Twenty Five Flashcards
(22 cards)
What is the embryological origin of breast tissue? Where can it develop? What is the functional unit? What are the parts of it? What is their epithelium like?
A. Modified sweat gland embryologiesHy derived from the skin
i. Breast tissue can develop anywhere along the milk line, which runs from the
axilla to the vulva (e.g., supernumerary nipples).
B. The terminal duct lobular unit is the functional unit of the breast (Fig. 16.1); lobules
make milk that drains via ducts to the nipple.
C. Lobules and ducts are lined by two layers ol epithelium.
1 , Luminal cell layer—inner cell layer lining the ducts and lobules; responsible for milk production in the lobules
2, Myoepithelial cell layer—outer cell layer lining ducts and lobules; contractile function propels milk towards the nipple.
What is breast tissue like before pregnancy? What drives the formation of breasts after menarche? Where is breast tissue most dense? What can happen to breasts prior to menstruation in the cycle? What happens to breast tissue during pregnancy? What happens to breast tissue after menopause? What is galactorrhea? What are some causes?
D. Breast tissue is hormone sensitive.
1 . Before puberty, male and female breast tissue primarily consists of large ducts
under the nipple,
2. Development after menarche is primarily driven by estrogen and progesterone;
lobules and small ducts form and are present in highest density in the upper
outer quadrant.
3 . Breast tenderness during the menstrual cycle is a common complaint, especially prior to menstruation.
- During pregnancy, breast lobules undergo hyperplasia.
i. Hyperplasia is driven by estrogen and progesterone produced by the corpus luteum (early first trimester), fetus, and placenta (later in pregnancy) - After menopause, breast tissue undergoes atrophy.
E. Galactorrhea refers to milk production outside of lactation.
1 . It is not a symptom of breast cancer.
2. Causes include nipple stimulation (common physiologic cause), prolactinoma of the anterior pituitary (common pathologic cause), and drugs.
What is acute mastitis? What is it associated with? Why? HOw does it present? What is the treatment?
A. Bacterial infection of the breast, usually due to Staphylococcus aureus
B. Associated with breast-feeding; fissures develop in the nipple providing a route of entry for microbes.
C. Presents as an erythematous breast with purulent nipple discharge; may progress to
abscess formation
D. Treatment involves continued drainage (e.g., feeding) and antibiotics (e.g.,
dicloxacillin).
What is periductal mastitis? What is it associated with? What is the pathophys? How does it present?
II. PERI DUCTAL MASTITI S
A. Inflammation of the subareolar ducts
B. Usually seen in smokers
1 . Relative vitamin A deficiency results in squamous metaplasia of”lactiferous ducts, producing duct blockage and inflammation.
C. Clinically presents as a subareolar mass with nipple retraction
What is mammary duct ectasia? What is the epidemiology? How does it present? What is seen on biopsy?
A, Inflammatio n with dilation (ectasia) of the subareolar ducts
1 , Rare; classically arises in multiparous postmenopausal women
B. Presents as a periareolar mass with green-brown nipple discharge (inflammatory debris)
1 . Chroni c inflammatio n with plasma cells is seen on biopsy
What is fat necrosis? What is it related to? How does it present? What does a biopsy show?
A. Necrosis of breast fat
B. Usually related to trauma; however, a history of trauma may not always be evident.
C. Presents as a mass on physical exam or abnormal calcification on mammography
(due to saponification)
D. Biopsy shows necrotic fat with associated calcifications and giant cells.
What is fibrocystic change? What is a possible pathophys? Epidemiology? How does it present? Benign or malignant? Explain more detail.
I. FIBROCYSTI C C H A N G E
A. Development of fibrosis and cysts in the breast
1 . Most common change in the premenopausal breast; thought to be hormone med iated
B. Presents as vague irregularity of the breast tissue Clumpy breast’), usually in the upper outer quadrant
C. Cysts have a blue-dome appearanc e on gross exam.
D. Benign, but some fibrocystic-related changes are associated with an increased risk for invasive carcinoma (increased risk applies to both breasts)
1 . Fibrosis, cysts, and apocrine metaplasia (Fig. 16,2)—no increased risk
2. Ductal hyperplasia and sclerosing adenosis -2 x increased risk
3 . Atypical hyperplasia—5 x increased risk
What is an intraductal papilloma? How is it characterized? How does it present? What must it be distinguished from? How is this done?
