Path Pt 1: Breast Flashcards
supernumerary nipples or breasts
persistence of epidermal thickenings along the milk line
normal ductal system may extend into the SQ tissue of the chest wall or axillary fossa (axillary tail of Spence)
- areas not clinically identified as breast tissue
- prophylactic mastectomies reduce, but do NOT eliminate the risk of breast cancer
- most breast tissue drains to axillary lymph nodes
accessory axillary breast tissue
congenitally inverted nipples are usually of little significance
- correct spontaneously during pregnancy or with simple traction
congenital nipple inversion
what is more of a concern than congenital nipple inversion?
acquired nipple inversion
- may indicate invasive cancer or inflammatory nipple disease
mastalgia, mastodynia
breast pain
- diffuse: usually due to premenstrual edema
- localized: often due to ruptured cysts, physical injury, infection
almost all painless masses are what?
benign
- only 10% of breast cancers present with pain
most commonly, masses are what?
cysts, fibroadenomas, or invasive carcinomas
- usually benign in premenopausal women
what are the likelihoods of malignancy with age?
- 10% < 40 years
- 60% > 50 years
NOTE: risk of malignancy in a woman with nipple discharge also increases with age
how are 1/3 of carcinomas detected?
palpable masses
why does screening have little effect on mortality?
because most palpable cancers have metastasized
what is considered the most worrisome for carcinoma if spontaneous, unilateral and the patient is >60?
nipple discharge
what is milky galactorrhea associated with?
increase in prolactin, hypothyroidism, endocrine anovulatory syndromes, methyldopa, phenothiazines
when is bloody or serous nipple discharge usually seen?
with a papilloma or cyst
- blood also seen during pregnancy due to rapid tissue remodeling
what should you think of in a patient >60 years old that presents with spontaneous unilateral discharge?
cancer
what is the most common site for breast carcinoma in females?
upper outer: 50%
20% central or sub-areolar (most common in males)
10% in remaining quadrants
what are the most common palpable masses in the breast?
cysts, fibroadenomas, and invasive carcinomas
benign lesions are more common with who?
premenopausal women
what are the principal signs of breast carcinoma?
densities and calcifications
what is the most common way to detect breast cancer?
mammogram
- increase sensitivity and specificity as patient ages: fibrous, radiodense tissue -> fatty radiolucent tissue
lesions that replease adipose tissue with radiodense tissue
- rounded = benign fibroadenoma or cyst
- irregular = invasive carcinoma
densities
- mammography identifies lesions 1cm in size vs 2-3cm by palpation
these form on sevretions, necrotic debris or hyalinized stroma
- usually benign lesion: clusters of apocrine glands, hyalinized fibroadenomas, sclerosing adenosis
calcifications
- if associated with malignancy: small, irregular, numerous and clustered -> ductal carcinoma in situ
rare, outside of lactational period
- caused by infections, autoimmune disease, or foreign body-type reactions to extravasated keratin secretions
inflammatory disorders of the breast
- “inflammatory breast cancer” mimics inflammation by obstruction dermal vasculature with tumor emboli
- ALWAYS consider in females with erythematous, swollen breast
- acute mastitis
- squamous metaplasia of lactiferous ducts
- duct ectasia
- fat necrosis
- lymphocytic mastopathy (diabetic mastopathy)
- granulomatous mastitis
types of inflammatory breast disorders
cracks and fissures of the nipple cause the breast to be vulnerable to bacteria during the first month of breast feeding
- erythematous and painful
acute bacterial mastitis
what organisms cause acute bacterial mastitis?
staphylococcus aureus (step less commonly) invade the tissue involving a single duct system or sector
what can happen if mastitis is left untreated?
can spread to the entire breast
- staph -> single or multiple abscesses
- strep -> cellulitis
what is the tx for mastitis?
abx, continue expression of breast milk, rarely requires surgery
subareolar abscesses, periductal mastitis, Zuska disease
- painful, erythematous subareolar mass that appears to be a bacterial abscess
- recurrent: fistula tunnels under smooth muscle of the nipple, opening to the skin at the edge of the areola
- inverted nipple
squamous metaplasia of lactiferous ducts
what are the risk factors for squamous metaplasia of lactiferous ducts?
