Chapter 23- The Breast Flashcards
What are the gene mutations commonly seen in breast cancer in the Ashkenazi Jew population
-BRCA1 and 2
What condition presents with Palpable periareolar mass with:
- Thick, White nipple excretions
- Skin retractions
- no pain or erythema
- 50-60 year old woman
Duct ectasia
IN the case of nonproliferative breast changes, what are the findings regarding diagnosis of the cysts
Mass will disappear with fine needle biopsy as the contents are removed
With regards to Proliferative breast disease without atypia, what are the findings for papillomas
-Large duct papillomas, with 80% producing discharge
What are the characteristics of Paget’s dissease and associations
- Milagnant cells extend from the DCIS via the lactiferous sinuses into nipple skin without crossing the basement membrane
- Allows ECF to seep into the nipple surface, with Paget cells being detected with nipple biopsy
How is DCIS most commonly found
Mammogram, usually due it calcifications with secretory material or necrosis
What are the three classifications of benign epithelial lesions
1) Nonproliferative breast changes
2) Proliferative breast disease without atypia
3) Proliferative breast disease with atypia
BRCA2 is associated with increased risk of which cancers
Male breast cancer Prostatic and pancreatic carcinomas Melanoma Gallbladder Bile duct
Which carcinoma has a diffuse infiltrative pattern with minimal desmoplasia,with signet ring cells with mucin droplets
Lobular carcinoma
What is the cause of the dimpling of the skin in the case of breast cancer
Carcinomas invade the pectoralis muscle or invade into the dermis
What is the risk of invasive carcinomas of the contralateral breast in DCIS
No risk/low risk
What is the most common subtype of breast cancer in patients with TP53 mutations
HER2 positive
What is the clinical presentation of lymphocytic mastopathy or sclerosing lymphocytic lobulitis
Single or multiple hard palpable masses or mammography can densities. Hard to obtain tissue via needle biopsy due to dense collagenized stroma
What are the morphological transition of HER2 positive cancers
Atypical apocrine adenosis
What is the risk of breast cancer if there is the presence of proliferative disease with atypia
4 to 5 times increased risk
Ashkenazi Jewish populations carry which mutations more commonly
1 in 40 carry:
- 2 mutations in BRCA1
- 1 mutations in BRCA2
What is the relative risk for those who had a child earlier in life
Lower risk (due to permanent changes in the terminal differentiation)
What is the most important prognosis of invasive carcinoma in the cause of metastasis.
Presence of metastasis to the axillary lymph nodes
What are the characteristics of the acute mastitis when caused by staphylococcal
Single or multiple abscesses
Which tumor marker set prognosis is irrelevant to size
ER-, HER+. (Metastasize when very small)
What is the state of differentiation in HER2+ tumors
Not well differentiated
What is the morphological transition changes seen in germline BRCA2 mutations
1) Flat epithelial atypia
2) Atypical ductal hyperplasia
3) Ductal carcinoma in-situ (DCIS)
What gene mutations are most responsible for familial breast cancers
BRCA1 and BRCA2 (80-90% of familial breast cancers)
What is the clinical presentation of fibroadenomas
-multiple, Bilateral and in the 20s-30s
What is the prognosis and treatment in the case of HER2 breast tumors
Antibodies to HER2 have lead to a very good prognosis
What grade is a tumor that has some tubular formation, but solid clusters or single infiltrating cells, with greater degree of pleomorphic and mitotic figures present
Grade 2
What grade is a tumor that has ragged nests or solid sheets of cells with enlarged irregular nuclei
Grade 3
What are the most common causes of palpable lesions of the breast
Cysts
Fibroadenomas
Invasive carcinomas
IN the case of nonproliferative breast changes, what are the findings regarding the adenosis
Increase in the number of acini per lobule:
-appearing as “flat epithelial atypia”
Which from of breast cancer is most common in older women and men
ER+, HER -, low proliferation
What is the prognosis of ER+, HER-, low proliferation
Good prognosis with most being cured with surgery with little risk of local recurrence
When adenocarcinomas are discovered, what is the state of majority of breast cancers with regards to the basement membrane
