Breast Pathologies Flashcards
1
Q
What are the two layers in a normal breast duct?
A
Glandular epithelial and myoepithelial cells
2
Q
What is mastalgia?
A
Breast pain, which can be cyclic or noncyclic
3
Q
What are common causes of noncyclic breast pain?
A
Ruptured cysts, physical injury, infections
4
Q
What percentage of breast masses are benign?
A
95%
5
Q
What is the average size of invasive carcinomas detected by mammography?
A
About 1 cm
6
Q
What is galactorrhea?
A
Milky discharge associated with elevated prolactin levels
7
Q
What can bloody or serous nipple discharges indicate?
A
Large duct papillomas and cysts
8
Q
What are the main types of breast disease?
A
- Inflammatory Breast Disease
- Benign Epithelial Lesions
- Nonproliferative Breast Changes/Fibrocystic Changes
- Proliferative Breast Disease
- Breast Carcinoma
9
Q
What is acute mastitis?
A
Bacterial infection associated with breastfeeding, usually Staphylococcus aureus
10
Q
What is periductal mastitis?
A
A condition characterized by painful erythematous subareolar mass, mimicking bacterial abscess
11
Q
What is mammary duct ectasia?
A
Painless palpable mass associated with thick, white nipple secretions
12
Q
What is fat necrosis in the breast?
A
A condition associated with breast trauma and surgery, presenting as a palpable mass
13
Q
What is lymphocytic mastopathy?
A
Single or multiple hard palpable masses associated with densely collagenized stroma
14
Q
What are the three main changes in fibrocystic changes?
A
- Cysts
- Fibrosis
- Adenosis
15
Q
What characterizes atypical hyperplasia in breast lesions?
A
Clonal proliferation with some features of carcinoma in situ, moderately increased risk of carcinoma
16
Q
What is the difference between atypical ductal hyperplasia and atypical lobular hyperplasia?
A
Atypical ductal hyperplasia resembles ductal carcinoma in situ, while atypical lobular hyperplasia is usually incidental
17
Q
What is the risk factor associated with proliferative breast disease without atypia?
A
Small increase in risk for breast carcinoma
18
Q
What is the significance of atypical hyperplasia in breast pathology?
A
It indicates a 4-5 fold increased risk of carcinoma
19
Q
What imaging technique can detect densities and calcifications in breast tissue?
A
Mammography
20
Q
What are the histological features of sclerosing adenosis?
A
Increased number of acini compressed and distorted with possible stromal fibrosis
21
Q
What is the role of digital breast tomosynthesis?
A
Provides extra views in mammography
22
Q
True or False: Fibrocystic changes are associated with an increased risk of breast cancer.
A
False
23
Q
Fill in the blank: Most painful masses in the breast are _______.
A
Benign
24
Q
What can cause chronic and granulomatous inflammation in the breast?
A
keratinizing Squamous metaplasia of lactiferous ducts
25
What is the typical age demographic for periductal mastitis?
90% are smokers, possibly related to Vitamin A deficiency
26
What is Atypical Ductal Hyperplasia?
Histologic resemblance to ductal carcinoma in situ (DCIS) – only partially fills ducts
## Footnote
Monomorphic proliferation of regularly spaced out cells that sometimes form cribriform spaces
27
What defines Atypical Lobular Hyperplasia?
Consists of cells identical to lobular carcinoma in situ (LCIS) and does not fill more than 50% of acini within lobule
## Footnote
Loss of E-cadherin expression (like LCIS)
28
List the types of breast disease.
* Inflammatory Breast Disease
* Benign Epithelial Lesions
* Nonproliferative Breast Changes/Fibrocystic Changes
* Proliferative Breast Disease
* Breast Carcinoma
* Breast stromal tumors
## Footnote
Includes various benign and malignant conditions
29
What are the benign epithelial lesions associated with proliferative breast disease?
* Epithelial hyperplasia
* Sclerosing adenosis
* Complex sclerosing lesion
* Papilloma
* Atypical Hyperplasia (ductal and lobular)
## Footnote
These lesions can be associated with an increased risk of breast cancer
30
What is the most common type of breast malignancies?
Almost all breast malignancies are adenocarcinomas
## Footnote
Terms ductal and lobular are used to describe subsets of both in situ and invasive carcinomas
31
What is carcinoma in situ?