90% of patients are smokers
- may be due to relative vitamin A deficiency, or toxic substance in tobacco smoke
keratinizing squamous metaplasia of the nipple ducts
- ductal system is plugged by shed cells -> dilation and eventually rupture of the duct
- acute inflammation may occur secondary to anaerobic bacterial infection
squamous metaplasia of lactiferous ducts
what happens when keratin spills into the surrounding periductal tissue?
intense chronic granulomatous response
what is the tx for squamous metaplasia of lactiferous ducts?
they commonly recur following drainage due to remaining keratinizing epithelium
- curative if the duct and fistula tract are surgically removed
palpable areolar mass
- associated with thick, white nipple secretions, +/- skin retraction
- pain and erythema are RARE
- IRREGULAR PALPABLE MASS MIMICS INVASIVE CARCINOMA CLINICALLY AND ON IMAGING
duct ectasia
what are the risk factors for duct ectasia?
susceptible females are multiparous and in their 5-6th decade
- NOT associated with smoking
ectatic dilated ducts with inspissated (thickened) secretions and lipid laden macrophages
- rupture -> periductal and interstitial inflammatory reaction with lymphocytes and plasma cells also joining the party
- formation of granulomas around cholesterol deposits and secretions -> irregular mass with skin and nipple retraction
duct ectasia
painless, palpable mass with skin thickening or retraction and/or mammographic densities or calcifications
- 50% of females have history of prior surgery or breast trauma
fat necrosis in the breast
what does acute fat necrosis look like on a histo slide?
neutrophils and macrophages
what does chronic fat necrosis look like on a histo slide?
fibroblasts and inflammatory cells lead to giant cells, calcifications and deposition of hemosiderin -> scar tissue (ill-defined, firm, grey white nodules containing small chalky white foci
single or multiple hard, palpable masses or mammographic densities
- dense collagenized stroma = difficult to need biopsy
- thick BM of atrophic ducts and lobules
- surrounded by prominent lymphocytic infiltrate
lymphocytic mastopathy (sclerosing lymphocytic lobulitis)
what patients is lymphocytic mastopathy most common in?
- *T1DM** or autoimmune
- thought to be autoimmune problem
may be due to systemic or localized granulomatous disease (TB, sarcoidosis)
- uncommon
- occurs in parous females, associated with lobules
- possibly a hypersensitivity reaction to antigens expressed by lactation
granulomatous mastitis
what is the tx for granulomatous mastitis?
steroids
what is caused by corynebacteria?
- causes a localized infection of TB or fungi due to the immunocompromise or adjacent to foreign objects (piercing or prosthesis)
cystic neutrophilic granulomatous mastitis
these lesions are detected by mammography or as incidental findings in surgical specimens
- three groups: nonproliferative, proliferative, atypical hyperplasia
benign epithelial lesions
these benign lesions are NOT associated with an increased risk of breast cancer
non-proliferative breast changes
small increase in the risk of subsequent carcinoma in either breast
- predictors of risk but unlikely to be true precursors of carcinoma
proliferative breast disease (without atypia)
has some but not all histological features required for diagnosis of carcinoma in situ
- moderately increased risk of carcinoma
atypical hyperplasia
group of morphological fibrocystic changes
- not associated with risk of breast cancer (non-proliferative)
- cystic change, often with apocrine metaplasia
- fibrosis
- adenosis
non-proliferative (fibrocystic) breast changes
what causes cysts in non-proliferative breast changes?
due to lobule dilation
- may coalesce into larger cysts
- unopened cysts contain turbid, semi-translucent brown-blue fluid (blue domed cyst)
- lined with flattened, atrophic epithelium or metaplastic apocrine cells
- calcifications commonly seen on mammography (concerning if they are solitary or firm to palpation)
what is the dx of cysts?
