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Repro II - PATH (Tobin) > Lecture 9: The Breast > Flashcards

Lecture 9: The Breast Flashcards

1
Q

How does the composition of breast change with aging and how is this related to imaging and ease of diagnosis?

A
  • Young women = ↑ fibrous interlobular stroma which appears radiodense or white on imaging; makes diagnosing tougher.
  • Older women have ↑ adipose tissue, which appears more radiolucent and helps with the interpretation of images
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2
Q

What 2 lesions of the breast arise in the intralobular stroma?

A
  • Fibroadenoma
  • Phyllodes tumor
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3
Q

What 4 lesions can arise in the interlobular stroma of the breast?

A
  • Fat necrosis
  • Lipoma
  • Fibromatosis
  • Sarcoma
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4
Q

What 4 lesions can arise in the large ducts of the breast?

A
  • Duct ectasia
  • Squamous metaplasia of lactiferous ducts
  • Large duct papilloma
  • Paget disease
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5
Q

What are milk line remnants and how do they most commonly come to attention clinically?

A
  • Supernumerary nipples or breast, anywhere from axilla –> perineum
  • Present as painful PRE-menstrual enlargements
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6
Q

What is the clinical significance of accessory axillary breast tissue; managed how clinically?

A
  • Potential site for malignancy or other lesions
  • Prophylactic mastectomies ↓ risk, but do NOT completely eliminate
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7
Q

Why is acquired nipple inversion of greater concern than congenital?

A

May indicate presence of an invasive cancer or an inflammatory nipple disease

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8
Q

Palpable masses of the breast are most commonly due to what 3 etiologies?

A
  • Cysts
  • Fibroadenomas
  • Invasive carcinoma
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9
Q

In what setting is nipple discharge most worrisome?

A

When spontaneous and unilateral; especially >60 y/o

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10
Q

What is the most common cause of bloody or serous discharge from th nipple?

A

Large duct papilloma

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11
Q

What characteristics of a density detected on mammogram is associated with benign vs. malignant lesions?

A
  • Benign = rounded densities
  • Malignant = irregular masses
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12
Q

How is DCIS most commonly seen on mammograms?

A

Calcifications –> small, irregular, numerous and clustered

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13
Q

When does acute mastitis typically occur and what are the signs/sx’s?

A
  • Typically during 1st month of breastfeeding
  • Breast is erythematous and painful, and fever is common
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14
Q

Squamous metaplsia of lactiferous ducts (aka recurrent subareolar abscess, periductal mastitis, and Zuska) disease commonly presents with what signs and sx’s?

A
  • Painful erythematous subareolar mass
  • Inverted nipple
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15
Q

Risk factors for squamous metaplsia of lactiferous ducts (aka recurrent subareolar abscess, periductal mastitis, and Zuska) include?

A
  • Smoking
  • Vitamin A deficiency
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16
Q

What are the key morphological features of squamous metaplsia of lactiferous ducts (aka recurrent subareolar abscess, periductal mastitis, and Zuska)?

A
  • Keratinizing squamous metaplasia of nipple ducts
  • Intense chronic granulomatous inflammation
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17
Q

What are the distinguishing features, signs and sx’s of duct ectasia?

A
  • Palpable periareolar mass w/ thick, white nipple secretions and occasionally skin retractionb
  • NO pain or erythema!
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18
Q

Duct ectasia most commonly occurs in which age group and what is a risk factor?

A
  • Women 40-60 y/o
  • Usually multiparous (birthed more than one child)
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19
Q

In duct ectasia the ectatic ducts are filled with inspissated secretions and numerous what?

A

Lipid-laden macrophages

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20
Q

What is the common clinical presentation of fat necrosis of the breast and what is a risk factor?

A
  • Painless, palpable mass + skin thickening or retraction
  • May also have mammographic densities or calcifications
  • 50% of women have hx of breast trauma or prior surgery
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21
Q

How does lymphocytic mastopathy (aka sclerosing lymphocytic lobulitis) most commonly present; associated with what underlying disorders?

A
  • Single or multiple HARD palpable masses or mammographic densities
  • Most common in women w/ T1DM or autoimmune thyroid disease
  • Autoimmune basis
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22
Q

What are the 3 principal morphological changes associated with nonproliferative breast changes (fibrocystic change)?

A
  • Cysts
  • Fibrosis
  • Adenosis
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23
Q

How can a FNA of a cyst associated with nonproliferative breast changes help confirm the diagnosis?

A

Dissapearance of the mass after FNA of its contents

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24
Q

The nonproliferative breast change, adenosis, is defined as what; and is a normal feature seen in which women?

A
  • ↑ in the number of acini per lobule
  • Normal feature of pregnancy
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25
Q

The acini of adenosis seen with nonproliferative breast change may show what histological change that is thought to be the earliest recognizable precursor of low-grade cancer?

