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Flashcards in Breast Pathology Deck (51):

What do we associate with milk line remnants?

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


What is galactorrhea?

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


What causes acute mastitis and how does it present?

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


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

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.


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

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


What causes a fat necrosis and how does it present?

cause: Usually related to trauma;

sx: mass on physical exam or abnormal calcification on mammography (saponification)

histo: necrotic fat w/ calcifications & giant cells


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

sx: Single or multiple very hard masses

histo: Collagenized stroma surrounding atrophic ducts & lobules w/lymphocyte infiltrate

risk: type 1 DM; autoimmune thyroid dz


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

Fibrosis with cysts in the breast


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

No increased cancer risk.

mammo: dense, cysts, calcifications

Histology: metaplasia, benign.


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

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


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

1.5-2x risk

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


What causes gynecomastia and how does it present?

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


What will epithelial hyperplasia look like?

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


What does sclerosing adenosis look like?

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.


What is a radial scar and how does it present?

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”)


What is an intraductal papilloma and how does it present?

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


How do we distinguish intraductal papilloma from papilloma carcinoma?

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


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?

4-5x increased risk for cancer

Aquired loss of 16q and 17p


Discuss the general appearence of atypical duct hyerplasia

Very monomorphic cells, cookie cutter, slit-like fenestrations

resembles DCIS, but only partially fills ducts


Discuss the general appearence of atypical lobular hyperplasia

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


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

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


Discuss the three major molecular subtypes of breast carcinoma

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


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

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)


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

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


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

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.


How do we treat the different cancer subtypes?

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


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

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


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

8-10x as much


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

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


What are the types of DCIS and whats the prognosis?

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})


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

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


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


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

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

HER2 overexpressed


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

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


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

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


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

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


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

well-differentiated tubules that lack myoepithelial cells

ER +, HER2/neu (-)


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

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

risk: older women (avg 70)

(Relatively good prognosis)


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

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


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

carcinoma in dermal lymphatics

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

Poor prognosis


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

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)


Discuss the prognosis and presentation of a micropapillary carcinoma

malignant cells form small papillary groups devoid of fibrovascular cores.

prognosis: worse, more aggressive

histo: microcalcifications


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

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


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

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



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

Estrogen sensitive- grows during pregnancy & painful during menstrual cycle

No risk of carcinoma

Mammogram: “popcorn” calcification/density


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

Fibroadenoma-like tumor w/overgrowth of the fibrous component

risk: ~60yo (unlike fribro, which is


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

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


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

Invasive carcinomas less than 2cm

Micrometastases or none to lymph node

No distant metastasis

87% 10 year survival


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

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

65% 10 year survival


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

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


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

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.


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

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.