confirmed after disappearance of the cysts due to fine needle aspiration of contents
occurs due to release of secretory material into the stroma from (often) ruptured cysts
- contributes to palpable nodularity of the breast
fibrosis
increase in the number of acini/lobule
- normal in pregnancy or focal change in nonpregnant females
- lined with columnar cells
- chromosome 16 deletion = FLAT EPITHELIAL ATYPIA
- mass and/or calcifications seen in the lumen
adenosis
what is the earliest recognizable precursor lesion of low-grade breast cancer?
chromosome 16 deletion -> flat epithelial atypia
- no increased risk of breast cancer
palpable masses in pregnancy or lactating women
- normal appearing breast tissue with exaggerated lactational changes
lactational adenoma
proliferations of epithelial cells without atypia
- small increase in risk of subsequent carcinoma of either breast
- **predictors of risk but unlikely to be true precursors of carcinoma
- no clonal lesions or genetic changes
proliferative breast disease without atypia
increase in number of luminal (ductal) and myoepithelial cells fill and distend ducts and lobules
- normal: ducts and lobules are lined with a double layer of myoepithelial cells and luminal cells
- irregular lumens found in the periphery (usually incidental finding)
epithelial hyperplasia
increase is number of ACINI are compressed and distored in the central portion of the lesion
- lumen compression due to stromal fibrosis (sclerosing part) -> histological pattern that closely mimics invasive carcinoma
sclerosing adenosis
sclerosing adenosis, papilloma, and epithelial hyperplasia
- radical scar irregularly shaped, mimics invasive carcinoma
- central nidus of entrapped glands in hyalinized stroma surrounded by long, radiating projections into stroma
- not associated with prior trauma or surgery
complex sclerosing lesion
growth within a dilated duct
- composed of intraductal lesions with fibrovascular cores lined by myoepithelial and luminal cells (both)
- 80% produce nipple discharge
- usually solitary and seen in the lactiferous sinuses of the nipple
- small duct = multiple and located deeper in the ductal system
- often seen with epithelial hyperplasia and apocrine metaplasia
papilloma
what causes bloody discharge in a papilloma?
infarct of stalk due to torsion
what causes serous discharge in a papilloma?
intermittent blockage and release of secretins
what is NOT a pre-cursor to cancer, unlike most other forms of metaplasia?
apocrine metaplasia
enlargement of the male breast, only BENIGN lesion of the male breast
- unilateral or bilateral button-like subareolar enlargement
- small increase risk of breast cancer
- increase in dense, collagenous connective tissue and epithelial hyperplasia of the duct lining with tapering micro-papillae
- no lobule formation
gynecomastia
imbalance between estrogens and androgens due to
- puberty
- aging
- decreased testicular androgen production
- hyperestrinism
- liver cirrhosis
- drugs (alcohol, marijuana, heroin, antiretroviral, steroids)
- klinefelter or functional testicular neoplasms
causes of gynecomastia
clonal proliferation with some, but not all, histological features of ductal carcinoma in situ (DCIS)
- moderate increase in the risk of carcinoma of the breast
- chromosome 16q loss or 17p gain (also seen in CIS)
- pagetoid spread
proliferative breast disease with atypia
partially fills duct - ductal carcinoma in situ fills the duct)
- may have cribiform spaces
- monomorphic epithelial proliferation
atypical ductal hyperplasia
cells identical to lobular carcinoma is situ (LCIS)
- atypical lobular cells that do not fill/distend > 50% lobule acini
- the atypical lobular cells may lie between the ductal basement membrane that the normal luminal cells
- LOSS OF E-CADHERIN (same as lobular carcinoma in situ)
atypical lobular hyperplasia
- 1.5-2x increased risk of cancer in proliferative disease
- 4-5x increased risk of cancer in proliferative disease with atypia
- <20% develop breast cancer and may choose surveillance over radical treatment options
- risk is increased in BOTH breasts, though ipsilateral may have higher risk
- tx may involve bilateral prophylactic mastectomy or estrogen antagonists (tamoxifen)
risk of carcinoma from BENIGN epithelial lesions
what is the most common non-skin malignancy in females?
carcinoma of the breast
- 2nd most common cause of cancer death in women after lung cancer
what are the three biological groups of adenocarcinoma of the breast?
