someone to familial breast cancer, which represents 10-12% of all breast cancers.

Answer 27

BRCA1 (17q21)~ familial breast & ovarian carcinoma.

BRCA2 (13q12-13)~familial /breast carcinoma in males.

TP53 (17p13.1)~ Li Fraumeni, triple neg cancers

CHEK2 (22q12.2)~ thyroid/kidney/colon/prostate

Question 28

Carcinoma in situ is how much more likely to develop into a spreading cancer?

Answer 28

8-10x as much

Question 29

15-30% of all carcinomas are ductal carcinomas in situ (DCIS). What is this and how does it present on imaging? Grossly?

Answer 29

Malignant proliferation of cells in ducts w/o invasion of the basement membrane

imaging: linear and branching calcifications within the ductal system; (similar to benign conditions: fibrocystic changes, sclerosing adenosis, fat necrosis)
gross: Lumina of the ducts are filled with chalky, yellow necrotic material

Question 30

What are the types of DCIS and whats the prognosis?

Answer 30

prognosis: Resection is usually curative

comedo type - high-grade pleomorphic cells w/ central necrosis & calcification in center of ducts (like blackhead). Imaging shows clustered or branching irregular calcifications

noncomedo– monomorphic epithelial cell population (types: papillary, micropapillary (big empty vacuolated space), solid or cribriform {cookie-cutter spaces})

Question 31

How does Paget’s Disease of breas compare to DCIS, and how does it present clinically?

Answer 31

DCIS spreads up the ducts (“marches up) to involve the skin of the nipple

rare

sx: nipple ulceration & erythema, eczema like, burning pruritus

Question 32

What do we see on staining for Paget’s and what gene issue is related to it?

Answer 32

Histology: epidermis invaded by malignant Paget cells (large w/abundant clear cytoplasm, hyperchromatic nuclei), PAS+ (high mucin content)

HER2 overexpressed

Question 33

How does lobular carcinoma in situ present? How do we treat it?

Answer 33

Malignant proliferation of cells in lobules w/o invasion of the basement membrane.

NO mass or calcifications
discovered incidentally on biopsy.

Histology: dyscohesive cells lacking E-cadherin adhesion protein bilaterally

Tx: tamoxifen (dec risk of subsequent carcinoma) & close follow-up

low risk of progression to invasive carcinoma

Question 34

What histology/imaging/PE findings tell us that we are looking at an invasive/infiltrating carcinoma?

Answer 34

sx: mass, dimpling of the skin or retraction of the nipple

PE: detected masses are usually >2cm

Mammograph: detected masses >1cm.

histo: loss of lobular architecture and ducts, firm white-tan mass

Question 35

How common are infiltrating ductal carcinomas and how do they present?

Answer 35

Most common type of invasive carcinoma in the breast, > 80% of cases

histo: anaplastic cells arranged in glands, surrounded by desmoplastic stroma
gross: irregular margins

Question 36

What subtype of carcinoma can lead to Tubular carcinoma and what does it look like?

Answer 36

well-differentiated tubules that lack myoepithelial cells

ER +, HER2/neu (-)

Question 37

Who gets mucinous carcinoma and what does it look like under the scope?

Answer 37

abundant extracellular mucin (‘tumor cells floating in a mucus pool’)

risk: older women (avg 70)

(Relatively good prognosis)

Question 38

Medullary carcinoma is associated with what gene and how does it present?

Answer 38

This guy presents with large, high-grade cells growing in sheets w/assoc lymphocytes & plasma cells, which all sounds horrible. However, grossly we see a well-circumscribed mass
can mimic fibroadenoma on mammography

Relatively good prognosis

a/w: BRCA1 carriers

Question 39

Inflammatory carcinoma is bad. Why? How does the patient present?

Answer 39

carcinoma in dermal lymphatics

sx: inflamed, swollen breast (block drainage of lymphatics) w/o discrete mass; can be
mistaken for acute mastitis

Poor prognosis

Question 40

What key histological findings so we see with invasive lobular carcinoma?

Answer 40

Invasive carcinoma grows in a single-file pattern

histo: discohesive, cells may exhibit signet-ring morphology.

No duct formation ( lack of E-cadherin, just like with lobular carcinoma in situ)

Question 41

Discuss the prognosis and presentation of a micropapillary carcinoma

Answer 41

malignant cells form small papillary groups devoid of fibrovascular cores.

prognosis: worse, more aggressive
histo: microcalcifications

Question 42

Male breast cancer is rare, but when we see it, what type is it?

Answer 42

Most common histological subtype is invasive ductal carcinoma; Lobular carcinoma is rare (the male breast develops very few lobules)

Question 43

What are fibroadenomas, who is at risk and how do they present?

Answer 43

benign tumor of intralobular stroma

Most common benign neoplasm of the breast;

sx: painless, well-circumscribed, mobile marble-like mass, upper outer quadrant, can grow large, rubbery movable like mass

risk:

Question 44

What pregnancy finding is linked to fibroadenoma and what will we see on mammogram?

Answer 44

Estrogen sensitive- grows during pregnancy & painful during menstrual cycle

No risk of carcinoma

Mammogram: “popcorn” calcification/density

Question 45

How is a Phyllodes tumor different from a fibroadenoma? What’s it look like on histology?

Answer 45

Fibroadenoma-like tumor w/overgrowth of the fibrous component

risk: ~60yo (unlike fribro, which is

Question 46

Stage 0 cancer involves what cancer, lymph node infiltration, metastasis (distant) and what survival rate?

Answer 46

DCIS or LCIS
No distant Metastasis
No lymph node metastasis
92% 10 year survival rate

Question 47

Stage 1 cancer involves what cancer, lymph node infiltration, metastasis (distant) and what survival rate?

Answer 47

Invasive carcinomas less than 2cm

Micrometastases or none to lymph node

No distant metastasis

87% 10 year survival

Question 48

Stage 2 cancer involves what cancer, lymph node infiltration, metastasis (distant) and what survival rate?

Answer 48

These guys are greater than 2cm but less than 5cm with 0 - 3 positive lymph nodes and no distant metastasis.

65% 10 year survival

Question 49

Stage 3 cancer involves what cancer, lymph node infiltration, metastasis (distant) and what survival rate?

Answer 49

Greater than 5 cm or inflammatory invasive. Could have any kind of LN involvement, still no distant metastasis, but these guys have only a 40% 10 year survival rate

Question 50

Stage 4 cancer involves what cancer, lymph node infiltration, metastasis (distant) and what survival rate?

Answer 50

Any size carcinoma can fit in this category and lymph nodes do not have to be involved, you just need distant metastasis. These folks have a 5% 10 year survival rate.

Question 51

Who typically gets ER positive or negative, HER2 positive or negative, etc?

Answer 51

ER positive and HER2 negative (low proliferation) = Older women, men, with cancers detected by mammogram. High proliferation means you got BRCA2.

HER2 positive (ER can be either) is seen in young women and is involved with the TP53 mutation

African American and Hispanic and young women with a BRCA1 mutation get everything negative.