Refers to cancer cells confined within ducts and lobules by a basement membrane - no capacity to metastasize
## Footnote
Includes ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS)
32
What are the major risk factors for recurrence after breast conservation therapy?
* High nuclear grade and necrosis
* Extent of disease
* Positive surgical margins
## Footnote
Mastectomy has a curative rate > 95%
33
What is Ductal Carcinoma in Situ (DCIS)?
Clonal proliferation of epithelial cells limited to ducts and lobules by basement membrane
## Footnote
Usually detected by mammography – calcifications or density
34
What characterizes Comedo DCIS?
Pleomorphic, high-grade nuclei and areas of central necrosis
## Footnote
A specific subtype of DCIS
35
What are the architectural patterns seen in DCIS?
* Cribriform DCIS: rounded spaces, calcified secretory material
* Micropapillary DCIS: complex bulbous protrusions with no fibrovascular cores
* Papillary DCIS: true papillae with fibrovascular cores lacking myoepithelial layer
## Footnote
These patterns help in the diagnosis of DCIS
36
What is the presentation of Paget Disease?
Unilateral erythematous eruption with a scale crust on nipple, often pruritic
## Footnote
Malignant DCIS cells extend from ducts into nipple skin without crossing the basement membrane
37
True or False: Breast cancer can spread throughout the ductal system extensively.
True
## Footnote
DCIS can spread extensively but is confined by the basement membrane
38
Fill in the blank: The term 'lobular' in breast cancer refers to invasive carcinomas biologically related to _______.
LCIS
## Footnote
Lobular and ductal classifications reflect tumor cell genetics and biology
39
What is Carcinoma in Situ?
Clonal proliferation of cells within ducts and lobules that grow in a dyscohesive fashion.
## Footnote
Loss of cellular adhesion due to dysfunction of E-cadherin gene (CDH1), contributing to cohesion of normal breast epithelial cells.
40
What percentage of all breast cancer cases does Carcinoma in Situ represent?
1-6% of all breast cancer cases.
## Footnote
Bilateral in 20-40% of cases.
41
What is the risk factor associated with Lobular Carcinoma in Situ (LCIS)?
Risk factor for developing invasive carcinoma in either breast.
## Footnote
1% per year, similar to untreated DCIS.
42
What are the common types of breast disease?
Inflammatory Breast Disease, Benign Epithelial Lesions, Nonproliferative Breast Changes, Proliferative Breast Disease, Breast Carcinoma.
## Footnote
Includes types like DCIS, LCIS, invasive carcinoma, and breast stromal tumors.
43
What is the most common malignancy among women globally?
Breast cancer.
44
What is the lifetime chance of developing breast cancer in the US?
1 in 8 chance.
45
What are the top cancer mortality rates in women?
#1 lung, #2 breast.
46
What factors contributed to the increase in breast cancer incidence in older women during the 1980s?
Introduction of mammography and use of postmenopausal hormonal therapy.
47
What are the main risk factors for breast cancer?
* Female sex
* Age
* Exposure to estrogen
* Genetic inheritance
* Environmental/lifestyle factors
* High breast density
* European descent/Ashkenazi Jewish populations.
48
True or False: The average age of breast cancer diagnosis is younger in African-American women compared to women of European descent.
True.
49
What are the three major molecular subtypes of breast cancer?
* Luminal (ER-positive)
* HER2 (HER2-positive)
* Triple Negative Breast Cancer (TNBC).
50
What is the defining feature of Luminal breast cancer?
ER+ and HER2-.
51
What is the defining feature of HER2 positive breast cancer?
HER2+; can be either ER-positive or ER-negative.
52
What is the defining feature of Triple Negative Breast Cancer (TNBC)?
ER-, HER2-, PR-.
53
What percentage of breast cancers is attributed to hereditary susceptibility genes?
1/4 to 1/3 of breast cancers.
54
What are high penetrance susceptibility genes for familial breast cancer?
* BRCA1/2
* TP53
* PTEN
* STK11
* CDH1.
55
What is the risk associated with BRCA1 and BRCA2 mutations?
80-90% of single gene familial breast cancers.
56
What is the common treatment approach for Luminal breast cancer?
