Breast

Question 1

Milkline Remnants

Answer 1

• produce hormone-responsive supernumerary nipples or breast tissue from axilla to perineum.
• find secondary to painful pre-menstrual enlargement.

Question 2

Accessory Axillary Breast Tissue

Answer 2

• normal ductal tissue extends into subQ tissue of axilla or chest wall.
• presentation: lump in setting of lactational hyperplasia.
  
  • can cause carcinoma outside breast.

Question 3

Congenital Nipple Inversion

Answer 3

• spontaneously corrects during pregnancy or with traction.

Question 4

Acquired Nipple Inversion

Answer 4

• concern for carcinoma or inflammatory conditions.

Question 5

Presentation of Breast Disease

Answer 5

• pain. cyclic has no pathologic correlate.
  
  • non-cyclic = localized, secondary to infection, trauma or ruptured cyst.
  • 95% painful masses benign.
  • 10% cancer presents with pain.
• discrete palpable mass. when <2cm. usually cysts, fibroadenomas, and carcinoma.
  
  • 10% dominant masses in women <40yrs are cancer.
  • 60% in women >50yrs malignant.
• nipple discharge. see in cancer when unilateral and spontaneous.
  
  • 7% malignancies in women <60yrs.
  • 30% in women >60yrs.
  • bloody or serous due to cysts or intraductal papillomas. benign in pregnancy.
• milky discharge = galactorrhea. outside pregnancy related to prolactin-producing pituitary adenomas, hypothyroidism, anovulatory cycles, or meds.
• mammographic signs with carcinomas = densities and calcifications.
  
  • neoplasms typically denser than breast tissue.
  • detect as small as 1cm.
  • calcifications on secretions, necrotic debris, hyalinized stroma.

Question 6

Acute Mastitis

Answer 6

• during 1st month lactation when breast vulnerable to bacterial infections (Staph and strep) thru nipple cracks and fissures.
• tx: antibiotics and breastfeeding.

Question 7

Periductal Mastitis

Answer 7

• aka recurrent subareolar abscess, squamous metaplasia of lactiferous ducts, and Zuska disease.
• squamous metaplasia of nipple ducts ⇒ keratin shedding and ductal plugging.
• ductal dilation and rupture ⇒ intense chronic and granulomatous inflammation.
• associated with smoking (90%).
• can get bacterial infections.
• recurrent causes periareolar fistulous tracts and/or nipple inversion.
• presentation: painful subareolar mass in both sexes.
• tx: surgery

Question 8

Mammary Duct Ectasia

Answer 8

• inspissation of secretions, ductal dilation without squamous metaplasia, periductal inflammation causes fibrosis and skin retraction.
• presentation: ill-defined, painless periareolar mass with viscous white nipple secretions.
  
  • multiparous women ages 50-70yrs.

Question 9

Fat Necrosis

Answer 9

• associated with prior trauma or surgery.
• go from hemorrhage with acute inflammation and liquefactive fat necrosis to chronic inflammation with giant cells and hemosiderin to scar tissue.
• presentation: painless palpable mass, skin thickening or retraction, or mammographic density and/or calcifications.

Question 10

Lymphocytic Mastopathy (Sclerosing Lymphocytic Lobulitis)

Answer 10

• collagenized stroma around atrophic ducts with prominent lymphocytic infiltrate.
• associated with type 1 diabetes and autoimmune thyroid disease.
• presentation: single or multiple, rock-hard, palpable masses.

Question 11

Granulomatous Mastitis

Answer 11

• associated with systemic diseases (sarcoidosis, Wegener granulomatosis), foreign bodies, granulomatous infections.
• granulomatous lobular mastitis = in parous women, from hypersensitivity responses to lactational epithelium.

Question 12

Monoproliferative Breast Changes (Fibrocystic Changes)

Answer 12

• benign. usually seen in lumpy breasts.
• morphology: cysts from lobular dilation and unfolding, coalesce. lined by flattened atrophic epithelium or metaplastic apocrine cells. have calcifications.
  
  • fibrosis from cyst rupture and inflammation.
  • adenosis = ↑ numbers of acini per lobule. in normal pregnancy, focal finding in non-pregnant breast.
    
    • enlarged but not distorted, lined by columnar epithelium. can have atypia. have calcifications.

Question 13

Proliferative Breast Disease without Atypia

Answer 13

• epithelial and stroma proliferation without cytologic or architectural atypia.
• morphology: epithelial hyperplasia = more than 2 cell layers around ducts and lobules.
  
