2/21 Breast Path - Corbett Flashcards

1
Q

graphic: breast anatomy

A

breast is modified sweat gland

organized into lobules connected to ducts connected to areola

fx unit: TDLU : terminal duct lobule unit

  • two epithelial layers
  1. luminal (simple columnar)
  2. myoepithelium
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2
Q

diff areas of breast that can be diseased

A
  1. nipple/areola
    • intraductal papilloma
    • abscess/mastitis
    • Paget’s disease
  2. terminal duct lobular unit
    • fibrocystic changes
    • ductal/lobular CIS
    • ductal cancer
    • lubular cancer
  3. stroma
    • fibroadenoma
    • Phylloides tumor
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3
Q

presentation of breast disease

A
  • mass
  • asymptomatic w pos screening test
  • nipple discharge
  • skin changes

[pain] - common problem, but rarely cancer

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4
Q

devpt of breast

A

mammary ridge forms at 4-5wk gestation from budding ectoderm → surrounding mesenchyme

extra thoracic milk streak typically regresses

  • if it doesnt? accessory nipple (polythelia) and mammary tissue (polymastia)
    • polythelia : most common on thorax below healthy breasts
    • polymastia : most often in axilla
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5
Q

breast infections

A

most commonly affects women 18-50y

usually a primary event affecting the skin overlying the breast

two types:

  1. lactational (most common)
    • bacterial invasion through irritated/fissured nipple → cellulitis
    • second postpartum week
    • assoc: milk stasis, duct obstruction
    • Staph aureus most common
  2. nonlactational
    • ​​ddx is critical - need to distinguish from cancer

sx: erythema, tenderness, induration, warmth, drainage, systemic sx

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6
Q

periductal mastitis

A

SMOKERS

infl condition of subareolar ducts

presents with periareolar infl

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7
Q

duct ectasia

A

can present as periareolar mass

ddx: cancer

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8
Q

fat necrosis of breast

A

50% assoc with trauma to breast

palpable mass present

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9
Q

proliferative changes and risk of breast cancer

A

can be associated with DUCTS, LOBULES, or STROMA

  • non prolif breast changes (ex. fibrocystic change) → no risk
  • proliferative breast diseaseslight risk, 1.5-2x
  • atypical hyperplasiahigh risk, 4-5x
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10
Q

nonproliferative changes

(fibrocystic changes)

A

most common BENIGN breast condition

conseq of cyclical breast changes occuring with menstrual cycles

confer little/no risk of cancer

  • simple cysts
  • fibrosis
  • adenosis (incr acini per lobule)
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11
Q

breast cysts

cyst rupture

A

30-50 age group

originate from lobule dilatation and coalescence (green, brown, clear fluid)

  • if rupture**?*
  • release of secretory material into adj stroma → chronic infl/fibrosis → palpable firmness of breast

histo

  • flattened epithelium
  • columnar epithelium with features of apocrine cells (like sweat glands)
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12
Q

apocrine metaplasia

A

cells resemble apocrine sweat glands

enlarged cells w abundant eosinophilic cytoplasm, apical snouts

put lots of secretion into lumen

not a concern

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13
Q

adenosis

A

incr in number of acini per lobule

normal with pregnancy

focal finding in non-lactating breast

see: normal number of cell layers

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14
Q

gynecomastia

vs pseudogynecomastia

A

benign enlargement of glandular breast tissue in men

related to imbalance in estrogen/testosterone

  • birth (high maternal estrogen)
  • adolescence (hormone levels fluctuating)
  • middl-aged and older men (if overweight, estrogen higher; test levels dropping)

usually bilat

see dilated ducts, periductal fibrosis

pseudogynecomastia: deposition of adipose tissue (not breast tissue)

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15
Q

proliferative changes

A

typically, incr number of cells

vary in size/shape BUT look BENIGN/normal

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16
Q

sclerosis adenosis

A

proliferative change

presents as mass or density

  • incr acini
  • stromal proliferation and fibrosis

masses of small glands within a fibrous stroma

17
Q

intraductal papilloma

A

proliferative change

hyperplastic epithelial growth with a STALK (multiple papillae in complex arborizing pattern)

presents with unilateral bloody nipple discharge

usually solitary and located beneath the areola

  • lactiferous sinuses
  • occasionally multiple
18
Q

atypical hyperplasia

A

INCREASED CANCER RISK : 3.7-5.3x

ducts or lobules are partially filled with relatively monomorphic proliferation of reg spaced cells (sometimes w cribriform spaces)

19
Q

fibroadenomas

A

proliferation sof epithelium and stroma

most common benign neoplasm of breast (caused by prolif of lobular stroma)

  • seen in young women 15-25
  • round, well circumscribed, mobile
  • often solitary
  • can vary in size with menses, incr during preg → estrogen responsive
20
Q