- estrogen receptor positive, HER2-negative = 50-65%
- estrogen receptor positive/negative, HER2-positive = 10-20%
- estrogen receptor negative, HER2-negative = 10-20%
rare in females < 25, rapid increase in incidence after 30
- increased risk due to western lifestyle: delayed pregnancy, fewer pregnancies, and decreased breastfeeding
- African American females have highest mortality rate as they have less access to screening and they have more aggressive cancers
- non-Hispanic women have the greatest risk, Ashkenazi jews are more likely to have BRCA1/2 mutations
risk factors for adenocarcinoma of the breast
earlier menarche or later menopause
- later pregnancy, or no pregnancy
- atypical hyperplasia or proliferative disease
- menopausal hormone therapy with estrogen and progestin over multiple years
risk factors for adenocarcinoma of the breast
what are most breast cancers?
estrogen receptor positive cacinoma
- no associated risk with oral contraceptive therapy
- oopherectomy (decreasing estrogen) causes 75% decrease in chance of breast cancer
- antiestrogenic drugs (tamoxifen or aromatase inhibitors) decrease risk of estrogen receptor positive breast cancer
4-6x increase risk of estrogen receptor positive or negative
- clusters in families
- related to other factors (late age at first birth, fewer children, hormone replacement therapy)
- may be due to failure or normal involution in older females
dense breast risk factors
Hodgkin patients in their teens and early 20’s have what?
20-30% increase risk over 10-30 years with radiation exposure
- moderate or heavy alcohol intake
- obese postmenopausal females due to increase risk of estrogen synthesis in fat deposits
- obese females > 40 have DECREASED risk due to anovulatory cycles and low progesterone levels
- probable small protective effect for physically active females
- no associated risk with intake of any foods
metabolism risk factors for breast carcinoma
why is it that the longer women breastfeed, the lower their risk of carcinoma?
lactation suppresses ovulation and may trigger terminal differentiation of luminal cells
- may explain lower rates in developing countries
12% of breast carcinomas occur due to what?
inheritance of susceptibility genes
- may be AD
- BRCA1/2, TP53, CHEK2 (all tumor supressors) 8% of familial breast carcinomas
what is Li-Fraumeni syndrome?
germline mutation in TP53, associated with HNPCC -> most commonly HER2-positive
what does a mutation in PTEN cause?
Cowden syndrome
what does a mutation in STK11 cause?
Peutz-Jeghers syndrome
what does a mutation in ATM cause?
ataxia telangiectasia
what is responsible for 80-90% of “single gene” occurrences?
BRCA 1/2 in breast carcinoma
- 3% of all breast cancers
- 30-90% penetrance depending on specific mutation
- also increased risk of other epithelial cancers (prostate or pancreatic)
located on chromosome 17q21
- marked increase in risk of ovarian carcinoma
- often poorly differentiated
- have medullary features (syncytial growth pattern with pushing margins and lymphocytic response)
- biologically similar to ER-neg, HER2-neg breast cancers identified as “basal-like” by gene expression profiling
BRCA1
located on chromosome 13.12.3
- more frequently associated with MALE breast cancer
- relatively poorly differentiated, more likely to be ER-positive
BRCA2
arise via the dominant pathway of breast cancer development in 50-60% of cases
- most common subtype of breast cancer in individuals who inherit germline mutations of BRCA2
- most common form of invasive breast cancer
- associated with chromosome 1q gains, chromosome 16q loss, and PIK3CA activating mutations
Er(+), HER2(+)
what are thought to be precursor lesions for ER(+), HER2(+) breast cancer?
same mutations as seen in flat epithelial atypia and atypical ductal hyperplasia
what type of breast cancers are termed “luminal”?
ER(+)
- most closely resemble normal breast luminal cells regarding mRNA expression
- dominated by genes regulated by estrogen
these represent 20% of all breast cancers, can be ER(+) or (-)
- associated with HER2 gene amplification on chromosome 17q
- can be over-expressed if there is ERBB2 mutation
HER2(+)
what is the most common cancer in patients with TP53 mutations (Li-Fraumeni syndrome)?
