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Endo/Repro II Test 1 > 3. Robbins Breast Pathology > Flashcards

3. Robbins Breast Pathology Flashcards

1
Q
A
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2
Q

What is the functional unit of the breast and where many breast cancers arise?

A

Terminal duct lobular unit = lobule + duct

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3
Q

Describe the TDLU.

A
  • In each lobe, lactiferous duct branches repeatedly, forming many terminal ducts, each connecting to a LOBULE, which contains many acini that makes milk (TERMINAL DUCT + LOBULE = TDLU)
  • Terminal duct can be broken down into:
      1. Intralobular terminal duct: within the duct, intralobular ducts carry milk from acini (functional unit of the breasts) => extralobular terminal duct for each lobule
      1. Extralobular terminal duct: attaches to the lobule
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4
Q

Describe breast epithelium.

A

Lines surface of ducts and lobules.

Contains 2 layers of epithelium, over BM.

    1. Luminal columnar epithelial cells: innermost layer that secretes milk
    1. Myoepthielial cells: outermost layer that are contractile and respond to oxytocin.
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5
Q

Breast stroma

A

2 different kinds

1. Intralobular stroma: surrounds acini and hormonally responsive fibroblast-like cells

2. Interlobular stroma: dense fibrous CT and fat

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6
Q

What 6 lesions can arise in the lobules and terminal ducts of the breast?

A
  1. Cysts
  2. Sclerosing adenosis
  3. Small duct papilloma
  4. Hyperplasia
  5. Atypical Hyperplasia
  6. Carcinoma
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7
Q

What are developmental disorders of the breasts?

A
  • 1. Milk line remnants
  • 2. Acessory axillary breast tissue
  • 3. Congenital nipple inversion
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8
Q

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

A
  • Breast tissue develops from embryonic structures called milk lines, two epidermal thickenings that form the breast and nipples.
  • Milk lines run from axilla => groin and form usually dissppear in development, except in breasts. Persistance of epidermal thickenings (milk line remnants) along the milk lines that form a 3rd nipple or breast (supernumerary nipples/breasts called polythelia/polymastia), usually below NL breasts.
  • Present as painful PRE-menstrual enlargements​
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9
Q

What is accessory axillary breast tissue?

A

NL ductual tissue extends to the subQ tissue of the chest wall or axilla.

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10
Q

What are clinical presentation of breast disease?

A
  1. Pain (mastalgia/masodynia): cyclic with period or noncylic: almost all painful masses are benign but 10% of breast cancers are painful
  2. Palpable mass
  3. Nipple discarge
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11
Q

Causes of:

  • Cyclic breast pain
  • Noncyclic breast pain
A
  1. Cyclic; often diffuse and due to premenstrual edema
  2. Noncyclic; often localized and due to ruptured cyst, injury, infection.
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12
Q

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

A
  1. Malignancy and other lesions can occur
  2. Prophylactic mastectomies ↓ risk, but do NOT completely eliminate
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13
Q

Why is acquired nipple inversion of greater concern than congenital?

A

Can indicate invasive cancer or an inflammatory nipple disease

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14
Q

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

A
  1. Cysts
  2. Fibroadenomas
  3. Invasive carcinoma
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15
Q

Are most palpable masses benign or malignant?

A
  • Benign in premenopausal women, but ↑ chance of malignancy with ↑ age: 60% > 50YO.
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16
Q

Why does screening for palpable masses have LITTLE effect on mortality?

A

Once a palpable mass is felt, the cancer is often metasized.

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17
Q

In what setting is nipple discharge most worrisome that it is cancer?

A

Spontaneous, unilateral and >60YO

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18
Q

In what situations do we most often see the following types of discharge:

1. Milky (galactorrhea)

2. Bloody or serous

A
  1. ↑ prolactin, hypothyroidism, endocrine anovulatory syndromes and meds (OC, TCA, methyldopa, phenothiazines)
  2. Cysts or large duct (intraductal) papillomas;
    1. ​blood = pregnancy
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19
Q

Where are benign breast masses and malignant breast cancers most common on the breast?

A
  • Benign: anywhere
  • Malignant breast cancer: Upper outer quadrant (50%) bc has most breast tissue > Subareolar/central region (20%)
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20
Q
  • ______\_ lesions are more common in premenopausal women
  • _______ lesions are more common in post-menopausal women (corollary ^^)
  • Only ____ of cancer are detected as a palpable mass. How are the others detected?
A
  • Benign => premenopausal
  • Malignant => post-menopausal
  • 1/3; mammogram
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21
Q
  • What are the the principal signs of breast cancer on mammograms, the most common way to detect breast cancer?
A
  1. Densities
  2. Calcifications
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22
Q

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

A
  • Benign fibroadenoma or cyst = rounded densities
  • Malignant = irregular masses
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23
Q

On mammogram:

Benign calcifications are usually due to:

Malignant calfications (ductal carcinoma in-situ) are described as:

A
  • Benign: clusters of apocrine cysts, hyalinized fibroadenomas and sclerosing adenosis
  • Malignant: small, irregular, numerous and clustered
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24
Q
  • Screening with mammograms has increased the diagnosis of _____________.
  • After mammogram, perform ____.
A
  • DCIS (ductal carcinoma in-situ), because it is most often detected by calcifications
  • Biopsy
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25
Q

Breast inflammation (mastitis) is RARE except during ________ and occurs due to what?

