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139 Cards in this Set
- Front
- Back
keratinizing squamous epithelium of breast
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dips into orifices at the nipple and then abruptly changes to a double-layered cuboidal epithelium lining the ducts
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two cell types that line the ducts and lobules
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contractile myoepithelial cells (meshlike pattern on BM) and luminal epithelial cells
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what cells produce milk
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lobular luminal cells
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2 types of breast stroma
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interlobular (dense fibrous CT mixed with adipose) and intralobular (envelopes acini of lobules-breast-specific hormonally responsive fibroblastic like cells with scattered lymphocytes)
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prepubertal breast
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large duct system ends in terminal ducts with minimal lobule formation
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colostrum vs milk
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high protein; high fat and calories
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changes in breast upon cesasation of lactation
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epithelial cells undergo apoptosis, lobules regress and atrophy and total size diminished; permanent increase in size and number of lobules remain
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when do supernumery nipples/breast generally become to attention
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painful premenstrual enlargements (heterotrophic, hormone-responsive foci)
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noncyclic causes of breast pain
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ruptured cysts, physical injury, infections, usually no specific lesion found; 95% benign
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most common palpable lesions
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invasive carcinomas, fibroadenomas, and cysts
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when does mass become palpable
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at least 2 cm in size; most common in premenopausal women
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where do carcinomas of breast tend to occur
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50% upper outer quadrant; 10% remaining quadrants, and ~20% in centra/subareolar region
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when is nipple discharge of concern
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unilateral and spontaneous
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milky discharge causes
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elevated prolactin, hypothyroidism, or endocrine anovulatory syndromes; oral contraceptives, tricyclic antidepressants, methyldopa, or phenothiazines
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bloody or serous nipple discharge causes
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usually benign; solitary large duct papillomas and cysts
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sensitivity and specificity of mammograms
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increase with age due to replacement of fibrous, radiodense tissue with fatty, radiolucent tissue
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densities of mammogram
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invasive carcinomas, fibroadenomas, or cysts
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calcifications of mammogram
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form on secretions, necrotic debris, or hyalinized stroma
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benign calcifications
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clusters of apocrine cysts, hyalinized fibroadenomas, and sclerosing adenosis
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cancerous calcifications
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small, irregular, numerous, clustered
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how often are carcinomas missed by mammogram
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10% cases
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acute mastitis
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most cases occur during 1st month of breastfeeding (cracks and fissures in nipples); usually staph, sometimes strep; erythematous and painful, fever often present
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staph mastitis
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localized area of acute inflammation that may progress to formation of single/multiple abscesses
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strep mastitis
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cause diffuse spreading infection that eventually involves entire breast; infiltrated by neutrophils and may be necrotic
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periductal mastitis (aka recurrent subareolar abscess, squamous metaplasia of lactiferous ducts, and Zuska disease)
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painful erythematous subareolar mass that clinically appears to be of infectous process; >90% smokers; not associated with lactation, reproductive history, or age
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morphology of periductal mastitis
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keratinizing squamous metaplasia of nipple ducts; keratin shed plugs ductal system causing dilation and eventually rupture of duct; intense chronic and granulomatous inflammatory response once keratin spills into surrounding periductal tissue
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mammary duct ectasia
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5th-6th decade in multiparous women; poorly defined periareolar mass associated with thick, white nipple secretions and sometimes skin retraction; pain and erythema uncommon
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morphology of mammary duct ectasia
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dilation of ducts, unspissation of breast secretions, marked periductal and interstitial chronic granulomatous inflammatory rxn
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what is within dilated ducts of mammary duct ectasia
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filled by granular debris containing numerous lipid-laden macrophages
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significance of mammary duct ectasia
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produces irregular palpable mass that mimics mammographic appearance in carcinoma
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fat necrosis
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painless, palpable mass, skin thickening or retraction, mammographic density, or mammographic calcifications; most have history of breast trauma or prior surgery
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lymphocytic mastopathy (sclerosing lymphocytic lobulitits)
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single/multiple hard palpable masses, may be bilateral; collagenized stroma surrounding atrophic ducts and lobules; type 1 diabetes or autoimmune thyroid disease
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granulomatous mastitis
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systemic granulomatous diseases (sarcoidosis or Wegener) and infections (mycobacteria, fungi)
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granulomatous lobular mastitis
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uncommon breast-limited disease in parous women; possibly hypersensitivity to antigens expressed by lobular epithelium during lactation
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3 groups benign breast lesions
