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ENRP Exam 1 > Breast Pathology > Flashcards

Breast Pathology Flashcards

1
Q

what signaling pathways play a major role in breast development?

A

Wnt
FGF
PTHrP (parathyroid hormone-related protein)

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2
Q

Poland syndrome

A

born with missing or underdeveloped muscles on one side of the body resulting in chest, shoulder, arm and hand abnormalities

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3
Q

milk line remnants/supernumerary nipples

A

failure of regression of the thickened ectodermal streaks during 2-3 months of development

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4
Q

polymastia

A

supernumerary nipples with breast tissue and ducts

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5
Q

accessory axillary breast tissue

A

in some women, the normal ductal system extends into the subcutaneous tissue of the axillary fossa

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6
Q

congenital nipple inversion

A

failure of the nipple to evert during development

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7
Q

acquired nipple inversion

A

may indicate invasive cancer or inflammatory nipple disease

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8
Q

lymphatic drainage of the lateral breast

A

external mammary –> scapular –> central –> axillary –> subclavicular

OR

interpectoral –> subclavicular

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9
Q

lymphatic drainage of medial breast

A

internal mammary nodes

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10
Q

what hormone stimulates breast development?

A

estrogen

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11
Q

physiologic breast changes during pregnancy

A

breast completely matures and becomes functional

lobules increase progressively in number and size

by the end of pregnancy, the breast is almost completely composed of lobules separated by a scant stroma

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12
Q

physiologic breast changes of pre-menopausal women

A

third decade

lobules and stroma start to involute and stroma is converted to adipose tissue

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13
Q

what are the two major epithelial structures of the breasts?

A

lobules and ducts

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14
Q

what are the two types of epithelial cells that make up a lobule/duct?

A

luminal cells

myoepithelial cells

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15
Q

what cell signaling pathways contribute to epithelial cells within the lobules/ducts?

A

calponin
a-smooth muscle actin
p63
CD10

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16
Q

what are the two types of stroma that make up breast tissue?

A

interlobular

intralobular

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17
Q

most common palpable benign lesions

A

cysts and fibroadenomas

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18
Q

most common palpable malignant lesions

A

invasive ductal carcinoma

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19
Q

what are mammographic densities and when are they concerning?

A

breast lesions that replace adipose tissue with radiodense tissue

concerning when they form irregular masses

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20
Q

what are mammographic calcifications and when are they concerning?

A

calcifications form on secretions, necrotic debris or hyalinized stroma

small, irregular, numerous and clustered calcifications are concerning

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21
Q

what percentage of invasive carcinomas are not detected by mammography?

A

10%

the reason why all papable masses require further investigation

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22
Q

you diagnose a breast “mass”, what’s the next step?

A

biopsy

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23
Q

acute mastitis

A

associated with first month of breastfeeding due to cracks and fissures in the nipples

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24
Q

what bacteria causes abscesses in the setting of mastitis?

A

staphylococci

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25
Q

what bacteria causes cellulitis in the setting of mastitis?

A

streptococci

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26
Q

squamous metaplasia of lactiferous ducts (SMOLD)

A

subareolar mass that mimics bacterial abscess

fistula tract often develops under the smooth muscle of the nipple

nipple inversion may also occur

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27
Q

which population is most at risk to developing SMOLD?

A

smokers due to vitamin A deficiency which alters ductal epithelium

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28
Q

duct ectasia

A

granulomatous and fibrotic inflammatory reaction due to duct rupture

*multiparous women in 5th-6th decade

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29
Q

clinical presentation of duct ectasia

A

palpable periareolar mass
white nipple secretions
skin retraction

*may resemble invasive carcinoma

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30
Q

clinical presentation of fat necrosis

A

painless, palpable mass
skin thickening or retraction
mammographic densities or calcifications

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31
Q

etiology of fat necrosis

A

breast trauma or surgery

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32
Q

lymphocytic mastopathy/sclerosing lymphocytic lobulitis

A

fibroinflammatory lesion secondary to autoimmune reaction

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33
Q

clinical presentation of lymphocytic mastopathy

A

hardened mass in women with DM1 or autoimmune thyroid disease

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34
Q

granulomatous lobular mastitis

A

rare disease that occurs in parous women

granulomas closely associated with lobules

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35
Q

cystic neutrophilic granulomatous mastitis

A

type of granulomatous mastitis caused by lipophilic Corynebacteria

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36
Q

which epithelial breast pathology has the highest risk of developing invasive carcinoma?

A

proliferative disease with atypia

ex: atypical ductal hyperplasia, atypical lobular hyperplasia

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37
Q

nonproliferative/fibrocystic changes

A

“lumps and bumps”

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38
Q

what morphologic changes are associated with fibrocystic changes?

