Breast Flashcards
Normal anatomy
Stroma - fat and fibrous tissue; far predominates
Ductal system containing 6-10 ducts that divide into smaller and smaller ducts, ending at lobules
Ducts drain at the nipple, which is the main excretory duct
The terminal ductal lobular unit is the structural unit of the breast, where pathology is observed
The terminal duct branches into lobules, each comprised of multiple acini –> acini is lined by epithelial and myoepithelial cells (these cells are LOST in carcinomas/malignant lesions, so their presence would indicate a benign lesion if there is some pathology)
The breast reaches full maturity during lactation, and acini proliferate within the lobules and produce milk
How do breast pathologies present?
Pain, lump, discharge or abnormality via ultrasound
30% of these women have NO PATHOLOGY (many lumps are just normal)
40% have FIBROCYSTIC CHANGES (non-neoplastic)
30% have NEOPLASMS, of which 20% are benign and 10% are cancerous
Developmental disorders of the breast
Along the MILK LINE (from axilla to pubis) –> breasts form along these lines
Can have supernumerary nipples or supernumerary breasts along his line (usually axilla or chest)
These are developmental abnormalities and are NOT NEOPLASMS
Inflammatory diseases of the breast
Acute Mastitis –> occurs most often during lactation because CRACKS in nipple may form –> bacterial entry STAPH AUREUS can lead to inflammation or abscess
Patients present with redness, induration, pain –> Treat with antibiotics
Fat necrosis –> usually after trauma/surgery –> causes the fat to LIQUEFY and DIE –> early, we see acute inflammation and liquefactive necrosis of fat;
Later we see macrophages infiltrating, eating the fat –> LIPOPHAGES; the necrotic area is eventually REPLACED BY A FIBROUS SCAR –> firm nodule that can MIMIC a carcinoma, obviously not cancerous
Fibrocystic Changes
MOST COMMON breast disorder –> account for the majority of breast biopsies
Related to HORMONAL IMBALANCES (usually high ESTROGEN –> contraceptives decrease incidence by BALANCING hormones)
Patients present with an often TENDER LUMP, especially premenstrual women, and the lumps are usually MULTIFOCAL and BILATERAL
Non-Proliferative Fibrocystic Changes
CYST formation, fibrosis, adenosis (lots of glands)
NO INCREASE IN CANCER RISK
Cysts are BLUE DOMED, MULTIFOCAL, VARIABLE
Line by APOCRINE METAPLASIA instead of cuboidal epithelial cells
ADENOSIS may also occur –> described as ill-defined mass caused by an increase in the number of acini per lobule
Proliferative Fibrocystic Changes
Sclerosing adenosis, epithelial hyperplasia, small duct papilloma, atypical hyperplasia
INCREASE RISK OF CANCER (1.5 - 2x)
Epithelial hyperplasia - ducts and acini expand in size due to proliferation of the epithelium
SCLEROSING ADENOSIS –> small lesion associated with calcification - detectable by mammography but usually not palpable due to tiny size
Atypical Epithelial Hyperplasia…
ATYPICAL DUCTAL HYPERPLASIA and ATYPICAL LOBULAR HYPERPLASIA –> associated with a MODERATELY increased cancer risk (5x); RARE;
Usually atypical ductal begins a “spectrum” –> followed by DUCTAL CARCINOMA in SITU (malignant but still within the duct)
–> followed by INVASIVE DUCTAL CARCINOMA
Gynecomastia
MALES! Presents as a SUBAREOLAR ENLARGEMENT and can be UNI or BILATERAL
Usually caused by an IMBALANCE of ESTROGEN and ANDROGEN hormones, but can also indicate CIRRHOSIS or a TESTICULAR TUMOR
Most commonly occurs in PUBERTY or the ELDERLY (more likely to have hormonal imbalances)
Microscopically –> proliferation of the connective tissue and ductal epithelium
NO INCREASED RISK OF CANCER
Fibroadenoma
BENIGN TUMOR of the STROMA
Most common tumor of the breast and in young women!
WELL CIRCUMSCRIBED –> bulges over the cut surface; DOES NOT ADHERE to breast tissue around it –> MOBILE MASS
Stromal element –> neoplastic, causes a great deal of FIBROSIS
Epithelial element –> causes ELONGATED and COMPRESSED ducts
Excision is completely curative; NOT a precursor to breast cancer
Increases in size and tenderness with estrogen
Phyllodes Tumor
BENIGN TUMOR of the STROMA; much larger and rarer than fibroadenoma
Usually in OLDER WOMEN, and the mass can be so large that it causes ULCERATION OF OVERLYING SKIN
Well circumscribed, associated with CYST formation
Biphasic –> epithelial component benign, while stromal component is neoplastic and determines tumor grade
Low grade and high grade can BOTH be treated by excision but high grade are LIKELY TO RECUR and become MALIGNANT/METASTASIZE
Large Duct/Intraductal Papilloma
BENIGN EPITHELIAL TUMOR
Presents with BLOODY NIPPLE DISCHARGE
Small, solitary, non-palpable lesion that occurs near the lactiferous ducts, thus causing the discharge
Papilloma fills the ducts, dilates it and may also fill the space with blood
Maintains the lining of the epithelial and myoepithelial cells and may form a WELL-DEFINED myoepithelial layer
SLIGHT increase in risk of cancer (1-2x)
Risk factors for breast cancer
Minority of women have genetic predisposition (BRCA)
Risk increases with age, family history (especially if relative had PRE-menopausal cancer), proliferative fibrocystic changes, having prior breast cancer
Exposure to ESTROGEN –> early menarche and late menopause will INCREASE RISK b/c of more estrogen exposure
Early and multiple births/breast feeding are PROTECTIVE –> pregnancy breaks the cycle and reduces exposure to estrogen
How do breast cancers predominantly metastasize?