A
  • Lactation
  • Infections, AI disease and FB reactions to leaked keratin or secretions.
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26
Q

What can mimic inflammation of the breast?

A

Inflammatory breast cancer bc it can obstruct dermal vasculature with tumor emboli

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27
Q

What are the types of inflammatory breast disorders?

A
  1. Acute mastitis
  2. Squamous metaplasia of lactiferous ducts
  3. Ductal ectasia
  4. Fat necrosis
  5. Lymphocytic mastopathy (diabetic mastopathy)
  6. Granulomatous mastitis
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28
Q

KEY WORDS:

  1. Mastitis
  2. Mammary Duct Ectasia
  3. Fat Necrosis
A
  1. Mastitis: erythema and tender
  2. Mammary Duct Ectasia: white discharge
  3. Fat Necrosis: due to trauma
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29
Q

What is acute bacterial mastitis?

Symptoms?

Tx?

A
  • During the 1st month of breastfeeding, sucking can cause trauma (cracks and fissures) of the nipple, making it vulnerable to bacteria, particulary S. aureus.
  • Breast is red, painful +/- fever
  • Tx: ABX, continue breastfeeding; rarely perform surgical drainage
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30
Q

What is Squamous Metaplasia of Lactiferous Ducts (also called what)?

A

Periductal mastitis; Recurrent subareolar abscess, and Zuska disease.

  • Inflammation of the subaerolar ducts seen in smokers, that forms a painful, red subaerolar mass with nipple retraction
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31
Q

What symptoms is commonly seen in Squamous Metaplasia of Lactiferous Ducts?

A

Inverted nipples

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32
Q

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

A
  1. Tobacco smoke
  2. Relative vitamin A deficiency
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33
Q

Key morphological features of squamous metaplasia of lactiferous ducts (aka recurrent subareolar abscess, periductal mastitis, and Zuska)?

A
  • Squamous metaplasia of lactiferous duct: Cuboidal epithelium => keratinzed squamous epithelium
    • => Keratin is shed and plugs ducts
    • => Ducts rupture and dilate
    • => Intense chronic granuloma inflammation
    • => fibrosis => myofibroblasts contracts => invert nipple
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34
Q

Treatment for Squamous Metaplasia of Lactiferous Ducts

A
  1. Simple incision drains abcesses; but can recur is keratinized epithelium stays
  2. En block surgical removal of duct and fistula cures
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35
Q

What is duct ectasia?

What is it caused by?

A
  • Benign chronic Inflammation and fibrosis of the subareolar duct => dilation due to build up of inflammatory debris=> irregular, palpable periareolar breast mass (painLESS and NOT red) below the nipple + white discharge
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36
Q

Clinical case of duct ectasia?

MC in who?

A

Older W (50-60 YO) with many children (multiparous) presents to the clinic with breast mass right below nipple with thick, white disharge.

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37
Q

In duct ectasia, the ectatic ducts are filled with what?

A
  1. Inspissated secretions
  2. Lipid-laden MO
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38
Q

What is the PRINCIPAL SIGNIFICANCE of ductal ectasia worrisome?

A

Mimics invasive carcinoma clinically and on imaging because it is more common in POST-menopausal women

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39
Q

What is fat necrosis of the breast?

A

Necrosis of breast fat, usually due to trauma or hx of prior surgery that causes benign inflammatory process that forms a [painless, palpable mass with thick skin/retraction] and form calcifications/densities.

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40
Q

What inflammatory cells do we see in fat necrosis of the breast in acute vs chronic?

A
  • Acute = MO and neutrophils;
  • Chronic= fibroblasts and inflamm cells form giant cells, calficiation and deposition of hemosiderin, forming scar tissue.
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41
Q

What are lymphocytic mastopathy (aka: ____________)?

A

Sclerosing lymphocytic lobulitis/ diabetic mastopathy

  • Single or multiple rock hard masses that on histology, show:
    1. Atrophic ducts surrounded by collagenized stroma
    2. Thick BM, surrounded by lympocytes
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42
Q

Lymphocytic mastopathy most commonly occurs in patients who have what?

A
  1. T1DM
  2. Autoimmune thyroid diseases

suggesting it is AI

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43
Q

How are benign epithlial breast lesions categorized?