A

cystic
fibrosis
adenosis

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39
Q

adenosis

A

increase in the number of acini per lobule

*normal feature of pregnancy

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40
Q

lactational adenomas

A

palpable masses in pregnant or lactating women

*regress with cessation of breastfeeding

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41
Q

proliferative breast disease without atypia

A

characterized by proliferation of epithelial cells without cytologic atypia

associated with a small increased risk of invasive carcinoma

42
Q

what morphologic changes are associated with proliferative breast disease without atypia?

A 
epithelial hyperplasia
sclerosing adenosis
complex sclerosing lesion
papilloma
gynecomastia
43
Q

clinical presentation of large duct papillomas

A

nipple discharge - serous or serosanguinous

44
Q

proliferative breast disease with atypia

A

clonal lesion characterized by proliferations of either ductal or lobular epithelial cells

have some but not all histo features of carcinoma in situ

associated with a moderate increase in risk of carcinoma

45
Q

what morphologic changes are associated with proliferative breast disease with atypia?

A

atypical ductal hyperplasia (ADH)

atypical lobular hyperplasia (ALH)

46
Q

what features are shared between ADH and ALH

A

express high levels of estrogen receptors (ER)
have a low rate of proliferation
may have acquired chromosomal aberrations such as losses of 16q, 17p or gains of 1q

47
Q

feature specific to ALH

A

loss of E-cadherin expression

*shared feature with LCIS

48
Q

feature specific to ADH

A

absence of cytokeratin 5/6 and diffuse positivity for ER

49
Q

3 major groups of breast cancers

A

ER+, HER2- (luminal)
HER2+
ER-, HER2- (triple negative)

50
Q

characteristics of hereditary breast cancer

A 
AD trait
high penetrance
early onset
bilateral or multifocal cancers
multiple primary cancers
51
Q

characteristics of familial breast cancer

A

low penetrance
variable age of onset
may result from common genetic background, similar environment or lifestyle factors

52
Q

which genes are associated with the highest susceptibility for breast cancer

A

BRCA1 –> Ch 17

BRCA2 –> Ch 13

53
Q

what is the most common pathogenesis of breast cancer

A

sporadic (65%)

54
Q

histological subtypes of low proliferation luminal breast cancers

A

tubular
grade 1 or 2 lobular
mucinous
papillary

55
Q

histological subtype of high proliferation luminal breast cancers

A

grade 3 lobular

56
Q

histological subtype of HER2+ breast cancer

A

apocrine

micropapillary

57
Q

histological subtypes of triple-negative breast cancers

A

medullary features

metaplastic

58
Q

most common gene mutations in all types of breast cancer

A

PIK3CA

TP53

59
Q

low proliferation luminal cancer

A

40-50%
older women and men
low grade with low recurrence rate
mets usually to bone

*responds well to antiestrogenic drugs

60
Q

high proliferation luminal cancer

A

10%
increased nuclear staining for Ki67
most common form associated with BRCA2

61
Q

how does estrogen contribute to luminal breast cancer

A

increases local production of growth factors
stimulates breast growth
proliferation leads to accumulated DNA damage
stimulates growth of premalignant or malignant cells

62
Q

recurrence pattern for luminal breast cancer

A

lowest rate of recurrence in the first 10 years

but recurrences continue with a steady rate over a long period of time

63
Q

recurrence pattern for HER2 breast cancer

A

mixed pattern with both early and late peaks

*late peak may be due to acquired resistance to therapy

64
Q

recurrence pattern for triple-negative breast cancer

A

occur within the first 8 years

*recurrences after this time are rare

65
Q

HER2 breast cancer

A

10-20% of all breast cancer
poorly differentiated
gene expression largely based on ER status

*most common subtype in patients with Li-Fraumeni syndrome (TP53 mutation)

66
Q

HER2 physiological role

A

receptor tyrosine kinase that promotes cell proliferation and opposes apoptosis

67
Q

proto-oncogene for HER2

A

ERBB2

*amplification leads to overexpression of HER2

68
Q

HER2 breast cancer treatment

A

trastuzumab (Herceptin)

*MoAb that binds and inhibits HER2

69
Q

triple-negative breast cancer

A

“basal-like” cancer –> expressed in basally located myoepithelial cells

estrogen-independent pathway and not associated with HER2 overexpression

young premenopausal women especially AA and Hispanics

likely to present as palpable mass between mammograms due to high proliferation

BRCA1 association

70
Q

carcinoma in situ

A

clonal proliferation that is confined to ducts and lobules
no extension beyond basement membrane
myoepithelial cells preserved
ductal (DCIS) or lobular (LCIS)

71
Q

how is carcinoma in situ detected on mammogram?

