Weibliche Geschlechtsorgane - Breast Flashcards
0
Q
Fibrocystic changes
- What are the subtypes of Fibrocystic changes?
- What is the most common subtype of Fibrocystic changes?
A
- nonproliferative and proliferative pattern
2. nonproliferative changes
1
Q
Fibrocystic changes
- How common are cyst formation and fibrosis in the breast?
- When do they occur?
- How does estrogen and oral contraceptives affect fibrocystic
changes?
A
- the most common breast abnormality seen in premenopausal
women - Fibrocystic changes tend to arise during reproductive age
and are most likely a consequence of the cystic breast changes
that occur normally in the menstrual cycle - They do not increase the incidence! However, oral
contraceptives may, in fact, decrease the risk
2
Q
Fibrocystic changes - nonproliferative changes
- Name the characteristics of nonproliferative changes!
- What does a cyst contain?
A
1.
- increased fibrous stroma
- dilatated ducts
- 1-5 cm in diameter cysts
- unopened cysts are brown to blue -> blue dome cysts
-> they are filled with watery, turbid/trüb fluid
The sexretions within the cysts may calcify
(On mammograms-> microcalcifications)
3
Q
Fibrocystic changes - nonproliferative changes
- What do you see histological?
A
1.
- A epithelial lining that in larger cysts may be flattened
(abgeflacht) or totally atrophic
- the lining cells are frequently large and polygonal with
granular and eosinophilic cytoplasma and small, round, deeply
chromatic nuclei -> apocrine metaplasia (always benign)
4
Q
Fibrocystic changes - Proliferative Change
- What layers do normal ducts and lobules have?
A
- Ducts and lobules of the breast have two layers:
- a layer of luminal cells
- which are overlying a second layer of myoepithelial cells
5
Q
Fibrocystic changes - Proliferative Change
- Epithelial Hyperplasia-
1. What characterizes epithelial hyperplasia?
A
- The presence of more than two cell layers.
-> the hyperplasia may consists of mild and orderly
or atypical hyperplasiaStill the epithelial hyperplasia contains cysts and fibrous
changes
6
Q
Fibrocystic changes - Proliferative Change
- Epithelial Hyperplasia-
1. How does an epithelial hyperplasia looks like histologically?
A
1.
- The ducts, ductules, or lobules may be filled with orderly
cuboidal cells within which small gland patterns (called
fenestrations) can be discerned.
-> the lumen is filled with cells of different morphology.
irregular slitlike fenestrations are prominent at the periphery
- Sometimes, the proliferating epithelium projects as multiple
small papillary excrescences into the ductal lumen
-> ductal papillomatosis - Occasionally hyperplasia produces microcalcifications on
mammography
7
Q
Fibrocystic changes - Proliferative Change
- Epithelial Hyperplasia-
1. What type of Epithelial hyperplasia is not so good?
A
- Atypical ductal and lobular hyperplasia
-> They are associated with an increased risk of invasive
carcinoma
8
Q
Fibrocystic changes - Proliferative Change
- Sclerosing Adenosis-
1. Why are sclerosing adenosis so important?
2. What is it?
A
- Even when they are rare, they are important because they
mimic clinical and morphological features of carcinoma
2. Sclerosing adenosis (SA) is a benign (non-cancerous) condition of the breast in which extra tissue develops within the breast lobules (the small portions of the glands that can produce milk.
Sclerosing adenosis often presents as a proliferation of elongated, obliterated, or distorted glands and tubules, in addition to hardening of surrounding collagen and stroma tissue.
