Breast Pathology Flashcards
(107 cards)
1
Q
The provided image is from what part of the breast?
A
normal breast: terminal duct lobular unit
2
Q
What are the two layers of normal duct epithelium?
A
myoepithelial layer & luminal cells (simple columnar)
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
4
Q
How does the male bread differ from the female breast?
A
- Male
- duct system ends in terminal buds without lobule formation
5
Q
What occurs in gynecomastia?
A
increase in stroma and epithelial cells resulting from an imbalance between estrogens (stimulate breast tissue) & androgens
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
7
Q
How is gynecomastia treated?
A
surgically by subcutaneous mastectomy
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
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)
10
Q
Individuals with fibrocystic change have what relative risk of developing breast cancer?
A
1.0
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
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
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)
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
15
Q
The provided histological slide was taken from a sample of what pathology?
A
Fibrocystic change
stromal fibrosis, cysts & adenosis
16
Q
What are the proliferative breast diseases without atypia?
A
- usual ductal epithelial hyperplasia
- sclerosing adenosis
- intraductal papilloma
- radial scar
17
Q
What are the nonproliferative breast changes?
A
fibrocystic changes
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
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
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
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
22
Q
Describe the histopathology associated with sclerosing adenosis
A
increased number of acini per terminal duct
archetectural distortion due to fibrosis
23
Q
What is the clinical presentation of sclerosing adenosis?
A
firm, rubbery consistency
may mimic breast cancer
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
24
The provided histological slide was taken from a sample of what pathology?
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*)
25
What is significance of the provided histological stain of sclerosing adenosis?
stain for myoepithelial marker p63 reveals a normal myoepithelial cell layer, but stain intensity may be reduced compared to normal breast tissue
26
What are the histological features of Intraductal Papilloma?
large duct papilloma occurs within a lactiferous duct, often subareolar
may be single lesion or multiple foci
27
Are large intraductal papillomas arising from large duct or multiple small duct papillomas associated with a higher risk of cancer?
multiple small duct papilloma
28
What is the clinical presentation of a patient with intraductal papilloma?
unilateral serous or bloody discharge (nonspecific finding)
29
The provided histological slide was taken from a sample of what pathology?
Intraductal Papilloma
* central fibrovascular core extends from the wall of a duct
* papillae arborize within the lumen & are lined by myoepithelial and luminal cells
30
What is a “radial scar” ?
stellate lesion of entrapped glands within hyalinized stroma
retains myoepithelial layer
ducts & lobules are compressed
31
What is the relative risk of a patient who has a radial scar developing invasive carcinoma?
2-3x
32
What is the clinical presentation of a radial scar?
mimic invasive carcinoma on clinical exam (firm mass) & mammography
33
What pathology is shown by the provided images?
* 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
34
What are the proliferative breast diseases with atypia?
atypical ductal hyperplasia
atypical lobular hyperplasia
35
What is the relative risk of
36
Individuals with proliferative breast disease **with** atypia have what relative risk of developing breast cancer?
4 - 5x
37
What are the histological features of atypical ductal hyperplasia?
* 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)
37
What are the histological features of atypical ductal hyperplasia?
* 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)
38
What variable differentiates atypical ductal hyperplasica from carcinoma in situ?
size
ADH: 1 or 2 completely involved ducts ≤ 2 mm in aggregate dimension
39
How can you differentiate Usual Ductal Hyperplasia from Atypical Ductal Hyperplasia?
UDH: polyclonal
ADH: monoclonal
40
The provided histological slide was taken from a sample of what pathology?
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)
41
What are the major differences between lobular & ductal epithelial hyperplasia?
**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
What are the major differences between lobular & ductal epithelial hyperplasia?
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
What is the clinical presentation of a patient with atypical lobular hyperplasia?
incidental finding
no mass lesions or microcalcifications
43
The provided histological slide was taken from a sample of what pathology?
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
What is the definition of carcinoma in situ & what are the types found in the breasts?
malignant clonal cell population limited to ducts & lobules by basement membrane (not invasive)
Types: ductal & lobular
45
Individuals with carcinoma in situ (CIS) have what relative risk of developing breast invasive cancer?
8 - 10X risk
**ALL** invasive carcinomas arise from CIS
46
Which Ductal Carcinoma In Situ has the highest risk of progression to invasive carcinoma?
