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S3B3 Pathology > Breast Pathology > Flashcards

Breast Pathology Flashcards

1
Q

The provided image is from what part of the breast?

A

normal breast: terminal duct lobular unit

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2
Q

What are the two layers of normal duct epithelium?

A

myoepithelial layer & luminal cells (simple columnar)

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3
Q

Describe the physiologic changes that occur with lactation.

A
  • Upper Left
    • TDLU in non-pregnant female of child-bearing age
  • Upper Right
    • Early pregnancy
    • epithelial cells proliferate with increase of size & # of lobules
    • lobule acini dilate & undergo secretory changes (can see secretory in the lumen)
  • Lower Left
    • cells become vacuolated w/ nuclear enlargment & prominent nucleoli
    • acinar lumina become progressively dilated & distended by accumulation of colostrum
  • Lower Right
    • large duct system (open cyan arrow) can be distinguished from TDLU (black solid arrow) by its absence of secretory changes
    • abrupt transition from terminal duct to TDLU
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4
Q

How does the male bread differ from the female breast?

A
  • Male
    • duct system ends in terminal buds without lobule formation
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5
Q

What occurs in gynecomastia?

A

increase in stroma and epithelial cells resulting from an imbalance between estrogens (stimulate breast tissue) & androgens

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6
Q

What are the most common causes of gynecomastia?

A

hyperestrinism due to

  • liver cirrhosis
  • klinefelter syndrome (XXY karyotype)
  • estrogen-secreting tumor (leydig or sertoli cell tumors)
  • adverse drug reactions
    • marijuana
    • antiretroviral rx
    • anabolic steroids
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7
Q

How is gynecomastia treated?

A

surgically by subcutaneous mastectomy

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8
Q

The provided sample is from a male patient – what is the pathology?

A

gynecomastia

proliferation of the ducts & hyperplasia of the stroma as well

periductal stroma is a slightly different color than the surrounding stroma

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9
Q

What are the common morphologic changes grouped under “fibrocystic changes”?

A
  • cysts
  • fibrosis
  • apocrine metaplasia
  • adenosis (increase in number of lobules in an area)
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10
Q

Individuals with fibrocystic change have what relative risk of developing breast cancer?

A

1.0

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11
Q

What pathology is shown in the provided image?

A

fibrocystic change - cyst

characteristic blue dome cyst

cysts can look like firm, solid masses when distended

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12
Q

The provided histological slide was taken from a sample of what pathology?

A

fibrocystic change - cyst

  • lined by flattened epithelial cells or cells with apocrine metaplasia
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13
Q

The provided histological slide was taken from a sample of what pathology?

A

Fibrocystic change - cysts

  • lined by flattened epithelial cells or cells with apocrine metaplasia
  • cells are larger, eosinophilic & cytoplasm has a lot of granules
  • ruffled appearance
  • large nucleus with large nucleoli
  • can also show calcifications (arrows on left image)
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14
Q

The provided histological slide was taken from a sample of what pathology?

A

Adenosis

increased acini per lobule

NOT sclerosing adenosis b/c the lumina are not compressed by a prominent stromal component

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15
Q

The provided histological slide was taken from a sample of what pathology?

A

Fibrocystic change

stromal fibrosis, cysts & adenosis

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16
Q

What are the proliferative breast diseases without atypia?

A
  • usual ductal epithelial hyperplasia
  • sclerosing adenosis
  • intraductal papilloma
  • radial scar
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17
Q

What are the nonproliferative breast changes?

A

fibrocystic changes

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18
Q

Individuals with proliferative breast disease without atypia have what relative risk of developing breast cancer?

A

1.5 - 2X

family history increases risk

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19
Q

What is usual ductal hyperplasia?

A

increased number of both luminal and myoepithelial cells (polyclonal proliferation of multiple cell types)

  • green: myoepithelial cells
  • red: luminal cells
  • yellow: intermediate cells
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20
Q

Usual ductal hyperplasia is usually associated with what clinical findings?

A

NO mass lesions

usually incidental microscopic finding

uncommonly associated with microcalcifications on mammogram

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21
Q

The provided histological slide was taken from a sample of what pathology?

A

Usual Ductal Hyperplasia

  • (Left) Mild
    • increased number of cells
  • (Right) Florid
    • cells surrounding lumina are elongated & chaotic
    • fenestrations (punched out areas) are variably sized & irregularly spaced & elongated around the periphery
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22
Q

Describe the histopathology associated with sclerosing adenosis

A

increased number of acini per terminal duct

archetectural distortion due to fibrosis

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23
Q

What is the clinical presentation of sclerosing adenosis?

