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Week 4 Flashcards

1
Q

Organization of adult breast tissue

A

Lobes: glandular units of the breast
-Composed of multiple lobules containing alveoli (milk producing units) that are connected by a ductal network that empties into single milk duct

Milk ducts from multiple lobes feed into the nipple

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2
Q

Terminal ductal lobular unit

A

TDLU = functional unit of breast

Each terminal duct has grapelike cluster of small acini (tubules) that form a lobule

Composed of:

  • epithelial (myoepithelial, luminal)
  • stromal components (intra, and interlobular stroma)
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3
Q

Non-lactating vs. lactating gland composition:

A

Non-lactating gland composition:
20% glandular, 40% intra gland fat, 24% subcutaneous fat, 7% retro fat

Lactating gland composition:
62% glandular, 7% intra gland fat, 24% subcutaneous fat, 7% retro fat

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4
Q

Embryogenesis of breast development:

_________ is secreted by epithelial cells → induce differentiation of _______ _________ → _________ ___________

A

PTHrP secreted by epithelial cells → induce differentiation of DERMAL mesenchyme → MAMMARY mesenchyme

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5
Q

Role of PTHrP in breast development

A

PTHrP secreted by epithelial cells → induce differentiation of DERMAL mesenchyme → MAMMARY mesenchyme

Mammary mesenchyme triggers morphogenesis of mammary gland and stimulates nipple formation

NO PTHrP → dermal mesenchyme fails to differentiate → Blomstrande Chondroplasia (no mammary gland)

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6
Q

“Witch’s Milk”

A

temporary milk secretion in both male and female neonates caused by elevated prolactin and decreased progesterone at parturition

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7
Q

Breast development during puberty is driven by what?

A

Estrogen and Progesterone increased → elaboration/growth of ducts and alveoli - driven by menstrual cycle

Formation of ductal network and lobules are regulated independently

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8
Q

Breast development during puberty:

Estrogen + GH –> ?

A

Estrogen + GH → elongation and branching of ductal network by increasing IGF-1 production in stromal cells

Once final stages of puberty are reached, growth hormone levels will be decreased → stop proliferation of branches even though estrogen continues

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9
Q

Breast development during puberty:

Progesterone –> ?

A

Progesterone (luteal phase of menstrual cycle) → stimulates side-branching and lobuloalveolar (TDLU) formation during menses

TDLUs capable of making milk proteins

Even after puberty ends, TDLU development continues

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10
Q

Breast development during puberty:

Macroscopic breast development

A

due to increase in fat accumulation in mammary adipose tissue

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11
Q

Mature nulliparous breast contains what?

A

Extensive branched-ductal network with attached lobules are present

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12
Q

What changes to breast tissue occur during pregnancy? (3)

A

Get extensive lobule formation

Differentiation of alveolar cells

Minimal or no milk secretion

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13
Q

Breast tissue during pregnancy:

Progesterone (3 functions)

A

Progesterone → alveoli elaboration, side branching, inhibits milk secretion

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14
Q

Breast tissue during pregnancy

Prolactin (2 functions)

A

Prolactin → side branching, lactogenesis

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15
Q

Breast tissue during pregnancy

Placental lactogen (1 function)

A

Placental lactogen → lactogenesis

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16
Q

Lactogenesis

A

differentiation of mammary gland to produce milk

Milk product synthesis initiated during pregnancy by actions of prolactin and placental lactogen, but milk secretion is held in check by high progesterone

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17
Q

Lactation

A

Copious milk secretion
Coordinated production and secretion of diverse milk components

Regulated by pituitary hormones - prolactin and oxytocin

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18
Q

What happens after lactation is finished?

A

Involution: apoptosis, glandular regression, and return to quiescence

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19
Q

Lactation initiation:

Milk secretion initiated by ____________ at parturition due to __________

Elevated _______ levels required to maintain milk synthesis and secretion

A

Milk secretion initiated by FALL in PROGESTERONE at parturition due to removal of placenta

Elevated prolactin levels required to maintain milk synthesis and secretion

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20
Q

Lactation requires ________ and ___________ of milk with feedback regulation

A

SECRETION and EJECTION

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21
Q

Milk Secretion requires __________ and __________

A

prolactin (for milk synthesis and secretion)

Milk removal

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22
Q

Milk removal is required for what?