HER2(+) breast cancer
what is the precursor lesion of HER(+) cancer?
atypical apocrine adenosis
how do you look for HEr(+)?
HER2 staining or FISH amplification
this cancer arises through a distinct pathway, independent of estrogen receptor mediated changed or HER2 amplifications
- 15% of all breast cancers
- MOST COMMON IN PATIENTS WITH GERMLINE BRCA1
ER(-), HER2(-)
sporadic forms of ER(-), HER2(-) often have loss of what, instead of BRCA1?
TP53
- BRCA1 can be methylated/silenced later via epigenetics
increased frequency in African American females
- basal-like pattern of mRNA expression that includes many genes that are expressed in normal myoepithelial cells
ER(-), HER2(-)
PIK3CA, HER2, MYC, CCND1, TP53, BRCA1/2
driver mutations of breast cancer
- subclonal heterogeneity contributes to tumor progression and resistance to treatment
- the neoplastic cells require the stroma for development (high density regions)
- fibrous stroma is a marker for risk
52% of all single gene hereditary cancers
- risk of breast cancer by age 70: 40-90%
- mutations are rare, inactivated in 50%
- tumor suppressor, transcription regulation, repair of dsDNA breaks
- poorly differetiated
- OFTEN TRIPLE NEGATIVE: ER(-), HER2(-), one other
- associated with other cancers: ovarian, male breast, prostate, pancreas, fallopian tubes
BRCA1
32% of all single gene hereditary cancers
- risk of breast cancer by age 70: 30-90%
- mutations and loss of expression are rare
- tumor suppressor, transcription regulation, repair of dsDNA breaks
- Biallelic germline mutations cause a rare form of Fanconi anemia
- associated with other cancers: ovarian, male breast, prostate, pancreas, stomach, melanoma, gallbladder, bile duct, pharynx
BRCA2
3% of all single gene hereditary cancers
- risk of breast cancer by age 70 >90%
- mutations in 20%
- LOH (loss of heterozygosity): 30-42%
- MOST FREQUENT IN TRIPLE (-) CANCERS
- tumor supressor
- most commonly mutation gene in sporadic breast cancers
- 53% are ER(-), HER2(-)
- associated cancers: sarcoma, leukemia, brain, adenocortical carcinoma
TP53
95% of all breast malignancies
- first arise in the duct/lobular system as CIS
- at presentation, 70% have breached the basement membrane and invaded the stroma (malignant)
adenomcarcinoma
neoplastic proliferation of epithelial cells confined to ducts and lobules by the basement membrane
- may be classified as ductal or lobular (LCIS or DCIS)
- actually arise from cells in the terminal duct lobular unit
CIS
malignant clonal proliferation of epithelial cells limited to ducts and lobules by basement membrane
- myoepithelial cells are preserved in involved ducts/lobules, though may be diminished
- can spread through the ductal system -> extensive lesions of an entire breast sector
- comedo or non-comedo
- most have multiple growth patterns
DCIS (ductal)
what is the dx of DCIS?
almost ALWAYS detected by mammography
- identified as calcifications with secretory material, necrosis
- less commonly identified as density due to periductal fibrosis
- rarely produces nipple discharge
- bilateral in 10-20% of cases
what are the risk factors for DCIS?
nuclear grade and necrosis predict local recurrence and progression to invasion better than architecture
these are usually detected as clustered or linear and branching areas of calcification on mammography
- may occasionally produce nodularity
comedo DCIS
what are the two defining features of comedo DCIS?
