16.1 - 16.4: Breast Pathology Flashcards
Breasts are derived from what layer, embryologically?
Skin layer
What is the milk line, and what is its significance?
The line from the axilla to the vulva, where the breasts develop from. This is where extra nipples can develop from
What is the functional unit of the breast?
Terminal duct-lobular unit—lobules make milk that drains via ducts to the nipple
All ducts and lobules of the breast have two layers of epithelium. What are these? What is the function of each?
- Luminal cell layer–protect the duct
- Myoepithelial cell layer–responsible for contraction of the duct during milk ejection
The highest density of breast tissue is where, anatomically?
Upper outer quadrant
What causes the breast TTP during menstruation?
Estrogen
What is galactorrhea?
Milk production OUTSIDE of lactation
True or false: galactorrhea is a symptom of breast cancer
False–never a s/sx
What causes milk ejection?
Nipple stimulation
What pituitary pathology can cause galactorrhea?
—-
Prolactinoma
What is the most common pathogen that causes acute mastitis?
S. Aureus
What makes breast tissue susceptible to mastitis with breast feeding?
Cracked develop during suckling, that allows for entry of pathogens
What are the s/sx of mastitis?
- Erythema
- Purulent nipple d/c
What is the treatment of mastitis? (2)
- Drainage (continue BF)
- ABX
What is the classic abx used in the treatment of mastitis?
Dicloxacillin
Should a woman who has mastitis continue breast feeding?
Yes–drains the area
What is periductal mastitis? In whom is it usually seen? How does it present?
- Inflammation of the subareolar ducts
- Usually seen in smokers
- Subareolar mass with nipple retraction
What type of epithelium lines the areolar ducts?
Columnar
What vitamin is the epithelium of the breast ducts dependent on? What is the significance of this?
Smokers lose the ability to use Vit A, causing the breast ductal tissue to turn to squamous.
This metaplasia to squamous causes an increase in keratin, which can clog the ducts and cause periductal mastitis
What causes the retraction seen with periductal mastitis?
Granuloma formation behind the nipple d/t chronic inflammation causes the recruitment of fibroblasts, and the retraction of the skin
What is mammary duct ectaisa?
Rare inflammation of the subareolar ducts that causes dilation of the subareolar ducts,
In whom does mammary duct ectasia develop in?
Multiparous, postmenopausal women
Green-brown nipple discharge = what breast pathology?
Mammary duct ectasia
What is the classic d/c associated with mammary duct ectasia?
Green-brown nipple discharge
What are the classic histological findings of mammary duct ectasia?
Chronic inflammation with plasma cells
Chronic inflammation with plasma cells on bx of the breast is indicative of what pathology?
Mammary duct ectasia
What is the usual cause of fat necrosis of the breast?
Trauma
How does fat necrosis of the breast usually present?
Mass on exam or calcification on mammography
What will biopsy of fat necrosis of the breast show?
Necrotic fat with associated calcification and giant cells
What causes the calcification of fat necrosis?
—–
Saponification-addition of Ca to fat necrosis
What is fibrocystic change of the breast? What causes this?
The development of cysts around the lobules of the mammary ducts, resulting in stress on the stroma, and resulting fibrosis
Variations in estrogen levels
In whom are fibrocystic changes of the breast most common? Why?
Premenopausal women–d/t wide variations in estrogen levels
What are the characteristic clinical findings of fibrocystic changes?
Lumpy breast in the upper, outer quadrant
What are the gross characteristics of fibrocystic changes?
Blue-domed cyst appearance on gross exam
Blue-domed appearance of a breast mass = ?
Fibrocystic changes
True or false: Fibrocystic change of the breast is benign, and carries NO increased risk for breast cancer
True
True or false: Fibrocystic change of the breast with apocrine metaplasia is benign, and carries NO increased risk for breast cancer
True
What is the one exception to the rule that metaplasia increases the risk for dysplasia?
Apocrine metaplasia
Is ductal hyperplasia of the breast benign or malignant? Does it carry an increased risk for cancer? If so, which type?
Benign, but there is a 2x risk for the development of invasive carcinoma
What is sclerosing adenosis of the breast, and is it benign or malignant? Does it carry an increased risk for cancer? If so, which type?