9
Q
Fibrocystic changes - Proliferative Change
- Sclerosing Adenosis-
1. How is the consistency of sclerosing adenosis?
2. What does the histologic view offer?
A
- Similary to breast cancer -> hard, rubbery consistency
- A characteristic proliferation of luminal spaces (adenosis)
lined by epithelial cells and myoepithelial cellsMarked stromal fibrosis, which may compress and distort the
proliferation epithelium, is always associated with the
Adenosis -> sclerosing adenosisThis overgrowth of fibrous tissue may completely compress the
lumina of the acini and ducts, so that they appear as solid
cords of cells- a pattern that is difficult to distinguish
histologically from invasive ductal carcinomaThey is a double layer of epithelium and myopeithelial elements
10
Q
Fibrocystic changes - Proliferative Change
- What increases the risk of breast cancer?
A
1.
Significantly increased risk:
- atypical hyperplasia (ductal or lobular hyperplasia)
Slightly increased risk:
- Moderate to florid hyperplasia (without atypia)
- ductal papillomatosis
- sclerosing adenosis
11
Q
Inflammatory processes
- Name the possible inflammatory processes
of the breast!
A
1.
- mastitis
- traumatic fat necrosis
12
Q
Inflammatory processes
- explain the pathogenesis of acute mastitis!
- What are the clinical symptoms?
- What do you see histologically?
A
1.
- bacteria, almost always staphylococcus areus, reaches the
breast tissue through the ducts or through cracks (Riss) on the
nipple
- The vast majority of cases arise during the early weeks of
nursing (stillen)
2.
- Pain
- Rubor (redding)
- Fiever
- early axilliar lymph node swelling
- inflammatory changes and abscesses may develope
3.
- a prominent lymphoplasmacytic infiltrate
- occasional granulomas in the periductyl strima
- the ducts are filled with granular debris and sometimes
leucocytes and lipid-laden macrophages
13
Q
Inflammatory processes
- fat necrosis is a possible inflammatory disease of the breast.
How does it look in early and in advanced state?
A
- fat necrosis commonly after trauma!
Early stage:
- small lesion
- sharply localized
- central focus of necrotic fat cells
-> surrounded by neutrophils and lipid-laden macrophages
and sometimes giant cells
Later:
- the lesion becomes enclosed by fibrous tissue and
mononuclear leukocytes
- and eventually replaced by scar tissue or a cyst consisting of
necrotic debris
- calicification may develop in the scar or the cysr wall
14
Q
Tumors of the breast - Benign tumors
Fibroadenoma
- How frequently does the fribroadenoma occur?
- What tissue does the fibroadenoma have?
- Does the tumor occur solitary or multiple?
A
- It is the most frequent benign neoplasm of the femal breast
1/3 of all young women are affected - This tumor is biphasic, by an percentage of 97%. It contains:
- epithelium-lined glands (drüsiger Anteil->epithelial, Adenom)
- fibroblastic stroma -> only the stroma cells are truly neoplastic!
(Mesenchymal, Fibrom) - mostly solitary, just 10% multiple
15
Q
Tumors of the breast - Benign tumors
Fibroadenoma
- When does it occure (age)?
- How is the consistency of the tumor?
A
- young women are affected: 20-35 years of age
- sharply seperated
- mobile
- hart
- not painfully!!!
16
Q
Tumors of the breast - Benign tumors
Fibroadenoma
- What supports the growing rate of the fibroadenoma?
- What shrinks the fibroadenoma?
- What shrinks the fibroadenoma?
A
1.
- pregnancy!!!
- late menstrual cycle!
- > the growth is stimulated by estrogen
2. The fibroadenoma may regress (zurückentwickeln) and calcify
after menopuase (postmenopausal)
17
Q
Tumors of the breast - Benign tumors
Intraductal Papilloma
Wie der Name schon sagt: papillomatöse Milchgangepithelwucherung (gefäßführendes Bindegewebe, mit Epithel überzogen)- also intraductal gelegen oder in Zysten
- What are the clinical symptoms?
A
1.
- serous nipple discharge(Absonderung)
- or bloody nipple discharge
- In rare instances: nipple retraction (Zurücknahme)
18
Q
Carcinoma
- Name the risk factors of breast cancer?
A
1.