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nonproliferative, proliferative, and atypical hyperplasia
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nonproliferative breast changes (fibrocytic changes aka "lumpy bumpy") 3 changes
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1) cystic change (often with apocrine metaplasia) 2) fibrosis 3) adenosis
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what are cysts lined by
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either flattened atrophic epithelium or metaplastic apocrine cells
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adenosis
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increase in number of acini per lobule
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proliferaative breast disease without atypia
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characterized by proliferation of ductal epithelium and/or stroma without cytologic or architectural features suggestive of carcinoma in situ
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sclerosing adenosis
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# acini at least double in uninvolved lobules; compressed and distorted in central portions, but dilated at periphery, myoepithelial cells usually prominent
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complex sclerosing lesion
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components of sclerosing adenosis, papillomas, and epithelial hyperplasia; central nidus of entrapped glands in a hyalinized stroma with long radiating projections into stroma
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papillomas
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multiple branching fibrovascular cores, each having a CT axis lined by luminal and myoepithelial cells; growth occurs within dilated duct
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large duct papillomas location
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usually solitary and situated in lactiferous sinuses of the nipple; >80% produce nipple discharge
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small duct papillomas location
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commonly multiple and located deeper within the ductal system
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atypical hyperplasia
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cellular proliferation resembling carcinoma in situ, but lacks sufficient qualitative or quanitative features for diagnosis as carcinoma; harbor some of the same aquired mutations present in carcinoma in situ
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atypical ductal hyperplasia
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resembles ductal carcinoma in situ (DCIS); relatively monomorphic proliferation of regularly spaced cells (sometimes with cribiform spaces)
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how is atypical ductal hyperplacia distinguished from DCIS
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limited in extent and only partially fills ducts
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atypical lobular hyperplasia
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proliferation of cells identical to lobular carcinoma in situ (LCIS), but do not fill or distend more than 50% of acini within a lobule; can involve contiguous ducts through pagetois spread
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pagetois spread
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atypical lobular cells lie btwn ductal BM and overlying normal ductal epithelial cells
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breast lesions and association with carcinoma risk
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nonproliferative = no increased risk; proliferative = mild increase risk; proliferative with atypia = moderate increase in risk
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Breat Cancer Risk Assessment Tool (BCRAT) incorporates what
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Age, age at menarche, age at first live birth, first-degree relatives with breast cancer, atypical hyperplasia, race, estrogen exposure, breast density, radiation exposure, carcinoma of contralateral breast or endometrium, geographic, diet, obesity, exercise, breastfeeding, environmental toxins, tobacco
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cancer specs of younger women
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ER neg or HER2/neu pos; opposite of cancer occuring in older women
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BRCA1
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increase risk of dvlp ovarian cancer (20-40% of carriers)
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BRCA2
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small risk for ovarian carcinoma (10-20%); male breast cancer
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BRCA1&2 associations
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higher risk for epithelial cancers like prostatic and pancreatic carcinomas; penetrance 30-90%; account for ~ 3% all breast cancers
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BRCA1 breast cancers
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commonly poorly differentiated, have 'medullary' features, do not express hormone receptors or overexpress HER2/neu; similar to basal-like breast cancers; inactive X chromosome and reduplication of active X; 13% medullary, 60% subset of medullary features
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medullary features
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syncytial growth pattern with pushing margins and lymphocytic response
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BRCA2 breast cancers
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relatively poorly differentiated, but are more often ER pos than BRCA1 breast cancers
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Li-Fraumeni syndrome
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germline mutation in p53
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Li-Fraumeni variant syndrome
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germline mutations in CHEK2
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Cowden syndrome
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PTEN tumor suppressor mutation
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Peutz-Jeghers syndrome
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LKBI/STK11
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ataxia telangiectasia
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ATM
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known high risk breast cancer genes
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account for about 1/4 familial breast cancers
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majority of sporadic breast cancers
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postmenopausal and are ER pos
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most likely cell type of origin for majority of breast carcinomas
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ER-expressing luminal cell
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ER-neg carcinomas may arise from
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ER-neg myoepithelial cells
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what are >95% breast malignancies
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adenocarcinomas
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adenocarcinoma divisions
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in situ and invasive carcinomas
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carcinoma in situ
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neoplastic proliferation limited to ducts and lobules by the BM
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current convention of "lobular" and "ductal"
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lobular = carcinomas of a specific type; ductal = more generally for adenocarcinomas that have no other designation
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DCIS