  • sclerosing adenosis = ↑ numbers of acini per lobut with central distortion and compression and peripheral dilation.
  • complex sclerosing lesions = have sclerosing adenosis, papillomas, epithelial hyperplasia.
  • papillomas = epithelial growth, associated with fibrovascular cores within dilated ducts.

Question 14

Proliferative Breast Disease with Atypia

Answer 14

• include atypical ductal and atypical lobular hyperplasia, sometimes with calcifications.
• morphology: lacks sufficient features to diagnose carcinoma but look like carcinoma in situ.
  
  • atypical ductal hyperplasia = limited extent but looks like ductal carcinoma in situ.
  • atypical lobular hyperplasia = looks like lobular carcinoma in situ but <50% of acini in lobule.

Question 15

Carcinoma of Breast

Answer 15

• most common non-skin malignancy in women.
• 1/8 chance by age 90.
• <20% mortality
• epidemiology: 1% in men, rare before 25yrs.
  
  • caucasians around 61 yr, hispanic 56yr, black 46yr.
  • in younger women = ↓ estrogen receptors or ↑ HER2/neu expression.
  • ↑ risk with 1st degree relatives.
  • atypical hyperplasia ↑ risk
  • 7% in whites, 5% blacks, 4% hispanics.
    
    • ↑ malignancy and mortality in blacks and hispanics.
  • ↑ risk from hormone replacement.
  • ↑ risk from breast density, radiation exosure, carcinoma of endometrium or contralateral breast.
  • risk from: diet (↑ by alcohol, ↓ by caffeine); obesity (reduces risk by anovulatory cycle), breastfeeding (reduces risk)
  • most ER positive, comes from ER expressing luminal cell
  • ER negative come from myoepithelial cells.
  • proliferative changes, atypical ductal/lobular hyperplasia = ER expression.
  • final step = in situ to invasive
• predictive factors: invasive vs in situ; distant metastases; lymph node metastases (most important without distant metastases); tumor size; locally advanced disease; inflammatory carcinoma.
  
  • overexpressed HER2/neu = worse prognosis but better response to trastuzumab.
  • lymphovascular invasion = poor prognosis, risk for recurrence.
  • aneuploidy = worse prognosis

Question 16

Hereditary Breast Cancer

Answer 16

• germline mutations in 12%.
• BRCA1 and BRCA2 are majority of mutations, 3% breast cancers.
  
  • poorly differentiated.
  • ↑ risk of ovarian, prostatic, and pancratic cancers.
• mutated CHEK2, p53, PTEN, LKB1/STK11 = 10%.

Question 17

Sporadic Breast Cancer

Answer 17

• risk factor: hormone exposure
  
  • ↑ number of target cells by stimulating breast growth.
  • risk for stablizing DNA mutations.

Question 18

Ductal Carcinoma In Situ (DCIS)

Answer 18

• 15-30% breast cancers.
• present with calcifications.
• bilateral in 10-20%.
• morphology: comedocarcinoma = ducts and lobules dilated by sheets of high grade pleomorphic cells with zones of central necrosis.
  
  • noncomedo DCIS = monomorphic populations of cells, varying nuclear grades. patterns are cribriform, solid, papillary, and micropapillary.
  • Paget disease = of nipple. malignant cells extend from ductal DCIS into nipple skin without crossing basement membrane. create erythematous eruption with scaly crust.
  • microinvasion = stromal invasion <0.1cm
• tx: mastectomy cures 95%.

Question 19

Lobular Carcinoma In Situ

Answer 19

• 1-6% breast cancers, incidental finding.
• no calcifications or stromal response.
• bilateral in 20-40%, most in premenopausal women.
• untreated ⇒ invasive cancer 1% per year.
• morphology: discohesive cells (loss of E-cadherin expression), with intracelular mucin forming signet ring cells. most express ER and PR.

Question 20

Invasive (Infiltrating) Carcinoma

Answer 20

• present as palpable masses or radiodense mammographic lesions.
  
  • radiodense are 1/2 size of palpable, only 20% involve nodes.
  • 50% palpable have nodal metastases.
• large can be fixed to chest wall, cause skin dimpling or nipple retraction.
• invade dermal lymphatics ⇒ lymphadema ⇒ peau d’orange appearance.
• inflammatory carcinoma = tumors that present with swollen, erythematous breast due to lymphatic invasion and destruction. poor prognosis.

Question 21

Invasive Carcinoma, No Special Type (NST; Invasive Ductal Carcinoma)

Answer 21

• 70-80% breast cancers.
• ‘Luminal A’ = 40-55% NST. ER positive, HER2/neu negative. well differentiated, in postmenopausal women. slow-growing, respond to hormone therapy.
• ‘Luminal B’ = 15-20% NST. ER positive, high grade, HER2/neu over-expression = triple positive.
  
