L27 - Pathology of the breast Flashcards

1
Q

Definition of the breast

A

The breast is a modified sweat gland that develops into a complete functional structure in the female, but remains rudimentary in the male.

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2
Q

Major components of the breast

A

 the skin
 the subcutaneous adipose tissue
 the functional glandular tissue.

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3
Q

Breast glandular tissue structure

A

The breast is divided into 15-25 lobes, each based on a branching duct system leading to the terminal duct-lobular unit which is the functional site of milk production. Each lobe is made up of 20-40 lobules:

Nipple -> lactiferous sinus -> lactiferous duct -> segmental duct -> terminal duct-lobular unit (terminal duct -> lobule -> acini)

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4
Q
A
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5
Q

Lining of breast acini

A

each acini lined by epithelial cells and a basal myoepithelial cell

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6
Q

stages of alteration of breasts

A

 development and puberty

 maturation and differentiation

 lactation (** Most developed stage of breasts)

 involution and senile atrophy.

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7
Q

Atrophy of breast (observations)

A

with ageing, the breast tissue begins to atrophy so there are more fat tissue than breast -> appear more translucent rather than whitish

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8
Q

Major reason for pathology in breasts

A

The sensitivity for ovarian hormones, hormones of pregnancy and other growth factors in the female breast predispose this organ to a number of pathological conditions.

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9
Q

Clinical presentations of breast diseases

A
  • pain,
  • presence of a dominant lump, or
  • abnormal nipple discharge.
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10
Q

epidemiology of breasts diseases

A

40% - Fibrocystic changes

30% - No disease

13% - Miscellaneous benign conditions

10% - Breast cancer

7% - Fibroadenoma

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11
Q

Why are benign breast conditions of interest

A

because they may mimic breast cancer - e.g. nipple discharge, breast lump

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12
Q

Benign breast conditions by categories

A

1) INFLAMMATORY LESIONS
- Acute mastitis & breast abscess
- Mammary duct ectasia
- Fat necrosis
- Granulomatous mastitis
2) FIBROCYSTIC DISEASES
- Cystic formation & fibrosis
- Apocrine metaplasia
- Epithelial hyperplasia
3) PROLIFERATIVE LESIONS
- Hyperplasia (ductal hyperplasia; lobular hyperplasia)
- Sclerosing adenosis
- Radial scars (complex sclerosing lesions)
4) BENIGN TUMORS
- Duct/intraduct papilloma
- Fibroadenoma

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13
Q

Types of breast Inflammatory lesions

A
  • Acute mastitis & breast abscess
    • Mammary duct ectasia
    • Fat necrosis
    • Granulomatous mastitis
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14
Q

Acute mastitis & breast abscess characteristics

A
  • uncommon except during lactation
  • may be the result of infection (bacterial entry) via the nipple due to abrasion or crack, acquired from the mouth of the baby during breastfeeding
  • four cardinal signs of inflammation (red, swollen, heat, pain)
  • **important to differentiate from inflammatory breast cancer (an advance stage of malignancy)
  • Benign inflammatory lesion
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15
Q

Mammary duct ectasia characterisitcs

A
  • uncertain aetiology
  • presents clinically as dilated ducts filled with cheesy material in the area adjacent to the aerola
  • Ulceration and dilation of the ducts allows liberation of lipids into the connective tissue stroma that leads to a chronic granulomatous inflammatory reaction.
  • Fibrosis can lead to nipple retraction and clinically mimic carcinoma
  • Benign inflammatory lesion
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16
Q
A

Mammary duct ectasia, because:

1) chessy material is observed filling the mammary duct

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17
Q
A

leakage of cheesy material into connective tissue - classical histological feature of mammary duct ectasia

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18
Q

Fat Necrosis characteristics

A
  • Most commonly seen in women with obese, pendulous breasts
  • due to trauma.
  • There is a localised firm or even hard mass which can on occasions be adherent to the skin and thus be easily mistaken for carcinoma
  • Traumatic rupture of fat cells results in a foreign-body granulomatous reaction and subsequent fibrosis and retraction
  • Benign inflammatory lesion
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19
Q

Other Granulomatous Lesions

A
  • florid foreign body type granulomatous reaction
  • Breast tuberculosis
  • Idiopathic granulomatous mastitis
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20
Q

florid foreign body type granulomatous reaction (e.g. Paraffinoma)

A
  • In the past foreign material such as paraffin wax (Paraffinoma) or silicone fluid were injected as means of increasing breast size (breast augmentation)
  • These could give rise to florid foreign body type granulomatous reaction.
  • Leading to fibrosis and cyst formation
  • holes here are filled with paraffin, much fibrosis, may be palpated as mass (empty round spaces due to lipids being dissolved by multinucleated giant cells)
  • benign breast inflammatory lesion, granulomatous in nature
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21
Q
A