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malignant clonal population of cells limited to ducts and lobules by BM; myoepithelial cells preserved, but may be diminished in #; acini distorted and unfolded and take on appearance of small ducts
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historic divisions of DCIS
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comedocarcinoma, solid, cribiform, papillary, and micropapillary; most have mixture of patterns
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comedocarcinoma
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presence of solid sheets of pleomorphic cells with 'high-grade' hyperchromatic nuclei and areas of central necrosis-commonly calcify (clusters or linear and branching microcalcifications)
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noncomedo DCIS
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monomorphic population of cells with nuclear grades low to high
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cribiform DCIS
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intraepithelial spaces are evenly distributed and regular in shape
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papillary DCIS
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grows into spaces along fibrovascular cores that typically lack the normal myoepithelial cell layer
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micropapillary DCIS
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bulbous protrusions without a fibrovascular core, often arranged in complex intraductal patterns
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Paget disease
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rare manifestation of breast cancer (1-4%); unilateral erythematous eruption with a scale crust; pruritis common-may be mistaken for eczema; malignant cells extend from DCIS within ductal system via lactiferous sinuses into nipple slin without crossing BM
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carcinomas in Paget disease
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poorly differentiated, ER neg, overexpress HER2/neu
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Lobular Carcinoma In situ (LCIS)
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incidental finding on biopsy-not associated with calcifications or stromal rxns; bilateral 20-40%; 80-90% occur before menopause
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what do cells of LCIS lack
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E-cadherin; results in cells appearing round without attachment to adjacent cells
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LCIS expression
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ER and PR pos; overexpression of HER2/neu not observed
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palpable masses and metastases
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axillary metastases in over 50% if palpable
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invasive carcinomas of no special type
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firm to hard, irregular border; grating sound when cut/scraped
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5 major patterns of gene expression
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luminal A and B, normal, basal-like, and HER2 positive
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luminal A (40-55% NST cancers)
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ER pos, HER2/neu neg; well or moderately well differentiated, postmenopausal women; slow growing, respond well to hormonal treatment; don't respond well to chemo
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Luminal B (15-20% NST cancers)
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also express ER but generally of higher grade, higher proliferation rate, and often express HER2/neu (triple positive); lymph metastases, respond to chemo
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Normal-breast like (6-10% NST cancers)
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well-differentiated ER-pos, HER2/neu neg; similar gene expression pattern as regular tissue
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Basal-like (13-25% NST cancers)
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absence of ER, PR, and HER2/neu; expression of myoepithelial cell markers (basal keratins, P-cadherin, p63, laminin), progenitor cells, or putative stem cells (cytokeratins 5 and 6); triple negative; high grade and proliferation rate; 15-20% chemosensitive
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types of cancers in the Basal-like category
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medullary carcinomas, metaplastic carcinomas (spindle cell or matrix producing), and carcinomas with central fibrotic focus
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HER2 positive (7-12% NST cancers)
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ER-neg that overexpress HER2/neu protein
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amplification in 90% HER2 positive NSTs
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segment of DNA on 17q21 that includes HER2/neu gene
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Trastuzmab (Herceptin)
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humanized monoclonal antibody specific to HER2/neu; doesn't cross blood-brain barrier
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lapatinib
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dual tyrosine kinase inhibitor that targets both EGFR and HER2/neu
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lobular carcinomas
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dyscohesive infiltrating tumor cells often arranged in single file or loose clusters/sheets; tubule formation absent; signet-ring cells common (intracytoplasmic mucin droplet)
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metastasis of lobular carcinoma of breast
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tends to occur to peritoneum and retroperitoneum, leptomeninges, GI tract, and ovaries/uterus
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CDH1
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gene that encodes E-cadherin; loss seen in LCIS and atypical lobular hyperplasia
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heterozygous germline mutations in CDH1 have high risk of
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dvlp lobulat carcinoma (if female) and gastric signet ring carcinoma (males and females)
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medullary carcinoma specs
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6th decade; well-circumscribed mass; may closely mimic benign lesion or present as rapidly growing mass; poorly differentiated; DCIS minimal or absent; no HER2/neu expression; lymph metastases infrequent; basal-like gene expression profile
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morphology of medullary carcinoma
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soft, fleshy, and well circumscribed
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histo of medullary carcinoma
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1) solid, syncytium-like sheets of large cells with vesicular, pleomorphic nuclei (>75% tumor mass) 2) frequent mitotic figures 3) moderate to marked lymphoplasmic infiltrate surrounding and within tumor 4) pushing (noninfiltrative) border
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medullary carcinoma prognosis
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slightly better than NST carcinomas
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BRCA1 and medullary carcinoma
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67% have hypermethylation of BRCA1 promoter
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mucinous (colloid) carcinoma specs
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older women (~71); grow slowly over years; usually diploid, well to moderately differentiated, ER pos; node metastases uncommon
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cells of mucinous carcinoma