A

micro Ca++ or periductal fibrosis

72
Q

describe the progression from normal breast tissue to luminal cancer (ER+)

A

germline BRCA2 mutation –> flat epithelial atypia
PIK3CA mutation –> atypical ductal hyperplasia
ADH –> DCIS –> invasive cancer

73
Q

describe the progression from normal breast tissue to HER2 cancer

A

germline TP53 mutation + HER2 amplification –> atypical apocrine adenosis –> DCIS –> invasive cancer

74
Q

describe the progression from normal breast tissue to triple-negative cancer

A

germline BRCA1 mutation + TP53 mutation + BRCA1 inactivation –> DCIS –> invasive cancer

75
Q

treatment for DCIS

A

lumpectomy vs mastectomy + chemo

post-op radiation + tamoxifen

76
Q

risk factors for DCIS progression

A

nuclear grade and necrosis
extent of disease
positive surgical margins

77
Q

paget disease of the nipple

A

rare manifestation of breast cancer that presents as unilateral erythematous eruption with scale crust

78
Q

what is the MOA of paget disease

A

malignant cells extend from DCIS within the ductal system via the lactiferous sinuses into the nipple skin without crossing the basement membrane

tumor cells disrupt the normal epithelial barrier, allowing extracellular fluid to seep out

79
Q

which cancer gene is associated with Paget disease?

A

HER2

80
Q

lobular carcinoma in situ

A

clonal proliferation of cells that grow in a discohesive fashion due to mutation in CDH1 that leads to loss of E-cadherin

always incidental finding (no mammogram findings)

bilateral in 20-40% of cases

risk factor for invasive cancer

ER+, HER2-

81
Q

lobular carcinoma pattern of metastasis

A

peritoneum and retroperitoneum
leptomeninges
GI tract
ovaries and uterus

82
Q

carcinoma of medullary pattern

A

associated with hypermethylation of BRCA1 (NOT germline)

associated with infiltrating T-cells

better prognosis than poorly differentiated carcinomas

83
Q

inflammatory carcinoma

A

3% of breast cancers
higher incidence in AA
very poor prognosis

84
Q

what skin finding is associated with inflammatory carcinoma?

A

peau d-orange –> due to extensive plugging of lymphovascular spaces of the dermis with carcinoma cells

85
Q

stage 0 breast cancer

A

DCIS
no mets
97% survival

86
Q

stage 1 breast cancer

A

invasive CA ≤ 2cm
no mets
87% survival

87
Q

stage 2 breast cancer

A

invasive CA > 2cm + 1-3 LNs involved
invasive CA > 2cm but ≤ 5 cm + 0-3 LNs involved
65% survival

88
Q

stage 3 breast cancer

A

invasive CA > 5cm with or without LNs
any size invasive CA + ≥ 4 LNs involved
inflammatory CA with or without LNs
40% survival

89
Q

stage 4 breast cancer

A

any size CA with or without LN + distal mets

5% survival

90
Q

carcinoma en cuirasse

A

extensive local disease, causing ulceration to the skin

occurs in untreated breast cancer

91
Q

gynecomastia

A

only benign lesion of the male breast

estrogen/androgen imbalance that leads to stimulation of breast tissue

subareolar enlargement that may be bilateral

92
Q

causes of gynecomastia

A 
liver disease
decreased testosterone
drugs
XXY karyotype
testicular neoplasms
93
Q

mnemonic for drugs causing gynecomastia

A

DISCOS

digoxin
isoniazid
spironolactone
cimetidine
o = estr"o"gens 
stilboestrol
94
Q

what is the lifetime risk of a male developing breast cancer?

A

0.11%

95
Q

fibroadenoma

A

most common benign tumor of the female breast

caused by mutations in MED12

96
Q

what drug is associated with the formation of fibroadenoma?

A

cyclosporine A given post-renal transplant

97
Q

are fibroadenomas associated with an increased risk of carcinoma?

A

yes - even higher if “complex” features are present

ex: large cysts, sclerosing adenosis, calcifications, or apocrine changes

98
Q

phyllodes tumor

A

similar to fibroadenoma however has higher cellularity, higher mitotic rate, nuclear pleomorphism, stromal overgrowth and infiltrative borders

high-grade are malignant whereas low grade resemble fibroadenoma

99
Q

what benign lesions arise within the breast stroma?

A

myofibroblastoma
lipomas
fibromatosis

100
Q

what is the most common malignant stromal tumor?

A

angiosarcoma

*associated with prior radiation or Stewart-Treves syndrome

101
Q

what secondary malignancies may arise in the breast?

A

lymphoma
skin
mets from another site

ENRP Exam 1 (20 decks)

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