-majority (70%) have breached the basement membrane
What are the markers that are almost alsways expressed by LCIS
- ER and PR
* never HER2
What are the descriptions a patient my describe nonproliferative breast changes
“Lumpy bumpy”
What tends to be the trend of prognosis of breast masses with regards to age
Younger women tend to have more benign compared to the malignant in older
What are the clinical presentations of fat necrosis of the breast
Similar to carcinoma in that:
-Painless palpable mass
-Skin thickening or retraction
-Mammography densities or calcifications
Aka firm, ill defined, grey-white nodules containing small chalky-white foci
What is the prognosis of Paget disease based on
The features of the underlying carcinoma
*Not affected by the presence or absence of DCIS
Which race has the highest mortality of breast cancer and what is the type most common
African American
-Agressive, ER-neg and high nuclear grade
ER-, HER- breast cancers are associated with which mutations
-BRCA1
BRCA1 is the common mutation seen in which tumors
Ovarian carcinoma
Prostatic and pancreatic carcinoma
What is the relation between risk of breast cancer and alcohol
Consumption increases the risk
Which form of ER+, HER-, high proliferation has a better prognosis
The one who have complete responsiveness to chemotherapy
What are the characteristics of the growth of lobular carcinoma in situ
- Discohesive fashion due to the loss of E-Cadherin via the CHD1
- can also occasionally be caused by catenin dysregulation
With regards to Proliferative breast disease with atypia, what are the findings for atypical ductal hyperplasia
Monomorphic proliferation of regularly spaced cells, sometimes in the cribriform plate
*Does not fill the entirely of the ducts, which separates if from carcinoma in situ
What are the determining factors in the prognosis of female breast cancer
- biological features of the tumor
- Extend of tumor spread
What is the prognosis of ER+ tumors with distant metastasis.
Very bad
What is the clinical significance of Duct ectasia
Must be differentiated from invasive carcinomas
What is the rate of responsiveness to chemo in strongly ER+ carcinomas
Loss responsive
Which findings in medullary carcinoma are associated with between outcomes
Lymphocytic infiltrates
Where are most breast carcinomas located
Upper outer quadrant (50%)
What are the findings in the cause of nonproliferative breast changes
- Cystic changes with apocrine metaplasia
- Fibrosis
- Adenosis
Which benign conditions are nipple discharge normal
- Elevated prolactin
- Hypothyroidism
- endocrine anovulatory Syndromes
- OC
- dopamine antidepressants
What can be used to differente between the tumors fibroadenomas and Phyllodes tumor
Both benign but:
- Fibros (20-30s) earlier than phyllodes (60s)
- high cellularity
- higher mitotic rate
- nuclear pleomorphism
- stromal overgrowth
- infiltrative borders
Which form of nipple inversion is of most concern and what is the cause
Acquired nipple retraction since its a sign of potential invasive cancer or inflammatory disease
What is the state of differentiation in ER-,HER2 tumors
No well differentiated
What are the characteristics of micropapillary carcinomas
Anchorage independent growth, where they have E cadherin by lack the adhesion to the stroma
What is the prognosis of DCIS
Good, with 95% if women being cured with mastectomy
HER2+ cancers arise through a pathway that is strongly associated with which amplifications
HER2 gene on chromosome 17q
Which patients are more likely to have inflammatory carcinoma
African American women and younger women
What are the two forms of Proliferative breast disease with atypia
- atypical ductal hyperplasia
- atypical lobular hyperplasia
What mutation is associated with medullary carcinomas
BRCA1
Which cancers are associated with CHEK2 mutations
- Prostate
- THyroid
- Kidney
- Colon
What are the characteristics of the cancers seen with BRCA1 mutations
Breast cancers are commonly poorly differentiated and triple negative (basal like) and TP53 mutations
“Medullary like:
What is the most common subtype of breast cancer in individuals who inherit BRCA2
ER+, HER2- (50-65%)
What is the rate of responsiveness of chemotherapy to ER and PR tumors
Very good, better than just one of the receptors.