A

firm, rubbery consistency

may mimic breast cancer

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24
Q

What features would you use to differentiate sclerosing adenosis from an invasive carcinoma?

A
  • Sclerosing adenosis
    • relatively well-circumscribed (non-infiltrative)
    • myoepithelial layer
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24
Q

The provided histological slide was taken from a sample of what pathology?

A

Sclerosing adenosis

  • TDLU is enlarged
  • acini are compressed & distorted by dense stroma
  • calicifications within some of the lumens
  • acini arranged in swillering pattern
  • outer border is well circumscribed (differentiator from carcinoma)
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25
Q

What is significance of the provided histological stain of sclerosing adenosis?

A

stain for myoepithelial marker p63 reveals a normal myoepithelial cell layer, but stain intensity may be reduced compared to normal breast tissue

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26
Q

What are the histological features of Intraductal Papilloma?

A

large duct papilloma occurs within a lactiferous duct, often subareolar

may be single lesion or multiple foci

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27
Q

Are large intraductal papillomas arising from large duct or multiple small duct papillomas associated with a higher risk of cancer?

A

multiple small duct papilloma

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28
Q

What is the clinical presentation of a patient with intraductal papilloma?

A

unilateral serous or bloody discharge (nonspecific finding)

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29
Q

The provided histological slide was taken from a sample of what pathology?

A

Intraductal Papilloma

  • central fibrovascular core extends from the wall of a duct
  • papillae arborize within the lumen & are lined by myoepithelial and luminal cells
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30
Q

What is a “radial scar” ?

A

stellate lesion of entrapped glands within hyalinized stroma

retains myoepithelial layer

ducts & lobules are compressed

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31
Q

What is the relative risk of a patient who has a radial scar developing invasive carcinoma?

A

2-3x

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32
Q

What is the clinical presentation of a radial scar?

A

mimic invasive carcinoma on clinical exam (firm mass) & mammography

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33
Q

What pathology is shown by the provided images?

A
  • Gross
    • stellate appearance with finger-like projections heading out into the surrounding fat
  • Microscopic
    • central very dense area with compressed ducts and lobules
    • “arms/corona” sticking out into the surrounding fat are generally longer than with invasive carcinoma
    • all glandular structures have a myoepithelial layer (non-invasive)
    • can have areas of papilloma, fibrocystic change, sclerosing adenosis & fibrosis
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34
Q

What are the proliferative breast diseases with atypia?

A

atypical ductal hyperplasia

atypical lobular hyperplasia

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35
Q

What is the relative risk of

A
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36
Q

Individuals with proliferative breast disease with atypia have what relative risk of developing breast cancer?

A

4 - 5x

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37
Q

What are the histological features of atypical ductal hyperplasia?

A
  • clonal proliferation
    • monomorphic, evenly placed epithelial cells involving terminal-duct lobular units
  • partially filled duct
  • 1 or 2 completely involved ducts ≤ 2 mm in aggregate dimension (differentiation from carcinoma in situ)
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37
Q

What are the histological features of atypical ductal hyperplasia?

A
  • clonal proliferation
    • monomorphic, evenly placed epithelial cells involving terminal-duct lobular units
  • partially filled duct
  • 1 or 2 completely involved ducts ≤ 2 mm in aggregate dimension (differentiation from carcinoma in situ)
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38
Q

What variable differentiates atypical ductal hyperplasica from carcinoma in situ?

A

size

ADH: 1 or 2 completely involved ducts ≤ 2 mm in aggregate dimension

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39
Q

How can you differentiate Usual Ductal Hyperplasia from Atypical Ductal Hyperplasia?

A

UDH: polyclonal

ADH: monoclonal

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40
Q

The provided histological slide was taken from a sample of what pathology?

A

Atypical Ductal Hyperplasia

  • Some bridges appear rigid (black open arrow)
  • Some bridges have a streaming pattern (black solid arrow)
  • Some spaces are round (cyan open arrow)
  • Some spaces are peripheral and irregular (cyan solid arrow)
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41
Q

What are the major differences between lobular & ductal epithelial hyperplasia?

A

E-cadherin is lost in lobular hyperplasia, so the cells do not stick together well

Lobular cells tend to be even more monotonous than ductal cells

Lobular hyperplasia tends to fill the lobules of the acinar structures – but LESS than 50% of the acini in a lobule by definition

41
Q

What are the major differences between lobular & ductal epithelial hyperplasia?