Anti-estrogen therapy; chemotherapy has little benefit.
57
What is the common treatment for HER2 positive breast cancer?
Antibodies that bind and block HER2 activity (e.g., Herceptin).
58
What is the typical presentation of Triple Negative Breast Cancer?
Clinically as a palpable mass, less likely to be detected on mammography.
59
What defines Invasive Carcinoma in breast cancer?
Penetrates basement membrane, majority are adenocarcinomas.
60
What is the average size of a palpable mass in Invasive Carcinoma?
2-3 cm.
61
What is the typical grading system used for breast cancer?
Nottingham Histologic Score.
62
What is the main characteristic of invasive carcinoma in breast cancer?
Mass with desmoplastic stromal reaction, irregular margins with stromal invasion
## Footnote
Variations exist; can invade pectoralis muscle and dermis, causing skin retraction.
63
What is the Nottingham Histologic Score used for?
Grading breast cancer histology
## Footnote
It categorizes tumors into Grade 1, Grade 2, and Grade 3 based on differentiation and other histologic features.
64
Define Grade 1 in the Nottingham Histologic Score.
Well differentiated, tubular or cribriform pattering, small uniform nuclei, low proliferation
65
Define Grade 2 in the Nottingham Histologic Score.
Moderately differentiated, high mitotic figures, greater pleomorphism, areas with solid cell clusters or single infiltrating cells
66
Define Grade 3 in the Nottingham Histologic Score.
Poorly differentiated, nests or solid sheets of cells, irregular enlarged nuclei, high proliferation, tumor necrosis
67
What are the special histological types of breast cancer?
Invasive lobular, medullary, mucinous, tubular, papillary, apocrine, micropapillary
## Footnote
Each type has unique genetic changes and clinical behaviors.
68
What is a characteristic feature of lobular carcinoma?
Loss of expression of E-cadherin (CDH1) and infiltrates as single cells (dyscohesive)
69
What is the prognosis for medullary pattern carcinomas?
Better prognosis than other poorly differentiated carcinomas despite being poorly differentiated
70
What is the appearance of mucinous (colloid) carcinoma?
Soft and rubbery, pale gray-blue gelatin appearance with large lakes of mucin
71
What are the histological features of tubular carcinoma?
Well-formed tubules, cribriform pattern, apocrine snouts, calcifications in lumens
72
What is the defining feature of papillary carcinoma?
True papillae, fibrovascular tissue lined by tumor cells
73
What characterizes apocrine carcinoma?
Resembles cells that line sweat glands, enlarged nuclei, eosinophilic granular cytoplasm
74
What is the definition of inflammatory carcinoma?
Extensive plugging of lymphovascular spaces of dermis with cancerous cells, no inflammation
## Footnote
Presents with erythema, swelling, and peau d’orange appearance.
75
What is the most important prognostic factor for invasive carcinoma?
Distant metastases, if present, indicate unlikely cure
76
What is the significance of axillary lymph node status?
Most prognostic factor in absence of distant metastases
77
What is the 10-year survival rate if no lymph nodes are involved?
70-80%
78
What is the 3-year survival rate for inflammatory carcinoma?
3-10%
79
What are the characteristics of male breast disease?
Gynecomastia, rare carcinoma with similar risk factors as females, most commonly luminal type (ER+, HER2-); BRAC2 mutation
## Footnote
Lifetime risk of male breast cancer is 0.11%.
80
What are the types of breast disease?
Inflammatory breast disease, benign epithelial lesions, proliferative breast disease, breast carcinoma
## Footnote
Includes DCIS, LCIS, invasive carcinoma, and stromal tumors.
81
What is a fibroadenoma?
Most common benign tumor of female breast, often in 20s-30s, associated with slight increased risk of cancer
## Footnote
Histology shows myxoid stroma and compressed epithelium.
82
What distinguishes a phyllodes tumor from a fibroadenoma?
Increased stromal cellularity, mitotic rate, nuclear pleomorphism, infiltrative borders
## Footnote
Phyllodes tumors can be low-grade or high-grade (malignant).
83
What is the prognosis for angiosarcoma of the breast?
Rare, <0.05% of breast malignancies; may occur sporadically or as a complication of therapy
84
What are myofibroblastomas?
