Lecture 9: The Breast Flashcards
1
Q
How does the composition of breast change with aging and how is this related to imaging and ease of diagnosis?
A
- Young women = ↑ fibrous interlobular stroma which appears radiodense or white on imaging; makes diagnosing tougher.
- Older women have ↑ adipose tissue, which appears more radiolucent and helps with the interpretation of images
2
Q
What 2 lesions of the breast arise in the intralobular stroma?
A
- Fibroadenoma
- Phyllodes tumor
3
Q
What 4 lesions can arise in the interlobular stroma of the breast?
A
- Fat necrosis
- Lipoma
- Fibromatosis
- Sarcoma
4
Q
What 4 lesions can arise in the large ducts of the breast?
A
- Duct ectasia
- Squamous metaplasia of lactiferous ducts
- Large duct papilloma
- Paget disease
5
Q
What are milk line remnants and how do they most commonly come to attention clinically?
A
- Supernumerary nipples or breast, anywhere from axilla –> perineum
- Present as painful PRE-menstrual enlargements
6
Q
What is the clinical significance of accessory axillary breast tissue; managed how clinically?
A
- Potential site for malignancy or other lesions
- Prophylactic mastectomies ↓ risk, but do NOT completely eliminate
7
Q
Why is acquired nipple inversion of greater concern than congenital?
A
May indicate presence of an invasive cancer or an inflammatory nipple disease
8
Q
Palpable masses of the breast are most commonly due to what 3 etiologies?
A
- Cysts
- Fibroadenomas
- Invasive carcinoma
9
Q
In what setting is nipple discharge most worrisome?
A
When spontaneous and unilateral; especially >60 y/o
10
Q
What is the most common cause of bloody or serous discharge from th nipple?
A
Large duct papilloma
11
Q
What characteristics of a density detected on mammogram is associated with benign vs. malignant lesions?
A
- Benign = rounded densities
- Malignant = irregular masses
12
Q
How is DCIS most commonly seen on mammograms?
A
Calcifications –> small, irregular, numerous and clustered
13
Q
When does acute mastitis typically occur and what are the signs/sx’s?
A
- Typically during 1st month of breastfeeding
- Breast is erythematous and painful, and fever is common
14
Q
Squamous metaplsia of lactiferous ducts (aka recurrent subareolar abscess, periductal mastitis, and Zuska) disease commonly presents with what signs and sx’s?
A
- Painful erythematous subareolar mass
- Inverted nipple
15
Q
Risk factors for squamous metaplsia of lactiferous ducts (aka recurrent subareolar abscess, periductal mastitis, and Zuska) include?
A
- Smoking
- Vitamin A deficiency
16
Q
What are the key morphological features of squamous metaplsia of lactiferous ducts (aka recurrent subareolar abscess, periductal mastitis, and Zuska)?
A
- Keratinizing squamous metaplasia of nipple ducts
- Intense chronic granulomatous inflammation
17
Q
What are the distinguishing features, signs and sx’s of duct ectasia?
A
- Palpable periareolar mass w/ thick, white nipple secretions and occasionally skin retractionb
- NO pain or erythema!
18
Q
Duct ectasia most commonly occurs in which age group and what is a risk factor?
A
- Women 40-60 y/o
- Usually multiparous (birthed more than one child)
19
Q
In duct ectasia the ectatic ducts are filled with inspissated secretions and numerous what?
A
Lipid-laden macrophages
20
Q
What is the common clinical presentation of fat necrosis of the breast and what is a risk factor?
A
- Painless, palpable mass + skin thickening or retraction
- May also have mammographic densities or calcifications
- 50% of women have hx of breast trauma or prior surgery
21
Q
How does lymphocytic mastopathy (aka sclerosing lymphocytic lobulitis) most commonly present; associated with what underlying disorders?
A
- Single or multiple HARD palpable masses or mammographic densities
- Most common in women w/ T1DM or autoimmune thyroid disease
- Autoimmune basis
22
Q
What are the 3 principal morphological changes associated with nonproliferative breast changes (fibrocystic change)?
A
- Cysts
- Fibrosis
- Adenosis
23
Q
How can a FNA of a cyst associated with nonproliferative breast changes help confirm the diagnosis?
A
Dissapearance of the mass after FNA of its contents
24
Q
The nonproliferative breast change, adenosis, is defined as what; and is a normal feature seen in which women?
A
- ↑ in the number of acini per lobule
- Normal feature of pregnancy
25
The acini of adenosis seen with nonproliferative breast change may show what histological change that is thought to be the earliest recognizable precursor of low-grade cancer?
**Nuclear atypia** (**"flat epithelial atypia****"**)
26
Proliferative breast disease without atypia is characterized by what; what is the association with carcinoma?