A

Risk of development into breast cancer

    1. Non-proliferative breast changes/fibrocytic: all benign; no increase risk in BC
    1. Proliferative breast changes, without atypia: SMALL increase risk in BC
    1. Atypical hyperplasia: moderate increase risk of cancer bc has SOME, but not all features to dx as CIS
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44
Q

3 types of nonproliferative breast changes (fibrocystic change),

A
  1. Cysts, often with apocrine metaplasia
  2. Fibrosis
  3. Adenosis
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45
Q
  • Non-proliferative breast changes (fibrocystic change) are a group of morphological fibrocystic changes of the breasts that are all benign => no risk of breast cancer (non-proliferative) that lead to ___________ most commonly in ________
A

lumpy-bumpy breasts in pre-menopausal women

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46
Q

Describe the non-proliferative breast changes

A
  1. Simple Cysts: Fluid filled, round cysts that contain dark fluid: turbid, semi-translucent brown-blue fluid (blue domed cyst) formed by the dilation of lobules and lined with [flat, atrophic epithelium] or [metaplastic apocrine cells]
  2. Fibrosis: Occurs when a cysts ruptures and releases secretory material into the => fibrosis, creating lumpy bumpy breasts
  3. Adenosis: ↑ # of acini/lobule that occurs normally during pregnancy
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47
Q

Diagnosis of Simple Cysts

A

Fine needle aspiration of cysts causes it to disappear

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48
Q

Adenosis,↑ in the number of acini per lobule, may show what histological change that is thought to be the earliest recognizable precursor of low-grade cancer, even though there is NO increase risk of breast cancer.

A

“Flat epithelial atypia” of columnar cells due to a Chr16q deletion.

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49
Q

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

A
  • Proliferations of epithelial cells without atypia, causing only a SMALL ↑ risk of breast cancer, but NOT true precursors to cancer
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50
Q

4 types of Proliferative Breast Disease without Atypia

A
  1. Epithelial hyperplasia
  2. Sclerosing adenosis
  3. Complex Sclerosing Lesion
  4. Intraductal papilloma
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51
Q

What is Epithelial Hyperplasia?

A
  • ↑ # of luminal and myoepithelial cell, which fill & distend ducts and lobules usually found incidentally.
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52
Q

What is Sclerosing Adenosis?

A
  • ↑ # of acini/glands and dense fibrosis in central part of the lesion => dense stroma compresses the glands
  • Often could undergo calcification.
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53
Q

What are complex sclerosing lesions?

A

Lesions that have compenents of

  1. sclerosing adenosis
  2. papilloma
  3. epithelial hyperplasia.
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54
Q

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

A

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

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55
Q

When do cysts cause concern?

A

When solitary and firm

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56
Q

Describe a radial sclerosing lesion.

A
  • Central area of entrapped glands in hyalinized stroma surrounded by long, radiating projections into stroma
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57
Q

Describe intraductal papillomas.

A

Fibrovascular projections lined with epithelial cells (both kinds) that extend inside of ducts (intraductal) that cause blood/serous discharge MC in premenopausal women

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58
Q

80% of papillomas present with bloody/serous discharge.

What is frequently seen with papillomas

A

epithelial hyperplasia & apocrine metaplasia (NOT a pre-cursor to cancer)

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59
Q

What is the ONLY benign lesion seen in the male breast?

A

Gynecomastia caused by androgen/estrogen imbalance.

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60
Q

What do we see physically in gynocomastia?

Associated with a increase risk of cancer?

A
  • Unilateral or bilateral buttonlike subareolar enlargement that is associated with a SMALL increase risk of breast cancer.
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61
Q

What is the seen histologically in gynecomastia?

A
  1. ↑ in dense collagen CT
  2. + epithelial hyperplasia of ducts
  3. + tapering micropapillae (NO lobule formation)
  4. No lobules form
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62
Q

What are some of the underlying risk factors for gynecomastia?

A
    • Cirrhosis–> liver is not metabolizing estrogen
    • Drugs –> alcohol, marijuana, heroin, antiretroviral’s, and anabolic steroids
  3. Puberty
  4. Klinefelters (M 47 XXY; male hypogonadism => decrease testosterone)
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63
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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64
Q

2 types of Proliferative Breast Diseases with Atypia

A
  1. Atypical ductal hyperplasia
  2. Atypical lobular hyperplasia
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65
Q

What is proliferative breast diseases with atypia?

A

Atypical hyperplasia that has with some, but not all, histological features of ductal carcinoma in situ (DCIS)

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66
Q

What is the difference between atypical ductal hyperplasia and atypical lobular hyperplasia?

A
  • Atypical ductal hyperplasia (ADH): histologically looks like DCIS (ductal carcinoma in-situ), but duct is PARTIALLY FILLED* with different cells:
    • Periphery = oriented columnar cells
    • Center = round cells.
    • Some spaces are round and peripheral spaces have slits.
  • Atypical lobular hyperplasia (ALH): histologically identical to LCIS: lobules are filled with discohesive cell growth (loose intercellular connections) dt lose of E-cadherin => cells become round/clump together, but do NOT take up more than 50% of lobule acini
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67
Q

What genetic abnormalities do we see in BOTH ADH and ALH?