- Increase in glands and surrounding stromal tissue
- Benign, but there is a 2x risk for the development of invasive carcinoma
Does atypical hyperplasia of the breast increase the risk of developing into cancer? If so, which type?
Yes–5x for invasive carcinoma
What is sclerosing adenosis of the breast? Is there a risk of this developing into cancer? How is this often detected, and why?
- Proliferation of glands (adenosis) with fibrosis of the stroma between them (sclerosis)
- Benign, but increases risk for ca x2
- Found on mammography d/t Ca deposition
True or false: benign lesions of the breast that carry an increase in the chances of cancer, increase the risk for the development of cancer in BOTH breasts, regardless of which breast the lesion was seen in
True
What is an intraductal papilloma? What is the classical presentation of this, and why?
- Growth of ductal epithelial cells into the duct, with a fibrovascular core.
- Bloody nipple discharge, since the growth is vascularized, and fragile
What are the two cell types that form the intraductal papilloma?
Ductal epithelial cells, and the myoepithelial cells
In whom are intraductal papillomas usually seen in? Intraductal papillary carcinoma?
- Premenopausal woman = papilloma
- Postmenopausal woman = carcinoma
What is the key histological difference between the intraductal papilloma and intraductal papillary carcinoma?
Lack of myoepithelial cells with intraductal papillary carcinoma
What are fibroadenomas?
Benign tumor of fibrous tissue and glands
What is the most common benign neoplasm of the breast?
Fibroadenoma
What are the clinical features of fibroadenomas?
Well circumscribed, mobile, marble-like mass
Are fibroadenomas estrogen sensitive?
Yes
Is there a risk for the development of carcinomas from fibroadenomas? If so, which type?
No
What are the general histological characteristics of fibroadenomas?
Glandular tissue encapsulated in fibrous tissue (sharply demarcated)
What are Phyllodes tumors?
Fibroadenomas-like tumors with overgrowth of the fibrous component
What are the classic histological findings of phyllodes tumors? What causes this?
Leaf-like projection–Fibrous tissue pushes out
Leaf-like projections on histology from a breast mass = ?
Phyllodes tumor
In whom are phyllodes tumors most commonly seen?
Postmenopausal women
Are Phyllodes tumors malignant?
—-
Can be
What are the the top three cancers by incidence?
- Breast/prostate
- Lungs
- Colorectal
What are the top three cancers by mortality?
- Lungs
- Breast/prostate
- Colorectal
All of the risk factors for the development of breast cancer generally involve what?
Higher estrogen exposure
Why is obesity related to breast cancer?
Adipose converts androgens to estrone
What are the relatives who, if they have cancer, increase the risk for you to develop cancer?
Mother, sister, daughter (1st degree relatives)
What is Paget’s disease of the nipple? How does it present?
DCIS that grows to involve the duct and skin
Presents as a nipple ulceration and erythema
What does DCIS become when it invades the BM?
IDC (invasive ductal CA)
What is ductal carcinoma in situ?
Tumor of the mammary ducts that has NOT invaded the basement membrane
How is DCIS appear on mammography?
Calcifications
What is comedocarcinoma? Why does it occur?
- DCIS that has caseous necrosis
- Occurs because there is no blood supply to the center of the duct
Can you feel DCIS?
No–need mammogram
What are the two benign lesions of the breast that can show calcifications on mammography?
- Fat necrosis
- Sclerosing adenosis
What are the histological characteristics of Paget’s disease of the nipple?
Large cells with a clear halo about the nucleus
What is the most common type of invasive breast cancer?
Invasive ductal carcinoma
What are the clinical features of invasive ductal carcinoma?
Presents as a mass with dimpling of the skin or retraction of the nipple
What are the histological characteristics of ductal carcinoma?
Duct-like structures in a desmoplastic stroma
Duct-like structures in a desmoplastic stroma = which breast pathology?
invasive ductal carcinoma
What are the four subtypes of ductal carcinoma?
- Tubular
- Mucinous
- Medullary
- Inflammatory
What is the prognosis for the tubular subtype of ductal carcinoma?
Good
What are the histological characteristics of the tubular subtype of ductal carcinoma?
