3. Breast Pathology Flashcards
Prepubertal female breast and in males the large duct system ends in terminal ducts. During reporductive years, after ovulation, and d/t estrogen and progesterone, cell proliferation continues, what stroma becomes markedly edematous?
Intralobular Stroma
edema goes away upon menstruation
With the onset of pregnancy is when the breasts completely mature and become functional, lobules increase in size and number, at the end of pregnancy the breast is completely lobules separated by scant stroma. After the 3rd decade of life, lobules and their specialized stroma start to?
Involute and intralobular stroma converts to radiodense fibrous* stroma w ADIPOSE
(older = mainly fat tissue)
What is the persistence of epidermal thickenings along a line causing supernumerary nipples or breasts (polythelia/ polymastia), symptomatic during preg, normally inferior to breasts, come to attention due to premenstrual enlargement?
Milk Line remnants (ectoderm rem)
What development DO occurs when normal ductal system extends into SQ tissue of the chest wall/axillary fossa, may be taken out but does not reduce risk breast cancer- can be site of malignancy?
Accessory Axillary Breast tissue
What occurs congenitally and has little significance, and usually correct spontaneously during pregnancy, where as an acquired version is of more concern, possibly indicating invasive cancer or inflammatory nipple disease?
Congenital Nipple Inversion
What anatomy of the breast is associated with the following?
Cysts, Sclerosing adenosis, Small duct papilloma, hyperplasia, atypical hyperplasia, Carcinoma
Lobules and Terminal Ducts
What anatomy of the breast is associated with the following?
Duct ectasia, Squamous metaplasia of lactiferous ducts, large duct papilloma, Paget disease
Large Ducts
What anatomy of the breast is associated with the following?
Fibroadenoma, Phyllodes Tumor
Intralobular Stroma
What anatomy of the breast is associated with the following?
Fat Necrosis, Lipoma, Fibromatosis, Sarcoma
Interlobular Stroma
Myoepithelial cells which line luminal cells of the ducts in the breasts have calponin, a-smooth muscle actin and what which is important in cancer?
p63
The most common symptoms of someone with breast disorders are pain, palpable mass, and nipple discharge. Pain, known as mastalgia if diffuse is due to premenstrual edema, if localized is due to ruptured cysts, injury or infection, almost all painful masses are?
Benign! (10% breast cancers present w pain)
Palpable mass is commonly cysts, fibroadenomas, or invasive carcinoma, usually benign in premenopausal women*, with an increased likely hood of cancer w increased age (60), how many of breast cancers are found due to a palpable mass?
1/3
What symptom is the most worrisome for carcinoma if spontanenous, unilateral and in pt older than 60, seen w manipulation or stimulation, may be blood or serous?
Nipple Discharge (think cancer in women >60 with spontaneous nipple discharge)
Mammogram detects small, nonpalpable, asymptomatic breast carcinoma, the principal signs of breast carcinoma are densities and calcifications, and is the MC means to detect breast cancer, with an increased sensitivity and specificity as?
the patient ages (since there is more fat)
more than 50% of cancers are found via this way
The breast is divided into four sections, RUQ, RLQ, LUQ, and LLQ, which are is the MC site for breast cancer because it has the most breast tissue?
Upper Outer Quadrant
males MC site is central/subareolar
What is a lesion seen on mammogram that replace adipose tissue with radiodense tissue, rounded = usually benign fibroadenomas or cysts, irregular usually carcinoma, identifies lesions 1cm in size vs 2-3cm by palpations?
Densities
What is seen on mammograms which form on secretions, necrotic debris or hyalinized stroma, usually benign lesions include clusters of apocrine glands, hyalinized fibroadenomas, sclerosing adenosis, if malignant will see small irregular numerous and clustered (DCIS)?
Calcifications
What inflammatory DO has cracks and fissures of the nipple which cause the breast to be vulnerable to bacteria during the first month of breast feeding, breast is erythematous, painful +/- fever?
Acute bacterial Mastitis
What syndrome is seen with complete absence of pectoralis muscle and breast tissue, where the nipple is hypoplastic and superiorly located?
Poland Syndrome (unilateral)
Women aged 50-54 should get mammograms q year, 55+ q2years, 50-69 screening is recommended…
MEOW
10% of breast carcinomas are not detected on mammography, usually due to radiodense tissue (younger women), 70-80% of cancers found on mammography are ?
already invasive, with metastasis
Acute bacterial Mastitis has bugss involved including staph A causing abscesses or strep causing cellulitis, treat with antibiotics and continued expression of?
