Describe the 2 kinds of normal Stromal Tissue in the breast.
Intralobular - responsive to hormonal influences = stromal and edematous
- important for breast lesions
Interlobular - regular CT and fat like everywhere else in the body
What are the two types of cells seen in ducts/lobules of the breast?
What are markers for each type?
which one is MORE helpful in determining if there is invasive BC or not?
Luminal cells -
- function for milk production and conduits in the ducts
- ER/PR markers in malignancy
Myoepithleial cells -
- function for contraction during milk ejection
INVASION = LOSS OF MYOEPITHELIAL CELLS
- Markers are p53, Heavy chain myosin, actin
What changes happen in lctation?
increased number and size of acini
Bubble presentation on lactation and vacuolization
Regress afterwards but not completely
breast changes in aging?
Fibrous tissue replaced by fat - that's why it's easier to see in mammograms of old women
What is the most common breast symptom?
Pain aka Mastalgia or Mastodynia
Cyclical w/ menses - no pathologic correlate
Non-cyclical - can be ruptured cyst or areas of injury/infection
Majority of painful masses are benign - 10% of breast cancers present w/ pain
Whta's the second most common breast symptom?
Discrete palpable masses
Palpable = more than 2 cm and not just diffusely lumpy bumpy
Likelihood of malignancy increases w/ age
MOST COMMON CAUSE - Fibroadenomas, cysts
Bloody nipple discarge - what's the worry?
most commonly benign lesions or cysts but malignancy risk incresases w/ age and worried about Solitary Large Dcut Papilloma - Intraductal Papilloma!
Increased Prolactin = galactorrhea
NOT associated w/ malignancy
Name the inflammatory conditions of the breast that we discuss.
Mammarry Duct ecxtasia
What is acute mastitis? cuases and presentation? treatment?
Most commonly seen during first month of nursing! Lactational mastitis
cracks and fissures in npple let in Staph Aureaus
can get abscess
Tx: complete drainage of milk and antibiotics
What is fat necrosis of the breast? Presentation? Causes? HIsto features?
Painless palpable mass
Skin thickening or retraction
**Mammographic densitiy of calcifications - can mimic malignancy
Caused from history of trauma or surgery OR can see implant from silicone implant capsule leak and get inflammatory reaction
See irregular steatocytes w/ no peripheral nuclei and inflammatory cells / macrophages responding to necrotic fat cells
Peridcutal Mastitis - aka?
MOST COMMON ASSOCIATION?
How does this happen?
Aka Recurrent Subareolar abscess, Squamous metaplasia of lactiferous ducts, Zuska disease
Painful red subareolar mass
>90% of patients are smokers!!!
See squamous metaplasia and keratinization of nipple ducts -> duct ruptures and granulomatous response to keratin results in red painful mass
Fistula tract may burrow beneath SM of nipple and open at edge of areola
Mammary duct ectasia - Who gets it? What not associated with it? Presentation? What causes presentaiotn?
seen in 5th/6th decade of life in multiparous women
NOT associated w/ cigarrete smoking
poorly defined palpable periareolar mass w/ skin retration
*THICK WHITE OR GREEN BROWN NIPPLE SECRETONS!!!! from broken down fatt secretions in milk and heomrrhage and then Histiocytes eat em up!
chronic inflammation and fibrosis around ectatic duct filled w/ debris
Can mimic irrgegular sape of carcinoma on mammogram
What are the Intralobular Stromal Tumors?
Fibroadenoma and Phyloidies tumor
Most common benign breast tumor? Presentation? Who gets it? What does it look like?
Seen before age 30
Palpable, MOBILE mass in young women and can see mammographic density in other women bc can grow fast and infarct
Regress after menopause and bigger in pregnancy
From Proliferation of Intralobular stroma
Wellcircumscirbed tumor of spindle stroma cells and strentched out epithelium
Phylloides tumor - presentation? significance? What does it look like?
Fibroadenoma will NEVER become malignant but phylloides tumors tend to recur and eventually turn high grade
Older patients 50-60 yo
LOW GRADE MALIGNANCY
rarely metastasize to lungs
see infiltrative border, increased mitosis and stromal cellularity
What are non-proliferative breast changes? Significance of them? What can they cause?
Fibrocystic changes - NO INCREASED RISK OF CANCER but can cause mass, calcifciations, pain and swelling
Regress after menopause
Cysts, Fibrosis, Adenosis
Fibrosis from cyst rupture
Adenosis - increased number of acini in lobule
Non-proliferative changes - Cysts - how do they present? What do the look like? What lines them?
Blue Dome cysts
ill-defined fibrous areas that are blue bc yellowish secretions that are fatty/milky
Smooth white areas of fibrosis
Apocrine lining of cysts - similar to sweat glands
Cuboidal, Apocrine, sometimes atypia
Calcifications are common
What are the Proliferative changes w/o Atypia of breast tissues?