- **Benign** lesions --\> **proliferation** of **epithelial** cells w/o atypia and are
- Associated w/ **small** ↑ **in risk** for carcinoma
27
Which lesions of proliferative breast disease without atypia has an irregular shape and can closely mimic invasive carcinoma mammographically, grossly, and histologically?
**Complex sclerosis lesion** --\> **radial sclerosis lesion** (aka **radial scar**)
28
What is the clinical significance of papilloma lesions as part of proliferative breast disease without atypia?
**80%** of **large papillomas** produce a **nipple discharge** can be **bloody** or **serous**
29
What are some of the underlying risk factors for gynecomastia?
- **Cirrhosis** of **liver** --\> ↑ **estrogen**
- **Drugs** --\> alcohol, marijuana, heroin, antiretroviral's, and anabolic steroids
30
What is the seen microscopically in gynecomastia?
↑ in **dense** **collagenous** **CT** + **epithelial hyperplasia** of **duct lining** w/ **tapering micropapillae** (**NO lobule formation**)
31
Is gynecomastia associated with an increased risk for cancer?
Yes, **small** ↑ **risk** due to being **proliferative breast disease without atypia**
32
What is atypical breast disease with atypia and what are the 2 morphologic forms?
- Clonal proliferation having **some**, but **not** all, of the histo. features required for dx of **CIS**
- **2 forms** = **atypical ductal hyperplasia** + **atypical lobular hyperplasia**
33
Which genetic feature of atypical lobular hyperplasia is shared with lobular carcinoma in situ?
Loss of **E-cadherin**
34
What is seen on biopsy of fat necrosis in the breast in both acute and chronic settings?
- **Acute** = liquefactive fat necrosis w/ neutrophils and macrophages
- **Chronic** = giant cells + calcifications and hemosiderin
35
Which in situ breast lesion is **rarely** palpable and almost always detected as calcifications on by mammography?
**Ductal carcinoma in situ (DCIS)**
36
Why is breast cancer in African American women associated with a higher overall mortality rate?
More likely to have **biologically aggressive** cancers --\> **ER-negative** and a **high nuclear grade**
37
What is the average age of diagnosis for breast cancer in white women, hispanics and blacks?
- **White women** = 61 y/o
- **Hispanics** = 56 y/o
- **Blacks** = 46 y/o
38
***BRCA1*** and ***BRCA2*** mutations are prevalent in which ethnicity?
**Ashkenazi Jews**
39
What is the most common risk factor shared between breast and endometrial carcinoma which ↑ risk for carcinoma of the contralateral breast?
Prolonged **estrogenic** stimulation
40
Based on the expression of estrogen receptors and HER2, what is the most common subtype of breast cancer?
**Estrogen receptor (+)** and **HER2 (-)**
41
Which genetic mutation associated with hereditary breast cancer is most frequenty assoc. w/ male breast cancer?
***BRCA2***
42
*BRCA1* associated breast cancers commonly have what kind of differentiation and growth features?
- **Poorly differentiated** w/ **"medullary features"**
- **Syncytial growth pattern** w/ pushing margins and a **lymphocytic** response
43
*BRCA1-*associated cancers are biologically similar to breast cancers with which estrogen receptor and HER2 expression; are identified as what?
- **ER (-)** and **HER2 (-)**
- **"Basal-like"**
44
What is the differentiation of *BRCA2-*associated breast cancers like and they are more likely to have what ER expression?
**Poorly differentiated**, most often are **ER (+)**
45
Which genetic mutation is associated with breast (female and male), ovarian, prostate, pancreas, stomach, gallbladder, bile duct, and pharynx cancer + melanoma?
*BRCA2*
46
Li-Fraumeni syndrome is due to genetic mutation in what and is associated with what cancers?
- ***TP53***
- **Breast** + **sarcoma** + **leukemia** + **brain tumors** + **adrenocortical carcinoma**
47
BRCA1 and BRCA2 are part of a large complex of proteins with what fuctions?
**Repair dsDNA breaks** through **homologous recombination**
48
Describe the pathway of breast cancer development starting with a germline BRCA2 mutations; which precursor lesions develop and what type of breast cancer?
- Germline ***BRCA2*** --\> Flat epithelial atypia
- Activating **PIK3CA** mutation ---\> Aytpical ductal hyperlasia
- **DCIS** ---\> **ER (+) -** **HER2(-) "luminal"** **breast cancer**
49
Flat epithelial atypia and atypical ductal hyperplasia often show which genetic mutations associated with developing ER(+) breast cancer?
**Germline *BRCA2*** and **activating *PIK3CA***
50
Describe the pathway to breast cancer including precursor lesions and mutations in pt's with germline TP53 mutations?