Breast milk
What is an inflammatory DO AKA subareolar abscess, periductal mastitis, or Zuska disease and is painful erythematous subareolar mass that appears to be bacterial abscess, recurrent: fistula tunnels under SM of nipple, opening skin at the edge of areola,, inverted nipple?
Squamous Metaplasia of Lactiferous Ducts
Squamous Metaplasia of Lactiferous Ducts occurs in 90% of people who smoke, may be due to relative Vit A deficiency or toxic substance abuse in smoke, the key feature is what metaplasia of the nipple ducts?
Keratinizing Squamous metaplasia
with Squamous Metaplasia of Lactiferous Ducts, the ductal system is plugged with shed cells causing dilation and rupture of the duct, keratin spills into periductal tissue, causing what intense response?
Chronic granulomatous response
recurs after draining, cured surgically
What inflammatory DO is a palpable peri-areolar mass associated with thick, white nipple secretions +/- skin retraction, pain and erythema are rare and irregular palpable mass mimics invasive carcinoma clinically and on imaging***?
Duct Ectasia
Duct Ectasia risk factors include multiparous females in the 50s/60s, NOT associated with smoking, will see ectatic dilated ducts with inspissated secretions and lipid laden mø, if ruptured see periductal inflamm reaction with lymphocytes and plasma cells, formation of what around cholesterol deposits and secretions forms the irregular mass/nipple retraction?
Granuloma formation
What inflamm DO is painless, palpable mass with skin thickening or retaction and or mammographic densities/calcifications, acute will see neutrophils/mø and chronic will see fibroblasts/inflamm cells leading to GIANT cells, w deposition leads to scar tissue?
Fat Necrosis in the Breast due to calcifications and hemosiderin deposition (chalky white deposit)
***50% due to prior surgery/breast trauma
What inflamm DO is a single/multiple hard palpable masses or mammographic densities, dense collagenized stroma is difficult to needle bx, thick BM of atrophic ducts/lobules, w prominent lymphocyte infiltrate, *****MC in type 1 DM or autoimmune thryoid dz?
Lymphocytic mastopathy (sclerosing lymphocytic lobulitis) - diabetic mastopathy
What inflamm DO may be due to systemic or localized disease (Tb/Sarcoidosis), uncommon, occurs in parous females, associated with lobules, possibly a hypersensitivity reaction to antigens expressed by lactation, tx w steroids?
Granulomatosis Mastitis
There are three groups of benign epithelial disorders including nonproliferative breast changes, proliferative without atypia, and proliferative breast disease WITH atypia, which come to attention as and incidental finding on biospy or by?
mammographic abnormality
nonproliferative breast changes are NOT associated with increased risk of breast carcinoma, and is a group of fibrocystic changes, including cysts, fibrosis and?
adenosis
What nonproliferative breast change is due to lobule dilation, which may coalesce into large cysts, contain turbid, semi-translucent brown blue fluid (blue domed cyst), lined with flattened atrophic epithelium or metaplstic apocrine cells, calcifications are seen, dx after its disappearance post FNA?
Cysts!
What nonproliferative breast change occurs due to release of secretory material into the stroma from ruptured cysts usually, contributing to palpable nodularity of the breast?
Fibrosis
What nonproliferative breast change causes an increase of acini and lobules, normal in pregnancy or focal change in nonpregnant females,lined w columnar cells, chr 16q deletion - flat epithelial atypia - earliest precursor lesions of low grade breast cancer?
Adenosis
What type of adenoma is palpable masses in pregnant or lactating women, normal appearing breast tissue with exaggerated lactational changes?
Lactational Adenoma
proliferative breast change without Atypia has proliferations of epithelial cells without atypia, small increased risk of subsequent carcinoma of either breast, predictors of *risk but unlikely to be true precursors of?
Carcinoma
What proliferative breast change without Atypia causes increase number of luminal (ductal) and myoepithelial cells fill and distend ducts and lobules, normally ducts/lobules have double layer of myoepi and luminal cells, has irregular lumens in periphery and usually incidentally found?
Epithelial Hyperplasia
What proliferative breast change without Atypia has increased # of *acini compressed and distorted in the central portion of the lesion, lumen compresion due to stromal fibrosis - histologically mimics invasive carcinoma?