VIA LYMPH NODES
Majority of tumors are in the UPPER-OUTER Quadrant of the breast and spread via AXILLARY NODES
Central or inner quadrant tumors spread via the INTERNAL MAMMARY LYMPH NODES
Later in the disease, they can progress HEMATOGENOUSLY
Breast Cancer Classification
NON-INVASIVE (15-30%) –> Ductal Carcinoma in Situ, Lobular Carcinoma in Situ
INVASIVE (75-80%) –> Invasive Ductal (most common), Invasive Lobular, Special Types (medullary, mucinous, tubular)
Ductal Carcinoma in Situ
NON-INVASIVE malignant breast cancer
Proliferation of the DUCTAL cells and is CONFINED to the BASEMENT MEMBRANE OF THE DUCTS
Presents microscopically as a few different patterns –> SOLID (homogenous proliferation), COMEDO (area of central necrosis), CRIBIFORM (hole-punches throughout)
Marked expansion of malignant epithelial cells that display nuclear pleomorphism and mitotic figures
Associated with PLEOMORPHIC CALCIFICATION (this is what we see on mammography, not very palpable)
Treatment can be CURATIVE since it is CONFINED and does not metastasize, but if not taken care of can eventually break through BM and become INVASIVE
Paget’s Disease
Variant of DCIS that involves the NIPPLE (Suggests underlying DCIS)
Presents with ECZEMA or ULCERATION of the nipple
Begins as underlying DCIS that travels along the duct to the nipple
Microscopically –> LARGE MALIGNANT CELLS that may have MUCIN IN THE CYTOPLASM (large cells in epidermis with a clear halo = Paget Cells)
Patients often also have SEPARATE but CONCURRENT INVASIVE CARCINOMA
Lobular Carcinoma in Situ
NON-INVASIVE LOBULAR CARCINOMA
Often found INCIDENTALLY – no calcifications, doesn’t form a mass
Usually MULTIFOCAL and BILATERAL
Morphology is BLAND –> acini expand with glandular proliferation, but are NOT atypical
Treat –> BILATERAL MASTECTOMY or HORMONAL
Increases risk of INVASIVE
General presentation of INVASIVE carcinomas?
Elicit a FIBROTIC rxn from the breast tissue, causing the tumor to STICK to the tissue around it –> this results in a FIRM, FIXED NODULE and it can cause DIMPLING of the skin or RETRACTION of the nipple
INVASIVE DUCTAL CARCINOMA
Ductal carcinomas make up the MAJORITY OF INVASIVE BREAST CARCINOMAS (Worst, Most invasive, and most common - 75% of all breast cancers)
Gross –> STELLATE MASS with INFILTRATIVE BORDERS –> mass is clearly delineated and NOT well-circumscribed, retracts when cut
Firm, fibrous, rock-hard mass
HAPHAZARD PROLIFERATION OF DUCTS and TUBULES!
INVASIVE LOBULAR CARCINOMA
Less common
Grossly presents similar to invasive ductal –> infiltrative, immobile, poorly-defined borders
Microscopically presents as ROW OF CELLS INVADING A FIBROTIC STROMA
Tumors are DIFFUSELY INFILTRATIVE and cells have LITTLE NUCLEAR PLEOMORPHISM
Often do not show up on mammography (due to diffuse pattern) –> false negatives!!
Often BILATERAL with multiple lesions in same location
Special Carcinoma Types
All have a better prognosis
MUCINOUS – well differentiated, infiltrating ductal carcinoma that produces abundant extracellular mucin, giving it a GELATINOUS appearance –> microscopically we see ducts floating in pools of mucin
MEDULLARY –> very rare, very large, very soft, well-circumscribed mass; does NOT cause fibrosis (soft); DOES elicit an inflammatory response - leads to a DENSE LYMPHOID INFILTRATE; cells have HIGH mitotic grade by a limited ability to metastasize because they secrete adhesion molecules – good prognosis
TUBULAR - consists of well-formed tubules and has an EXCELLENT prognosis
Reproductive Risk Factors
How many cycles a woman is exposed to - early menarche, late menopause, use of exogenous estrogen after menopause, older age at first pregnancy, nulliparity, lack of breastfeeding
Genetic Risk Factors
Hereditary risk factors - single gene mutation that significantly enhances one’s risk
Responsible for 5-10% of all breast cancers –> Shift the average age down
BRCA1/2 –> not only increase risk of BREAST but also OVARIAN
P53 - causes Li-Fraumeni syndrome, which increases the risk of many cancer types
PTEN causes Cowden’s disease, which increases thyroid and breast cancer
FAMILIAL predisposition - suggest a multifactorial inheritance pattern rather than a single gene; responsible for 20-25% of all breast cancers
Inherited mutations display AUTOSOMAL DOMINANT patterns mostly – can’t ignore paternal lineage! Could have had breast cancer genes that didn’t manifest cause he’s a dude (i.e. a man is just as likely to pass it to his daughters as a woman is)
Mammography
Usually 2 views –> Medial Lateral Oblique, and Cranial Caudal –> help determine breast quadrant
Look for SYMMETRY, MASS, CALCIFICATIONS
Coarse calcifications –> benign, not worrisome
FINE calcifications –> worrisome and potentially malignant
Types of Biopsy
Fine needle aspiration –> less detail, least invasive procedure
Core needle biopsy – gives more structural detail than fine needle; often performed with image guidance
Excisional biopsy – when the surgeon excises the ENTIRE MASS
Incisional biopsy – takes out a bigger piece of tissue than the core needle, but doesn’t excise everything