- tumors with pleomorphic, high grade nuclei
2. areas of central necrosis
lacks high grade nuclei or central necrosis
- cribiform pattern: rounded spaces within ducts (cookie cutter) or solid pattern
- micropapillary pattern: bulbous protrusions with fibrovascular core in complex intraductal patterns
- true papillae pattern: fibrovascular core without myoepithalial cell layer
Non-comedo DCIS
what is the tx for DCIS?
surgical excision and radiation/tamoxifen
- mastectomy 95% curative
rare, unilateral erythematous eruption and scale crust (map-like)
- pruritis is common, may be confused with eczema
- malignant cells extend via the lactiferous sinuses into nipple skin, without crossing the basement membrane -> disruption of the epithelial barrier -> extracellular fluid leakage only nipple surface
Paget Disease of the Nipple
- paget cells are larger than surrounding keratinocytes and are seen singly or in small clusters within the epidermis
- the cells have pale cytoplasm containing mucopolysaccharide with stains PAS positive
what is the dx of Paget disease of the nipple?
nipple biopsy or cytology of exudate
- 50-60% have palpable mass that indicates there is also invasive carcinoma
- carcinomas are poorly differentiated, Er(-), HER2(+)
- IF NO PALPABLE MASS, TYPICALLY ONLY DCIS
clonal proliferation of cells within ducts and lobules growing in a discohesive fashion due to acquired loss-of function mutation of E-cadherin
- cells identical to hyperplasia or invasive carcinoma
- cells expand, but do not distort spaces, preserving the underlying lobular architecture
- 2x chance of being bilateral than DCIS, must check the other breast after being found
LCIS
what is the dx of LCIS?
- *ALWAYS AN INCIDENTAL BIOPSY FINDING**
- not associated with calcifications of stromal reactions that produce mammographic densities
- incidence did NOT decrease after introduction of mammogram screening
- E-cadhern (-)
- ER(+), PR(+), HER2(-)
- LCIS is bilateral in 20-40% of cases
uniform population of cells with oval/round nuclei and small nucleioli
- mucin (+) signet ring cells
- lack of E-cadherin = rounded cells not attached to adjacent cells (discohesive)
- does not form cribiform spaces or papillae (like DCIS)
- no involvement with nipple skin
- no necrosis or secretions = no calcifications
LCIS
what is LCIS a risk factor for?
invasive carcinoma
- develops in 25-35% of women over 20-30 years
- risk is almost as high in the contralateral breast (unlike DCIS)
- 3x more likely to get invasive lobular carcinoma from LCIS than DCIS
what is the tx for LCIS?
close follow up with mammographic screening since the risk of progression is similar to DCIS
- bilateral prophylactic mastectomy, tamoxifen can also be done
ER(+), HER2(-), low proliferation
- most common subtype of cancer in older females and males
- most commonly detected via mammography
- most common in females on hormone replacement therapy
- often found at an early stage and cured by surgery
invasive carcinoma
what is the tx for invasive carcinoma?
hormone therapy (gene expression is regulated by estrogen receptors) - chemotherapy not helpful
estrogen receptor levels may be low and progesterone receptor may be low or absent
- MOST COMMON CARCINOMAS ASSOC WITH BRCA2 GERMLINE MUTATION
- mRNA expression similar to other ER(+) cancers
- 10% show a complete response to chemo, better prognosis than patients who don’t respond
ER(+), HER2(-), high proliferation
second most common molecular subtype of invasive breast cancer
- 50% are ER(+), but there is low expression and absent progesterone receptor
- more common in young, non-white females
- half of patients with TP53 mutations (Li-Fraumeni syndrome) are ER(+)/HER2(+)
- mRNA: increased HER2 expression and increase expression of proliferating genes
HER2(+)
what is the dx of HER2(+)?
subtype is identified via protein over-expression or gene amplification
- detect HER2 with antibody or FISH
what is the tx of HER2(+)?
1/3 respond completely to targeted monoconal Ab therapy (trastuzumab) that binds and blocks HER2 receptor activity = excellent prognosis
- many pts have resistance to trastuzumab due to truncated HER2
most common in young, premenopausal females (especially African American or Hispanic)
- palpable mass between mammographies due to high proliferation and rapid growth
- share genetic similarities with serous ovarian carcinomas
ER(-), HER2(-) = Basal-like triple negative carcinoma
majority of carcinomas arising in women with BRCA1 mutations are of this type
- must do assay for protein or gene amplification to determine if targeting ER or HER2 is indicated
ER(-), HER2(-)
- metastasize when small -> viscera + brain
what is the tx of ER(-), HER2(-)?