With regards to Proliferative breast disease with atypia, what are the findings for atypical lobular hyperplasia
- Cells distend into the acini within the lobule
* Does not distend or fill more that 50%, which separates it from carcinoma in situ
What is the prognosis of micropapillary carcinomas
Poor prognosis
Which other cancers are associated with mutations in TP53
Sarcomas, leukemias, brain tumors, adrenocortical tumors
What are the characteristics of the breast calcifications that are associated with malignancy
Small, irregular, numerous and clustered
Bloody or serous nipple discharge is most indicative of which condition
-Large duct papillomas and cysts
With regards to Proliferative breast disease without atypia, what are the findings for epithelial hyperplasia
-Increased numbers of luminal and myoepithelial cell types
What is the location of metastasis in the case of ER+, HER-, low proliferation
Bone
What are the findings in Proliferative breast disease without atypia
- Epithelial hyperplasia
- Sclerosing adenosis
- Complex sclerosing lesion
- Papilloma
What are the mutations genetically in the BRCA2 mutations
- 1q gain
- 16q loss
All with downstream PIK3CA mutation activations
With regards to Proliferative breast disease without atypia, what are the findings for complex sclerosing lesions
- Components of sclerosing adenosis, papillomas, and epithelial hyperplasia
- Central Indus of entrapped glands in a hyalinized stroma surrounded by long radiating projections into the stroma
Which mutation should be considered in a family with male breast cancer
BRCA2
What are the risk factors for high likely recurrence of DCIS
1) High nuclear grade
2) extent of disease
3) positive surgical margins
Which patient population is commonly seen to have lymphocytic mastopathy
Women with T1D and/or autoimmune thyritis
What condition is commonly seen to have mucin positive signet ring cells
LCIS
What is the cause of supernumerary nipples/breasts and how do they normally present
Milk line remnants and commonly arise as a result of painful premenstrual enlargements
Which race has the highes incident of breast cancer in the US
Non-Hispanic white
What are the characteristics of the acute mastitis when caused by streptococcal
Cellulitis
IN the case of nonproliferative breast changes, what are the findings regarding the cystic changes
Associated with apocrine metaplasia:
-semi-translucent fluid of a blue or brown color (aka blue-dome cysts)
What are the general findings/descriptions of nonproliferative breast changes
-fibrocystic changes
What are the characteristics of the different breast densities and what are their prognosis
- Rounded (benign as in fibroadenomas or cysts)
- Irregular (invasive carcinomas)
What is the relation between risk of breast cancer and age of first menstration
Younger the first menstration (before age 11) , the increased risk of 20%
How is it that MRI are able to pick up breast carcinomas
The increased contrast fluid uptake by the cancer cells due to their vascularity and blood flow
What are the characteristics of noncomedo DCIS
-Lacks high grade nuclei or central necrosis
Patients with lobular carcinoma are at a higher risk for which condition
Gastric signet ring cell carcinoma
What are the three divisions of breast carcinomas
1) ER positive, HER-2 negative (50-65%)
2) ER negative, HER-2 negative (10-20%)
3) HER-2 positive (10-20%)
What is the dominating feature in the ER+, HER-, low proliferation
ER dominated, so very responsive in the case of women with estrogen replacement
Most breast carcinomas are of which type
Adenocarcinoma that arise in the duct/lobular system
What is the prognosis of breast erythema and skin thickening
Very bad. As they have distant metastasis
*aka cooper ligaments that mimic the skin of an orange peel
Most breast malignancies are of which type
Adenocarcinomas
Women who receive cyclosporin A following a renal transplant commonly develop which condition
Multiple and bilateral fibroadenomas, which will regress following treatment cessation
Which condition present morpholigically with unilateral erythematous eruption with a scale crust
Paget’s disease, commonly with itching and eczema look alike
What are the characteristics of comedo DCIS
- Tumor cells with pleomorphic, high grade nuclei
- Area of Central necrosis
What are the state of markers for carcinomas with Paget’s disease when it is a palpable mass
ER-, over expression of HER2
How was the rate of breast cancers changed recently
All have stayed constant, but ER pos,HER-2 neg have increased
Which patient population is more likely to develop a squamous metaplasia of lactiferous ducts
Smokers (90%), usually due to lack of Vitamin A that alter the differentiation of the ductal epithelium.
