Pathoma Breast Pathology

Question 1

What is galactorrhea and some causes?

Answer 1

Galactorrhea - Milk production outside lactation (i.e. breastfeeding/lactorrhea). Common causes include drug-induced (i.e. neuroleptic drugs, cimetidine, birth control pills), prolactinoma, or nipple stimulation (i.e. a woman adopts a child and wants to breastfeed it can happen)
NOT breast cancer

Question 2

What is periductal mastitis, what is the pathogenesis, and who tends to get it?

Answer 2

Painful subareolar mass which occurs as keratinizing squamous metaplasia occurs in the ducts, which causes duct blockage and inflammation. There will be a granulomatous response to spilled keratin, and chronic inflammatory infiltrate.

Occurs in smokers -> have a relative vitamin A deficiency, causing squamous metaplasia

Question 3

What can periductal mastitis be confused for?

Answer 3

Can be confused for breast cancer -> subareolar mass, and nipple is often retracted

Question 4

What is mammary duct ectasia and what inflammatory infiltrate is seen?

Answer 4

Inflammation with dilation (ectasia) of subareolar ducts

-> chronic inflammatory infiltrate with plasma cells and lipid-laden macrophages is seen on biopsy

Question 5

What is the classical presentation of mammary duct ectasia and what can it be confused with?

Answer 5

Presents as periareolar mass with “green-brown” nipple discharge due to inflammatory debris.
-> try to remember it as being dilated full of “green-brown nipple discharge”

Happens in post-menopausal women, so easily confused with breast cancer.

Question 6

What benign entity is most likely to mimic breast cancer both clinically and on mammography? What is its pathogenesis?

Answer 6

Fat necrosis

• > trauma leads to formation of a hard mass which is necrotic
• > dystrophic calcification (due to saponification) allows it to be seen on mammography

Question 7

What will patients present with clinically in fat necrosis and what will biopsy show? Treatment?

Answer 7

Present clinically with a benign lump, often with skin retraction. Patients often remember no traumatic event.

Biopsy shows necrotic fat cells and giant cells (inflammatory infiltrate lining fat cells)

Question 8

What is the single most common change in the premenopausal breast and what is the cause? What age group is susceptible?

Answer 8

Fibrocystic changes -> older premenopausal women (>35 years).

Thought to be due to abnormal hormonal response / sensitivity

Question 9

What is the typical presentation of fibrocystic changes? How does it usually occur, and is it a benign entity?

Answer 9

Breast pain, swelling, and tenderness which is associated with areas of nodularity, induration, and gross cysts

• > vague irregularity of breast tissue, especially upper outer quadrant
• > often bilateral (equal on both sides)

Fibro = Areas of fibrosis between expanded cysts
Cystic = Lobular units become cystic and dilated, often with bleeding into them due to erosion of nearby blood vessels - "blue dome cysts"

Inherently a benign entity but some changes which can occur related to this condition increase your risk for invasive breast cancer.

Question 10

What is the common fibrocystic-related change which is notably NOT associated with increased risk of cancer?

Answer 10

Apocrine metaplasia - eosinophilic blebbing at epithelial surface

Will arise in conjunction with the common benign changes of fibrosis and cystic blue dome dilations

Question 11

What two lesions are associated with roughly 2x risk of breast cancer as fibrocystic changes? How will the lumens look on the ductal one?

Answer 11

1. Usual ductal hyperplasia - excess benign cells lining ducts-> lumens will appear irregular (indicates benign), a type of proliferative change
2. Sclerosing adenosis - adenosis = glands, sclerosing = fibroblasts, this is a normal looking hyperplasia of acini with intermixed fibrosis. Often becomes calcified (confusable on mammogram)

Question 12

What fibrocystic lesions are at greater risk (5x) of progressing to breast cancer? How will the lumens of the ductal one appear?

Answer 12

1. Atypical ductal hyperplasia - lumens within the proliferated ducts appear more round than usual ductal hyperplasia, and cells are monomorphic / atypical
2. Lobular hyperplasia - increased number of cells lining each lobule, look like “marbles in a petri dish” acini

Question 13

Which breast is affected with an increased cancer risk due to fibrocystic changes?

Answer 13

Both breasts are -> much like LCIS, fibrocystic changes can be treated as a risk factor for the development of breast cancer in either breast.

Question 14

What is the most common cause of serous or blood nipple discharge? How can you tell if it’s benign or malignant? What age is the typical presentation?

Answer 14

Intraductal papilloma
-> papillary growth into a large duct, typically under the areola.

Can see two layers of cells (luminal layer, myoepithelial layer) to know it’s not malignant (malignant = loss of myoepithelial layer).

Typically presents in a PREmenopausal female -> another way to differentiate it from papillary carcinoma

Question 15

What is the most common benign neoplasm of the breast, and who tends to get it?

Answer 15

Fibroadenoma, usually in premenopausal women <35

Question 16

What is the growth pattern of fibroadenoma and does it increase your risk for cancer?