A

Nuclear atypia (“flat epithelial atypia“)

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26
Q

Proliferative breast disease without atypia is characterized by what; what is the association with carcinoma?

A
  • Benign lesions –> proliferation of epithelial cells w/o atypia and are
  • Associated w/ small ↑ in risk for carcinoma
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27
Q

Which lesions of proliferative breast disease without atypia has an irregular shape and can closely mimic invasive carcinoma mammographically, grossly, and histologically?

A

Complex sclerosis lesion –> radial sclerosis lesion (aka radial scar)

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28
Q

What is the clinical significance of papilloma lesions as part of proliferative breast disease without atypia?

A

80% of large papillomas produce a nipple discharge can be bloody or serous

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29
Q

What are some of the underlying risk factors for gynecomastia?

A
  • Cirrhosis of liver –> ↑ estrogen
  • Drugs –> alcohol, marijuana, heroin, antiretroviral’s, and anabolic steroids
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30
Q

What is the seen microscopically in gynecomastia?

A

↑ in dense collagenous CT + epithelial hyperplasia of duct lining w/ tapering micropapillae (NO lobule formation)

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31
Q

Is gynecomastia associated with an increased risk for cancer?

A

Yes, small ↑ risk due to being proliferative breast disease without atypia

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32
Q

What is atypical breast disease with atypia and what are the 2 morphologic forms?

A
  • Clonal proliferation having some, but not all, of the histo. features required for dx of CIS
  • 2 forms = atypical ductal hyperplasia + atypical lobular hyperplasia
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33
Q

Which genetic feature of atypical lobular hyperplasia is shared with lobular carcinoma in situ?

A

Loss of E-cadherin

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34
Q

What is seen on biopsy of fat necrosis in the breast in both acute and chronic settings?

A
  • Acute = liquefactive fat necrosis w/ neutrophils and macrophages
  • Chronic = giant cells + calcifications and hemosiderin
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35
Q

Which in situ breast lesion is rarely palpable and almost always detected as calcifications on by mammography?

A

Ductal carcinoma in situ (DCIS)

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36
Q

Why is breast cancer in African American women associated with a higher overall mortality rate?

A

More likely to have biologically aggressive cancers –> ER-negative and a high nuclear grade

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37
Q

What is the average age of diagnosis for breast cancer in white women, hispanics and blacks?

A
  • White women = 61 y/o
  • Hispanics = 56 y/o
  • Blacks = 46 y/o
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38
Q

BRCA1 and BRCA2 mutations are prevalent in which ethnicity?

A

Ashkenazi Jews

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39
Q

What is the most common risk factor shared between breast and endometrial carcinoma which ↑ risk for carcinoma of the contralateral breast?

A

Prolonged estrogenic stimulation

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40
Q

Based on the expression of estrogen receptors and HER2, what is the most common subtype of breast cancer?

A

Estrogen receptor (+) and HER2 (-)

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41
Q

Which genetic mutation associated with hereditary breast cancer is most frequenty assoc. w/ male breast cancer?

A

BRCA2

42
Q

BRCA1 associated breast cancers commonly have what kind of differentiation and growth features?

A
  • Poorly differentiated w/ “medullary features”
  • Syncytial growth pattern w/ pushing margins and a lymphocytic response
43
Q

BRCA1-associated cancers are biologically similar to breast cancers with which estrogen receptor and HER2 expression; are identified as what?

A
  • ER (-) and HER2 (-)
  • “Basal-like”
44
Q

What is the differentiation of BRCA2-associated breast cancers like and they are more likely to have what ER expression?

A

Poorly differentiated, most often are ER (+)

45
Q

Which genetic mutation is associated with breast (female and male), ovarian, prostate, pancreas, stomach, gallbladder, bile duct, and pharynx cancer + melanoma?

A

BRCA2

46
Q

Li-Fraumeni syndrome is due to genetic mutation in what and is associated with what cancers?

A
  • TP53
  • Breast + sarcoma + leukemia + brain tumors + adrenocortical carcinoma
47
Q

BRCA1 and BRCA2 are part of a large complex of proteins with what fuctions?

A

Repair dsDNA breaks through homologous recombination

48
Q

Describe the pathway of breast cancer development starting with a germline BRCA2 mutations; which precursor lesions develop and what type of breast cancer?

A
  • Germline BRCA2 –> Flat epithelial atypia
  • Activating PIK3CA mutation —> Aytpical ductal hyperlasia
  • DCIS —> ER (+) - HER2(-) “luminal” breast cancer
49
Q

Flat epithelial atypia and atypical ductal hyperplasia often show which genetic mutations associated with developing ER(+) breast cancer?

