Breast L1 and L2 - L77/L78 Flashcards Preview

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Flashcards in Breast L1 and L2 - L77/L78 Deck (54):
1

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 

2

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 

 

3

What changes happen in lctation? 

increased number and size of acini

 

Bubble presentation on lactation and vacuolization

 

Regress afterwards but not completely 

4

breast changes in aging? 

Fibrous tissue replaced by fat - that's why it's easier to see in mammograms of old women 

5

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 

6

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

7

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! 

8

Milky Discharge? 

Increased Prolactin = galactorrhea 

NOT associated w/ malignancy

9

Name the inflammatory conditions of the breast that we discuss.

Acute mastits

Fat necrosis

Periductal mastitits

Mammarry Duct ecxtasia 

10

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 

11

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 

12

Peridcutal Mastitis - aka? 

Presentation? 

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 

see picture 

A image thumb
13

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 

14

What  are the Intralobular Stromal Tumors? 

Fibroadenoma and Phyloidies tumor

 

15

Most common benign breast tumor? Presentation? Who gets it? What does it look like? 

Fibroadenoma 

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 

16

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 

*Leaf-like architecture 

17

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

18

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

19

What are the Proliferative changes w/o Atypia of breast tissues? 

Epithelial Hyperplasia

Sclerosing Adenoisis 

Intraductal Papilloma

Complex Sclerosing lesion

20

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 

21

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 

 

22

What is Intraductal Papilloma? (vs papillary carcinoma) 

Large Duct Papilloma 

 subareolar, solitary 

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

23

What is Proliferative Breast disease w/o Atypia? Causes? Can men get it? What do you see? Cancer? 

GYNECOMASTIA!!!!

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 

24

What are the Proliferative Breast Diseases w/ Atypia? 

Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia 

25

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

- Multicentric

- Minority progress tocancer

Cancer risk is 4-5x in either breast and absolute risk is 13-17% in 15 years 

26

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

27

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%)

See chart

A image thumb
28

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

 

 

29

Histologic features of DCIS high vs low grade? 

Low grade - unform cells w/ rigid structures w/in duct, 

Calcifications in open spaces

Swiss Cheese

High grade - Central necrosis

pleomorphic cells 

30

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 

SEE PIC

A image thumb
31

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 

 

See picture

A image thumb
32

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 

33

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

34

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 

35

What is most bresat cancer? 

Invasive Ductal CArcinoma

36

What are some Benign causes of Calcifications on mammography? 

Other than those what does calcifcation on mammography imply? 

Fat Necrosis

Sclerosising adenosis 

 

 

Calcifications, and not masses, result from dead cells in lumen of ducts (Dystrophic calcifications) and are the biggest indicator for ductal carcinoma

37

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 

38

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

Irregular borders

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

39

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 

20% BILATERAL 

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 

40

What is the Histology and interesting patterns of Invasive Lobular carcinoma? 

Bland cells infiltirate SINGLE CELL AT A TIME W/ NO REACTION!

indian File 

 

No palpable and invisible on imaging 

can look like lymphocytes in stroma and so easily missed! 

41

What are breast cancers w/ more favorable prognoses? 

Medullary Carcinoma

Colloid aka Mucinous Carcinoma

Tubular Carcinoma (BEST ONE TO GET!)

42

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 

43

What do you see in Metaplastic Carcinoma? 

Non-Glandular (metaplastic) Differentiaiton

Spindle CEll carcinoma

Squamous cell carcinoma

Sacromatous - Maligntant Chondorid/Osteodid - Matrix producing carcinoma

 

BAD PROGNOSIS

44

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 

45

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 

46

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

47

Ancillary IHC testing for hormone receptor status can be.......

Positive Prognostic Factor

Positive Predictive Factor 

48

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 

49

What is KI-67? 

Proliferation index that can be measured by IHC 

50

HER2+ tumors are more likely what kind of histology? 

APOCRINE - ductal NOS 

apocrine - overexpressed androgen receptors 

seen in young non-white women 

P53 mutation 

51

What histologic type of tumors are Basal like aka Triple negative? 

Medullary

Metaplastic

Lymphoepithelial

52

BRCA2 associated with? 

Luminal B high proliferation high histo grade ER + ductal invasive carcinomas and male prostate and breast cancer

53

What is the epi profile for Basal like triple neg tumors? 

Mutation

Treatment?

Young, AA, Hispanic 

BRCA 1

 

Bilateral MAstectomy indicated

Dramatic response to chemo and relapse quickly but can come back w/ vengence

54