Complex Sclerosing lesion
What do you see in Epithelila hyperplasia? risk for cancer?
Lumen filled w/ heterogenous, mixed population of luminal and Myoepithelial cell types
Mild - small increase in numers and no risk
Mod / severe - elevated risk for cancer when more filled
What do you see in Sclerosing Adenosis/ What is it? Cancer risk?
Adenosis = Increased number of Acini in lobules
Fibrosis scar w/ it and cut lobules into several then see scarring and get *Calcifications!!!!
Can mimic cancer histologically bc pseudoinfiltrative pattern
Slightly elevated risk of cancer in both breasts
*Radial Sclerosing LEsion - central area dense fibrosis and Florid hyperplasia and cysts
What is Intraductal Papilloma? (vs papillary carcinoma)
Large Duct Papilloma
PRESENTS w/ Bloody nipple discharge but is benign!
Seen in younger women - premenopausal and there are 2 layers of cells lining it (myoepithelial and epithelial)
vs Papillary Carcinoma which is older women and loss of Myoepithelial layer
What is Proliferative Breast disease w/o Atypia? Causes? Can men get it? What do you see? Cancer?
Imbalance between Estogens that sitmulate breast tissue and androgens
seen in Puberty and Old age
*CIRRHOSIS and medications
Male breasts may develop but they do not have lobules!
Epithelial hyperplasia of ducts (no lobules)
Stromal edema and fibrosis
small increased risk BC
What are the Proliferative Breast Diseases w/ Atypia?
Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia
ADH - what drives proliferation? What does it look like? Cancer Risk?
*Overexpression of ER/PR drives malignant proliferation
See Ductal Proliferation w/ some (not all) features of DCIS
- can be aneuploid, clonal, or have MI
- Minority progress tocancer
Cancer risk is 4-5x in either breast and absolute risk is 13-17% in 15 years
ALH - what do you see? Cancer risk? Genetics?
Hallmark of Lobular? (vs ductal)
Acinar Proliferation but not fully LCIS
Multi-Focal and Bilateral = LOBULAR
Often an incidental finding
Might share or progress to genetics of LCIS - loss of E-cadherin protein from gene mutation
Cancer risk 4-5x EITHER BREAST
Abs risk 13-17% in 15 years
Discuss the 3 different low grade vs high grade pathways to carcinoma in the breast.
1) ER+ Proliferative Disease = germline BRCA 2 mutations w/ Hormone driven sequence from flat epithelial atypia to Atypical Ductal Hyperplasia to DCIS to invasive cancer that is ER+ HER2- aka Luminal (50-60%)
2) ER- TP53 germline mutation and HEr2 amplification to Atypical Apocrine Adenosis to DCIS to HER2+ Carcinoma (20%)
3) ER - germline BRCA 1 mutation + TP53 mutations to DCIS to high grade ER-/HER2- "Basal-like" carcinoma (15%)
What is DCIS? Where is it detected? What is detected?
RISK FOR CANCER? Tx?
DCIS = malignant clonal proliferation of epith cells limited to ducts by BM and preservation of Myoepithelial cells
Driven by ER/PR
30% low grade progress but most high grade progress to invasive
50% of mamographically detected cancers
Micro-calcifications - branching
DONT GO AFTER ADH bc generalized risk but you DO go after DCIS bc Direct precursor for invasion right there so get rid of it!
Invasive cancer risk 8-10x IPSILATERAL - same site as DCIS
Histologic features of DCIS high vs low grade?
Low grade - unform cells w/ rigid structures w/in duct,
Calcifications in open spaces
High grade - Central necrosis
What is comedo DCIS? Significance of it? Gross and Micro?
Comedocarcinoma - high grade DCIS w/ Central NEcrosis
more likely to produce a mass and progress to invasive cancer
Gross: Fibrotic mass w/ white necrotic material in dilated ducts ("comedons like acne"
Micro: high grade solid DCIS w/ LOTS of central necrosis and Fibrosis - desmoplastic reaction
What is PAget's Disease of the Nipple? what do you see?
See Hyperemia and Ulceration
PAget's = spread of malignant cells into the epidermis through the LActiferous ducts and into skin - disrupt tight squamous epithelial cell barrier and get oozing scaly crust
What are the features of Lobular CArcinoma in situ that we should DEF KNOW?!?!?! Treatment?
LCIS = MULTIFOCAL AND BILATERAL
Loss of expression of ECADHERIN CDH1
Cancer Risk 8x in EITHER BREAST - BILATERAL
Most LCIS is not a direct precursor to invasive carcinoma but a marker of incrased risk bilaterally
"Discohesive Cells distending Acine - bag of marbles feeling"
Indication for Bilateral Mastectomy
TAMOXIFEN for low risk progression
General - Proliferative Epithelial lesions (w/ or w/o atypia):
Symptoms or no?
