Breast Flashcards
Most common type of fibrocystic lesions
Nonproliferative changes
Brown to blue dome cysts filled with watery turbid fluid May calcify Apocrine metaplasia (polygonal abundant granular eosinophilic cytoplasm and small round deeply chromatic nuclei)
Fibrocystic changes
Presence of more than normal 2 cell layers of the ducts and lobules of breast (ie luminal overlying myoepithelial cell)
Epithelial hyperplasia
Proliferative fibrocystic change
Small gland fenestrations Ductal papillomatosis (small papillary excrescences into duct lumen) Micrpcalcifications Atypical ductal hyperplasia occasionally Atypical lobular hyperplasia
Epithelial hyperplasia
Proliferative fibrocystic change
Mimics carcinoma
Hard😟, rubbery
Proliferation of luminal space (adenosis) lined by epithelial cells and myoepithelial cells small glands within fibrous stroma
Stromal fibrosis compresses epithelium and lumen of ducts
Double layered epithelium
Sclerosing adenosis
Fibrosis, cystic change, apocrine metaplasia, mild hyperplasia
Minimal or no inc risk of breast carcinoma
Moderate to florid hyperplasia without atypia
Ductal papillomatosis
Sclerosing adenosis
Slightly inc risk 1.5-2 fold
Atypical hyperplasia whether ductular or lobular
Significantly inc risk 5 fold
Prolif fibrocystic change are bilateral multifocal asoc with inc risk of carcinoma
Nonbacterial chronic inflammation of breast assoc with inspissation of breast secretions in main excretory ducts
Mammary duct ectasia
Plasma cell mastitis
Most distinguishing feature of breast inflammatory change is
lymphoplasmacytic infiltrate and granulomas in periductal stroma
inoccuous lesion with central focus of necrotic fat surrounded by neutrophil and lipid laden mac with giant cells
Fat necrosis
Most common benign neoplasm of breast
Premenopausal women in 20s and 30s
Biphasic with fibroblastic stroma and epithelium lined glands the former of which is neoplastic
Well circumscribed, mobile, marble-like mass
Related to inc
Fibroadenoma
estrogen
Fibroadenoma-like tumor with overgrowth of fibrous component
Biphasic
Stromal element forming epithelium leaflike projections
Cleft like spaces with spindle stroma
Arises de novo
Leaf-like projections
Most commonly seen in postmenopausal women
Benign, localized but may be malignant
Phyllodes tumor
Cystosarcoma phyllodes
Tx: wide excision or mastectomy
Benign neoplastic papillary growth in lactiferous ducts
Fibrovascular core lined with eithelial and myoepithelial cells
Serous bloody nipple discharge
Small subareolar tumor
Nipple retraction
Delicate branching growths within dilated duct
Multiple papillae with a double layrred core covered by epithelial cell and outer luminal of myoepithelial cell
Intraductal papilloma
Most common location of breast tumors
Upper outer quadrant 50%
Central portion 20%
high grade nuclei with extensive necrosis extruding from transected
ducts on application of gentle pressure
dystrophic calcification inside cells
Comedo DCIS
other types: cribriform solid micropapillary papillary
Frequently assoc with DCIS
Calcification
Extension of DCIS up lactiferous ducts into contiguous skin of nipple unilateral crusting exudate over the nipple and areolar skin
Paget disease of nipple
Malignant proliferation of cells in lobules
Monomorphic bland, round nuclei occuring loosely in cohesive clusters within lobules
No invasion of BM
Mucin vacuoles forming signet rings
Dyscohesive cells lacking e-cadherin
Multifocal and bilateral (20-40%)
Premenopausal (80-90)
Subsequent invasive carcinomas arise in either breast
A marker of inc risk of carcinoma in both invasive ductal and lobular breasts and direct precursor of some cancers
LCIS
Tx: Tamoxifen and close follow up
Rf for Breast CA
Estrogen exposure
Long menarche and menopause
Atypical proliferative lesions
Family hx of breast cancer in a first degree
10% of all breast CA are inherited mutations in
BRCA1
BRCA2
Estrogen receptor expressing tumors respond to
Tamoxifen
HER2/NEU overexpressing tumors respond to
Trastuzumab/Herceptin