Tubular structures within a sea of desmoplasia and fibrous tissue
What are the histological characteristics of the mucinous subtype of ductal carcinoma?
Mucinous glands in a ton of mucus
What is the prognosis for the mucinous subtype of ductal carcinoma?
Good (“can’t go anywhere because stuck in mucus”)
What are the clinical features of inflammatory ductal carcinoma? What causes this?
Peu d’orange–inflammation of the breast d/t blockage of the dermal lymphatics
What are the histological characteristics of inflammatory carcinoma?
Neoplastic cells within the lymphatics
What two pieces do you need to diagnose inflammatory carcinoma? What is the prognosis?
-Histological findings + clinical inflammation
Poor prognosis
Inflammatory carcinoma of the breast looks similar clinically to what pathology? What may lead you to suspect carcinoma?
- Mastitis
- Failure of mastitis to resolve with abx
What are the histological characteristics of medullary carcinoma of the breast?
High grade Atypia in a sea of inflammatory cells
BRCA1 mutations have a large increase in what type of breast cancer?
Medullary subtype of invasive ductal carcinoma
What is lobular carcinoma in situ?
Tumor of the lobules of the breast that have not invaded the BM
Does LCIS produce mass or calcification?
No
True or false: LCIS is usually multifocal, and bilateral
True
What is the classic histological characteristic of LCIS? Why does this occur?
Dyscohesive cells in the lobules d/t a lack of E-cadherin
What is the protein that LCIS lacks? What histological characteristics does this cause?
- E-Cadherin
- Discohesive
What is the major significance of lobular carcinoma in situ?
Major risk factor for the future development of breast cancer
What is the treatment for LCIS? What is not? Why?
- Tamoxifen
- Not resected, since it is a risk factor for CA, not CA in itself
What is the MOA of tamoxifen? Trastuzumab?
- Tamoxifen = ER receptor antagonist
- Trastuzumab = Her2/neu receptor antagonist
Is the risk for LCIS developing into cancer high or low
Low risk factor
What are the histological characteristics of invasive lobular carcinoma? Why?
- Grows in a single file pattern (indian file)
- Lack of E-Cadherin
What is the single most important prognostic factor for breast cancer (in terms of TNM staging)?
Metastases
What is the single most useful prognostic factor for breast cancer? Why?
- Spread to lymph nodes
- More useful than mets, since most patients do not present with mets
What is the means by which we ascertain if there is spread of breast cancer via the lymphatic system? How does this work?
Sentinel lymph node biopsy–inject radioactive dye and assess which tier of lymph nodes has cancer
What are the three key prognostic factors for the responsiveness of breast cancer to therapy?
- ER+
- PR+
- HER2/neu gene amplification
What is the cause of upregulation of the HER2/neu receptor?
Gene amplification
Why is it that ER or receptor tagging leads to the development of dark nuclei? Why is this not seen with HER2/neu?
- The receptors translocates to the nucleus to alter gene expression
- HER2/neu is a surface receptor
What is triple negative breast cancer, and what is the prognosis for this? In what ethnicity is this usually seen in?
- HER2/neu -, ER- and PR- breast cancer—–poor prognosis
- African americans
Tumor at a premenopausal age is suggestive of what sort of cancer etiology?
Hereditary
Multiple tumors is suggestive of what sort of cancer etiology?
Hereditary
BRCA1 gene mutation increases the risk for what two cancers?
Breast and ovarian
BRCA2 mutation increases the risk for what cancer?
Breast carcinoma in males
What type of ovarian cancer odes BRCA1 predispose patients to?
Serous cystadenoma and fallopian tube tumors
Why doesn’t prophylactic mastectomy reduce the risk for breast cancer to 0?
Usually still breast tissue remaining in axilla or pectoralis muscles
Where, anatomically, does male breast cancer develop?
Subareolar mas under the nipple
What type of breast cancer do males usually get? Why? What are the two hereditary etiologies of male breast cancer?
- Invasive ductal CA (no lobules for CA to develop in)
- BRCA2 or Klinefelter syndrome
What is the genotype for Turner’s syndrome? klinefelters?
- Turners = X0
- Klinefelters = XXY