A
  1. Loss of Chr 16q
  2. Gain of Chr 17p
  • *** Both also seen in CIS
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68
Q

Which genetic feature of atypical lobular hyperplasia (ALH) is shared with lobular CIS?

A
  • Loss of E-cadherin
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69
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 MO
  • Chronic = giant cells + calcifications and hemosiderin => scar tissue
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70
Q

What is the most common non-skin malignancy in females?

A

Breast cancer

  • 2nd leading cause of cancer deaths in women, after lung cancer
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71
Q

_____ of women in the US will get breast cancer by 90 YO

A

12.4% or 1/8

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72
Q

Almost all breast cancers are ______ and can be divided based on ________

A
  • Adenocarcinomas
  • if they express estrogen receptor (ER) and HER2
73
Q

3 categories of breast cancers based on predictive markers, in order of MC to LC (each have different treatments and outcomes)

A
    1. ER (+) / HER2 (-) = 50-65%
    1. ER (+/-) / HER2 (+) = 10-20%
    1. ER (-) / HER2 (-) = 10-20%
74
Q

Incidence and epidemiology of breast cancer

A
  • Most common in white women >60YO
    • Rare in females <25
    • After 30
      • ​incidence of ER (+) ↑
      • incidence of ER (-) and HER2 (+) are relatively constant
75
Q

Risk factors that increase risk of breast cancer

Dense breasts on mammogram = higher risk of ____.

A
  1. Western lifestyle: later pregnancy, less pregnancies, and decreased breastfeeding
  2. W women (Non-hispanic women > Ashkenazi Jews) > hispanics > AA
  3. Estrogen exposure
    1. MHT
    2. Earlier menarche or later menopause
    3. Obesity
    4. Breast feeding = protective
  4. Age of pregnancy: later or no PG (younger bb= more protective)
  5. Benign breast disease
  6. Dense breasts on mammogram = 4-6 fold risk risk of ER +/-.
  7. Radiation
  8. Carcinoma of contralateral breast or endometrium
76
Q

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

A
  1. More likely to have aggressive cancers: ER (-) and a high nuclear grade
  2. Unequal access to care
77
Q

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

A
  1. White = 61 y/o
  2. Hispanics = 56 y/o
  3. Blacks = 46 y/o
78
Q

BRCA1 and BRCA2 mutations are particularly prevalent in which ethnicity?

A

Ashkenazi Jews

79
Q

Breast cancer diagnosed in ppl under 50 is most common in who?

A

1. AA (35%)

2. Hispanics (31%)

80
Q

QUESTIONS:

  1. Do oral contraceptives increase risk of BC?
  2. Does Oophorectomy or Antiestrogenic drugs reduce risk of estrogen receptor (+) BC?
A
  1. no
  2. yes
81
Q

Who is more likely to have an increase risk of BC:

  • 1. Obese post-menopausal F
  • 2. Obese F under 40
A
  • Obese postmenopausal females due to estrogen synthesis in fat depots
    • Obese females < 40 ↓ risk due to anovulatory cycles & ↓ progesterone levels
82
Q

Why do we see lower rates of breast cancer in developing countries where they breastfeed their kids longer?

A
  • Lactation suppresses ovulation => trigger terminal differentiation of luminal cells
83
Q

Breast cancer can be familial or sporadic.

FAMILIAL BREAST CANCER

A
84
Q

FAMILIAL BREAST CANCER

  • Inheritance:
  • Makes up____% of breast cancer.
  • Susceptibility genes include: ___________
  • 80-90% of single-gene familial breast cancers are due to _____ mutations
A
  • AD
  • 12%
  • Tumor suppressor genes BRCA1, BRCA2, TP53, CHEK2
  • BRCA1 and BRCA2
85
Q

What is the function of BRCA genes?

A

Tumor suppresors that repair dsDNA breaks via homologous recombination

86
Q

Cancers BRCA1/BRCA2 mutations increase risk for

A
  • BRCA1 = higher risk of developing ovarian cancer (20-40%); fallopian
  • BRCA2 = lower risk for developing ovarian cancer (10-20%); stomach, melanoma, GB, BD, pharynx
  • Both increase risk of developing epithelial cancer (prostatic and pancreatic), male breast cancer (more often due to BRCA 2)
87
Q

How are BRCA mutations commonly diagnosed?

A

Genetic testing is hard due to variants, but restritcted to those with a strong family history (Ashkanazi Jews) .