A

Germline BRCA2 and activating PIK3CA

50
Q

Describe the pathway to breast cancer including precursor lesions and mutations in pt’s with germline TP53 mutations?

A
  • TP53 + HER2 amplification –> Atypical apocrine adenosis
  • DCIS –> HER2 (+) breast cancer
51
Q

What is the most common subtype of breast cancer in pt’s with Li-Fraumeni Syndrome?

A

HER2 positive

52
Q

What is the precursor lesion of HER2 positive breast cancers?

A

Atypical apocrine adenosis —> DCIS

53
Q

What is the most common subtype of breast cancer arising in patients with germline BRCA1 mutations?

A

ER (-) and HER2 (-) = “Basal-like”

54
Q

Sporadic tumors that are ER(-) HER2(-) have which genetic mutations?

A
  • Loss-of-function in TP53
  • May have epigenetic silencing of BRCA1
55
Q

What are the best predictors of local recurrence and progression to invasion for DCIS?

A

Nuclear grade and necrosis

56
Q

What are the 2 features which define comedo DCIS?

A

1) Tumors cells with pleomorphic, high-grade nuclei
2) Areas of central necrosis

57
Q

What are the morphological features of noncomedo DCIS, including cribiform and micropapillary DCIS?

A
  • Cribiform may have rounded (cookie cutter-like) spaces within ducts
  • Micropapillary has bulbous protrusions without a fibrovascular core, often arranged in complex intraductal patterns

*Pic on left = cribiform DCIS and on right = micropapillary DCIS

58
Q

What is seen on mammography with comedo DCIS?

A

Clustered or linear and branching areas of calcification

59
Q

Which ER and HER2 expression is most common of the carcinoma underlying Paget disease of the breast?

A

Poorly differentiated, ER (-) and HER2 (+)

60
Q

If patient presents with Paget disease of breast but does not have a palpable mass then what do they have?

A

DCIS

61
Q

What are the 3 major risk factors for recurrence and progression of DCIS?

A

1) High nuclear grade and necrosis
2) Extent of disease
3) Positive surgical margins

62
Q

What is the proliferation of cells like in LCIS and how is it discovered clinically?

A
  • Discohesive proliferation due loss of E-cadherin
  • ALWAYS an incidental finding on biopsy, there are NO calcifications or mammographic findings
  • As a result, its incidence did not ↑ after introduction of mammograms
63
Q

Between DCIS and LCIS, which is found bilateral more often?

A
  • LCIS is bilateral in 20-40% of cases****
  • DCIS is bilateral in 10-20%
64
Q

Which genetic mutation is associated with LCIS?

A

CDH1 leading to loss of E-cadherin

65
Q

What is the typical morphology and characteristic cell types found with LCIS?

A
  • Uniform population of cells w/ oval or round nucloli involving ducts and lobules
  • Mucin (+) signet-ring cells are common
  • Pagetoid spread is common, but LCIS does NOT involve nipple skin
66
Q

LCIS is associated with what type of ER and HER2 expression?

A
  • Almost always express ER (+) and PR (+)
  • HER2 is NOT observed
67
Q

LCIS is a risk factor for what?

A

Invasive lobular carcinoma in either breast!

68
Q

ER-positive, HER2-negative, high proliferation breast cancer is the most common type of carcinoma associated with what germline mutation?

A

Germline BRCA2

69
Q

ER-positive, HER2-negative, low proliferation breast cancer is most common type seen in which patients?

A
  • Older women and men
  • Most common type detected by mammographic screening
70
Q

What is the recurrence and metastatic behavior of ER-positive, HER2-negative, low-proliferation breast cancers like?

A
  • Lowest recurrence rate, late, >10 years
  • Metastasis late —> bone and long survival w/ metastasis is possible
71
Q

How does ER-positive, HER2-negative, low-proliferation respond to chemotherapy vs. high-proliferation types?

A
  • Low-proliferation = poor response to chemo, but respond well to hormonal tx
  • High-proliferation = has a higher % of complete response to chemo
72
Q

ER-positive, HER2-negative, high-proliferation will have increased nuclear staining for what?

A

Ki67

73
Q

What are the typical patient groups affected by HER2-positive breast cancers?

A
  • Young women
  • Non-white women
  • TP53 mutation carriers = Li-Fraumeni
74
Q

What is the metastasis and behavior of HER2-positive breast cancer like?

A

Can metastasize when small and early, often to viscera and brain, but also bone

75
Q

Why have some HER2-positive cancers become associated with a better outcome?

A

- >1/3 respond completely to chemo agents designed to block HER2 (Herceptin)

- Cancers that respond have excellent prognosis

76
Q

ER-negative, HER2-negative (“basal-like) breast cancers are most commonly seen in whom?