Benign? Cancer risk?
No symptoms but frequently detected as mammographic abnormalities
Classified according to risk of cancer to EITHER BREAST
majority are not precursors to cancer just markers of risk
DCIS vs LSCIS risk for cancer in general
DCIS = direct precursor for invasive cancer in SAME breast
LCIS = mixed bag - most are not direct precursors but marker of increased BILATERAL risk
What is most bresat cancer?
Invasive Ductal CArcinoma
What are some Benign causes of Calcifications on mammography?
Other than those what does calcifcation on mammography imply?
Calcifications, and not masses, result from dead cells in lumen of ducts (Dystrophic calcifications) and are the biggest indicator for ductal carcinoma
What is the most powerful prognostic and predictive factors?
TNM stage - most powerful prognostic and can be predictive
N most powerful but M determines whether cure is possible
What is most common type of breast cancer? How does it present on imaging? and in Histo? How does it spread?
INVASIVE DUCTAL CARCINOMA - 85% all breast cancers
Presents w/ ill-defined or stellate/spiculated mass on imaging
Rock hard mass from desmoplastic reaction
Histo - Ductal so trying to recapitulate nests/lobules
Spreads hematogenously to Bone, Lung, Brain and Liver as well as to LN
What is the presentation of Invasive Lobular carcinoma?
Where do Mets go?
Genes? --> Genes related to increased risk for what other cancer?
ILC 5-10% breast cancer
MULTICENTRIC - Diffuse and poorly defined
Mets to CSF on menigneal coverings, BM (anemia/transcytopenia), Uterus, and Peritoneum
Bi-allelic loss of expression of CDH1 - E-Cadherin --> Increased risk Gastric Signet Ring cell Carcinoma
What is the Histology and interesting patterns of Invasive Lobular carcinoma?
Bland cells infiltirate SINGLE CELL AT A TIME W/ NO REACTION!
No palpable and invisible on imaging
can look like lymphocytes in stroma and so easily missed!
What are breast cancers w/ more favorable prognoses?
Colloid aka Mucinous Carcinoma
Tubular Carcinoma (BEST ONE TO GET!)
There are 4 subtypes of Invasive ductal carcinoma - name them and they're main feautres:
1) Medullary Carcinoma - BRCA muts in younger patients, ugly high grade malignant tumors but behaves well bc of Inflammatory response
2) Colloid/Mucinous Carcinoma - litlte old lady tumor w/ mucin lakes and good prognosis
3) Tubular Carcinoma - Best one to get - only 1 cell type and desmoplasia
4) Invasive Micropapillary - BAD
- lymphatic vessel invasion and LN involvement - breast red and swollen
- DERMAL LYMPHATICS
- looks like Acute Mastitis
What do you see in Metaplastic Carcinoma?
Non-Glandular (metaplastic) Differentiaiton
Spindle CEll carcinoma
Squamous cell carcinoma
Sacromatous - Maligntant Chondorid/Osteodid - Matrix producing carcinoma
How do you evaluate LN involvement in breast cancer?
Sentinel LN biopsy - sensitive and specific predcitor of full axillary status
Axillary LN dissection for + LN
Lymphatic/Vascular invasion is a _______ prognostic factor
Especially important in what T/N/M stages of tumors?
Negative Prognostic but can inform treatment choices
Important in T1 LN tumors - ID subset of patients at increased risk for distant mets
What do you see in Inflammatory breast carcinoma? Significance?
Skin Erythemia and Peu-d-orange (dimpling in skin)
WORST CLINICAL SITUATION THERE IS
tumor in dermla lymphtatics
< a few months to live
Ancillary IHC testing for hormone receptor status can be.......
Positive Prognostic Factor
Positive Predictive Factor
HER2/NeU is what kind of gene change? What's happening there? Signigicance?
HER2/NEU = C-ERB2
Oncogene that encodes a cell surface protein from GFR family
By iteslf is NEGATIVE prognostic but POSITIVE PREDICTIVE!!!!
Amplification/Overepxression in tumors means eligible for treatment w/ Trastuzumab
What is KI-67?
Proliferation index that can be measured by IHC
HER2+ tumors are more likely what kind of histology?
APOCRINE - ductal NOS
apocrine - overexpressed androgen receptors
seen in young non-white women
What histologic type of tumors are Basal like aka Triple negative?
BRCA2 associated with?
Luminal B high proliferation high histo grade ER + ductal invasive carcinomas and male prostate and breast cancer
What is the epi profile for Basal like triple neg tumors?
Young, AA, Hispanic
Bilateral MAstectomy indicated
Dramatic response to chemo and relapse quickly but can come back w/ vengence