88
Q

BRCA1

  • Located:
  • % of single-gene heriditary breast cancers:
  • Features (2)
  • Markers
  • Biologically similar to what type of breast cancers and thus, called what?
A
  • Chr17q21
  • 52%
  • Features:
    1. Poorly differentiated with medullary features (syncytial growth-pattern w/ pushing margins and lymyphocytes);
    2. have TP53 mutations
  • Basal-like (triple negative): ER (-), HER2 (-), Progesterone (-)
  • ER (-)/HER2 (-) breast cancers, thus they are called basal-like
89
Q

BRCA2

  • Located:
  • % of single-gene heriditary breast cancers:
  • Feature (1)
  • Marker:
  • Biallelic germine mutation will cause what?
A
  • 13q12-13
  • 32%
  • Features
    1. Poorely differentiated
  • More often ER (+)
  • rare Fanconi anemia
90
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
91
Q

TP53 (Familial BC)

  • Most common what?
  • Markers
A
  1. Most common mutated gene in sporadic breast cancer
  2. 50% are ER (-)/ HER2 (+)
92
Q

CHEK2

  • Associated cancers:
  • Increases risk for:
  • Markers:
A
  • Prostate, thyroid, kidney and colon
  • ↑ risk for breast cancer after exposed to radiation
  • 70-80% are ER (+)
93
Q

SPORADIC BREAST CANCER

  • What is the MAJOR risk factor to sporadic BC?
    • ​How?
A

Hormone exposure: estrogen =>

  1. Stimulates breast growth in puberty, menstrual cycles and PG =>
  2. Proliferation of epithelium => damaged DNA accumlates =>
  3. Damage is fixed => Risk of cancer increases
  4. Hormones stimulate growth of premalignant/malignany cells and stromal cells
94
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

95
Q
  • Almost all of breast cancers are _____ that arise from what?
  • When detected, what is their status?
A
  • Adenocarcinomas, that arise from a precursor lesions (DCIS/LCIS)
  • When detected, majority breached BM and invaded stroma.
96
Q

Describe how ER (+)/ HER2 (-) breast cancer develops

  • Which precursor lesions develop
  • What type of breast cancer?
A
  1. Germline BRCA2 => [Flat epithelial atypia]
  2. PIK3CA mutation => [Aytpical ductal hyperlasia]
  3. [DCIS] => ER (+) / HER2(-) “luminal” invasive breast cancer
97
Q

Describe how HER2 (+) breast cancer develops

  1. Which precursor lesions develop
  2. What type of breast cancer?
A
  1. TP53 mutation + HER2 amplification –> [Atypical apocrine adenosis]
  2. [DCIS] –> HER2 (+) invasive breast cancer (can be ER+/-)
98
Q

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

A

HER2 (+)

99
Q

What is the precursor lesion of HER2 (+) breast cancers?

A

Atypical apocrine adenosis —> DCIS

100
Q

ER (-)/HER2 (-) basal-like triple-negative cancer

  • How do they arise?
  • Most often is seen in breast cancer associated with what mutations?
  • MC in who?
A
  • Pathways not associated with ER/HER2
  • Mutations:
    1. Familial/heriditary = BRCA1****
    2. Sporadic = LOF TP53
  • African - Americans
101
Q

Development of neoplastic cells depend on what?

A
  1. Interactions with stromal cells in the local environment
102
Q

What are the 2 CIS (carcinoma in-situs), which arise from the terminal duct lobular unit (TDLU)?

A
  1. Ductal carcinoma in-situ (DCIS)
  2. Lobular carcinoma in-situ (LCIS)
103
Q

DCIS (ductal carcinoma in-situ)

  • Definition :
  • Bilateral/unilateral?
  • Pattern:
  • Detected:
  • Complications:
A
  • Definition: Tumor cells grow from the wall of the ducts, into and fill the lumen, but limited by an intact BM
  • Bilateral in only 10-20% of cases
  • Pattern (2):
      1. Comedo DCIS
      1. Non-comedo (cribiform pattern)
  • Detected:
    • Always by mammogram bc forms microcalfications, but nipple discharge is rare
  • Complications:
    • Paget syndrome: unilateral red eruption and crusty nipple indicative of invasive carcinoma caused when cancer cells migrate along the lacteriferous duct, without crossing BM => nipple skin => inflammation, ECF leaks onto nipple => blody nipple discharge that dries and forms crusts
104
Q

Describe the comedo and non-comedo morphology of DCIS.

A
  1. Comedo:
    1. On mammogram: clustered or linear and branching calcifications
    2. Histo:
      1. Central necrosis
      2. Pleomorphic nuclei
  2. Non-comedo (many patterns)
    1. Cribiform pattern: round cells in ducts (cookie cutter)
    2. Micropapillary pattern: Bulbous protrusions w/t fibrovascular core in complex intraductal patterns
    3. True papillae pattern: Fibrovascular core without myoepithelial cell layer
105
Q

Non-comedo DCIS does not have what features?

A

central necrosis or pleomorphic nuclei

106
Q

DCIS:

Best predictors of local recurrence and invasion

A
  1. Nuclear grade and necrosis
  2. Extent of disease
  3. Positive surgical margins
107
Q

What is this

A

Comedo DCIS

  • A= linear and branching calficications on mamogram
  • B= central areas and necrosis and pleiomorphic nuclei
108
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

109
Q

Treatment of DCIS

A
  • Surgical excision and radiation/tamoxifen = Mostly curative
  • Mastectomy = Cure in 95%; keeping breast increases risk of reccurance
110
Q

When malignant cells in DCIS extend via the lactiferous sinuses into nipple skin, without crossing the basement membrane, what is it called?

