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139 Cards in this Set

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