CH16 - Breast Pathology Flashcards
What is the breast?
modified sweat gland; embryologically derived from the skin
From where can breast tissue develop?
anywhere along the milk line, which runs from the axilla to the vulva (e.g., supernumerary nipples).
What is the functional unit of the breast?
the terminal duct lobular unit
What do the lobules make?
milk that drains via ducts to the nipple
What are the lobules and ducts lined by?
two layers of epithelium, luminal cell layer and myoepithelial layer
What is the luminal cell layer? Its function?
inner cell layer lining the ducts and lobules; responsible for milk production in the lobules
What is the myoepithelial cell layer? Its function?
outer cell layer lining ducts and lobules; contractile function propels milk towards the nipple.
What is the breast tissue sensitive to?
hormone
What does the male and female breast tissue primarily consist of before puberty?
large ducts under the nipple
What is the development after menarche primarily driven by?
estrogen and progesterone; lobules and small ducts form and are present in highest density in the upper outer quadrant.
What happens to the breast during the menstrual cycle?
Breast tenderness during the menstrual cycle is a common complaint, especially prior to menstruation.
What happens to the breast during pregnancy?
breast lobules undergo hyperplasia.
What is hyperplasia driven by?
estrogen and progesterone produced by the corpus luteum (early first trimester), fetus, and placenta (later in pregnancy)
What happens to breast tissue after menopause?
breast tissue undergoes atrophy.
What does galactorrhea refer to?
milk production outside of lactation.
Is galactorrhea related to breast cancer?
It is not a symptom of breast cancer.
What causes galactorrhea?
include nipple stimulation (common physiologic cause), prolactinoma of the anterior pituitary (common pathologic cause), and drugs.
What are the inflammatory conditions of the breast?
Acute mastitis, periductal mastitis, mammary duct ectasia, fat necrosis,
What is acute mastitis?
Bacterial infection of the breast, usually due to Staphylococcus aureus
What is acute mastitis associated with?
breast-feeding; fissures develop in the nipple providing a route of entry for microbes.
What does acute mastitis present as?
an erythematous breast with purulent nipple discharge; may progress to abscess formation
What does the treatment of acute mastitis involve?
continued drainage (e.g., feeding) and antibiotics (e.g., dicloxacillin).
What is periductal mastitis?
Inflammation of the subareolar ducts
What is periductal mastitis usually seen in?
smokers
In periductal mastitis, relative vitamin A deficiency results in what?
squamous metaplasia of lactiferous ducts, producing duct blockage and inflammation
How does periductal mastitis clinically present?
as a subareolar mass with nipple retraction
What is mammary duct ectasia?
Inflammation with dilation (ectasia) of the subareolar ducts
What is the frequency of mammary duct ectasia?
Rare
In whom does mammary duct ectasia classically arise?
in muciparous postmenopausal women
What does mammary duct ectasia present as?
a periareolar mass with green-brown nipple discharge (inflammatory debris)
What is seen on biopsy of mammary duct ectasia?
Chronic inflammation with plasma cells
What is fat necrosis for the breast?
It is necrosis of breast fat
What is fat necrosis usually related to?
trauma; however, a history of trauma may not always be evident
What does fat necrosis present as?
a mass on physical exam or abnormal calcification on mammography (due to saponification)
What does biopsy of fat necrosis of the breast show?
shows necrotic fat with associated calcifications and giant cells.
What is fibrocystic change?
Development of fibrosis and cysts in the breast
What is the most common change in the premenopausal breast?
Fibrocystic change; thought to be hormone mediated
What does fibrocystic change present as?
vague irregularity of the breast tissue (lumpy breast), usually in the upper outer quadrant
In fibrocystic change what is seen on gross exam?
Cysts have a blue-dome appearance on gross exam.
Is fibrocystic change malignant or benign?
benign, but some fibrocystic-related changes are associated with an increased risk for invasive carcinoma (increased risk applies to both breasts)
For what type of fibrocystic change is there no increased risk for carcinoma?
Fibrosis, cysts, and apocrine metaplasia
For what type of fibrocystic change is there 2x increased risk for carcinoma?