A

Paget Disease of the Nipple

111
Q

Pagets Disease of the Nipple

  • Tumor markers
  • Cell morphology
  • Stain
  • If palpable mass is felt =
  • If palpable mass is not felt =
A
  • ER (-)/ HER2 (+)
  • Morphology
    • Single or small clusters of large cells (larger than surrounding keratinocytes) in epidermis
    • Pale cytoplasm w/ mucopolysaccharide
  • Seen on PAS
  • Invasive carcinoma
  • only DCIS
112
Q

LCIS (Lobular carcinoma in-situ)

  • Definition :
  • Bilateral/unilateral?
  • Pattern:
  • Detected:
  • Complications:
A
  • Proliferation of tumor cells WITHIN lobule that is limited by an intact BM, causing the alveoli to enlarge. Unlike DCIS, LCIS typically crosses BM to form invasive lobular carcinoma.
  • Bilateral (20-40%) of cases
  • Pattern: Discohesive cells due to LOF of adhesion protein E-cadherin => cells become round and clump together
  • Incidental biopsy finding, bc does not form calcifications or stromal reactions on mammogram
113
Q

LCIS

  • Did we see a decrease incidence of LCIS after mammograms were introduced?
  • Is a mass formed?
  • Markers
A
  • No
  • No mass is formed
  • ER(+), PR(+), HER2(-)
114
Q

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

A
  1. Uniform population of discohesive round cells with oval/round nuclei in ducts and lobules
  2. Mucin (+) signet-ring cells are common
  3. Pagetoid spread is common, but LCIS does NOT involve nipple skin
115
Q

Which genetic mutation is associated with LCIS?

A

CDH1 leading to loss of E-cadherin

116
Q

____ is a risk factor invasive lobular carcinoma in either breast!

A

LCIS (not itself invasive tho)

117
Q

Treatment for LCIS

A

Close clinical follow up with mammographic screening since the risk of progression is similar to DCIS

118
Q

What is the most common form of invasive breast cancer?

A

ER (+)/ HER2 (-) luminal invasive breast cancer

119
Q

ER (+)/ HER2 (-) low proliferation “luminal” breast cancer

  • Present in ____ of breast cancers.
  • Most commonly seen in?
  • State when detected?
  • Metastasis
  • Treatment
A

40-50%

  1. Older women and men
  2. Most common type detected by mammographic screening
  3. F on HRT
  • Found at an early stage and cured by surgery; ↓ recurrence
  • Metasasize after a long time to bone
  • Antiestrogenic drugs
120
Q

What is the recurrence and metastatic behavior of ER-(+), HER2-(-), low-proliferation breast cancers like?

A
  • Lowest recurrence rate, occurs late, >10 years
  • Metastasis after a long time => bone and can survive long time w/ metastasis
121
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

122
Q

ER(+), HER2(-), High Proliferation “Luminal Breast Cancer”

  • Present in ____ of breast cancers.
  • Most commonly seen in?
  • Increased nuclear staining for:
  • Treatment
A
  • 10%
  • BRCA 2 mutations
  • Ki67
  • Chemotherapy
123
Q

ER-(+), HER2-negative, high-proliferation will have increased nuclear staining for what?

A

Ki67

124
Q

HER2 (+) invasive carcinoma

  • ___ most common type of invasive breast cancer
  • Most commonly seen in?
  • Metasis
  • Treatment
A
  • 2nd (10-20%)
  • MC in:
    1. Young, non-white women
    2. TP53 mutations = Li-Fraumeni (HER2+/ER+)
  • Metastasize when small and early => viscera, brain and bone
  • Targeted chemo to block HER2 (Herceptin)
125
Q

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

A
  1. >1/3 respond completely to Herceptin (trastuzumab), a monoclobal AB, that inhibits HER2
    1. Some resistance is developing (tumors are shortening HER2 binding site)
  2. Cancers that respond have excellent prognosis
126
Q

ER(-), HER2(-) == “Basal-like” triple negative carcinoma

  • How do they present?
  • MC in:
  • Unique feature
  • Metasis
  • Recurrance
A
  • Because highly proliferative and grow SO fast, presents as a palpable mass in between mammograms
  • Most common in
    1. Young, premenopausal females (especially African American or Hispanic)
    2. BRCA1 mutations
  • Share many genetic similarities with serous ovarian carcinomas
  • Metastastize when small and early –> viscera, brain and bone;
  • Recurrences = common (within 5 years)
127
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

128
Q

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

  • Survival after distant metastasis is ___
A

30% completely respond to chemo

= rare

129
Q

Which invasive cancer is most common in young, premenopausal F (especially African American and Hispanic)

A

Basal like; triple negative carcinoma

130
Q

Morphology of Invasive Carcinoma

  • Gross and mammographic appearance of invasive carcinoma depends on _________.
  • MC: invasive carcinomas are described how?
  • How do invasive carcinomas present?
    *
A
  • Reaction with the stroma.
  • Hard, irregular radiodense masses due to desmoplasic reaction
  • On mammogram or mass
    • Mammogram: < 1cm
    • Mass: 2-3cm
    • Thus, dx earlier on mammogram
      *
131
Q

Larger invasive carcinomas can invade what structures?