Sclerosing Adenosis
What proliferative breast change without Atypia is sclerosing adenosis, papilloma and epi hyperplasia with a RADIAL scar- irregular shaped, mimics invasive carcinoma, central nidus of entrapped glands in hyalinized stroma surrounded by long radiating projections into stroma- not assoc w trauma/ surg?
Complex Sclerosing Lesions
what proliferative breast change without Atypia is a growth within a dilated duct composed of intraductal lesions with fibrovascular cores* lined by myoepi and luminal cells, 80% produce nipple discharge either of blood due to infarct of stalk or serous d/t blockage and release of secretions?
Papilloma
most come to clinical attention due to small palpable masses or as densities or calcifications on mammos
proliferative breast change without Atypia- papillomas are usually solitary and seen in the lactiferous sinuses of the nipple, small duct = multiple and located deeper in the ductal system, often seen w epi hyperplasia and aprocrine metaplasia which is not a ?
precursor to cancer (unlike most other metaplasias)
What is enlargment of the male breast, only benign lesion seen, unliteral or bilateral button like subareolar enlargement, small increased risk of breast cancer, on morph will see increase in dense collagenous CT and epi hyperplasia of the duct lining with tapering micro-papillae, no lobule formation?
Gynecomastia
Gynecomastia is caused by imbalance between estrogens and androgens due to puberty, aging, dec. testicular androgen production, liver cirrhosis, drugs and which chromosomal abnormality?
Klinefelter or function testicular neoplasms (XXY)
proliferative breast disease with atypia is clonal proliferation with some but not ALL histo features of ductal carcinoma in situ DCIS, where there is a moderate increase in?*
*risk fo carcinoma of the breast
MODERATE
What proliferative breast disease with atypia partially fills the ducts, may have cribriform spaces and monomorphic epithelial proliferation?
Atypical Ductal Hyperplasia
5-17% of bx performed for calcifications
What proliferative breast disease with atypia has cells identitical to lobular carcinoma in situ (LCIS), atypical lobular cells that do not fill/ distend >50% lobule acini, which lie between the ductal BM and the normal luminal cells, ***Loss of E cadherin (like LCIS)?
Atypical Lobular Hyperplasia
(Rare, <5%)
Both have chromosomal loss of 16q or 17p gain
Risk of carcinoma from Benign epithelial lesions….
No risk in nonproliferative
1.5-2x risk in proliferative w/out atypia
4-5x risk in prolif WITH atypia
what fold risk if someone has carcinoma in situ?
8-10x risk (25-30%)
Carcinoma of the breast is the MC non-skin malignancy in females, 2nd MC cause of death behind lung cancer, almost all are adenocarcinomas and are divided into 3 groups, Estrogen Receptor ER+ HER2 - (65%), ER + HER2+ (10%) and?
ER - , HER2 -, progestin -
TRIPLE NEGATIVE = BAD = 10%
Carcinoma of breast is rare in females less than 25, increase incidence after 30, by age 90 females have a 1 in 8 chance of geting breast carcinoma. MC in caucasians over 60, under 50 is 35% AA, death rate from breast cancer has declined except for which ethnicity?
African American Women
Risk factors for breast carcinoma include western life, age, race (white), age at menarch, age at first live birth (later preg bad), estrogen exposure, radiation exposure, fam hx, and what?
germline mutations
hereditary, lifestyle, environment
Approximately 12% of breast cancers occur due to inheritance of an identifiable susceptibility gene (hereditary), may be autosomal dominant, BRCA1/2, TP53, CHEK2 (tumor suppresors) account for 8% of all familial breast carcinomas, germline mutations in TP53 causes what syndrome, which is assoc w HNPCC (most commonly HER2+)?
LiFraumeni Syndrome
BRCA1/2 are reponsible for 80-90% of single gene familial breast cancers and 3% of all breast cancers, BRCA1 is located on 17q21, marked increase in which cancer, poorly differentiated, medullary features and basal-like ? (likely to be ER-/HER2-
Ovarian Carcinoma
The following is describing familial or hereditary breast cancer? Autosomal Dominant Earlier Age of Onset Bilateral/Multifocal Multiple Primary cancers Clustering of rare cancers in family
Hereditary
The following is describing familial or hereditary breast cancer?
NO feathures of hereditary cancer syndromes
variable age onset
no specific pattern
may result from chance clustering
genetic background/lifestyle/environment
Familial
BRCA2 is located on chromosome 13q12-13, more frequently associated with what male cancer, and is relatively poorly differntiated, more likely to be ER +?