  • present with nodal metastases, respond to chemo.
• ‘Normal breast-like’ = 6-10% NST. well differentiated, ER positive, HER2/neu negative.
• ‘Basal-like’ = 13-15% NST. lack ER, PR, or HER2/neu = triple negative. express myoepithelial cell markers.
  
  • many have mutated BRCA2.
  • many high grade, proliferative, aggressive.
  • 15-20% respond to chemo.
• ‘HER2 positive’ = 7-12% NST. ER negative, over-express HER2/neu from 17q21 amplification. poorly differentiated, aggressively metastatic.
• ER pos respond to hormone blockade.
• HER2/neu respond to combo of chemo and monoclonal Ab (trastuzumab).
• morphology: firm to hard, irregular border, gritty sensation on cutting.
  
  • range from well differentiated with tubules, small round nuclei, rare mitoses to poorl differentiated with sheets and nests of cells with enlarged irregular nuclei, multiple mitoses, focal necrosis.

Question 22

Invasive Lobular Carcinoma

Answer 22

• palpable mass or mammographic density.
• 25% invade with little desmoplasia.
• well-differentiated and mod differentiated = diploid, ER pos, associated with LCIS, similar genes to luminal A.
• poorly differentiated = aneuploid, lack hormone receptors, over-express HER2/neu.
• lobular = metastasize to peritoneum and retroperitoneum, GI tract, leptomeninges, ovaries, uterus.
• morphology: hallmark = discohesive infiltrating tumor cells, single-file or loose clusters. signet ring appearance, minimal desmoplasia.

Question 23

Medullary Carcinomas

Answer 23

• after age 60yr.
• rapidly growing, well circumscribed masses.
• ‘basal-like’ expression pattern.
• 2/3rds have hypermethylation of BRCA1 promoter.
• better prognosis than NST.
• over-expression of intercellular adhesion molecules and E-cadherin ⇒ limit metastatic spread.
• morphology: soft and fleshy, pushing border, little desmoplastic response.
  
  • solid sheets of large cells with vesicular pleomorphic nuclei, prominent nucleoli, multiple mitoses, lymphoplasmocytic infiltrate.

Question 24

Mucinous (Colloid) Carcinoma

Answer 24

• slow-growing, well-differentiated, ER pos.
• around age 71yr.
• nodal metastases common.
• morphology: soft to rubbery, gel-like consistency.
  
  • malignant cells in cluster within large mucin lakes.

Question 25

Tubular Carcinoma

Answer 25

• found as small irregular mammographic densities, women in 40’s. multifocal and/or bilateral.
• associated with atypical lobular hyperplasia, LCIS, low-rade DCIS.
• 95% well-differentiated, diploid, ER pos, HER2/neu neg.
• good prognosis.

Question 26

Fibroadenomas

Answer 26

• most common benign tumor of female breast.
• during reproductive years, calcify after menopause.
• present as rubbery, well circumscribed palpable masses, ovoid densities, calcifications.
• hormone responsive, grow during pregnancy.
• polyclonal hyperplasias of lobular stroma, respond to cyclosporine.

Question 27

Phyllodes Tumor

Answer 27

• most common >60yrs.
• palpable mass.
• stroma overgrows epithelial component, form clefts and slits and create bulbous protrusions.
• ↑ cellularity, mitotic activity, stromal overgrowth, infiltrative borders
• high grade have EGF receptor amplification
• cured by wide lcoal excision.

Question 28

Benign Stromal Lesions

Answer 28

• tumors of interlobular stroma, made of stromal cells without epithelial components.
• ex: pseudoangiomatous stromal hyperplasia and fibromatosis, myofibroblastoma, lipomas.

Question 29

Malignant Stromal Tumors

Answer 29

• rare.
• angiosarcoma = most common. primary tumor in young women after radiation therapy for breast cancer or in skin of chronically edematous arm after mastectomy (Stewart-Treves syndrome).
  
  • high grade, poor prognosis.

Question 30

Gynecomastia

Answer 30

• in men.
• uni- or bilateral.
• button-like subareolar enlargement.
• indicator of estrogen and androgen imbalance.
• during puberty, Klinefelter syndrome, hormone-producing tumors, men with cirrhosis, drug side effect.
• ductal epithelial and stromal hyperplasia.

Question 31

Male Breast Carcinoma

Answer 31

• rare.
• risk factors: 1st degree relatives, estrogen exposure
• associated with BRCA2 mutation.
• tend to invade skin and chest wall earlier and present at higher stages.