A
    1. Pectoralis muscle => fixed to the chest wall
    1. Dermis => skin dimpling or nipple retraction
132
Q

Grading of breast cancers is done using the Nottingham Histologic Score.

What factors does this take into consideration?

A
  1. Tubule formation
  2. Nuclear pleomorphism
  3. Mitotic rate
133
Q

Grade 1

A
  1. Tubular pattern
  2. Small and round nucli
  3. Low proliferation
134
Q

Grade 2

A
  1. Some tubule pattern; solid clusters of infiltrating cells
  2. More nuclear pleomorphism
  3. Mitotic figures are present
135
Q

Grade 3

A
  1. Ragged nests/solid sheets of cells invade
  2. Enlarged, irregular nuclei
  3. Increase proliferation; tumor necrosis
136
Q

Describe the morphology of the following:

  1. ER (+)/HER (-)
  2. HER2 (+)
  3. ER (-)/ HER2 (-)
A
  1. Essentally all well-differentiated carcinomas (but can range from well-poor)
    1. Mucinous, lobula, papillary and cribiform
  2. Most are poorly differentiated and no specific morphological pattern
    1. 50% = apocrine
    2. 40% = micropapillary
  3. Almost all are poorly differentiated; circumscribed pushing borders + central fibrosis necrosis; prominent lymphocytic infiltrate (medullary features; medullary carcinoma)
137
Q

_____ proto-oncogene encodes HER2, a RTK located where?

HER2 cancers are caused by ______

A
  • ERBB2
  • On the cell surface
  • ERBB2 amplification => overexpression of HER2 => growth and survial of tumor cells.
138
Q

Lobular carcinoma

  • Genetic abnormality
  • Morphology
  • Detection
  • Often, what markers?
A
  • GA: Biallelic loss of CDH1
  • Morphology
    1. Discohesive cells diffusely infiltrate in a single-file pattern “linear array” (d/t loss of E-cadherin), thus, no desmoplastic response
    2. Signet-ring cells with mucin in cytoplasm
    3. No ducts/tubules form bc no E-cadherin
  • Detection: Hard to detect or dx on mammogram
  • Often, ER +
139
Q

What is this?

A

Lobular carcinoma

140
Q

Inflammatory Carcinoma

  • Most common in?
  • Presentation:
  • Morphology:
  • Prognosis:
A
  • Most common in African-Americans
  • Presentation:
    1. Tumor cells in dermal lymphatics => decreases drainage from breast => swollen, red breast without a mass (mimic acute mastitis)
    2. Peau d’orange
  • Morphology:
    • Extensive invasion and proliferation in lymphatic channels
  • Prognosis: VERY poor and most have distant metastases: 3 year survival is 3-10%
141
Q

Peau d’ orange = think of?

A

inflammatory carcinoma

142
Q

Medullary Carcinoma

  • Genetic abnormality
  • Presents as
  • Morphology
  • Detection
  • Markers
  • Prognosis
A
  • Many features of BRCA1- associated carcinomas
    • 60% of cancers in BRCA1 carriers have medullary features
    • 13% of cancers in BRCA1 carriers are medullary cancer
  • Presents:
    • Soft, well circumscribed mass with pushing (non-infiltrative border) because little desmoplasia
  • Morphology
    1. Syncytial sheets of large cells with pleomorphic nuclei, prominent nucleloi
    2. Mitotic figures
    3. Lymphocytes and plasma cells surround & in the tumor
  • Markers: ER- / HER2-
  • Lymphoplasmocytic infiltrates in tumor increase survival and better response to chemo
143
Q

Mucinous (colloid) Carcinoma Morphology

  • Genetic abnormality
  • Presents as
  • Morphology
  • Detection
  • Markers
  • Prognosis
A
  • Presents as: Soft and rubbery/ pale blue-grey gelatin circumscribed mass with pushing borders.
  • Morphology
    • Cells are arranged in groups within large lakes of mucin
      *
144
Q
A

Medullary carcinoma

145
Q
A

Mucinous carcinoma

146
Q

The outcome for women with breast cancer is dependent on what?

A
  1. Biological feature of the cancer (molecular and histologic type)
  2. Extent the cancer spread (stage) when it is diagnosed.
147
Q

What is feature of BREAST cancer has prognostic significance?