A

E-cadherin is lost in lobular hyperplasia, so the cells do not stick together well

Lobular cells tend to be even more monotonous than ductal cells

Lobular hyperplasia tends to fill the lobules of the acinar structures – but LESS than 50% of the acini in a lobule by definition

42
Q

What is the clinical presentation of a patient with atypical lobular hyperplasia?

A

incidental finding

no mass lesions or microcalcifications

43
Q

The provided histological slide was taken from a sample of what pathology?

A

Atypical Lobular Hyperplasia

  • lobules are filled
  • monotonous cells are typically smaller than ductal epithelial cells (would be (-) E-cadherin)
  • signet ring cells (black arrows, right image)
    • lipid vacoule & nucleus is pushed to the side
44
Q

What is the definition of carcinoma in situ & what are the types found in the breasts?

A

malignant clonal cell population limited to ducts & lobules by basement membrane (not invasive)

Types: ductal & lobular

45
Q

Individuals with carcinoma in situ (CIS) have what relative risk of developing breast invasive cancer?

A

8 - 10X risk

ALL invasive carcinomas arise from CIS

46
Q

Which Ductal Carcinoma In Situ has the highest risk of progression to invasive carcinoma?

A

Comedo Ductal Carcinoma In Situ

47
Q

How are ductal carcinoma in situ most commonly identified?

A

calcification on mammogram

48
Q

What are the architectural subtypes of Ductal Carcinoma In Situ & their respective features?

A
  • Comedo DCIS
    • high grade cytology (well-differentiated)
    • (-) ER expression
    • amplification Her2/neu
    • aneuploid w/ p53 mutations
  • Noncomedo DCIS
    • many histologic patters
    • nuclear grade varies from low to high
49
Q

What stains are always performed on samples of breast carcinoma in situ?

A

estrogen receptors (ER)

progesterone receptors (PR)

Her2/neu gene

proliferation marker

50
Q

How can you differentiate Atypical Ductal Hyperplasia (ADH) from Ductal Carcinoma In Situ (DCIS)?

A
  • ADH:
    • irregularly shaped, irregularly spaced glands
    • fairly monomorphous luminal type cells
  • DCIS
    • even more monomorphous luminal type cells
    • architecture loses streaming/lining-up
    • may have much more regularly punched out areas, or it may be completely solid
    • will typically have larger ducts than ADH
51
Q

The provided histological slide was taken from a sample of what pathology? Also identify the type of each image.

A

DCIS

  • Left: non-comedo type
    • very regular, round punched out spaces (even though variably sized)
    • cellular morphology looks relatively normal
  • Right: comedo type
    • nucleus are larger w/ prominent nucleoli
    • area of central necrosis
    • will often have calcifications
52
Q

What is Paget Disease of the Breast?

A

Extension of DCIS into lactiferous ducts and into nipple skin

often (50-60%) associated with underlying mass (carcinoma)

53
Q

What pathology is shown by the provided image?

A

Paget Disease of the Breast

  • erythema
  • crusting
  • scaling
  • focal epidermal erosion
  • often pruritic - excoriation (compulsive skin picking)
54
Q

The provided histological slide was taken from a sample of what pathology?

A

Paget Disease of the Breast

type of adenocarcinoma in situ

55
Q

How can you differentiate Paget Disease from melanoma?

A

Paget is:

(+) PAS -stains bright pink

(+) mucicarnine

56
Q

What is the clinical presentation of a patient with a lobular carcinoma in situ?

A

incidental finding

no mass lesion

no mammographic density / calicification

usually occur prior to menopause

often multifocal & bilateral

57
Q

What are the cell markers associated with Lobular Carcinoma in Situ?

A

(-) E-cadherin

(+) ER/PR

(-) Her2

58
Q

What fraction of individuals diagnosed with lobular carcinoma in situ eventually develop invasive carcinoma?

A

⅓

59
Q

The provided histological slide was taken from a sample of what pathology?

A

Lobular Carcinoma In Situ

  • filling of acinar structures with monomorphic cells
  • expansion of lobules - larger lesion than with ALH
  • may see occasional signet ring cell
60
Q

What condition is shown in the provided slide & what is the significance of this specific stain?