Male breast cancer
What gene causes familial breast/ovarian cancer, 52% of all hereditary ca, associated with ovarian, lower male breast cancer, prostate, pancreas, fallopian tube, breast carcinomas are POORLY differentiated and triple negative BASAL LIKE, have TP53 mutations as well?
BRCA1 (17q21)
What gene causes familial breast and ovarian cancer, 32% of all hereditary breast ca, assoc w ovarian, male breast cancer, prostate, pancreas, melanoma, GB, bile duct and pharynx, Biallelic germline mutation cause of rare form of Fanconi anemia*?
BRCA2 (13q12-13)
What gene causes Li fraumeni, 3% of hereditary breast ca, >90% chance of getting it, assoc with sarcoma, leukemia, brain tumors, adrenocortical carcinoma, is the most commonly mutated gene in sporadic breast cancer; 53% ER-/HER2+?
TP53 (17p13.1)
What gene accounts for 5% of hereditary breast cancers, assoc w prostate, thyroid, kidney and colon cancer, may increase risk for breast cancer after radiation exposure; 70-80% ER+?
CHEK2 (22q12.1)
What gene accounts for 5% of hereditary breast cancers, assoc w prostate, thyroid, kidney and colon cancer, may increase risk for breast cancer after radiation exposure; 70-80% ER+?
CHEK2 (22q12.1)
What ethnicity does BRCA1 and BRCA2 occur at a much high incidence?
Ashkenazi JEWS
The major risks for sporadic breast cancer are related to hormone exposure: gender, age at menarche and menopause, repoductive history, breastfeeding and exogenous estrogens, main difference between hereditary and sporadic is? (+environmental factors)
Hereditary: 1 inherited damaged gene + 1 spontaneous damaged gene
Sporadic: 2 spontaneous damaged genes
Estrogen is a promoter of breast cancers, stimulates breast growth during puberty, menstrual cycles and pregnancy, proliferation of breast epithelium leads to accumulated DNA damage, damage may become fixed, repeated cycles increase risk for cancer, once premalig and malig changes are present, hormones do what?
stimulate growth of the bad cells and stromal cells, aiding in tumor growth
Almost all (95%) of breast malignancies are adenocaricnomas that first arise in what, as a precursor lesions, at the time of clinical detection the majority (70%) have breached the BM and invaded the stroma :/ ?
duct/lobular system as CIS
ER+/HER2- arise via the dominant pathway of breast cancer development in 50-65% of all cases, MC subtype of breast cancer in individuals who inherit germline mutations of BRCA2, MC form of invasive breast cancer, and are termed what?
Luminal - most closely resemble normal breast luminal cells regarding mRNA expression, dominated by genes regulated by estrogen
HER2+ is 20% of all breast cancers and can be ER-/+, assoc w HER2 gene amplification on 17q, overexpressed if there is ERBB2 mutations, MC type of cancer in patients with what mutation? (has precursor of atypical apocrine adenosis)
TP53 germline mutations (Li Fraumeni Syndrome)
stain for HER2 or FISH amplication
ER-/HER2- arise via distinct pathway independent of estrogen receptor mediated changes or HER2 amplifications, 15% of all breast cancers, MC in patients with which germline mutation, increased freq in AA females, basal-like / triple negative?
MC in germline BRCA1 **
*Recognizable precursor lesions for ER+ HER2- carcinomas include flat epithelial atypia and atypical?
hyperplasia
What is a neoplastic proliferation of epithelial cells confined to ducts and lobules by the basement membrane, may be classified as ductal or lobular, and actually arise from cells in the terminal duct lobular unit*?
Carcinoma in Situ CIS
What in situ is a malignant clonal proliferation of epithelial cells limited to ducts and lobules by BM, myoepi cells are preserved in involved ducts and lobules, dx via mammography usually, with calcifications with secretory material/necrosis, less commonly ID as density, no nipple discharge, bilateral in 10-20%?
Ductal Carcinoma in Situ DCIS
Risk factors for DCIS for progression to invasive caricnoma include nuclear grade and necrosis predict local recurrence and progression to invasion better than architecture, extent of dz, and positive surgical margins (multi centric), what morphology type is detected as clustered or linear and branching areas of calcification on mamo?