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cells arranged in clusters and small islands of cells within large lakes of mucin
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morphology of mucinous carcinoma
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soft, rubbery, pale gray-blue gelatin appearance/consistency; borders pushing or circumscribed
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tubular carcinoma specs
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women late 40s; uncommon-10% tumors <1cm; 95% diploid, ER pos, and HER2/neu neg; well differentiated; axillary metastases <10%; excellent prognosis
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tubular carcinoma morphology
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well-formed tubules
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tubular carcinoma histo
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myoepithelial layer is absent-tumor cells in direct contact with stroma; cribiform pattern seen sometimes; apocrine snouts typical; calcification may be present within lumens
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what can tubular carcinomas be mistaken for
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benign sclerosing lesions
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what are tubular carcinomas associated with
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atypical lobular hyperplasia, LCIS, or low grade DCIS
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invasive papillary carcinoma
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rare <1% invasive cancers; usually ER pos and have favorable prognosis
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invasive micropapillary carcinomas
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rare <1% invasive cancers; more likely ER neg and HER2 pos; lymph metastasses common and poor prognosis
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metaplastic carcinoma
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includes variety of rare types of breast cancer (<1%) like matrix-producing, squamous cell, and carcinomas with prominent sindle cell component; triple negative, often express myoepithelial proteins, and appear related to basal-like carcinomas; lymph metastases infrequent, poor prognosis
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prognosis of breast cancer is determined by
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pathologic exam of primary carcinoma and axillary lymph nodes
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major prognostic factors
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1) invasive carcinoma vs in situ disease 2) distant metastases 3) lymph node metastases 4)tumor size (2nd most important) 5) locally advanced disease 6) inflammatory carcinoma
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lymph spread of breast cancer
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first to one or two sentinel nodes
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minor prognostic factors
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Histologic subtype, histologic grade (nottingham Histologic Score-nuclear grade, tubule formation, and mitotic rate), estrogen and progesterone receptors, HER2/neu overexpression, lymphovascular invasion, proliferative rate, DNA content, response to neoadjuvant therapy, gene expression profiling
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stromal tumor types
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intralobular and interlobular
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intralobular tumors
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breast-specific biphasic tumors fibroadenoma and phyllodes tumor; may elaborate GFs for epithelial cells, resulting in the proliferation of non-neoplastic epithelial component of these tumors
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interlobular tumors
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same types of tumors found in CT in other sites of body (lipomas and angiosarcomas) as well as pseudoangiomatous stromal hyperplasia, myofibroblastomas, and fibrous tumors
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fibroadenoma specs
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most common benign tumor; occur in 20s and 30s; frequently multiple and bilateral; calcifications
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morphology of fibroadenoma
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spherical nodules that are usually sharply circumscribed and freely moveable; rubbery, grayish whit nodules that bulge above surrounding tissue and often contain slitlike spaces
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cyclosporin A after renal transplantation
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almost half dvlp fibroadenomas
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phyllodes tumor specs
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most in 6th decade; palpable masses, most benign; nodal metastases rare, but may recur locally
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morphology of phyllodes tumors
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larger lesions often with bulbous protrusions-presence of nodules of proliferating stroma covered by epithelium
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what distinguished phyllodes from fibroadenomas
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cellulariity, mitotic rate, and infiltrative borders
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tumors of interlobular stroma of breast
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stromal cells without accompanying epithelial component
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pseudoangiomatous stromal hyperplasia and fibrous tumors present as
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circumscribed palpable masses or mammographic densities in premenopausal or older women on hormone replacement; benign proliferations of interlobular fibroblasts and myofibroblasts
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myfibroblastoma
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myofibroblasts; more common in males
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fibromatosis
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clonal proliferation of fibroblasts and myofibroblasts; presents with irregular, infiltrating mass that can involve skin and muscle; locally aggressive, doesn't metastasize
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adenomatous polyposis coli gene (APC)
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negatively regulates the nuclear trascription factor B-catenin
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malignant stromal tumors include
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angiosarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, chondrosarcoma, and osteosarcoma; usually present as bulky mass; lymph metastases rare; hematogenous spread to lung common
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stewart-Treves syndrome
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angiosarcomas arise in skin of an arm rendered chronically lymphedematous by prior mastectomy and lymph node dissection
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lymphomas that arise in the breast are primarily what type
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diffuse large B-cell type
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nonmammary metastases to breasts
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rare; contralateral breast carcinoma; melanomas and lung cancers
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normal male breast
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nipple, rudimentary duct system ending in terminal buds without lobule formation
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morphology of gynecomastia in male
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increase dense collagenous CT and marked micropappillary epithelial hyperplasia of duct lining; lobule formation rare
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