A

Lobular carcinoma in situ

Stain for E-cadherin

(+) will be dark brown

myoepithelial cells will be (+), but lobular cells will be (-) or weakly (+)

61
Q

Invasive breast cancer is most commonly caused by what type of tumor? What are the 3 subtypes?

A

Adenocarcinoma

  1. ER-positive, HER2-negative (50-65%)
  2. ER- (-/+), HER2-positive (10-20%)
  3. ER-negative, Her2-negative (10-20%)
62
Q

What type of invasive carcinoma is ER-positive, HER2-negative?

A

Luminal - most common

63
Q

What are the two types of luminal invasive carcinoma of the breast?

Each type most commonly affects what demographics?

They each respond to what type of treatment?

A
  • Low proliferation (luminal A)
    • low-grade, well differentiated w/ low proliferation index
    • older women & men
    • response to hormonal Rx, minimal response to chemo Rx
  • High proliferation (luminal B)
    • higher grade & proliferation index
    • will have a weaker (+) ER stain
    • associated with BRCA 2 germline mutation
    • response to chemoRx & trastuzumab
64
Q

Why do low grade cancers typically have minimal response to chemoRx?

A

Chemo targets rapidly dividing cells & low-grade carcinomas are not growing very rapidly

65
Q

What type of invasive carcinoma of the breast is Her2-positive and ER-(+/-)?

A

Her2 enriched

high grade & proliferation rate

66
Q

Her2 enriched carcinomas are most commonly seen in what demographics?

They are commonly associated with what mutation?

They respond to what type of treatment?

A

young, non-white women

TP53

Response to tratuzumab & chemoRx / radiation

67
Q

What type of invasive carcinoma of the breast are ER-negative, Her2-negative?

A

basal-like “triple negative”

patterns of mutations resemble high-grade serous ovarian carcinomas

68
Q

Basal-like carcinomas of the breast most commonly affect what demographics of people? What is the treatment?

A

young, Black & Hispanic women

Associated with BRCA1 mutations

aggressive course; small percentage respond to chemo/radiation

69
Q

What are high risk factors associated with invasive carcinoma of the breast?

A
  • Increasing age
  • female sex
  • obesity
  • first-degree relative with breast cancer
  • previous biopsy with atypical hyperplasia
  • white
  • increased estrogen levels (endogenous or exogenous)
70
Q

What factors increase the probability of a hereditary etiology of breast cancer?

A
  • multiple affected first-degree relatives
  • tumor(s) occur before menopause
  • multiple cancers (GI, etc.)
  • male breast cancer (BRCA 2 )
  • family members with ovarian carcinomas (BRCA1 & BRCA2)
71
Q

Hereditary cancers are associated with mutations in genes with what types of functions?

A
  • tumor suppressor genes
  • genes with some role in halting the cell cycle to repair DNA damage or repairing the damage
72
Q

BRCA1 is what type of gene? It is associated with what type of cancer?

A

tumor suppressor gene

breast & ovarian

basal subtype (triple negative)

73
Q

BRCA2 is what type of gene? It is associated with what type of cancer?

A

tumor suppressor gene

breast & ovarian cancer

more common in male breast cancer

73
Q

BRCA2 is what type of gene? It is associated with what type of cancer?

A

tumor suppressor gene

breast & ovarian cancer

more common in male breast cancer

74
Q

Li-Fraumeni Syndrome is associated with mutations to what gene? It is associated with what type of cancers?

A

TP53 (tumor suppressor gene)

breast cancer, sarcoma, leukemia, brain tumors

75
Q

CHEK2 is what type of gene? It is associated with what type of cancer?

A

cell cycle checkpoint kinase - recognition & repair of DNA damage

may increase risk for breast cancer after radiation exposure

(usually ER-positive)

75
Q

CHEK2 is what type of gene? It is associated with what type of cancer?

A

cell cycle checkpoint kinase - recognition & repair of DNA damage

may increase risk for breast cancer after radiation exposure

(usually ER-positive)

76
Q

What clinical features are associated with breast carcinoma?

A
  • occult (incidental finding)
  • palpable mass lesion &/or prominent nodes
  • skin dimpling
  • nipple retraction
  • nipple discharge
  • dermal edema
  • mass with overlying skin ulceration
77
Q

What clinical presentation is shown in the provided image?

A

dermal edema

nipple retraction

78
Q

What aspects of the provided mammogram are indicative of invasive carcinoma?

A

radiodense mass compared to the normal fibroadipose tissue

it is an irregular mass

the white areas (cyan arrow) are calcifications

79
Q

What is the most common breast malignancy?