Comedo DCIS
Comedo DCIS may sometimes produce nodularity, and is define by tumors with pleomrophic, high grade nuclei and areas of central?
necrosis
what is the second type of DCIS which lacks high grade nuclei or central necrosis, and has cribriform* pattern of rounded spaces within ducts (cookie cutter look), also has a micropapillary pattern and true papillae pattern?
Non-comedo DCIS
Tx of DCIS is either surgical excision and radiation+tamoxifen, mastectomy cures 95%, if untreated, 1% progresses to invasive cancer, higher grade = high risk of progression, is bilaterality more common in DCIS or LCIS?
LCIS - less worried about it popping up in other breast as we are in LCIS
What disease of the nipple presents as unilateral erythematous eruption and scale crust (map-like), pruritus is common and may be confused w eczema, malignant cells (DCIS) extend via lactiferous sinuses into nipple skin, doesnt cross BM, disrupts epithelial barrier = extracellular fluid leakage onto nipple surface?
Pagets Dz of the Nipple - looks like dry skin
Paget cells are larger than surrounding keratinocytes and are seen singly or in small clusters in the epidermis, the cells have pale cytoplasm containing mucopolysaccharide that stains with PAS, detected on nipple bx, 50-60 have papable mass w invasive carcinoma (poorly differentiated/ER-/HER2+) , if there is no palpable mass than what can be assumed?
There is only DCIS, not invasive carcinoma
What in situ is clonal proliferation of cells within ducts and lobules growing in a discohesive fashion due to acquired loss of function mutation of E cadherin protein (CDH1 gene) which is a tumor supressor adhesion protein?
Lobular Carcinoma In Situ LCIS
LCIS cells are 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, so check other breast… How is LCIS usually found/diagnosed?
Incidental biopsy finding since not assocaited with califications or stromal reactions that produce mammo densities
LCIS always expresses ER and PR (HER2-), there are no masses, on morphology, there is uniform population of cells with oval round nuclei and small nuceloli, mucin + signet ring cells*, and lack E cadherin (-) so can see rounded cells not attached to?
adjacent cells (discohesive)
LCIS does not form cribriform spaces or papillae, no involvement w nipple skin, no necrosis or secretions-no calcifications, associated with what type of spread- cells see between basement membrane and luminal cells?
Pagetoid Spread
LCIS is a risk factor for invasive carcinoma, develops in 35% of women over 20-30 years, risk almost as high in contralateral breast, 3x more common to get invasive lobular carcinoma from LCIS than DCIS, tx usually clinical followup to monitor, may due bilateral prophylactic?
mastectomy
Invasive carcinomas are divided based on molecular and morphological characteristics into severeal subgroups. ER+ HER2- (LOW proliferation) known as luminal is the MC form of invasive cancer- 65%, also MC in older females/males, MC detected via mammography and MC in females on?
Hormone replacement therapy
found at early stage and cured by surgery
treatment for ER+ HER2- (LOW proliferation) is gene expression regulated by estrogen receptors, hormone therapy is standard- anti-estrogen (tamoxifen), metastasis takes greater than 6 years, MC met to?
BONE-responds well to antiestrogenic drugs
no response to chemo, relapse late, >10 years-low reccurrance rate
High proliferation ER+ HER2- is when ER levels may be low and progesterone may be absent, MC carcinomas associated with BRCA2* germline mutations, mRNA expression is higher, inc expression of prolif genes, and inc chr abberations, what percent show a complete response to chemo?
10%
MC met to Bone
Relapse is intermediate
Low proliferation ER+HER2- histologically shows well or moderately differentiated lobular, tubular and mucinous types, high proliferation shows?
Poor differentiated Lobular type
*****INC nuclear staining for Ki67
HER2+ cancers is the second most common, 20% of all breast cancers, 50% are ER+, more common in YOUNG non white females*, subtype identified via protein over expression or gene amplicafication to detect HER2 with antibody or via?
FISH
HER2+ cancers have some apocrine histologic types, more common in TP53 mutation carriers (ER +), metastasizes to bone, visceral AND brain all common, relapses within 10 years, survival w mets is rare, 15% ER+ respond to chemo, what % of ER-?
30%!