- **TP53** + **HER2** amplification --\> **Atypical apocrine adenosis**
- **DCIS** --\> **HER2** (**+**) **breast cancer**
51
What is the most common subtype of breast cancer in pt's with Li-Fraumeni Syndrome?
**HER2 positive**
52
What is the precursor lesion of HER2 positive breast cancers?
**Atypical apocrine adenosis** ---\> **DCIS**
53
What is the most common subtype of breast cancer arising in patients with germline *BRCA1* mutations?
**ER (-)** and **HER2 (-)** = **"Basal-like"**
54
Sporadic tumors that are ER(-) HER2(-) have which genetic mutations?
- Loss-of-function in ***TP53***
- May have epigenetic silencing of ***BRCA1***
55
What are the **best predictors** of local recurrence and progression to invasion for DCIS?
**Nuclear grade** and **necrosis**
56
What are the 2 features which define **comedo** DCIS?
1) Tumors cells with **pleomorphic**, **high-grade** **nuclei**
2) **Areas of central necrosis**
57
What are the morphological features of **noncomedo** DCIS, including cribiform and micropapillary DCIS?
- **Cribiform** may have **rounded** (**cookie cutter-like**) spaces within ducts
- **Micropapillary** has **bulbous** protrusions **without** a fibrovascular core, often arranged in complex intraductal patterns
\***Pic** on **left = cribiform DCIS** and on **right** **= micropapillary DCIS**
58
What is seen on mammography with **comedo** DCIS?
**Clustered** or **linear** and **branching** areas of **calcification**
59
Which ER and HER2 expression is most common of the carcinoma underlying Paget disease of the breast?
**Poorly differentiated**, **ER (-)** and **HER2 (+)**
60
If patient presents with Paget disease of breast but does not have a palpable mass then what do they have?
**DCIS**
61
What are the 3 major risk factors for recurrence and progression of DCIS?
1) **High nuclear grade** and **necrosis**
2) **Extent of disease**
3) **Positive surgical margins**
62
What is the proliferation of cells like in LCIS and how is it discovered clinically?
- **Discohesive** proliferation due loss of **E-cadherin**
- **ALWAYS** an **incidental finding** on **biopsy**, there are **NO calcifications** or mammographic findings
- As a result, its incidence did not ↑ after introduction of mammograms
63
Between DCIS and LCIS, which is found bilateral more often?
- **LCIS** is **bilateral** in **20-40%** of cases**\*\*\*\***
- **DCIS** is **bilateral** in **10-20%**
64
Which genetic mutation is associated with LCIS?
***CDH1*** leading to loss of **E-cadherin**
65
What is the typical morphology and characteristic cell types found with LCIS?
- **Uniform** population of cells w/ **oval** or **round nucloli** involving **ducts** and **lobules**
- **Mucin (+) signet-ring cells** are **common**
- **Pagetoid spread** is common, but LCIS does **NOT** involve nipple skin
66
LCIS is associated with what type of ER and HER2 expression?
- Almost always express **ER (+)** and **PR (+)**
- **HER2** is **NOT** observed
67
LCIS is a risk factor for what?
**Invasive lobular carcinoma** in **either breast!**
68
ER-positive, HER2-negative, high proliferation breast cancer is the most common type of carcinoma associated with what germline mutation?
**Germline** ***BRCA2***
69
ER-positive, HER2-negative, **low proliferation** breast cancer is most common type seen in which patients?
- **Older women** and **men**
- **Most common** type detected by **mammographic screening**
70
What is the recurrence and metastatic behavior of ER-positive, HER2-negative, low-proliferation breast cancers like?
- **Lowest recurrence rate**, late, **\>10 years**
- **Metastasis** late ---\> **bone** and **long survival** w/ metastasis is possible
71
How does ER-positive, HER2-negative, low-proliferation respond to chemotherapy vs. high-proliferation types?
- **Low-proliferation** = poor response to chemo, but respond **well** to **hormonal tx**
- **High-proliferation** = has a higher % of complete response to chemo
72
ER-positive, HER2-negative, high-proliferation will have increased nuclear staining for what?
**Ki67**
73
What are the typical patient groups affected by HER2-positive breast cancers?
- **Young women**
- **Non-white** **women**
- ***TP53*** mutation carriers = **Li-Fraumeni**
74
What is the metastasis and behavior of HER2-positive breast cancer like?
Can metastasize when **small** and **early**, often to **viscera** and **brain,** but also **bone**
75
Why have some HER2-positive cancers become associated with a better outcome?
**- \>1/3** respond **completely** to **chemo** agents designed to **block HER2 (Herceptin****)**
**-** Cancers that respond have **excellent** prognosis
76
ER-negative, HER2-negative ("basal-like) breast cancers are most commonly seen in whom?