A

Invasive Ductal Carcinoma

80
Q

How are invasive ductal carcinomas graded?

A

tubule formation (more = lower grade)

nuclear pleomorphism

mitotic rate

81
Q

What are the histological features of invasive ductal carcinoma?

A

desmoplastic fibrous stromal response

heterogeneous microscopic patterns

82
Q

What are the general ER/PR and HER2/neu expression patterns of invasive ductal carcinoma?

A

⅔ express ER/PR

⅓ overexpress HER2/neu

82
Q

What are the general ER/PR and HER2/neu expression patterns of invasive ductal carcinoma?

A

⅔ express ER/PR

⅓ overexpress HER2/neu

83
Q

What pathology is shown in the provided image?

A

invasive ductal carcinoma

white masses

(readily seen agains yellow adipose)

84
Q

The provided image is what type of carcinoma?

A

Luminal Type A

ER(+)/Her2(-)

  • Left
    • prominent component of well-formed tubules
    • lowe grade nuclei
    • rare/absent mitoses
  • Right
    • Strong estrogen receptor expression
85
Q

The provided image is an example of what type of carcinoma?

A

Luminal B

  • Left
    • less well-formed tubules
    • intermediate to high grade nuclei
    • high proliferative rate
  • Right
    • positive for estrogen receptor, but weaker staining
    • some cells are negative for ER
86
Q

The provided image is an example of what type of carcinoma?

A

Her2(+)/ER(-)

  • Left
    • large, pleomorphic nuclei
    • no glandular differentiation
    • high proliferative rate
  • Right
    • Her2+ staining stron expression
87
Q

What type of pathology is shown in the provided image?

A

Invasive lobular carcinoma

  • small monotonous cells
  • linear infiltrative pattern
  • loss of E-cadherin (CDH1 gene)
88
Q

What pathology is shown in the provided image?

A

Inflammatory breast cancer

  • breast is swollen, hot, tender w/ skin thickening & edema
  • poor prognosis
89
Q

What are the histological features associated with inflammatory breast cancer?

A

dermal lymphatic involvement by tumor

90
Q

The provided histological slide is from what pathology?

A

Inflammatory carcinoma

  • numerous tumor emboli in dermal lymphatics
    • causing obstruction & resulting edema
    • thickening of dermis
    • swelling of breast
91
Q

What is the most common benign tumor of female breast?

A

fibroadenoma

92
Q

What is the clinical presentation of a patient with a fibroadenoma?

Treatment?

A

discrete, movable, painless mass

peak in 3rd decade

“shelled out” - no need for wide excision

92
Q

What is the clinical presentation of a patient with a fibroadenoma?

Treatment?

A

discrete, movable, painless mass

peak in 3rd decade

“shelled out” - no need for wide excision

93
Q

What pathology is depicted in the provided image?

A

Fibroadenoma

  • tan, glistening, very well circumscribed
94
Q

The provided histological slide is from what pathology?

A

Fibroadenoma

  • tumors of fibrous stroma & epithelium
95
Q

What is Phyllodes Tumor?

Treatment?

A

rare tumor of women over 40

fast growing - similar to fibroadenoma, but can be malignant

complete excision w/ wide margins

96
Q

How can you differentiate a fibroadenoma from Phyllodes tumor?

A

increase in stromal cellularity, mitoses, nuclear pleomorphism as compared to fibroadenoma

phyllodes tumor has infiltrating borders

97
Q

What condition is shown in the provided images?

A

Phyllodes Tumor

  • Leaf-like architecture (protruding tumor nodules w/in cystic cavity)
  • tan/fleshy surface
  • small cleft-like slits correspond to areas stromal overgrowth
97
Q

What condition is shown in the provided images?

A

Phyllodes Tumor

  • Leaf-like architecture (protruding tumor nodules w/in cystic cavity)
  • tan/fleshy surface
  • small cleft-like slits correspond to areas stromal overgrowth
98
Q

The provided histological slide is from what pathology?

A

Phyllodes Tumor

  • arises from intralobular fibroblast
  • proliferating stromal cells
  • stimulate non-neoplastic epithelial cell growth
  • large “leaf-like” structures
99
Q

What risk factors are associated with male breast cancer?

A
  • first degree relative with breast cancer
  • BRCA2 mutation
  • Klinefelter syndrome
  • hyperestrinism
  • NOT gynecomastia

S3B3 Pathology (6 decks)

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