- risk increases after age 30
- Family history
- early menarche < 12
- late menopause > 1,5-2,0
- late pregnancy or nulliparous
- benign breast disease: with and without atypia hyperplasia
Other factors
- obesity
- oral contraceptives - maybe, maybe not
- Alcohol
- Cigarette
- Exogenous estrogen like homone replacement therapy
19
Q
Carcinoma
- Name the genetic changes!
A
1.
- Overexpression of the HER2/NEU proto-oncogen
- Amplification of RAS and MYC genes
- Mutation in BRCA I or BRCA 2
- Estrogen Rezeptor (ER)-positive or negative
- Progesteron Rezeptor (PgR)- positive or negative
20
Q
Carcinoma
- Describe the HER2/NEU proto-oncogene?
A
1.
- this mutation occurs in 30% of invasive breast cancer
- this gene is member of the epidermal growth factor receptor
family
21
Q
Carcinoma
- Describe the BRCA I and BRCA 2 genes!
A
1.
- 1/3 of women with hereditary breast cancer have these mutations
- they are classic tumor supressor genes
- cancer arises only when both alleles are inactivated
- these gens are believed to function in a common DNA repair pathway
22
Q
Carcinoma
- Why is estrogen causing breast cancer?
A
1.
Estrogen stimulates the production of growth factors, such as transforming growth factor-Alpha or fibroblast growth factor
–> these may promote tumor development through paracrine and autocrine mechanisms
23
Q
Cancer
- Name factors which increase estrogen?
A
Increased Exposure to Estrogen due:
- long duration of reproductive life
- nulliparity
- late age at birth
- ovarian tumors!!
24
Cancer
What are the two major categories of breast cancer?
Breast cancers are classified according to wether they have or have not penetrated the limiting basement membrane:
Those that remain within this boundary are termed in situ carcinomas, and those that have spread beyond it are designated invasive or infiltrating carcinomas.
Thus:
- Noninvasive
- Invasive (Infiltrating)
25
Cancer
Name all Noninvasive carcinomas!
- Ductal carcinoma in situ (DCIS)
| - Lobular carcinoma in situ (LCIS)
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Cancer
Name the Invasive carcinomas!
1. invasive ductal carcinoma
2. invasive lobular carcinoma
3. Medullary lobular carcinoma
4. Colloid carcinoma (mucinous carcinoma)
5. Tubular carcinoma
6. Other types
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Cancer
Which subtype of invasive carcinoma is the most common type?
The invasive ductal carcinoma
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Cancer
Where do habe most women breast cancer? (Location)
First: In the upper outer quadrant ->50%
Second: Central portion -> 20%
29
Cancer
Is it usual that women have cancer on both titties?
About 4% of women with breast cancer have bilateral primary tumors or sequential lesions in the same breast
30
Cancer
Where do DCIS and LCIS usually arise?
DCIS and LCIS: both usually arise from cells in the terminal
| duct lobular unit
31
Noninvasive Cancer - DCIS
Name the histological subtypes of DCIS!
DCIS has a wide histologic appearance. Architectural patterns often are mixed and include:
- solid type
- comedo type
- cribriform type
- papillary type
- micropapillary type
- "clinging" (anliegend, eng) type
32
Noninvasive Cancer - DCIS
Name the universal histologic features of DCIS!
1. DCIS tends to fill and distort (verzerren) ductlike spaces
2. Nectosis may be present in any subtype of DCIS
3. Nuclear appearance (Aussehen des Zellkernes):
They tend to be not changing (uniform) and range from
-> bland(blass) and monotonous [low nulcear grade] to
pleomorphic [high nuclear grade]
33
Noninvasive Cancer - DCIS
Describe the Comedo-Subtype?
Comedo-Subtype
1. cells have high-grade nuclei
2. central necrosis is extensive
3. Toothpaste like necrosis
4. Calcification!!! are frequently associated with DCIS
-> as either calcified necrotic debris or calcified secretory
material
34
Noninvasive Cancer - DCIS
How many women are diagnosed at the DCIS stage?