Phylloides tumor

A

common in 40-50y

most offten BENIGN

  • assoc with chromosomal changes

key features

  • cellularity
  • mitotic rate
  • nuclear pleomorphism
  • stromal overgrowth
21
Q

breast cancer

risk factors

A

1. AGE

2. estrogen related (breast tissue has E receptors → constant exposure if it’s overabundant)

  • early menarche
  • late menopause
  • nulliparity
  • first full term preg after 30
  • obesity/incr BMI
  • long term/hi dose estrogen replacement tx

3. genetic

  • first degree relative with breast cancer
  • genetic predisposition: BRCA1, BRCA2
  • hx of breast, ovarian, endometrial cancer

4. radiation

  • prior radiation to breast area (ex. tx for Hodgkin’s disease)
  • high breast tissue density
22
Q

genetic risks of breast cancer

A

1 cause: “single gene” familial BC

80-90% BRCA1 and BRCA2

  • gen pop frequency: 1/400
  • having confers 10-30x higher risk than genpop
  • 3% of all breast cancer
23
Q

BRCA genes

A

tumor suppresor genes

code for large, multifx proteins:

  • repair of ds DNA breaks
  • transcription
  • ubiquitination
24
Q

BRCA1 related breast cancer

A

early onset (under50)

high rate of bilateral breast tumors

usually high grade, aneuploid

triple negative → poor prognosis

25
Q

breast cancer breakdown

noninv vs inv

A

non-invasive

  1. ductal carcinoma in situ
  2. lobular carcinoma in situ

invasive

  1. invasive ductal carcinoma 70-80
  2. invasive lobular carcinoma 8
  3. mixed ductal/lubular 7
  • medullary carcinoma - high grade/BRCA1
  • tubular carcinoma - good prognosis
26
Q

ductal carcinoma in situ

A

no inv of basement membrane

two types:

  1. Comedo: cells with high grade nuclei (atypical) AND central necrosis
  2. non-Comedo

​also…Paget disease

27
Q

Paget disease

A

nipple/areola disease

  • intraepidermal extension of malignant ductal epithelial cells through lactiferous ducts and ductules into epidermis
  • cytokeratin7 (CK7): specific, sensitive marker for mammary PD

sx

  • persistent dermatitis in nipple and adj areas
  • eczematous skin lesions assoc with erythema, scaling, itching, ulceration

assoc with DCIS, but often has a palpable mass linked to it → atypical presenting cancer!

28
Q

lobular carcinoma in situ

A

NOT considered true breast cancer → marker for incr risk of invasive cancer in same/both breasts

loss of E cadherin → single file proliferation??

29
Q

invasive breast cancer

A
  • palpable mass
  • abnormal screening mamogram (microcalcifications, nonpalp mass)

see: skin changes, breast erythema, edema

  1. invasive ductal carcinoma (70-80)
    • most commonly dx’d
    • spreads via lymphatics
  2. invasive lobular carcinoma (8)
    • “indian file cell arrangement”
    • multifocal w lymphatic spread
  3. medullary carcinoma 5
  4. coloid carcinoma <5
  5. tubular carcinoma 1-2
30
Q

key breast cancer markers

A

ER: estrogen receptor

PR: progesterone receptor

HER2/neu: epidermal growth factor receptr

common groupings of cancers

  • majority of cases: ER+/HER2-
  • HER2+ → trastuzumab tx
  • ER-/HER2+ → women: young, African descent, BRCA
31
Q

atypical presentations (1-2%)

A
32
Q

inflammatory breast cancer

A

invasive ductal carcinoma cells block dermal lymphatic vessels

highly aggressive

typically ER-/PR-

  • younger women, esp AfAm
  • more in obese

sx: swelling of breast, erythema affecting 1/3+, rapid onset, heaviness/burning/tenderness

initial treatment: CHEMOTHERAPY before surgical mgmt

33
Q

adjuvant tx for breast cancers

taxanes

anthracyclines

hormone tx

aromatase inhibitors

targeted tx

A
  • taxanes
    • taxol
  • anthracyclines
    • adriamycin (cardiotoxicity)
    • cyclophosphamide (hemorrhagic cystitis)
  • hormone tx
    • tamoxifen (selective estrogen receptor modulator for ER+ breast ca)
      • partial agonist in bone and endometrium
      • antagonist in breast
  • aromatase inhibitors (suppress pl estrogen levels in postmenop women via block of aromatase: req for estrogen synth)
    • anastrozole (no partial agonist activity → incr risk of bone breaks)
  • targeted tx
    • herceptin
34
Q

selective estrogen receptor modulators

A

diff profiles in diff areas (agonist/antagonist activities)

ex. tamoxifen

35
Q

know profile difference between tamoxifen and anastrozole and why

A

tamoxifen: SERM
anastrozole: aromatase inhibitor