Comedo Ductal Carcinoma In Situ
47
How are ductal carcinoma in situ most commonly identified?
calcification on mammogram
48
What are the architectural subtypes of Ductal Carcinoma In Situ & their respective features?
* 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
What stains are always performed on samples of breast carcinoma in situ?
estrogen receptors (ER)
progesterone receptors (PR)
Her2/neu gene
proliferation marker
50
How can you differentiate Atypical Ductal Hyperplasia (ADH) from Ductal Carcinoma In Situ (DCIS)?
* _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
The provided histological slide was taken from a sample of what pathology? Also identify the type of each image.
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
What is Paget Disease of the Breast?
Extension of DCIS into lactiferous ducts and into nipple skin
often (50-60%) associated with underlying mass (carcinoma)
53
What pathology is shown by the provided image?
Paget Disease of the Breast
* erythema
* crusting
* scaling
* focal epidermal erosion
* often pruritic - excoriation (compulsive skin picking)
54
The provided histological slide was taken from a sample of what pathology?
Paget Disease of the Breast
type of adenocarcinoma in situ
55
How can you differentiate Paget Disease from melanoma?
Paget is:
(+) PAS -stains bright pink
(+) mucicarnine
56
What is the clinical presentation of a patient with a lobular carcinoma in situ?
incidental finding
no mass lesion
no mammographic density / calicification
usually occur prior to menopause
often multifocal & bilateral
57
What are the cell markers associated with Lobular Carcinoma in Situ?
(-) E-cadherin
(+) ER/PR
(-) Her2
58
What fraction of individuals diagnosed with lobular carcinoma in situ eventually develop invasive carcinoma?
⅓
59
The provided histological slide was taken from a sample of what pathology?
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
What condition is shown in the provided slide & what is the significance of this specific stain?
Lobular carcinoma in situ
Stain for E-cadherin
(+) will be dark brown
myoepithelial cells will be (+), but **lobular cells will be (-)** or weakly (+)
61
Invasive breast cancer is most commonly caused by what type of tumor? What are the 3 subtypes?
Adenocarcinoma
1. ER-positive, HER2-negative (50-65%)
2. ER- (-/+), HER2-positive (10-20%)
3. ER-negative, Her2-negative (10-20%)
62
What type of invasive carcinoma is ER-positive, HER2-negative?
Luminal - most common
63
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?
* 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
Why do low grade cancers typically have minimal response to chemoRx?
Chemo targets rapidly dividing cells & low-grade carcinomas are not growing very rapidly
65
What type of invasive carcinoma of the breast is Her2-positive and ER-(+/-)?
Her2 enriched
high grade & proliferation rate
66
Her2 enriched carcinomas are most commonly seen in what demographics?
They are commonly associated with what mutation?
They respond to what type of treatment?
young, non-white women
TP53
Response to tratuzumab & chemoRx / radiation
67
What type of invasive carcinoma of the breast are ER-negative, Her2-negative?
basal-like “triple negative”
patterns of mutations resemble high-grade serous ovarian carcinomas
68
Basal-like carcinomas of the breast most commonly affect what demographics of people? What is the treatment?
young, Black & Hispanic women
Associated with BRCA1 mutations
aggressive course; small percentage respond to chemo/radiation
69
What are high risk factors associated with invasive carcinoma of the breast?
* Increasing age
* female sex
* obesity
* first-degree relative with breast cancer
* previous biopsy with atypical hyperplasia
* white
* increased estrogen levels (endogenous or exogenous)
70
What factors increase the probability of a hereditary etiology of breast cancer?
* 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
Hereditary cancers are associated with mutations in genes with what types of functions?
* tumor suppressor genes
* genes with some role in halting the cell cycle to repair DNA damage or repairing the damage
72
BRCA1 is what type of gene? It is associated with what type of cancer?
tumor suppressor gene
breast & ovarian
basal subtype (triple negative)
73
BRCA2 is what type of gene? It is associated with what type of cancer?
tumor suppressor gene
breast & ovarian cancer
more common in male breast cancer
73
BRCA2 is what type of gene? It is associated with what type of cancer?
tumor suppressor gene
breast & ovarian cancer
more common in male breast cancer
74
Li-Fraumeni Syndrome is associated with mutations to what gene? It is associated with what type of cancers?