Answer 16

Small, well-circumscribed mass, usually solitary. Includes fibrous component (fibro-) with proliferative connective tissue, and a gland component (-adenoma).

It is estrogen-sensitive, so it grows during pregnancy and prior to menstruation.

No increased risk of cancer.

Question 17

What neoplasm should be suspected if what was presumed to be a fibroadenoma does not regress after menopause? What is its growth pattern?

Answer 17

Phyllodes tumor

• > fibroadenoma-like (both proliferations of glands and stroma) but has an overgrowth of the “fibrous” mesenchymal component of the tumor
• > They have a very cellular stroma -> sarcomatous type tumor (stroma can be very ugly, much less benign looking than fibroadenoma).
• > characteristic “leaf-life” projections of fibrous tissue on biopsy

Question 18

What is the pattern of spread of phyllodes tumor and what must be done to deal with them? How do they spread if they become malignant?

Answer 18

Usually benign, and must be resected with wide margins (like pleomorphic adenoma) to prevent recurrence.

If they become malignant (rare) they will spread by blood rather than lymph nodes due to being a sarcoma.

Question 19

What is Paget disease and what will it look like on the patient? Is this DCIS or invasive cancer?

Answer 19

Extension of neoplastic adenocarcinoma cells through the ducts to involve the skin of the nipple (intraepithelial adenocarcinoma cells)

Appears as ulceration and erythema of the nipple

It can be either DCIS or invasive adenocarcinoma

Question 20

How will Paget disease appear histologically? How should you manage it?

Answer 20

Similar to extramammary Paget disease
-> “Paget cells” clear cytoplasm in the epidermis, either singly or in clusters.

Patient generally needs biopsy with removal of the lump since it’s almost always associated with underlying carcinoma when in the breast

Question 21

What is the most common type of breast cancer? How does it present classically on the outside and with a mammogram?

Answer 21

Invasive ductal carcinoma.

Presents as a firm, fibrous, rock-hard mass with dimpling of the skin or retraction of the nipple due to desmoplasia.

Often has a characteristic stellate shape on mammogram with little tentacles reaching out -> ductal proliferations going everywhere.

Question 22

What are the four main subtypes of invasive ductal carcinoma?

Answer 22

1. Tubular carcinoma
2. Mucinous carcinoma
3. Medullary carcinoma
4. Inflammatory carcinoma

Question 23

What is the most classic subtype of invasive ductal carcinoma? Prognosis?

Answer 23

Tubular carcinoma - well-differentiated tubules that lack myoepithelial cells (malignant), surrounded by desmoplastic stroma -> good prognosis

Question 24

What is mucinous carcinoma? Prognosis?

Answer 24

Invasive ductal carcinoma characterized by abundant extracellular mucin

“Cells are stuck in mucus so they can’t go anywhere” - good prognosis -> rarely metastasizes

Question 25

What is medullary carcinoma / who gets it?

Answer 25

Invasive ductal carcinoma with large, high-grade cells associated with lymphocytes / plasma cells -> breast tissue looks like a massive lymph node

-> good prognosis, in BRCA1 carriers have highest risk (but still not the most common cancer type in this group)

Question 26

What characterizes inflammatory carcinoma grossly and microscopically and what is it also called?

Answer 26

Characterized by carcinoma in dermal lymphatics
-> also called “peau d’orange” from thickened, erythematous, orange-peel like rough skin surface

Prognosis is very poor since it has already spread to lymphatics, may be confused for Paget disease / acute mastitis

Question 27

What does lobular carcinoma in situ (LCIS) resemble and how is it usually discovered?

Answer 27

Resembles atypical lobular hyperplasia -> difference is in the amount of hyperplasia

It is usually discovered via incidental biopsy, because it lacks clinical and mammographic signs (no mass or calcifications)

Question 28

Is LCIS usually solitary? What does it mean? How is it treated?

Answer 28

It is often multifocal and bilateral

Treated as a super risk factor, as risk of cancer is usually for invasive DUCTAL carcinoma.

Observe closely and give tamoxifen hormonal therapy. (ER antagonist as breast, agonist at bone/uterus)

Question 29

How does invasive lobular carcinoma appear histologically? Why?

Answer 29

Appears as an orderly row of cells “single file” pattern due to being discohesive - loss of E-cadherin.

• > will not form glands
• > minimal desmoplasia

Question 30

Does lobular carcinoma present with a mass?

Answer 30

Typically does not present with a mass due to lack of desmoplasia. Often radiographically silent for this reason as well.

Question 31

What is the most common type of male breast cancer and what are the presenting symptoms?

Answer 31

Invasive ductal carcinoma (males have few lobules)

Symptoms: skin and chest fixation more common (desmoplasia has less breast tissue to work with)

• > subareolar mass is common
• > nipple discharge may be present

Question 32

What are the risk factors for male breast cancer?

Answer 32

Hyperestrogenic states: Klinefelter syndrome.

BRCA2