- **Young premenopausal women**
- **African Americans**
- **Hispanics**
77
ER-negative, HER2-negative ("basal-like) breast cancer shows a number of genetic similarities with what other carcinoma?
**Serous ovarian carcinoma**; associated w/ ***BRCA1***
78
What are the recurrences and metastatic behavior of ER-negative, HER2-negative ("basal-like) like?
- Often **metastastize** when **small** and **early** --\> **viscera, brain** and **bone**
- **Recurrences** is **common** and generally **within 5 years**
79
What is the response rate to chemo for ER-negative, HER2-negative ("basal-like) breast cancers?
**30% completely** respond to **chemo**
80
What is the hitological hallmark of lobular carcinoma?
**Discohesive** infiltrating tumors cells, often w/ **signet-ring cells** containing intracytoplasmic **mucin**
81
What is the characteristic pattern of metastatic spread with lobular carcinoma?
- **Peritoneum** and **retroperitoneum**
- **Leptomeninges** (carcinomatous meningitis)
- **GI tract**
- **Ovaries (Kruckenberg)** and **Uterus**
82
Which genetic mutations is observed in a majority of medullary carcinoma?
**Hypermethylation** of ***BRCA1*** leading to ↓ regulation
83
What is the prognosis of medullary carcinoma and what histological finding is associated with higher survival rates?
- **Good prognosis**
- Presence of **lymphocyte infiltrates** in tumor assoc. with **higher survival** and **greater response to chemo**
84
Which special type of invasive breast cancer is associated with tumor cells arranged in clusters and small islands of cell within large lakes of mucin?
**Mucinous (colloid) carcinoma**
85
ER-negative, HER-negative tumors can have many histologic appearances, but which is most common?
**Medullary carcinoma**
86
Inflammatory carcinoma is more often seen in whom; what is prognosis; what is characteristic clinical finding?
- **African Americans**
- **Very poor prognosis** - **3 year survival** of **3-10%**
- ***Peau d'orange*** due to blockage of **lymphatics** by tumor
- Tumor extensively **invades** and **proliferates** WITHIN **lymphatics**
87
Tubular carcinoma is somtimes mistaken for what lesion; what immunohistochemical feature can help differentiate between the 2?
- Sometimes mistaken for **benign sclerosing lesion**, like a **radial sclerosing lesion**
- Immunostain for **ER** can help since almost all special subtypes of breast cancer are **ER (+)**
88
What is the most important prognostic factor for invasive breast carcinoma in the absence of distant metastases?
**Axillary lymph node** status
89
How is ER(+) and PR(+) related to therapeutic response?
- **Majority** respond to **hormonal therapy**
- **Less** likely to respond if **only** (+) for ER or PR
90
Breast cancers that are ER (-) or PR (-) respond best to what type of therapy?
**Chemotherapy**
91
Who is most often affected by Fibroadenomas and how do they present based on age?
- **Most common BENIGN** tumor of **female** breast; most occur **20-30 y/o**
- Frequently **multiple** and **bilateral** palpable mass (**younger** women)
- **Older women** more likely to have radiographic **density** or **clustered calcifications**
92
Which benign tumor of the breast may fluctuate in size during pregnancy and menstrual periods; and is associated with women receiving cyclosporin A after renal transplants?
Fibroadenoma
93
Fibroadenomas are catergorized as what type of proliferative lesions of the breast and how is this related to risk of cancer?
- Proliferative changes **WITHOUT** atypia
- Confer a **mild** ↑ risk for **cancer**
94
How does the age of presentation for phyllodes tumor differ from that of fibroadenomas?
**Most present in 50's**, which is **10 years later** than fibroadenomas
95
Overexpression of which transcription factor is associated with higher tumor grade and more aggressive behavior when assoc. w/ phyllodes tumor?
**HOXB13**
96
How are phyllodes tumors distinguished from fibroadenomas based on histology?
- **Bulbous protrusions** look like a **leaf**
- **Higher cellularity + mitotic rate**
- **Nuclear pleomorphism**
- **Stromal overgrowth + Infiltrative borders**
97
How likely is lymphatic spread of a phyllodes tumor based on grade and what is a special clinical consideration?
- **Regardless** of **grade**, **lymphatic spread = RARE**
- **Axillary LN dissection** = contraindicated
98
Which benign tumor of the breast is unusual in that it is equally as common in both women and men?
Myofibroblastoma
99
Who do most sporadic angiosarcomas of the breast arise in, what is their grade and prognosis?
- **Young women** (mean age = **35 y/o**)
- **High grade** and **poor prognosis**
100
What are risk factors acquired angiosarcomas of the breast and when do they arise?
- **Secondary** to **radiation therapy**
or
- **Edema**
- Most often arising **5-10 years after tx**