TP53 (tumor suppressor gene)
breast cancer, sarcoma, leukemia, brain tumors
75
CHEK2 is what type of gene? It is associated with what type of cancer?
cell cycle checkpoint kinase - recognition & repair of DNA damage
may increase risk for breast cancer after radiation exposure
(usually ER-positive)
75
CHEK2 is what type of gene? It is associated with what type of cancer?
cell cycle checkpoint kinase - recognition & repair of DNA damage
may increase risk for breast cancer after radiation exposure
(usually ER-positive)
76
What clinical features are associated with breast carcinoma?
* occult (incidental finding)
* palpable mass lesion &/or prominent nodes
* skin dimpling
* nipple retraction
* nipple discharge
* dermal edema
* mass with overlying skin ulceration
77
What clinical presentation is shown in the provided image?
dermal edema
nipple retraction
78
What aspects of the provided mammogram are indicative of invasive carcinoma?
radiodense mass compared to the normal fibroadipose tissue
it is an irregular mass
the white areas (cyan arrow) are calcifications
79
What is the most common breast malignancy?
Invasive Ductal Carcinoma
80
How are invasive ductal carcinomas graded?
tubule formation (more = lower grade)
nuclear pleomorphism
mitotic rate
81
What are the histological features of invasive ductal carcinoma?
desmoplastic fibrous stromal response
heterogeneous microscopic patterns
82
What are the general ER/PR and HER2/neu expression patterns of invasive ductal carcinoma?
⅔ express ER/PR
⅓ overexpress HER2/neu
82
What are the general ER/PR and HER2/neu expression patterns of invasive ductal carcinoma?
⅔ express ER/PR
⅓ overexpress HER2/neu
83
What pathology is shown in the provided image?
invasive ductal carcinoma
white masses
(readily seen agains yellow adipose)
84
The provided image is what type of carcinoma?
Luminal Type A
ER(+)/Her2(-)
* Left
* prominent component of well-formed tubules
* lowe grade nuclei
* rare/absent mitoses
* Right
* Strong estrogen receptor expression
85
The provided image is an example of what type of carcinoma?
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
The provided image is an example of what type of carcinoma?
Her2(+)/ER(-)
* Left
* large, pleomorphic nuclei
* no glandular differentiation
* high proliferative rate
* Right
* Her2+ staining stron expression
87
What type of pathology is shown in the provided image?
Invasive lobular carcinoma
* small monotonous cells
* linear infiltrative pattern
* loss of E-cadherin (CDH1 gene)
88
What pathology is shown in the provided image?
Inflammatory breast cancer
* breast is swollen, hot, tender w/ skin thickening & edema
* poor prognosis
89
What are the histological features associated with inflammatory breast cancer?
dermal lymphatic involvement by tumor
90
The provided histological slide is from what pathology?
Inflammatory carcinoma
* numerous tumor emboli in dermal lymphatics
* causing obstruction & resulting edema
* thickening of dermis
* swelling of breast
91
What is the most common benign tumor of female breast?
fibroadenoma
92
What is the clinical presentation of a patient with a fibroadenoma?
Treatment?
discrete, movable, painless mass
peak in 3rd decade
“shelled out” - no need for wide excision
92
What is the clinical presentation of a patient with a fibroadenoma?
Treatment?
discrete, movable, painless mass
peak in 3rd decade
“shelled out” - no need for wide excision
93
What pathology is depicted in the provided image?
Fibroadenoma
* tan, glistening, very well circumscribed
94
The provided histological slide is from what pathology?
Fibroadenoma
* tumors of fibrous stroma & epithelium
95
What is Phyllodes Tumor?
Treatment?
rare tumor of women over 40
fast growing - similar to fibroadenoma, but can be malignant
complete excision w/ wide margins
96
How can you differentiate a fibroadenoma from Phyllodes tumor?
increase in stromal cellularity, mitoses, nuclear pleomorphism as compared to fibroadenoma
phyllodes tumor has infiltrating borders
97
What condition is shown in the provided images?
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
What condition is shown in the provided images?
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
The provided histological slide is from what pathology?
Phyllodes Tumor
* arises from intralobular fibroblast
* proliferating stromal cells
* stimulate non-neoplastic epithelial cell growth
* large “leaf-like” structures
99
What risk factors are associated with male breast cancer?
* first degree relative with breast cancer
* BRCA2 mutation
* Klinefelter syndrome
* hyperestrinism
* **NOT** gynecomastia