A

Milk removal required to maintain glandular integrity and milk production

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23
Q

Milk Ejection requires ________ and _________

A

oxytocin and suckling

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24
Q

Suckling stimulated afferent activation of hypothalamus causes what?

A

→ Inhibit dopamine → release of prolactin from anterior pituitary in pulses

→ Oxytocin release from posterior pituitary

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25
Oxytocin stimulates what?
contraction of myoepithelial cells that surround alveoli stimulating milk ejection
26
Prolactin pulse size and frequency regulated by _________
Pulse size and frequency regulated by SUCKLING stimulus - suckling required to maintain prolactin levels
27
Factors affecting lactation:
Anxiety, stress Delayed lactation initiation Pituitary disorders or damage Excessive weight -Obesity can also impair mom’s ability to mobilize energy for milk production
28
Cellular pathways of milk secretion: (5)
1) Classical secretion proteins 2) Apocrine secretion - lipids 3) Ion transport 4) Transcytosis 5) Paracellular serum substances
29
Main difference between human and cow milk
High oligosaccharides in human milk
30
What happens to the tight junctions during lactation?
During lactation tight junctions closed, but prior to lactation up to day 3 - tight junctions are open and allow movement of IgA, lactoferrin, etc. into breast milk
31
3 main phases of breast milk
1) Colostrum 2) Transitional 3) Mature milk Milk also varies DURING feeding (foremilk vs. hindmilk), varies throughout the day, and varies in volume
32
Colostrum - 4 main features
1) Yellow in color 2) High in IgA and lactoferrin (anti-infection properties) 3) Higher protein, lower fat and lactose 4) Facilitates establishment of lactobacillus and passage of meconium
33
Transitional milk - 4 main features
day 2-14 Immunoglobulins and protein decrease Lactose and fat increase Increase in calories Vitamin changes
34
Mature milk: water and lipid content?
Water: largest quantity of any constituent, maintains infant hydration Lipids: provides 50% of calories, variety of lipids, varies during feeding
35
Mature milk Proteins
Casein and whey (PRIMARILY WHEY) Lactoferrin - inhibits growth of Fe dependent bacteria in GI tract Immunoglobulins (sIgA) + other antimicrobial factors
36
Mature milk carbohydrates, trace elements, and vitamins
Carbohydrates - Lactose (galactose and glucose) Trace elements: iron (no risk of deficiency in 1st 6 months), zinc Vitamins: Vitamin D
37
How does milk volume vary as infants grow?
Volume increases as infant grows - 1st month (22oz), 6 months (30oz), 12 months (25 oz)
38
How does maternal malnutrition effect milk content/production?
Maternal malnutrition → reduced milk supply, but minimally alters macronutrient content Consumption > maintenance needs does NOT enhance milk production
39
How does maternal diet effect mineral content of milk
Diet affects content of vitamins in human milk, however, most mineral content is independent of maternal intake EXCEPTIONS: selenium, iodine
40
How does maternal fluid consumption effect milk?
Fluid consumption important for milk synthesis Fluid consumption > maintenance needs does NOT enhance milk production
41
Advantages of breast milk over formula: For infant: (3)
Immunologic protection Neurodevelopmental benefits (bonding) Reduced likelihood of atopy, diabetes, obesity later in life
42
Advantages of breast milk over formula: For Mother: (6)
``` Prevent postpartum hemorrhage Weight loss Lactational amenorrhea/birth spacing Reduced risk of chronic conditions Bonding/stress reduction Economic benefits ```
43
Hospital practices that support vs. undermine breastfeeding: Positive: (6)
``` BF in 1st hour Skin to skin contact Rooming in Lactation consultants Peer role modeling Ad lib nursing/feeding ```
44
Hospital practices that support vs. undermine breastfeeding: Negative: (6)