Ductal hyperplasia and sclerosing adenosis
For what type of fibrocystic change is there 5x increased risk for carcinoma?
Atypical hyperplasia
What is intraductal papilloma?
Papillary growth, usually into a large duct
What is intraductal papilloma characterized by?
fibrovascular protections lined by epithelial (luminal) and myoepithelial cells
What does intraductal papilloma classically present as?
bloody nipple discharge in a premenopausal woman
What must intraductal papilloma be distinguished from?
papillary carcinoma, which also presents as bloody nipple discharge
What is papillary carcinoma characterized by?
fibrovascular projections lined by epithelial cells without underlying myoepithelial cells
When does the risk of papillary carcinoma increase?
with age; thus, it is more commonly seen in postmenopausal women.
What is fibroadenoma?
Tumor of fibrous tissue and glands
What is the most common benign neoplasm of the breast?
fibroadenoma; usually seen in premenopausal women
What does fibroadenoma present as?
a well-circumscribed, mobile marble-like mass
Does the fibroadenoma respond to estrogen?
Yes it is estrogen sensitive and grows during pregnancy and may be painful during the menstrual cycle
Is fibroadenoma malignant or benign?
it is benign with no increased risk of carcinoma
What is phyllodes tumor?
Fibroadenoma-like tumor with overgrowth of the fibrous component;
What is characteristically seen on biopsy of phyllodes tumor?
leaf-like projections are seen on biopsy
In whom is phyllodes tumor most commonly seen?
in postmenopausal women
Is phyllodes tumor benign or malignant?
It can be malignant in some cases
What is the frequency of breast cancer?
It is the most common carcinoma in women by incidence (excluding skin cancer)
What is the 2nd most common cause of cancer mortality in women?
Breast cancer
What are the risk factors for breast cancer?
they are mostly related to estrogen exposure; 1. Female gender 2. Age?Cancer usually arises in postmenopausal women, with the notable exception of hereditary breast cancer. 3. Early menarche/late menopause 4. Obesity 5. Atypical hyperplasia 6. First-degree relative (mother, sister, or daughter) with breast cancer
What is ductal carcinoma in situ?
Malignant proliferation of cells in ducts with no invasion of the basement membrane
What is ductal carcinoma often detected as on mammography?
Often detected as calcification on mammography; DCIS does not usually produce a mass.
Mammographic calcifications can also be associated with what?
benign conditions such as fibrocystic changes (especially sclerosing adenosis) and fat necrosis.
For calcification of breast tissue what is necessary to distinguish between benign and malignant conditions?
biopsy of breast calcifications
What are the histologic subtypes of DCIS based on?
architecture; comedo type is characterized by high-grade cells with necrosis and dystrophic calcification in the center of ducts
What is Paget disease of the breast?
is DCIS that extends up the ducts to involve the skin of the nipple
What does Paget disease presents as?
nipple ulceration and erythema
What is Paget disease of the breast almost always associated with?
an underlying carcinoma.
What is invasive ductal carcinoma?
Invasive carcinoma that classically forms duct-like structures
What is the most common type of invasive carcinoma in the breast?
Invasive ductal carcinoma, accounting tor > 80% of cases
What does invasive ductal carcinoma present as?
a mass detected by physical exam or by mammography
For invasive ductal carcinoma, what is the size of clinically detected masses?
they are usually 2 cm or greater
For invasive ductal carcinoma what is the size of mammographically detected masses?
They are usually 1 cm or greater
For invasive ductal carcinoma what is the size of advanced tumors?
they may result in dimpling of the skin or retraction of the nipple.
For invasive ductal carcinoma, what deos biopsy usually show?
duct-like structures in adesmoplastic stroma; special subtypes of invasive ductal carcinoma include
What is tubular carcinoma characterized by?
well-differentiated tubules that lack myoepithelial cells;
What is the prognosis for tubular carcinoma?
relatively good prognosis
What is mucinous carcinoma characterized by?
carcinoma with abundant extracellular mucin (tumor cells floating in a mucus pool)
In whom does mucinous carcinoma tend to occur?
in older women (average age is 70 years)
What is the prognosis for mucinous carcionoma?