30% respond well to chemotherapy
- local recurrence is common, even with mastectomy
- prolonged survival after distant metastasis is rare
calcifications on mammography without densities
- hard, irregular radiodense masses with a desmoplastic stromal reaction
ER(-), HER2(-)
grating sound when scraped due to small, central pinpoint foci or streaks of chalky white desmoplastic stroma with occasional calcification
- sometime present with well-circumscribed masses with sheets of tumor cells with little stromal reaction
ER(-), HER2(-)
variable differentiation, with most of well differentiated tumors in this group
- may present with mucinous, papillary, cribiform or lobular patterns
- high proliferation type expresses Ki67
ER(+), HER2(-)
almost all are poorly differentiated
- many have circumscribed pushing borders with central fibrotic or necrotic center
- prominent lymphocytic infiltrate (carcinoma with medullary features)
- spindle cell, squamous and matrix producing patterns may be seen
- DCIS is very limited or ot present
- express basal keratins
ER(-), HER2(-)
well or moderately differentiated lobular, tubular, and mucinous
ER(+), HER2(-) LOW proliferation
poorly differentiated, lobular
ER(+), HER2(-) HIGH proliferation
some apocrine
HER2(+), ER(+/-)
medullary, adenoid cystic, secretory, metaplastic
ER(-), HER2(-)
biallelic loss of CDH1 which encodes E-cadherin
- tumors are discohesive and may not incite a desmoplastic response
lobular carcinoma
- histo: discohesive infiltrating tumor cells, signet ring cells containing intracytoplasmic mucin droplets
many features of BRCA1 associated carcinomas
- most not associated with BRCA1 mutations, 2/3 are downregulated
- presence of lymphocytic infiltrates within the tumors associated with higher survival rates and great response to chemo
medullary carcinoma
characteristic pattern of anchorage independent growth
- the cells still express E-cadherin and are adherent to each other, but DO NOT RETAIN THE STROMA
micropapillary carcinoma
hard, irregular mass
- diffuse infiltrative pattern with minimal desmoplasia
- difficult to palpate or detect with imaging
- presence of discohesive, infiltrating tumor cells (E-cadherin negative)
- signet ring cells with intracytoplasmic mucin droplets
- indian filing: single cells lined up like box cards
- no tubule formation
lobular carcinoma morphology
soft or rubery and has a pale gray-blue gelatin appearance
- cells clustered in small islands with large mucin lakes
mucinous (colloid) carcinoma
- consists of well-formed tubules
- may be mistaken for a benign sclerosing lesion
- cribiform pattern may be present
- apocrine snouts are typical
- calcifications may be seen in lumens
- associated with flat epithelial atypia, atypical hyperplasia, LCIS or low grade DCIS
tubular carcinoma
produces true papilla: fronts of fibrovascular tissue lined by tumor cells
- two special histologic types frequently overexpress HER2
papillary carcinoma
HER2(+)
- cells resemble those that line sweat glands
- enlarged round nuclei with prominent nucleioli and abundant eosinophilic or granular cytoplasm
apocrine carcinoma
forms hollow balls of cells that float within intercellular fluid creating structures that mimic the appearance of true papillae
micropapillary carcinoma
most common subtype of ER(-), HER2(-)
- soft due to minimal desmoplasia
- presents as a well circumscribed mass
- solid, syncytium sheets of large cells with large, pleomorphic nuclei, prominent nucleioli
- frequent mitotic figures
- lymphocytoplasmic infiltrate surrounding and within the border
- **pushing (non-infiltrative) border
- DCIS is minimal or absent
medullary carcinoma
ER(-), HER2(-)
- mimics lactating breasts by forming dilated spaces filled with eosinophilic material
secretory carcinoma
extensive invasion and proliferation within lymphatic channels
- causes swelling that mimics non-neoplastic inflammatory lesions
- typically high grade with very poor prognosis
- do not belong to any specific molecular subtype
inflammatory carcinoma
4-14% associated with BRCA2 mutations
- much more likely for tumors to be ER(+)
- present as 2-3cm palpable, subareolar mass, +/- discharge
- close to the skin and underlying thoracic wall
- can invade structures -> ulcerations
- 50% have metastasized at presentation (lungs, brain, bone, liver)
male breast cancer
- tx: mastectomy + axillary LN dissection
what is the most important factor in absence of distant metastasis of breast cancer?