``` Separation for infant and mom Mother discouraged BF/limited time suckling Convert formula feeding D/C packs with formula Lack of support Pacifier use ```
45
Baby friendly hospital initiative (BFHI)
promotes, protects, and supports breastfeeding through “10 Steps to Successful Breastfeeding for Hospitals” as outlined by UNICEF and WHO
46
“The Golden Hour”
infant nursed (skin to skin) within first hour after birth
47
Medical contraindications for breastfeeding
medications, active untreated alcohol or drug abuse, infections (untreated TB, HIV) Breastfeeding recommended in developing countries unless women have access to formula AND clean water Galactosemia - infant can’t metabolize breast milk
48
Recommendations for infant feeding practices:
Recommend that women exclusively breastfeed for about 6 months, continue to breastfeed through first or second year of life with appropriate complementary feeding initiated at 6 months
49
Newborn’s Adaptation to Extrauterine Life: First 1-3 days:
- Colostrum (high fat, protein, Igs, low volume) - Practice breastfeeding Energy source: 1) Glycogen stores last about 12 hours (stimulated by intrauterine GCC) 2) Low glucose → low insulin, increased glucagon → increased gluconeogenesis 3) “Stress” → lipase → release of TG → glycerol and fatty acids
50
Frequency of breastfeeding:
Variable time between feeds, on demand (30 min to hours) 8-12 times per day Thorough emptying of breast is important Duration of 10-30 min
51
Patterns of weight loss and regain by the infant:
Infants expected to lose 5-7% of their birth weight Typically stop losing weight by 5 days (because mom’s breast milk has come in) Start gaining 15-30 g/d Regain of BW by 7-14 days
52
Common issues with breastfeeding:
Poor attachment Primary lactation failure - RARE “Insufficient milk syndrome” - COMMON Mastitis Maternal return to work Poor infant growth
53
“Insufficient milk syndrome”
COMMON Inadequate milk removal → inadequate milk production Factors: Maternal - stress, medical problems, separation from infant, older maternal age Infant - LBW/prematurity, poor suck/latch neurologic issues, lethargy, illness, formula supplementation
54
Formula vs. Breastfeeding: | 1) Atopy:
Expose infants to allergens present in formula, increase risk of atopy Breast feeding has less risk of atopy compared to formula fed infants
55
Formula vs. Breastfeeding: | 2) Diabetes
Infants fed with BM vs. cow’s milk formula → lower risk of autoantibody in breastfed group 10 years later
56
Formula vs. Breastfeeding: | 3) Obesity
evidence is mixed if BF protects infant from obesity later on
57
Formula vs. Breastfeeding: | 4) Infant growth
Formula fed infants 0.65 kg more than a BF infant BF infants at risk of being labeled as “growth faltering” due to slower growth → WHO growth standards for infants through age 2 are new standard
58
Breast histology transition from outer skin to inner ductule?
Squamous epithelium overlying skin → enters nipple and becomes a double-layered cuboidal epithelium lining the ducts Anything more than 2 cell layers is ABNORMAL Successive branching of large ducts → terminal duct lobular unit (TDLU)
59
Male breast histology
NO tubules (acini), ductal structures surrounded by small amount of adipose and fibrous tissue
60
TDLU: Epithelial Component: (2)
1) Contractile Myoepithelial cells (MEC) | 2) Luminal epithelial cells
61
Contractile Myoepithelial cells (MEC)
contain myofilaments, form mesh like pattern on basement membrane Assist in milk ejection during lactation Structural support for lobules MEC layer LOST in invasive breast cancer
62
Luminal epithelial cells
overlay myoepithelial cells ONLY lobular luminal cell capable of producing milk
63
TDLU: Stromal Component (2)
1) Interlobular stroma | 2) Intralobular stroma
64
Interlobular stroma
dense fibrous CT + adipose
65
Intralobular stroma
envelopes acini of lobules, contains breast-specific HORMONALLY RESPONSIVE fibroblast-like cells + scattered lymphocytes
66
Breast histology: Childhood:
breast composed of branching ductal system without lobular units
67
Breast histology: Puberty