Uncreened population: only 5%
Screened population: 40%
--> because DCIS is rarely palpable or radiologically detectable
But there are good mammography to detect calcifications
35
Noninvasive Cancer - DCIS
What kinde of therapy is prefered?
How is the long-term survival?
Mastectomy
97% long-termed survival after simple mastectomy
36
Noninvasive Cancer - DCIS
Women with extensive high nuclei-grade DCIS, with very small
undetected areas of invasion endangered of what?
Small high grade-nuclei DCIS which is undetected may lead to
-> distant metastases without local recurrence
And at least 1/3 of these women develop invasive carcinoma
37
Noninvasive Cancer - DCIS
Women with DCIS may may get invasive carcinoma. Where is the new invasive carcinoma going to develop?
When invasive carcinoma does develop, it usually is in the same breast and quadrant as the earlier DCIS
38
Noninvasive Cancer - DCIS
How do you treat DCIS?
- By surgery and irradiation!!!
- Treatment with antiestrogenic agents such as tamoxifen and
armoatase also may decrease the risk of recurrence
39
Paget disease of the nipple
How is paget disease of the nipple related to breast cancer?
Paget disease of the nipple is caused by the extension of DCIS up
the lactiferous ducts and into the contigous (unmittelbar) skin of the nipple.
```
It produces a unilateral crusting exudate over the nipple and
areolar skin (Warzenhof)
```
In almost all cases, an underyling carcinoma is present, and approximately 50% of the time this carcinoma is invasive
40
Noninvasive Cancer - LCIS
How does LCIS looks histologically?
1. LCIS usually expands but does not alter the acini of lobules
2. Like DCIS it is confinded by a basement membrane and do not
invade into stroma or lymphovascular channels
3. Cells are monomorphic with bland (blass), round nuclei
4. The cells occur in lossely cohesive clusters within lobules
5. Intracellular mucin vacuoles are common and sometimes
signet ring (Siegelring) cells
6. Just rarely there are calcification. Most of the tome no
calcifications
41
Noninvasive Cancer - LCIS
1. How are most LCIS screened?
1. Incidental because LCIS does not have calcification, which
results in a negativ mammography!
42
Noninvasive Cancer - LCIS
How many women with LCIS develop invasive carcinoma?
Approximately 1/3 of women with LCIS
43
Noninvasive Cancer - LCIS
Where does subsequent (anschließend) invasive carcinomas arise?
Unile with DCIS, subsequent invasive carcinoma may arise in either breast
44
Noninvasive Cancer - LCIS
What kind of invasive cancer develop from LCIS?
Most of the time these cancers are invasive lobular carcinomas.
However invasive ductal carcinoman from DCIS
45
Noninvasive Cancer - LCIS
LCIS is both a marker of an increased risk of carcinoma in XXX breast and a XXX XXX of some cancers.
LCIS is both a marker of an increased risk of carcinoma in both breast and a direct precursor of some cancers.
46
Noninvasive Cancer - LCIS
What is the treatment of LCIS?
Either chemoprevention with tamoxifen alkng with some clinical
and radiologic follow-up evaluation.
Or less commonly, bilateral prophylactic mastectomy
47
Invasive (infiltrating) Carcinoma - Invasive ductal carcinoma
The invasive ductal carcinoma is used for all carcinomas that
cannot be subclassified into one of the specialized types.
How many cancers fall into this group?
The majority! 70-80% of cancers
48
Invasive (infiltrating) Carcinoma - Invasive ductal carcinoma
What is typically the precursor of the invasive ductal carcinoma?
Usually DCIS and rarely LCIS
49
Invasive (infiltrating) Carcinoma - Invasive ductal carcinoma
What does the invasive ductal carcinoma produce?