Relatively good prognosis
What is medullary carcinoma characterized by?
large, high-grade cells growing in sheets with associated lymphocytes and plasma cells
How does medullary carcinoma grow?
as a well-circumscribed mass that can mimic fibroadenoma on mammography
What is the prognosis for medullary carcinoma?
Relatively good prognosis
In whom is there an increased incidence of medullary carcinoma?
in BRCA1 carriers
What is inflammatory carcinoma characterized by?
carcinoma in dermal lymphatics
What does inflammatory carcinoma present as classically?
as an inflamed, swollen breast (tumor cells block drainage of lymphatics) with no discrete mass; can be mistaken for acute mastitis
What is the prognosis for inflammatory carcinoma?
Poor prognosis
What is lobular carcinoma in situ?
(LCIS) Malignant proliferation of cells in lobules with no invasion of the basement membrane
How is LCIS usually discovered?
Its usually discovered incidentally since it does not produce a mass or calcifications
What is LCIS characterized by?
dyscohesive cells lacking E-cadherin adhesion protein
Describe LCIS.
It is often multifocal and bilateral
What is the treatment for LCIS?
Treatment is tamoxifen (to reduce the risk of subsequent carcinoma) and close follow-up; low risk of progression to invasive carcinoma
Can LCIS become invasive?
low risk of progression to invasive carcinoma
What is invasive lobular carcinoma?
Invasive carcinoma that characteristically grows in a single-file pattern, cells may exhibit signet-ring morphology
In invasive lobular carcinoma, what happens to the duct?
No duct formation due to lack of E-cadherin
What is the prognosis in breast cancer based on?
TNM staging.
What is the most important factor in breast cancer?
Metastasis is the most important factor, but most patients present before metastasis occurs,
What is the most useful prognostic factor (given that metastasis is not common at presentation)? How is this performed?
Spread to axillary lymph nodes; sentinel lymph node biopsy is used to assess axillary lymph nodes.
In breast cancer, what are predictive factors used for?
predict response to treatment.
What is the most important predictive factor for breast cancer?
estrogen receptor (ER), progesterone receptor (PR), and HER2/neu gene amplification (overexpression) status.
In breast cancer what is the presence of ER and PR associated with?
a response to antiestrogenic agents (eg tamoxifen); both receptors are located in the nucleus
What is the HER2/neu amplification associated with?
response to trastuzumab (Herceptin), a designer antibody directed against the HER2 receptor
What is HER2/neu?
it is a growth factor receptor present on the cell surface
In breast cancer, what are triple-negative tumors?
they are negative for ER, PR, and HER2/neu
What is the prognosis for triple negative tumors?
They have a poor prognosis; African American women have an increased propensity to develop triple-negative carcinoma,
What percentage of breast cancer cases does hereditary breast cancer represent?
10% of breast cancer cases
What are the clinical features that suggest hereditary breast cancer?
includes multiple first-degree relatives with breast cancer, tumor at an early age (premenopausal), and multiple tumors in a single patient
What are the most important single gene mutations associated with hereditary breast cancer?
BRCA I and BRCA2 mutations
What is the BRCA1 mutation associated with?
breast and ovarian carcinoma.
What is the BRCA2 mutation associated with?
breast carcinoma in males.
What might women with a genetic propensity to develop breast cancer choose to do?
undergo removal of both breasts (bilateral mastectomy) to decrease the risk of developing carcinoma.
What is the risk associated with bilateral mastectomy?
a small risk for cancer remains because breast tissue sometimes extends into the axilla or subcutaneous tissue of the chest wall.
What is male breast cancer?
Breast cancer is rare in males (represents 1% of all breast cancers).
How does breast cancer usually present?
as a subareolar mass in older males; 1. Highest density of breast tissue in males is underneath the nipple. 2. May produce nipple discharge
What is the most common histological subtype for breast cancer in males?
invasive ductal carcinoma.
What is the frequency of lobular carcinoma in males?
it is rare (the male breast develops very few lobules),
What is breast cancer in males associated with?
Associated with BRCA2 mutations and Klinefelter syndrome