estrogen + progesterone stimulation → proliferation of glandular tissue → formation of lactiferous ducts and interlobular duct system that are stable and unaffected by fluctuating hormone levels during menstrual cycle, pregnancy, and lactation TLDUs are dynamic and change with hormone levels
68
Breast histology: Menstrual cycle
increased size/nodularity 1st half → lobules quiescent After ovulation → estrogen and progesterone rise → cell proliferation, proliferation of acini per lobule, intralobular stroma become edematous Menstruation → fall in estrogen and progesterone induces regression of lobules and stromal edema disappears
69
Breast histology: Pregnancy - onset
breast completely mature and functional Lobules increase progressively in number and size By end of pregnancy breast composed almost entirely of lobules with scant stroma separating them
70
Breast histology: Pregnancy - After delivery
luminal cells of lobules produce colostrum (high protein), which changes to milk (higher fat and calories) over next 10 days as progesterone levels drop
71
Breast histology: Cessation of lactation:
breast epithelium/stroma remodeled extensively Epithelial cells undergo apoptosis, lobules regress/atrophy and total breast size is diminished Full regression does NOT occur Permanent increase in size and number of lobules
72
Breast histology: Postmenopausal involution
lobules and specialized stroma start to involute Involution of TDLUs Duct system remains Decrease in intralobular stroma, increase in fatty tissue Lobular atrophy complete in elderly
73
Accessory Breasts of nipples:
can occur anywhere along embryonic mammary ridges Accessory nipple usually just below normal breast Accessory/ectopic breast tissue may be in lower axilla
74
Congenital Inversion of Nipples
benign, but similar to a change that may indicate underlying cancer
75
Juvenile hypertrophy
rare condition in adolescent girls Breasts (usually both) markedly enlarge due to hormonal stimulation No endocrine abnormality detected
76
Gynecomastia
enlargement of one or both breasts in a male Typically idiopathic, caused by excessive estrogen stimulation Other causes: liver disease, drugs, testicular tumors, metabolic or endocrine disorders
77
Gynecomastia Microscopic features
normal breast tissue, ductal epithelial hyperplasia, stromal edema, loose fibrosis around ducts
78
Apocrine metaplasia:
Histologic alteration of epithelium of TDLUs → cells resemble apocrine sweat gland epithelium -fibrocystic change
79
Blue-dome cysts:
Larger cyst that arise in TDLU Unilocular Contain brown fluid which give a blue color to intact cyst -fibrocystic change
80
Sclerosing adenosis
can be mistaken clinically for INVASIVE CARCINOMA NO cysts - proliferation of acini with marked fibrosis that can compress/distort lumens of acini and ducts → solid cords of cells Myoepithelial cells are not lost Diffuse microcalcifications which may mimic carcinoma on mammography -fibrocystic change
81
Acute mastitis and abscess:
Occurs usually at onset of lactation → cracks in nipple and stasis of milk predispose to infection Staph. Aureus is most common infecting agent Mastitis → redness, swelling, pain and tenderness If abscess forms → requires drainage of pus MUST rule out INFLAMMATORY BREAST CARCINOMA
82
Chronic mastitis
uncommon NOT due to lactation NO infectious agent Occurs in perimenopausal women due to obstruction of lactiferous ducts by inspissated luminal secretions
83
3 types of chronic mastitis
Mammary duct ectasia Plasma Cell Mastitis Granulomatous mastitis
84
Granulomatous mastitis
Rarely get foamy histiocytes and fibrosis
85
Plasma Cell Mastitis
Primary infiltrate is PLASMA CELLS
86
Mammary duct ectasia
Obstruction → dilation of ducts (mammary duct ectasia) and periductal chronic inflammation
87
Periductal Mastitis
painful erythematous subareolar mass, recurrent Usually in smokers Squamous epithelium extends down into nipple and duct → formation of abscess Occurs in both men and women NOT associated with lactation, age or reproductive history NOT infectious