*MC w Li Fraumeni Syndrome TP53
HER2 is encoded by protooncogene ERBB2, a member of RTK family (GF receptor), in some breast cancers, ERBB2 is amplified leading to over expression of HER2+ (causing the cancer), there with be STRONG membrane staining for?
antibody to HER2 (protein overexpression) or HER2 amplification w FISH
HER2+ cancer is treated with targeted chemo to block HER2, also known as what, which is a monoclonal Ab that binds and inhibits HER2, works in 1/3 of pts, but many pts have resisitance due to truncated HER2 without drug binding site?
Herceptin (trastuzumab)
prior tx w this drug has poor outcome second time around
ER-HER2-PR- aka basal like triple negative carcinoma is the MC in young PREmenopausal females, especially AA or hispanic, least understood of all but most common w BRCA1 germline mut, it is poorly differntiated and most like to come up as a palpable mass between?
Mammographies (year to year) due to rapid proliferation and growth
ER-HER2-PR- aka basal like is genetically similar to serous ovarian carcinomas, assay for protein or gene amplification must be done to determine if targeting ER or HER2, metastasize when small, bone 40%, visceral 35% and?
brain 25%
30 % of ER-HER2-PR- aka basal like pts respond to chemo (high), relapse usually happens quick in less than 5 years, most dont survive metastasis, histological types include medullary, adenoid cystic, secretory and?
metaplastic (bad)
Triple negative carcinomas are characterized by genomic instability due to numerous chromosomal changes, a high proliferative rate and expression of many proteins typical of myopeithelial cells such as?
Basal keratins (means ER-)
Ki67 protein staining common for high prolif ER+HER2-
Invasive carcinoma on mammography shows calcifications without densities usually <1cm, hard irregular radiodense masses with demosplastic stromal reaction, general morphology: grating sound when scraped, sometimes well circumscribed masses w sheets of tumor cells w little stromal reaction, what location of tumor causes nipple retraction?
Central location of tumor
ER+HER2- is mainly WELL differentiated tumors, may present with mucinous, papillary, cribriform, or lobular patterns, high proliferation type expresses?
Ki67
HER2+ carcinomas are poorly differentiated, some moderately, not assoc w specific pattern, 50% of apocrine and 40% of micropapillary carcinomas fit in this category, associated what is more extensive than other types of caricnomas?
DCIS
ER-HER2-PR- is POORLY differentiated, may have circumscribed ‘pushing’ borders with central fibrotic or necrotic center, medullary features (prominent lymphocytic infiltrate), expresses what?
Basal keratins
What carcinoma has biallelic loss of CDH1 which encodes Ecadherin, tumors are discohesive infiltrating cells, w signet* ring cells containing intracytoplasmic mucin droplets?
Lobular Carcinoma (MC type to present as occult primary)
Lobular Carcinoma female and male pts with heterozygous germline mutations have an increased risk of gastric signet ring cell carc, it metastasizes to peritoneum/retroperitoneum, leptomeninges (carcinomatous meningitis), GI tract and?
Ovaries! Krukenberg/ and Uterus
What carcinoma has many features of BRCA1, 13% arise in BRCA1 carriers exhibit this subtype, 60% of cancer arising in BRCA1 carrier have a subset of medullar features, most are not associated with germline BRCA1 however, 2/3 are downregulated/hypermethylated BRCA1. Presence of lymphocytic infilatrates within the tumors is associated with higher?
survival rates and greater response to chemo
Lobular carcinoma is a hard irregular mass with diffuse infiltrative pattern w minimal desmoplasia, difficult to palpate, there is no tubule formation and what is see histological, seen as single cells lined up like box cars?
Indian filing
usually bilateral
What type of carcinoma is soft or rubbery and has the consistency and appearance of pale gray-blue gelatin, the borders are circumscribed and the tumor cells are arranged in clusters and small islands of cells within large lakes of mucin?
Mucinous (colloid) Carcinoma
Medullary carcinoma is MC a subtype of ER-,HER2-, soft due to minimal desmoplasia, circumscribed mass, characterized by solid, syncytium sheets of large cells w large pleomorphic nuclei, prominent nucleoli (75% of mass), mitotic figures, DCIS is minimal with what type of border?
Non infiltrative, pushing border
What carcinoma makes up only 3%, higher incidence in african americans, with a VERy poor prognosis: 3 yr survival is 3-10%, seen with extensive invasion and proliferation of lymphatic channels= Peau d’orange*, causes swelling, high grade?