Benign lesions made of stromal cells without an epithelial component
85
What is the role of gene expression profiling in breast cancer?
Identifies tumors that are slow to proliferate and respond to antiestrogen therapy, indicating patients who may not need chemotherapy
86
List medications commonly assoc. w/ galactorrhea
oral contraceptives, TCAs, methyldopa, phenothiazines
87
50% of all malignant mass are found in which quadrant of the breast?
upper outer quadrant
88
what breast neoplasm is assoc. w/ 90% smokers?
painful erythematous subareolar mass
89
T or F: mammary duct ectasia is assoc. w/ smokers?
false
90
mammary duct ectasia commonly presents in what decades of life?
5th and 6th
91
Describe the morphology of mammary duct ectasia.
acute: dilated ducts filled w/ secretions and lipid-laden macrophages
chronic: granulomas and fibrosis produce irregular mass w/ nipple retraction
92
describe the gross features of fat necrosis?
skin thickening and retraction
densities and calcifications may show on mammogram
gray-white nodules containing small chalky-white foci
93
what is another term for lymphocytic mastopathy
sclerosing lymphocytic lobulitis
94
lymphocytic mastopathy is assoc. w/ what medical conditions?
Type I DM & autoimmune thyroid disease
95
describe the microscopic characteristics of lymphocytic mastopahty?
atrophic ducts and lobules within stroma of a thickened BM
96
granulomatous mastitis may manifest w/ what systemic granulomatous diseases?
tuberculosis
sarcoidosis
97
T or F: granulomatous lobular mastitis occurs mostly in parous women.
true
98
what would you expect to find in the lobules of a pt. w/ granulomatous lobular mastitis?
lipid vacuoles surrounded by neutrophils
99
list the 2 breast stromal tumors.
fibroadenoma
phyllodes tumor
100
describe the gross characteristics of cysts
dilation of lobules w/ brown-blue colored fluid: "blue-domed cysts"
101
describe the microscopic characteristics of cysts
flat atrophic epithelium
metaplastic apocrine cells
eosinophilic cytoplasm
calcifications common
102
at what point does a fibrocystic change become fibrosis?
when the cysts rupture
103
define adenosis.
increase in the number of acini per lobule
104
T or F: adenosis is considered normal in the pregnant pt..
true
105
what are the histologic characteristics of benign epithelial hyperplasia?
irregular lumens at the periphery
distend ducts
106
how is a complex sclerosing lesion histologically defined?
heterogenous lesions w/ components of sclerosing adenosis, epithelial hyperplasia and papillomas
107
what do complex sclerosing lesions look like under the microscope?
radial scar; mimics invasive ca
central nidus of entrapped glands in hyalinized stroma surrounded by long radiating projections
108
what are the general histologic characteristics of papilloma?
apocrine metaplasia
multiple branching fibrovascular cores growing within a dilated duct
109
compare and contrast the histological differences b/t large and small duct papillomas.
Large:
solitary
within lactiferous sinuses of nipple
nipple discharge (may be bloody)
Small:
multiple
depper in ductal system
calcifications
110
benign epithelial lesions w/ atypia contain high density of what kind of receptors?
estrogen receptors
111
T or F: ALL breast carcinomas arise from cells in the terminal duct lobular unit
True
112
T or F: DCIS commonly produces nipple discharge.
false
113
cribriform DCIS is commonly described as what
"cookie cutter"
114
Malignant DCIS can be distinguished from traditional DCIS via what biomarker indications
ER-, HER2+
115
T or F: LCIS is not assoc. w/ calcifications or densities
true
116
LCIS can be idendified by what biomarker indications?
ER/PR+ & HER2-
117
BRACA1/2 increases risk for these cancers in males?
epithelial cancers of the prostate and pancreas
118
BRAC1/2 mutations also increase risk for what other malignancies in male and females.
female: ovarian
male: breast
119
BRAC1 breast cancer is of what subtype?
TNBC
poorly differentiated
120
list the ER negative breast cancers
BRCA1 & Germline TP53 mutations
121
T or F: Germline BRCA2 mutations cause luminal invasive cancer
true
122
what tumor suppressor gene is assoc. w/ BRCA1
TP53
123
what tumor suppressor gene is assoc. w/ BRCA2?