With regards to Proliferative breast disease without atypia, what are the findings for sclerosing adenosis
Increased number of acini that are compressed and distorted in a central position of the lesion (forms a swirling pattern, but is wll circumscribed). May have irregular slitlike fenestrations in the periphery
Essentially all well circumscribed tumors are of which markers
ER+, HER-
Which tumors arise from the intralobular stroma
- Fibroadenomas
- phyllodes Tumor
What is the risk of breast cancer if there is the presence of proliferative disease without atypia
1.5 to 2 times increased risk
IN the case of nonproliferative breast changes, what are the findings regarding the chromosome with flat epithelial atypia
16q
What patients are HER2+ breast cancers most commonly seen in
-Young women and nonwhite women
In the case of breast cancers, what are the type of mutations seen
Loss of tumor suppressor genes such as BRCA 1 and 2, TP53, CHEK2
ER+ and HER- carcinomas have what rate of proliferation
Fast
With regards to Proliferative breast disease with atypia, what are the mutated chromosomes
Loss of 16q
gain of 17p
What is the cause of acute bacterial mastitis
Occurs in the first month of breastfeeding in which bacterial enters the cracks and fissures in the nipple
What is the most common benign tumor of the breast
Fibroadenomas
Phyllodes tumors are associated with which mutation/changes
-gains in 1q
What is the only sarcoma that is common in the breast and when are they commonly seen
Angiosarcoma, following radiation about 10 years later
Calcifications of the breast are assocaited with which prognosis
Benign
What is the method of spread for LCIS
Pagetoid spread, which is the presence of neoplastic cells between the basement membrane and overlying luminal cells
What are the bacteria most commonly causing acute bacterial mastitis
- Staph Aureus**
- Streptococci
What is the presenting on a a squamous metaplasia of the lactiferous ducts
Painful erythematous subareolar mass that appears like a bacterial abscess
TP53 or Li Fraumeni syndrome is common to see carcinomas with which markers
-ER+, HER2+
Which carcinoma is described as soft/rubbery with the consistency and appearance of being pale blue-grey gelatin
Mucinous
Which patients are most commonly seen to have ER-,HER- tumors
Premenopausal women
-African Americans and Hispanic women
What is the prognosis of overexpression of HER tumors
Not very good
What are the factors for DCIS that indicate higher risk for recurrence and progression
-Nuclear grade and necrosis
Which breast cancer risk increases with age
-ER positive risk increased with age
What is the relative risk of breast cancer in women with a family member with it
15-20% of women
Which women tend to have BRCA1 mutations
African Americans
Which conditions can cause gynocomastia in males
- Cirrhosis of the liver (metabolized estrogen)
- Excess estrogen or testosterone levels dropping
What is the association of nonproliferative breast changes with breast cancer
No increased risk
When are ER-,HER- breast cancers most likely to emerge
In between mammograms (due to the high proliferation rate)
Which tumor is defined by a grating sound with cut or scraped (like a water chestnut)due to a central pinpoint foci or streaks of chalky-white desmoplastic stroma and occasional foci of calcification
Invasive carcinoma
HOXB13 are associated with which characteristic in phyllodes tumor
- higher grade
- more aggressive
ER+, HER2 -, high proliferation is most associated with which mutation
BRCA2
Where are the common locations of metastasis for ER-,HER- breast cancers
Bone
Brain
Viscera
How is LCIS most commonly found
Incidental finding as it is not associated with calcification or densities
With regards to Proliferative breast disease with atypia, what are the findings atypical lobular hyperplasia with regards to mutations
Loss of E caderhin
What are the percentages of the location of breast carcinomas
Upper outer- 50%
Each other quadrant- 10%
Central region- 20%
What is the prognosis of a tumor with exuberant desmoplastic stromal response
Not good as likely an invasive carcinoma
What is the only breast tumor that is equally likely in males and females
-Myofibroblastoma
Invasive carcinomas following LCIS are most likely to be of which kind
Lobular carcinoma (3x more likely)
Which mutation is associated with higher risk of male breast cancer
BRCA2
What is the risk of invasive carcinomas of the contralateral breast in LCIS
High risk, as both have the same risk
Which form of discharge is the most concerning
Spontaneous and unilateral
Lobular carcinoma tend to have which mutation
CDH1 for cadherin
What grade is a tumor that has Tubular pattern with small round nuclei with low proliferation rate
Grade 1
ER positive cancers are considered to resemble what
Luminal tumors, by resembling normal breast luminal cells
Morphology of ecstatic dilated ducts filled with insipiated secretions with chronic inflammation and fibrosis and numerous lipid laden macrophages are indicative of which condition
-Duct Ectasia