Inflammatory Carcinoma (dermal lymphatics are filled w metastatic carcinoma that blocks lymphatic drainage = coopers ligaments tethered to edmatous skin = peau d'orange)
Male breast cancer has similar risk factors as females, 3-8% associated with klinefelter, dx at 60-70, 4-14% are assoc w germline BRCA2* more likely for tumors to be ER+, presents as a 2-3cm palpable mass located where, +/- discharge?
Subareolar Mass
Male breast cancer is close to the skin and underlying thoracic wall, if small still can invade structures = ulceration, similar dissemination as women, 50% metastasized at presentation and at higher stages, why?
Less tissue so advances quick
Tx w mastectomy and axillary LN dissection
Breast cancer prognosis depends on biologic features ( molecular/histological) and extent of mets, distant mets = poor prognosis, remaining patients based on pathology of tumor and lymph nodes… what is the most important factor in absence of distant metastases?
Axillary Mets no nodal =80% 10yr survival 1-3 nodes= 40% 10+ nodes= 10-15% ********
Tumor size less than 1cm has 90% 10yr survival, >2cm has 77%, size doesnt matter for HER2+ and ER- because the met quite small. If the sentinel LN is negative, it is highly unlikely there is distant mets, but if there is, what is the chance for survival?
Cure is unlikely, though some remissions have occured in women w ER+
The most favorable outcome for breast cancer is well differentiated ER+,HER2- low proliferation, and the least favorable breast cancer is?
Poorly differentiated, ER- and or HER2+
As with many solid tumors, what of breast cancers is a major challenege to success of therapy, as it increases the likelihood of emergence of more aggressive, therapy resisitant subclones?
profound genetic heterogeneity
What carcinoma is a dreaded complication that must be prevented in order to maintain the best possible quality of life, assoc w extensive local disease with ulceration of the skin, common in women of areas with limited resources?
Carcinoma en Cuirasse (carcinoma of breastplate)
What in males is a button like subareolar enlargment common during puberty/very old men, may be bilateral, due to estrogen and androgen imbalance that leads to stimulation of breast tissue and on histo can see dense collagenous CT and ductal epithelial hyperplasia?
Gynecomastia
(liver dz, dec testosterone, drugs - DISCO
digoxin/isoniazid/spironolactone/cimetidine/ estrogens/ stilboestrol- XXY karyotype, testicular neoplasms that secrete hCG)
There are two subtypes of stromal tumors; intrAlobular which are biphasic tumors such as fibroadenoma and phyllodes tumors, and intErlobular tumors such as lipoma, sarcoma, fibromatosis and?
fat necrosis
What is polyclonal hyperplasia of lobular stroma, MC benign tumor of female breast, not found in men, MC in 20-30s, present w palpable mass (older women show densities or clustered calcifications), epithelium is hormonally responsive, inc in size due to lactational changes in preg, and complication include infarction/inflammation?
Fibroadenoma
Fibroadenomas can be very small to large, well circumscribed, rubbery, greyish white nodules that bulge above surrounding tusse and contain slit like spaces, have delicate myxoid stroma, epi is surrounded by stroma or compressed and distorted by it, almost 1/2 women receiving what after renal transplant develop this?
Cyclosporin A
considered a proliferative change without atypia
What is a intralobular stromal tumor MC in 6th decade, detected as palpable mass or seen on mammo, most are not cystic and behave in benign manner, chr 1q gains is most frequent but sometimes HOXB13 overexpression = higher tumor grade and more aggressive clinical behavior?
Phyllodes Tumor
Phyllodes Tumors can be small to large, larger lesions have bulbous protrusions due to nodules or proliferating stroma covered by epithelium, some make a cystic space, higher cellularity, mitotic rate, nuclear pleomorphism stromal growth than fibroadenomas, its gross look is said to look ?
Looks Leaf-life
*lymphatic spread rare, LN dissection contraindicated
Most interlobular stromal lesions are common (stromal cells without epithelial component)- myofibroblastoma, lipomas, and fibromostosis. What is the MC malignant interlobular stromal lesion but only makes up 0.5% of breast masses in sporadic younger women (35)?
Angiosarcomas
What interlobular stromal lesion is a clonal proliferation of fibroblasts and myofibroblasts that presents as an irregular infiltrating mass that can involve both skin and muscle… ***locally aggressive; does not metastasize?
Fibromatosis
Angiosarcomas are either sporadic (35) or a complication of therapy such as edema (lymphedma post axillary LN removal), or 5-10 years post what? occur in breast parenchyma, high grade, poor prognosis
RADIATION