A
  • Young premenopausal women
  • African Americans
  • Hispanics
77
Q

ER-negative, HER2-negative (“basal-like) breast cancer shows a number of genetic similarities with what other carcinoma?

A

Serous ovarian carcinoma; associated w/ BRCA1

78
Q

What are the recurrences and metastatic behavior of ER-negative, HER2-negative (“basal-like) like?

A
  • Often metastastize when small and early –> viscera, brain and bone
  • Recurrences is common and generally within 5 years
79
Q

What is the response rate to chemo for ER-negative, HER2-negative (“basal-like) breast cancers?

A

30% completely respond to chemo

80
Q

What is the hitological hallmark of lobular carcinoma?

A

Discohesive infiltrating tumors cells, often w/ signet-ring cells containing intracytoplasmic mucin

81
Q

What is the characteristic pattern of metastatic spread with lobular carcinoma?

A
  • Peritoneum and retroperitoneum
  • Leptomeninges (carcinomatous meningitis)
  • GI tract
  • Ovaries (Kruckenberg) and Uterus
82
Q

Which genetic mutations is observed in a majority of medullary carcinoma?

A

Hypermethylation of BRCA1 leading to ↓ regulation

83
Q

What is the prognosis of medullary carcinoma and what histological finding is associated with higher survival rates?

A
  • Good prognosis
  • Presence of lymphocyte infiltrates in tumor assoc. with higher survival and greater response to chemo
84
Q

Which special type of invasive breast cancer is associated with tumor cells arranged in clusters and small islands of cell within large lakes of mucin?

A

Mucinous (colloid) carcinoma

85
Q

ER-negative, HER-negative tumors can have many histologic appearances, but which is most common?

A

Medullary carcinoma

86
Q

Inflammatory carcinoma is more often seen in whom; what is prognosis; what is characteristic clinical finding?

A
  • African Americans
  • Very poor prognosis - 3 year survival of 3-10%
  • Peau d’orange due to blockage of lymphatics by tumor
  • Tumor extensively invades and proliferates WITHIN lymphatics
87
Q

Tubular carcinoma is somtimes mistaken for what lesion; what immunohistochemical feature can help differentiate between the 2?

A
  • Sometimes mistaken for benign sclerosing lesion, like a radial sclerosing lesion
  • Immunostain for ER can help since almost all special subtypes of breast cancer are ER (+)
88
Q

What is the most important prognostic factor for invasive breast carcinoma in the absence of distant metastases?

A

Axillary lymph node status

89
Q

How is ER(+) and PR(+) related to therapeutic response?

A
  • Majority respond to hormonal therapy
  • Less likely to respond if only (+) for ER or PR
90
Q

Breast cancers that are ER (-) or PR (-) respond best to what type of therapy?

A

Chemotherapy

91
Q

Who is most often affected by Fibroadenomas and how do they present based on age?

A
  • Most common BENIGN tumor of female breast; most occur 20-30 y/o
  • Frequently multiple and bilateral palpable mass (younger women)
  • Older women more likely to have radiographic density or clustered calcifications
92
Q

Which benign tumor of the breast may fluctuate in size during pregnancy and menstrual periods; and is associated with women receiving cyclosporin A after renal transplants?

A

Fibroadenoma

93
Q

Fibroadenomas are catergorized as what type of proliferative lesions of the breast and how is this related to risk of cancer?

A
  • Proliferative changes WITHOUT atypia
  • Confer a mild ↑ risk for cancer
94
Q

How does the age of presentation for phyllodes tumor differ from that of fibroadenomas?

A

Most present in 50’s, which is 10 years later than fibroadenomas

95
Q

Overexpression of which transcription factor is associated with higher tumor grade and more aggressive behavior when assoc. w/ phyllodes tumor?

A

HOXB13

96
Q

How are phyllodes tumors distinguished from fibroadenomas based on histology?

A
  • Bulbous protrusions look like a leaf
  • Higher cellularity + mitotic rate
  • Nuclear pleomorphism
  • Stromal overgrowth + Infiltrative borders
97
Q

How likely is lymphatic spread of a phyllodes tumor based on grade and what is a special clinical consideration?

A
  • Regardless of grade, lymphatic spread = RARE
  • Axillary LN dissection = contraindicated
98
Q

Which benign tumor of the breast is unusual in that it is equally as common in both women and men?

A

Myofibroblastoma

99
Q

Who do most sporadic angiosarcomas of the breast arise in, what is their grade and prognosis?

A
  • Young women (mean age = 35 y/o)
  • High grade and poor prognosis
100
Q

What are risk factors acquired angiosarcomas of the breast and when do they arise?

A
  • Secondary to radiation therapy

or

  • Edema
  • Most often arising 5-10 years after tx

Repro II - PATH (Tobin) (7 decks)

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