axillary metastasis
- no nodal involvement = 70-80%
- 1-3 lymph nodes = 35-40%
- 10+ lymph nodes = 10-15%
what does it mean if sentinel LN’s are negative?
it is unlikely that the cancer has spread any further
- pt can be spared complete axillary dissection
when is tumor size less important?
HER2(+) and ER(-), may metastasize when small
- proliferative rate is related and important in this subtype
- may respond better to chemotherapy
- *coopers ligaments tethered to edematous skin = peau d’orange**
- dermal lymphatics are filled with metastatic carcinoma that blocks lymphatic drainage
present with breast erythema and skin thickening = very poor prognosis (pt often have distance metastasis)
- may be confused with mastitis
inflammatory carcinoma
- 60% are ER(-), while 40-50% are HER2(+)
tumor cells are present within vascular spaces in about half of all invasive carcinomas
- strongly associated with the presence of lymph node metastasis
- poor prognostic factor for local recurrence
lymphovascular invasion
what are the most and least favorable subtypes of lymphovascular invasion?
most favorable: well differentiated ER+, HER2-, low proliferation
least favorable: poor differentiation ER+, HER2+
what does a high proliferative rate usually mean?
poor prognosis, but potentially better response to chemotherapy
dreaded complication of breast cancer, common in women in areas with limited resources
- patients that don’t receive treatment and get extensive local disease with ulceration of the skin
carcinoma en curiasse (carcinoma of the breastplate)
what are the two types of stroma in the breast?
- intralobular: fibroadenoma, phyllodes tumors
2. interlobular: tumors are similar to others found in CT throughout the body (lipoma, angiosarcoma)
most common benign tumor of the female breast
- polyclonal hyperplasia of the lobular stroma
- most commonly in 20-30 year olds
- present with palpable mass
- epithelium is hormonally responsive
- increase in size due to lactational changes in pregnancy
fibroadenoma
- can be very small to large
- well-circumscribed, rubbery, grey-white nodules that bulge above the surroinding tissue and contain slit-like spaces
- delicate and myxoid stroma resembles normal intra-lobular stroma
what causes a fibroadenoma?
almost half of women receiving cyclosporin A after renal transplantation develop multiple and bilateral fibroadenomas that regress after cessation of treatment
- may be associated with clonal cytogenic aberrations confined to the stromal component
- considered a proliferative change without atypia
tumors that arise from intralovular stroma, but are much less common than fibroadenomas
- most common in 6th decade
- detected as palpable mass or seen on mammography
- most are cystic and behave in a benign mannor
- chromosome 1q gains
- HOXB13 overexpression
phyllodes tumor
- can be small to large, LEAF-LIKE
- larger lesions have bulbous protrusions due to nodules of proliferating stroma covered by epithelium
- higher cellularity, mitotic rate, nuclear pleomorphism, stromal overgrowth, infiltrative borders (vs. fibroadenomas)
- high grade = difficult to distinguish from malignant sarcomas as they can have a foci of mesenchymal differentiation
phyllodes tumor
why is lymph node dissection contraindicated in phyllodes tumors?
BECAUSE LYMPH NODE SPREAD IS RARE
what is the only breast tumor equally common in both males and females?
myofibroblastoma
fat containing lesions, benign, only importance is to distinguish them from malignancies
lipoma
clonal proliferation of fibroblasts and myofibroblasts that present as irregular infiltrating mass that can involve both skin and muscle
fibromatosis
- locally aggressive, does not metastasize
the only sarcoma that occurs with any frequency in the breast (still less than 0.5% of malignancies)
- occur in the breast parenchyma of young females (35 year olds)
- high grade poor prognosis
- sporadis, or complication of therapy (edema, or 5-10 years after radiation)
angiosarcoma