A. Papillary growth, usually into a large duct
B. Characterized by fibrovascular protections lined by epithelial (luminal) and myoepithelial cells
C. Classically presents as bloody nipple discharge in a premenopausal woman
D. Must be distinguished from papillary carcinoma, which also presents as bloody nipple discharge
1 . Papillary carcinoma is characterized by fibrovascular projections lined by epithelial cells without underlying myoepithelial cells,
2. Risk ot”papillary carcinoma increases with age; thus , it is more commonl y seen
in postmenopausal women.
What is a fibroadenoma? Epidemiology? How does it present? Benign or malignant? Hormone sensitivity? Implications?
III. F I B R O A D E N O M A
A. Tumo r ot’fibrous tissue and glands (Fig. 16.3)
B. Most commo n benign neoplasm of the breast; usually seen in premenopausal women
C. Presents as a well-circumscribed, mobile marble-like mas s
D. Estrogen sensitive—grows during pregnanc y and may be painful during the menstrual cycle
E. Benign, with no increased risk of carcinoma
What is a phyllodes tumor? epidemiology? Benign or malignant?
A. Fibroadenoma-like tumo r with overgrowth of the fibrous component; characteristic ‘leaf-like’ projections are seen on biopsy (Fig. 16.4),
B. Most commonl y seen in postmenopausal women
C. Can be malignant in some cases
Epidemiology of breast cancer? Risk factors?
A. Most commo n carcinoma in women by incidence (excluding skin cancer)
B. 2nd most commo n cause of cancer mortality in women
C. Risk factors 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 menopaus e
4. Obesity
5. Atypical hyperplasia
6. First-degree relative (mother, sister, or daughter) with breast cancer
What is a ductal carcinoma in situ? How does it present? What else might have this presentation? How are they distinguished? What is comedo type? What is paget disease of the breast? How does it present?
II. DUCTA L C A R C I N O M A IN SIT U (DCIS )
A. Malignant proliferation of cells in ducts with no invasion of the basement membrane
B. Often detected as calcification on mammography; DCIS does not usually produce amass.
I, Mammographi c calcifications can also be associated with benign conditions such as fibrocystic changes (especially sclerosing adenosis) and fat necrosis.
2. Biopsy of calcifications is often necessary to distinguish between benign and malignant conditions.
C, Histologic subtypes are based on architecture; comedo typ e is characterized by high-grade cells with necrosis and dystrophic calcification in the center of ducts (Fig.16.5).
D. Paget disease of the breast is DCIS that extends up the ducts to involve the skin of the nipple (Fig. 16.6).
1 . Presents as nipple ulceration and erythema
2. Paget disease of the breast is almost always associated with an underlying carcinoma.
What is an invasive ductal CA? Epidemiology? Presentation? What is the biopsy like? What are 4 subtypes?
III. INVASIVE DUCTA L C A R C I N O M A
A. Invasive carcinoma that classically forms duct-like structures
B. Most c o m m o n typ e of invasive carcinoma in the breast, accounting tor > 80% of cases
C. Presents as a mass detected by physical exam or by mammograph y
1 . Clinically detected masses are usually 2 cm or greater.
2. Mammographically detected masses are usually 1 cm or greater.
3 . Advanced tumors may result in dimpling of the skin or retraction of the nipple.
D. Biopsy usually shows duct-like structure s in a desmoplasti c stroma; special subtypes of invasive ductal carcinoma include Tubular, mucinous, medullary, and inflammatory
What is tubular CA? How is it characterized? Prognosis? What is mucinous CA? Characterized? Epidemiology? Prognosis?
1 . Tubular carcinoma—characterized by well-differentiated tubules thai lack myoepithelial cells (Fig. 16.7A); relatively good prognosis
- Mucinous carcinoma—characterized by carcinoma with abundant extracellular muci n (‘tumo r cells floating in a mucus pool’, Fig. 16.7B)
i. Tends to occur in older women (average age is 70 years)
ii. Relatively good prognosis
What is medullary Ca? How is it characterized? How does it grow? What does it mimic on mammography? Prognosis? What is it associated with?