PIK3CA
124
which molecular subtype/s of breast cancer is/are HER2+
Germline TP53 mutations
125
what is the most common metastatic site for breast cancers
bone
126
what is the biggest risk factor for luminal breast cancer?
estrogen exposure
127
luminal breast cancer is defined by what?
ER+ and HER2-
128
compare and contrast the 2 different types of luminal breast cancers?
PR+- well differentiated and slow growing
PR-: poorly differentiated & high proliferative rate
129
The HER2 gene is located on which chromosome?
17q
130
T or F: HER2 is a tumor suppressor gene. Explain your reasoning.
false
encodes for a receptor tyrosine kinase that promotes cell proliferation and opposes apoptosis
131
what is the most common breast cancer subtype in pts. w/ Li-Fraumeni Syndrome
TP53 germline mutation
132
what is the precursor lesion for TNBCs?
presence of TP53 mutations
133
T or F: invasive carcinoma can also invade dermis and cause retraction/dimpling of skin
true
134
List the cytoplasmic contents of lobular carcinoma?
mucin w/o tubule formation
135
what are the cancer cells of lobular carcinoma called?
signet ring cells
136
lobular carcinoma commonly metastases to what regions?
retro/peritoneum, GI tract, ovaries, uterus, leptomeninges
137
T or F: over half of BRCA1 carcinomas are of the medullary pattern
true
138
T or F: the infiltrating lymphocytes seen with the medullary pattern are B-cells
false
they are T-cells
139
medullary carcinomas are often of what molecular subtype of breast cancer?
TNBC
140
T or F: the medullary pattern is often soft w/ poorly defined borders
false
it is usually a soft, well-circumscribed mass w/ pleomorphic nuclei
141
describe the histologic characteristics of micropapillary carcinoma.
hollow balls of cells that float in intercellular fluid; this creates structures that mimic appearance of true papillae
142
mucinous, tubular, & papillary carcinomas are usually what?
ER+ & HER2-
143
apocrine and micropapillary carcinomas are usually what?
HER2+
144
describe the gross characteristics of inflammatory carcinoma
Peau d'oragne: the entire breast looks like a big orange
breast tissue is tethered by cooper ligaments to give this appearance
145
what is the 10-year survival rate if 1-3 lymph nodes are invoved
decreases to 35-45%
146
T or F: removal of involved lymph nodes is assoc. w/ decreased future reoccurance
false
147
which breast cancer subtype wins the gold medal for highest survival rate and best prognosis
Expression of ER, PR, and HER2
148
how is stage T0 breast cancer defined?
ductal carcinoma in situ
149
how is stage T1 defined
invasive carcinoma <2cm
150
what are the parameters for a T2 stage?
invasive carcinoma >2cm & <5cm
151
T3 is defined how
invasive carcinoma > 5cm
152
define the N stages
N-lymph node invovlement
0 - no invovlement
1-micrometastases
2-1-3 LNs
3->4 LNs
4-
153
an M4 stage indicates what
distant metastasis is present
154
T or F: gynecomastia is assoc. w/ lobules
false
hyperplasia of duct lining only
155
hyperestrinism in males is assoc. with what factors?
cirrhosis
decreased androgen production w/ age
steroids
alcohol
heroin
marijuana
antiretroviral drugs
156
gynecomastia is assoc. with what diseases
testicular neoplasms
klinefelter syndrome
157
what mutation is assoc. w/ fibroadenomas?
MED12
158
what are the gross characteristics of fibroadenoma?
well circumscribed
rubbery
grayish
slit-like spaces
159
T or F: phyllodes tumors are assoc. w/ MED12 mutations
true
160
unlike fibroadenoma, phyllodes tumors usually present later or earlier in life
later (6th decade)
161
what term is often used to describe the histologic appearance of phyllodes tumors?
"leaf-like" architecture
162
T or F: malignant tumors of interlobular stroma are rare
true
163
what is angiosarcoma?
a rare malignant tumor of the interlobular stroma that primarily affects young women
164
the most common primary breast lymphomas are of what type of lymphocyte?
B-cells
165
primary breast t-cell lymphomas are more commonly assoc. with what?
chronic inflammation
166
although rare, what malignancies commonly metastasize to the breast tissues?
melanomas
ovarian cancers