A

SIZE*

Chest wall involvement/Pec mustcle

148
Q

What is the most favorable cancer based on biology?

Least favorable?

A
  • Most: Well-differentiate ER+ low proliferative
  • Least: Poorly differentiated ER- and/or HER2+
149
Q

What is a major challenge to the success in therapy of breast cancer?

A

Genetic heterogeneity of breast cancer

=> increases liklihood of aggressive, therapy-resistant cancer

150
Q

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

A

Medullary carcinoma

151
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 (+)
152
Q

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

A

Axillary lymph node status

153
Q

Male Breast Cancer

  • RF
  • MC age diagnosed
  • MC mutation
  • Marker
  • Presentation
A
  • RF: same a F
  • Age: 60-70 YO
  • Mutation: BRCA2 mutation
  • Marker: ER+
  • Presentation: 2-3cm palpable, subareolar mass with discharge
154
Q

Male Breast Cancer

  • Metasteses
  • Distant metasteses
  • Typically presents at ____ stages than women, but have similar prognosis stage-for-stage
A
  • Axillary LN (50% of cases)
  • Lungs, liver, bone and brain
  • Higher
155
Q

What 2 features of breast cancer have POOR prognosis?

A
  1. Distant metastases
  2. Inflammatory carcinoma
156
Q

What does it mean if sentinel LN are negative?

A

Unlikely that the cancer has spread any further & patients can be spared complete axillary dissection

157
Q

Risk of __________ ↑ with size of primary tumor (independent factors)

A

Axillary metastases

158
Q

Node (-), <1cm = 90% 10 year survival

Node (-), > 2cm = 77% 10 year survival

Size is less important for __________, carcinomas, which can metastasize when small

A

HER2(+) and ER (-) carcinomas

159
Q

What causes peau d’ orange in inflammatory carcinoma?

A

Coopers ligaments tethered to edematous skin

160
Q

Predictive markers in inflammatory carcinoma

A
  • 60% => ER -
  • 40-50% => HER2 +
161
Q

What is strongly indicative of lymph node metastases?

A

Tumor cells are present within vascular spaces (lymphatic or small capillaries) in about 1/2 of all invasive carcinomas

162
Q

Proliferative rates are more important for what cancers?

A

ER (+) HER2 (-) carcinomas

163
Q

What are the stromal tumors of the breast?

A

Two types

  1. Intralobular biphasic tumors: fibroadenoma, phyllodes tumors
  2. Interlobular tumors: lipoma and angiosarcoma
164
Q

What is the most common benign tumor of the female breast?

A

Fibroadenoma

165
Q

Fibroadenoma

  • Who is most often affected by Fibroadenomas and how do they present based on age?
A
  • Premenopausal women (20-30 YO)
  • Younger women = multiple and bilateral palpable mass that fluctuates in size during pregnany and menstrual cycle because responsive to estrogen.
  • Older women = radiographic density/clustered calcifications
166
Q

Fibroadenoma

  • Morphology:
  • Presenation
  • Can males get fibroadenomas?
A
  • Epithelium of ducts is surrounded by stroma (peri-canicular) and can be compressed
  • Well-circumscribed, rubbery, greyish-white bulges with slit-like spaces
  • NO: males do not have intralobular stroma
167
Q

Which benign tumor of the breast may fluctuate in size during pregnancy and menstrual periods; and occurs with women who get cyclosporin A after kidney transplants?

A

Fibroadenoma

168
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
  • Mild ↑ risk for cancer
169
Q

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

A

60’s (post-menopausal women), which is 10-20 years later than fibroadenoma

170
Q

Phylloides Tumors

  • Presentation
  • Histology
  • How do we differentiate from fibroadenoma?
A
  • Most often present as a palpable mass.
  • Histology
    1. Leaf-like bulbous protrusions due to increased stoma cells and overgrowth
  • Different from fibroadenoma because
    1. Higher cellularity + mitotic rate + nuclear pleomorphism
    2. Overgrowth of stroma + Infiltrative borders
171
Q

Fibroadenoma or phyllodes tumor: which is associated with acquired changes in chromosome, most often a gain of 1q?

A

Phylloides tumor

172
Q

Overexpression _________ is associated with higher grade and more aggressive phyllodes tumor?

A

HOXB13

173
Q

Most phyloides tumors are ____-grade.

A

Low grade, which recur but DO NOT metastasize. Can also be intermediate and high grade.

174
Q

Where does phylloides tumor spread?

A

Regardless of grade, lymphatic spread is rare, lymph node dissection is contraindicated

175
Q

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

A

Myofibroblastoma

176
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
177
Q

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

A

1. Radiation therapy

2. Edema

  • Most often arising 5-10 years after tx
178
Q

Fibromatosis: clonal proliferation of fibroblasts and myofibroblasts that form a irregular infiltrating mass that can involve both skin and muscle.

Descibe their behavior

A

locally aggressive; does not metastasize

Endo/Repro II Test 1 (23 decks)

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