breast pathology Flashcards
where is the tissue of highest density in breast?
upper outer quadrant
milk production occurs in the….
terminal duct lobular unit
all are drained by collecting duct
all ducts and lobules in breast tissue have two epithelial layers…..
luminal cells (outer layer) - milk production
myoepithelial layer (inner layer) - contractile function
galactorrhea
production of milk NOT during lactation
caused by nipple stimulation, prolactinoma of anterior pituitary, and drugs
is NOT a symptom of breast cancer!
acute mastitis
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
how to treat acute mastitis?
drainage and dicloxacillin
periductal mastitis
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
mammary duct ectasia
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
fat necrosis
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
Lymphocytic Mastopathy
Sclerosing Lymphocytic Lobulitis
- 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
granulomatous mastitis
Can be caused by granulomatous diseases (wegener, sarcoid) or infection
fibrocystic changes
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
sclerosing adenosis
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
if two cell layers are present it is not ____
a carcinoma
when fibrocystic changes show atypical hyperplasia –>
increased risk 5x of carcinoma
o Acquired loss of 16q and 17p; Clonal proliferation with some features of carcinoma in situ
o Atypical ductal hyperplasia
monomorphic luminal cells, evenly spaced with peripheral slit like spaces
only partially involving ducts
atypical lobular hyperplasia
small monomorphic round cells in lumens; like LCIS but do not fill >50% of acini in a lobule
Intraductal Papilloma
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
papillary carcinoma
fibrovascular projections lined by epithelial cells without underlying myoepithelial cells; common in older age
only 1 cell layer type
fibroadenoma
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
phyllodes tumor
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
which do you treat with wide excision: fibroadenoma or phyllodes tumor?
phyllodes tumor
BOTH fibroadenoma and phyllodes tumor….
*both fibroadenoma and phyllodes are biphasic (both have epithelial and stromal overgrowth);
AND
arise INTRAlobular
risk factors for breast cancer
• Risk factors: female, age, lifetime estrogen exposure (early menarche/late menopause), obesity, first degree family history
most common mutation in sporadic breast cancer?
p53
DCIS
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
two types of DCIS
• 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
Paget disease of the breast
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
LCIS
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
most useful factor to predict progression of in situ to invasive carcinoma?
metastasis to axillary lymph nodes
presence of ER and PR in carcinoma is associated with…
response to antiestrogenic agents
= response to TAMOXIFEN
both receptors are in nucleus
presence of HER2/neu in carcinoma is associated with
response to trastuzumab (antibody against HER2 receptor which is on cell surface)
triple negative tumors
are negative for all: ER, PR, and HER2/neu
VERY poor prognosis
increased incidence in AA women
unresponsive to drugs - must use chemo
ER ___ HER2neu ____?
1) young women, nonwhite, tp53 mutation
2) young women, BRCA1 mutation, AA and hispanic
3) BRCA2 mutation, older men and women
1 ER+ or -, HER2neu +
2 ER-, HER2neu -
3 ER+, HER2neu -
invasive ductal carcinoma
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
tubular carcinoma
well-differentiated tubules that lack myoepithelial cells; ER+/HER2neu-
good prognosis
types of invasive breast cancer associated with ER-/HER2-
medullary
cystic
secretory
metaplastic
types of invasive breast cancer associated with HER2+ (ER + or -)
apocrine
types of invasive breast cancer associated with ER+/HER2-
lobular, tubular, and mucinous
• Mucinous carcinoma
tumor cells floating in abundant mucus; usually older (70yo+); good prognosis (better than IDCNST)
• Medullary carcinoma
– 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
• Inflammatory carcinoma
carcinoma in dermal lymphatics; presents as inflamed swollen breast (blocked lymph drainage) with no discrete mass; can be mistaken for acute mastitis; poor prognosis
IDC-NST, micropapillary and lobular
order from best px to worst px
lobular > IDC-NST > micropapillary
Invasive Lobular Carcinoma
grows in a single-file pattern; cells may display signet-ring morphology; No duct formation due to lack of E-cadherin
hereditary breast cancer
classic features?
common mutations?
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
male breast cancer
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)
what is a main cause of gynecomastia?
Chronic alcoholism can cause micronodular sclerosis and can lead to impaired estrogen metabolism and gynecomastia!