88
Fat necrosis of breast -early vs. late phase
uncommon disease Stretching and narrowing of arteries in pendulous breasts → ischemia Early phase: neutrophil + necrotic fat cells Later phase: macrophages, giant cells, fibrosis, and calcification May present as a HARD MASS - suspicious for carcinoma on physical exam
89
Fibroadenoma
solitary, discrete, regular, mobile mass Composed of proliferating ducts in proliferating fibroblastic stroma Most common benign neoplasm in breast, typically in young women Origin is TDLU Can have complex features (epithelial hyperplasia) → predispose to breast CA TX = surgical excision
90
Lactating adenoma
palpable mass in pregnant or lactating women Normal appearing breast tissue with physiologic adenosis and lactational changes - exaggerated focal response to hormonal influence Discrete, soft, well circumscribed, rounded mass
91
Intraductal papilloma
benign neoplasm originating in major lactiferous duct near nipple Presents with bloody nipple discharge and small subareolar mass
92
Intraductal papilloma Appearance
Papillary mass projecting into lumen of large duct Numerous delicate papillae composed of fibrovascular core covered by layer of epithelial and myoepithelial cells Must distinguish from PAPILLARY CARCINOMA
93
Phyllodes tumor
rare, composed of intralobular stroma and ductal epithelium Range from benign to malignant
94
Benign Phyllodes tumor
Benign Appearance: massive size, leaf-like clefts and slits Benign epithelium overlying a stromal overgrowth Benign ones have NO cytologic atypia or mitoses
95
Non-Proliferative Fibrocystic Changes:
Cysts / fibrosis Epithelial hyperplasia ABSENT
96
Fibrocystic change
asymptomatic or pain + nodularity Due to hormonal changes
97
Proliferative Fibrocystic Changes:
Cysts / fibrosis Epithelial hyperplasia PRESENT
98
Lobular hyperplasia includes _______ and ________
hyperplasia of acinar epithelium Atypical lobular hyperplasia LCIS (Lobular Carcinoma in situ)
99
Atypical lobular hyperplasia
< 50% of lobules filled with epithelial cell proliferation | Acini have increased number of cell layers
100
LCIS (Lobular Carcinoma in situ)
>50% of lobules filled and distended by epithelial proliferation Higher risk of malignancy (BILATERAL - not just in the one side)
101
Ductal hyperplasia includes _______, __________, and ___________
terminal duct hyperplasia Usual hyperplasia, atypical ductal hyperplasia, DCIS
102
Usual hyperplasia
mild, moderate, florid hyperplasia Increase in epithelial layer (>2 cell layers) which distends terminal ducts
103
Usual hyperplasia: MILD
papillary tufts projecting into lumen
104
Usual hyperplasia: MODERATE
epithelial cells proliferate to bridge and create arcades
105
Usual hyperplasia: FLORID
solid mass which fills duct and distends lumen, may have irregular fenestrations - cell crowding, overlapping, mixed proliferation of epithelial cells and myoepithelial cells
106
Atypical ductal hyperplasia:
Architectural cytologic features of carcinoma in situ, but lack complete criteria for diagnosis Associated with higher risk of cancer than usual hyperplasia
107
DCIS (Ductal carcinoma in situ):
Malignant cells confined within basement membranes of ducts without invasion of surrounding stroma
108
Cancer Risk and Hyperplasia: Minimal / no risk: (6)
1) Duct ectasia 2) Cysts 3) Apocrine metaplasia 4) Fibrosis 5) Mild hyperplasia (>2 but < 4 cells thick) 6) Fibroadenoma without complex features
109
Cancer Risk and Hyperplasia: Slightly increased risk: (4)
Hyperplasia (moderate to florid) Papilloma Sclerosing adenosis Fibroadenoma with complex features
110
Cancer Risk and Hyperplasia: Moderate increased risk: (2)
Atypical ductal hyperplasia (ADH) Atypical lobular hyperplasia (ALH)
111
Cancer Risk and Hyperplasia: Markedly increased risk: (2)
Ductal carcinoma in situ (DCIS) → risk of invasive ductal CA Lobular carcinoma in situ (LCIS) → risk of BOTH ductal and lobular CA and can be ipsilateral or other side

Life Cycles (8 decks)

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