3 . Medullary carcinoma—characterized by large, high-grade cells growing in
sheets with associated lymphocytes and plasma cells
i. Grows as a well-circumscribed mass that can mimi c fibroadenoma on mammography
ii. Relatively good prognosis
iii. Increased incidence in BRCAI carriers
What is inflammatory CA? How does it present? What can it be mistaken for? What is the prognosis?
- Inflammatory carcinoma—characterized by carcinoma in dermal lymphatics
(Fig. 16.8}
i. Presents classically as an inflamed, swollen breast (tumor cells block drainage of lymphatics) with no discrete mass; can be mistaken for acute mastitis
ii. Poor prognosis
What is lobular carcinoma in situ? Presentation? What are the cells like? Distribution throughout breasts? What is the treatment? Risk of progression?
IV. LOBULAR C A R C I N O M A IN SITU (LCIS1
A. Malignant proliferation of cells in lobules with no invasion of the basement membrane
B. LCIS does not produce a mass or calcifications and is usually discovered incidentally on biopsy.
C. Characterized by dyscohesive cells lacking E-cadherin adhesion protein
D. Ofte n multifocal and bilateral
E. Treatment is tamoxifen (to reduce the risk of subsequent carcinoma) and close follow-up; low risk of progression to invasive carcinoma
What is invasive lobular CA? How is it characterized? What are the cells like?
V. INVASIVE LOBULAR C A R C I N O M A
A. Invasive carcinoma that characteristically grows in a single-file pattern (Fig. 16.9);
cells may exhibit signet-ring morphology.
1 , No duct formation due to lack of E-cadherin.
What is the most important factor for staging and prognosis with breast cancer? What is the most useful factor? What is performed to assess this?
A. Prognosis in breast cancer is based on T N M staging.
1 , Metastasis is the most important factor, but most patients present before metastasis occurs,
2. Spread to axillary lymph nodes is the most useful prognostic factor (given that metastasis is not commo n at presentation); sentinel lymph node biopsy is used to
assess axillary lymph nodes.
What are 3 predictive factors that predict response to treatment? What treatments do they indicate? Explain how they work? What are triple negative tumors? What clinical significance do they have? Epidemiology?
B. Predictive factors predict response to treatment.
I. Most important factors are estrogen receptor (ER), progesterone receptor (PR), and HER2/neu gene amplification (overexpression) status.
- Presence of ER and PR is associated with response to antiestrogenic agents (e.g.,tamoxifen); both receptors are located in the nucleus (Fig. 16.10).
J. HER2/neu amplification is associated with response to trastuzumab (Herceptin), a designer antibody directed against the HER2 receptor; HER2/neu is a growth
factor receptor present on the cell surface (Fig. 16.11).
- ‘Triple-negative’ tumors are negative for ER, PR, and HER2/ne u and have a poo r
prognosis; African American women have an increased propensity to develop triple-negative carcinoma,
How common is hereditary breast cancer? What are some clinical features that suggest hereditary breast cancer? What are the most important single gene mutations? What do they predispose patients to? What might they implicate for treatment?
VII. HEREDITARY BREAS T CANCE R
A. Represents 10% of breast cancer cases
B. Clinical features that suggest hereditary breast cancer include multiple first-degree relatives with breast cancer, tumo r at an early age (premenopausal), and multiple
tumors in a single patient.
C. HRCA I and HRCA2 mutations are the most important single gene mutations
associated with hereditary breast cancer.
1 . BRCA1 mutation is associated with breast and ovarian carcinoma.
2. BRCA2 mutation is associated with breast carcinoma in males.
D. Wome n with a genetic propensity to develop breast cancer may choose to undergo
removal of both breasts (bilateral mastectomy) to decrease the risk of developing
carcinoma.
1 . A small risk for cancer remains because breast tissue sometimes extends into the axilla or subcutaneous tissue of the chest wall.
How common is breast cancer in males? Presentation? Where is the highest density of breast tissue in males? What is the most common histological subtype? Which subtype is rare? What is it associated with?
A. Breast cancer is rare in males (represents 1 % of all breast cancers).
B. Usually presents as a subareolar mass in older males
1 . Highest density of breast tissue in males is underneath the nipple.
2. May produce nipple discharge
C. Most commo n histological subtype is invasive ductal carcinoma.
1 . Lobular carcinoma is rare (the male breast develops very few lobules),
D. Associated with BRCA2 mutations and Klinefelter syndrome