The invasive ductal carcinoma produces a desmoplastic response, which replaces normal breast fat and forms a hard,
palpable mass-> resulting in a mammographic density
50
Invasive (infiltrating) Carcinoma - Invasive ductal carcinoma
What is the microscopic appearance of the invasive ductal carcinoma?
The appearance is heterogenous:
1.Ranging from tumors with well-developed tubule formation and
low-grade nuclei to tumors consisting of sheets of anaplastic
cells
2. They may be areas of necrosis
3. Invasion of lymphovascular spaces may be seen
4. The tumor margins typically are irregular
51
Invasive (infiltrating) Carcinoma - Invasive ductal carcinoma
What genes does the tumor rexpress?
2/3: express estrogen receptors or progesteron receptors
1/3: overexpress HER2/NEU
52
Invasive (infiltrating) Carcinoma - Invasive Lobular carcinoma
How do the cells look like?
Morphological like LCIS cells
53
Invasive (infiltrating) Carcinoma - Invasive Lobular carcinoma
Is the invasive lobular detectable?
Most manifest as papable masses or mammographic densities
However, a significant subgroup may exhibit a diffusely invasive pattern without a desmoplastic response and may be clinical occult
54
Invasive (infiltrating) Carcinoma - Invasive Lobular carcinoma
How do they metastazises?
They are more frequently bilateral and multicentric (10-20%)
1. they more frequently spread to cerebrospinal fluid
2. serosal surface
3. gastrointestinal tract
4. ovary
5. uterus
6. bone marrow
55
Invasive (infiltrating) Carcinoma - Invasive Lobular carcinoma
Which gene expression is common and which is rare?
Most all invasive lobular carcinoma express hormon rezeptors
However, HER2/NEU overexpression is rare
56
Invasive (infiltrating) Carcinoma - Invasive Lobular carcinoma
How frequent are invasive lobular carcinoma?
20% of all breast cancers
57
Inflammatory carcinoma
How does the breast look like when the women has inflammatory carcinoma?
1. enlarged breast
2. swollen breast
3. erythematous breast
4. usually without palpable masses
58
Inflammatory carcinoma
How is the cancer characterized?
1. the underlying tumor is generally poorly differenciated
2. the tumor is diffusely infiltrative
3. the carcinoma involves dermal lymphatic spaces
-> the resultant blockage of these channels leads to edema
and the resulting characteristic clinical inflamed appearance
-> true inflammation is absent or just very minimal
59
Inflammatory carcinoma
1. Do these inflammatory carcinoma metastasizes?
2. what is the 5-year survival rate?
Yes to distant sides
5 years survival is under 50% and lower if the cancer metastasizes
60
Medullary Carcinoma
1. How common are medullary carcinoma?
2. How does the cancer looks like?
1. very rare, less than 1%
2. These cancer consists of sheets of large anaplastic cells with
wellcircumscribed pushing boarders
There is invariably a pronounced lymphoplasmacytic infiltrate
DCIS is absent or minimal
61
Medullary Carcinoma
1. What genes are associated with medullary carcinoma and
which are not?
1. BRCA I is associated - however most of the time negativ
Estrogen- and progesteron-Rezeptors are negativ (no
association)
No overexpression of HER2/NEU
--> triple-negative
62
Colloid (mucinous) carcinoma
1. How common is the colloid carcinoma?
2. What characterizes this tumor
1. Very rare
2. The colloid tumor is characterizes by the ability of producing
abundant quantities of extracellular mucin, which disserts into
surrounding stroma
63
Colloid (mucinous) carcinoma
What do colloid carcinoma and medullary carcinoma have incommon?
Both could be mistaken for fibroadenomas
64
Tubular carcinomas
1. How common are they?
2. can you feel them?
3. How do they look microscopically?
4. How is the prognosis?
1. rare, but they are 10% of all invasive carcinoma smaller than
1 cm found with mammography screening
2. tubular carcinomas rarely are palpable
3.
- well formed tubes
- low-grade nucle
4. metastases are rare and the prognosis is exellent