Clinically enlarged swollen erythematous breast without palpable mass
Poorly differentiated and infiltrative
Involves dermal lymphatic spaces with blockage of channels leading to edema
Minimal to absent inflammation
Inflammatory carcinoma
Rare carcinoma 1%
Sheets of large anaplastic cells with pushing borders
Pronounced lymphoplasmacytic infiltrate
Inc frequency in BRCA1 mutation
Lack estrogen and progesterone receptors, do not express HER2/Neu
Triple negative
Medullary carcinoma
Rare subtype
Producing abundant quantities of extracellular mucin dissecting into surrounding stroma
Soft gelatinous
Express hormone receptors
Colloid mucinous carcinoma
Palpable masses with well formed tubules low grade nuclei
Prognosis is excellent
Express hormone receptor and do not show HER2/Neu
Tubular carcinoma
Enlargement of male breast from
Excess estrogen
Due to cirrhosis and inability of liver to metabolize estrogen
Klinefelter’s, anabolic, pharma agent
Inc CT and epithelial hyperplasia of ducts
Lobules formation rare
Button like subareolar swelling develops in both breasts
Gynecomastia
Rare in men Subareolar mass under nipple Nipple discharge Invasive ductal Diagnosed at advance age Tumor infiltrates skin and thoracic wall rapidly Resemble invasive carcinomas BRCA2 and Klinefelter Syndrome
Male breast Carcinoma
Highest density of ductal system in males
in females
Subareolar area
Upper outer quadrant
Each ductal system occupies more than one quadrant
Mammograms in young women are typically
radiodense or white in appearance
mass forming lesions or calcifications (radiodense) detection is difficult
Density of a young woman’s breast stems from predominance of
fibrous interlobular stroma
paucity of adipose
Drugs that cause galactorrhea
Digitalis Anti-psychotics Anti-depressants TCAs Estrogen/birth control pills D2 antagonist Reserpine Methyldopa
Reserpine SE
Psychosis
Squamous metaplasia of lactiferous ducts
Recurrent Subareolar mass with nipple retraction
Inflammation of subareolar ducts
Associated with smokers 90% and Vit A deficiency
Zuska disease
Periductal mastitis/abscess
Periductal mastitis/abscess
Key feature:
Keratinizing squamous metaplasia of nipple ducts
Intense chronic inflammation with granulation tissue and fibrosis
Tx: enbloc removal
Complication: fistula
Squamous metaplasia is produced because of these 2 risk factors
Lack of vitamin A for highly specialized epithelium
Smoking (dec Vit A)
Inflammation and dilation of subareolar ducts
Clasically arises from multiparous postmenopausal women
Lacks squamous metaplasia of nipple ducts
End of spectrum:
Fibrosis = skin and nipple retraction
Mammary duct ectasia
Gross appearance of fibrocystic change
Bluedome appearance
Proliferative disease without atypia Moderate or florid hyperplasia Sclerosing adenosis Papilloma Complex sclerosing Lesion radial scar Fibroadenoma with simple features
5-7% risk
Mild increase
Proliferative change with atypia
Moderate inc risk
Risk reduction of breast ca may be done by
Prophylactic mastectomy
Giving of estrogen antagonist like tamoxifen
Tamoxifen inc risk for
Endometrial ca
Modified apocrine sweat glands
Embryologically derived from skin
6-10 major duct system (12-20 lobules)
Breast
Order of duct branching
Lactiferous sinus -> ducts branch -> terminal duct -> cluster of acini/lobules
Functional unit of breast
Terminal ductal lobular unit
2 cell types lining ducts and lobules
2 types of stroma
Histology
Myoepithelial cells (contractile) Luminal epithelial cells
Interlobular stroma
Interlobulat stroma: hormonally responsive
Keratinizing stratified squamous epithelium (skin) changing to double layered cuboidal epithelium lining ducts and lobules (TDLU)
Covered by stratified squamous epithelium
Pigmented and supported by smooth muscle
NAC
function in nipple lubrication becoming prominent during pregnancy
Areolar glands of Montgomery
Other conditions that promote calcification on mammography
fat necrosis
sclerosing adenosis
Swollen
Erythrma
Pea d orange
Frequently mistaken for mastitis
Inflammatory breast cancer
Invasive lobular carcinoma
histological landmark due to loss of e cadherin
Indian file pattern
Her2 /neu
ERB
CD340
Milk production outside of lactation
Not a symptom of breast cancer
Causes:
Nipple stimulation
Prolactinoma of anterior pituitary (most common)
Drugs
Galactorrhea
Congenital nipple inversion may be corrected
with pregnancy
Acute mastitis most common etiologic agents
Staph aureus
Streptococcus (diffuse)
Usually related to trauma or prior surgery
Mass on PE
Calcifications on mammography
Fat necrosis
Fat necrosis biopsy:
Necrotic fat with associated calcifications and giant cells
Saponification
Ill defined nodules with hemorrhage
Development of fibrosis and cyst
Most common change in premenopausal women (25-40)
Unopposed estrogen stimulation
Clinically a lumpy breast on the upper outer quadrant
Decreased risk by:
Fibrocystic change
OCP use
Cysts with apocrine metaplasia (no inc risk)
Fibrosis: rupture of cyst leading to secretory material released into stroma -> inflammation and fibrosis (no increased risk)
Sclerosing adenosis 2x
Inc number of acini per lobule
Often are calcified
Ductal hyperplasia 2x
Atypical hyperplasia 5x
Fibrocystic change -> benign
Hallmark of intraductal papilloma
Bloody nipple discharge in a premenopausal
Intraductal papilloma must be differentiated from papillary carcinoma by checking presence of
Myoepithelial cells (intraductal) Postmenopausal women (papillary)
Characterized by proliferation of ductal epithelium and or stroma without cytologic or architectural features suggestive of carcinoma
Proliferative breast disease without atypia
Morphology:
epithelial hyperplasia: >2 layers
sclerosing adenosis: inc lobules with fibrosis
complex sclerosing adenosis: with epithelial hyperplasia sclerosing adenosis
papilloma: within dilated duct, fibrovascular core
Most common carcinoma by indicdence 2nd most common by mortality Risk factors most commonly related to estrogen exposure: female age early menarche/late menopause obesity atypical hyoerplasia prior biopsy 5x 1st degree relative with breast cancer
Breast cancer
Means to detect small, nonpalpable, asymptomatic breast carcinomas
Sensitivity and specificity increases with age (radiodense fibrous tissue gradually replaced with radioluscent fatty tissue)
Mammographic screening
Routine screening not recommended
10% chance of mammographic lesion being malignant
Age 40-49
Screened every 2-3 years
25% chance of mammographic lesion being malignant
Age 50-74
Mammographic signs of CA
densities and calcifications
Neoplastic proliferation that is limited to ducts and lobules by an intact basement membrane
CA in situ
Tumor cells penetrate through basement membrane and invade the stroma have potential to invade vasculature and metastasize
Invasive or infiltrative CA
95% of breast carcinomas are?
adenocarcinoma
Malignant proliferation of cells in ducts
No invasion of the basement membrane
Detected as calcification on mammography
DCIS
Tx: Mastectomy 95%
Clasically forms duct like structures
Most common type of invasive carcinoma
Presents as palpable mass by physical exam and as calcifications on mammography
Advance tumors may result to skin dimpling and nipple retractions
Biopsy:
Invasive ductal carcinoma
Duct like structures in desmoplastic stroma
Special subtypes Tubular Mucinous Medullary Papillary Metaplastic Inflammatory
Most important prognostic factor
Metastasis
Most useful factor
Spread to axillary lymph nodes
Used to assess biopsy
Sentinal lymph node biopsy
Most important predictive factors
ER
PR
HER-2-NEU Amplification
Predict response to antiestrogenic agents (Tamoxifen)
ER
PR
Associated with response to trastuzumab
Cell surface growth factor receptor
Poorer survival
Poor prognosis?
Her-2-Neu Amplification
Triple negative
10% of breast cancer
Multipel first degree relatives with breast cancer
Tumors at premenopausal age
Multiple tumors
BRCA1 and BRCA2
BRCA 1:
BRCA 2:
Hereditary breast cancer
Breast and ovarian
Breast cancer in males
Tx: if with genetic propensity, prophylactic mastectomy