Paraffinoma

  • florid foreign body type granulomatous reaction.
  • used to occur when women wanted to augment their breasts -> inject paraffin (inert)
  • [fig. 1] holes here are filled with paraffin, much fibrosis, may be palpated as mass
  • [fig. 2] empty round spaces due to lipids being dissolved multinucleated giant cells
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22
Q

Breast tuberculosis

A
  • An uncommon complication of pulmonary tuberculosis caused by mycobacterium tuberculosis;
  • benign breast inflammatory lesion, granulomatous in nature
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23
Q

Idiopathic granulomatous mastitis

A
  • benign breast inflammatory lesion, granulomatous in nature
  • may have an autoimmune base.
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24
Q

Breast fibrocystic disease (cause, epidemiology, types, presentations)

A

- Cause: Cyclical hormonal influences do not affect all parts of the breast equally in each cycle. Hormonal imbalances such as excess of oestrogens, a deficiency of progestrone as well as abnormal end- organ metabolism of hormones are all thought to contribute to the pathogenesis of this multi- patterned disease.

- Epidemiology: Most common around 30 years of age (younger females), it is rare after the menopause.

- Types: cystic formation & fibrosis; apocrine metaplasia; epithelial hyperplasia

- Presentation:

i) Accumulation of liquids in mammary ducts, thus forming cysts
ii) May present in come-and-go manner: after menstruation, estrogen start accumulating -> just before mens. high estrogen, so high water retention -> cysts are filled with fluid and woman may detect a palpable lump which may disappear after mens due to lowered estrogen -> come-and-go
iii) tends to be generalised but frequently a localised area draws attention to the disease.
iv) The breast tissue is firmer and more nodular than usual - but not hard and fixed to surrounding tissues as in carcinoma.
v) Pain present due to breasts bring streched
vi) Cysts 2-10 mm in diameter may be seen and they frequently occur in clusters. Large cysts occur.

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25
Q
A

[Fig 1]

  • whitish areas due to stromal fibrosis
  • black, smooth in outline,well-circumscribed
  • congested areas are due to increased vascularity or fluid

[Figure 2]

Labelling

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26
Q

Clinical procedures for fibrocystic breast disease

A
  • ultrasound used to differentiate between solid and cystic lesion
  • Cystic lesions may be resolved simply with needle -> after puncture, fluid removed usually clear (if stained with blood may indicate malignancy)
  • Resection not necessary
27
Q

Cystic formation and fibrosis

A
  • increase in fibrous stroma (stromal fibrosis) and formation of cysts of various sizes which can be microscopic or larger.
  • Stromal fibrosis - epithelial lining of ducts have undergone metaplasia -> may also have proliferation of epithelium
28
Q

Apocrine metaplasia

A
  • the ductal epithelium changes to pink cells with budding of the luminal aspect.
  • abundance of eosinophilic/pinkish cytoplasm and enlarged and prominent nucleoli of apocrine cells observed (see fig.)
29
Q
A

Fibrocytic disease - Apocrine metaplasia

  • abundant eosinophilic/pinkish cytoplasm
  • apocrine cells have prominent nucleoli
30
Q

Epithelial hyperplasia

A
  • proliferation of ductal lining epithelium
  • the more severe and atypical the degree of hyperplasia, the greater degree it can be associated with increased chance of malignancy
  • haphazard proliferation -> when they form sieve like, well organized spaces; more likely ductal carcinoma in situ
31
Q

Proliferative lesions typed

A

1) Hyperplasia (ductal hyperpasia & lobular hyperplasia)
2) Sclerosing Adenosis
3) Radial scars (complex sclerosing lesions)

32
Q

Hyperplasia

A
  • may involve the ducts (ductal hyperplasia) or the lobules (lobular hyperplasia)
  • Ductal hyperplasia -> Number and size of ducts increase
  • Lobular hyperplasia -> acini increased in number making the whole terminal lobule enlarged
33
Q

Sclerosing adenosis

A
  • Adenosis refers to enlargement of breast lobules. If there are many enlarged lobules near one another, this collection may be large enough to be palpable.
  • Sclerosing adenosis is a special type of adenosis in which the enlarged lobules are distorted by fibrous tissue and simulate malignancy.
  • May be found during childbearing and peri-menopausal years.
34
Q

Radial scars (complex sclerosing lesions)

A
  • distortion of normal arrangement of breast tissue (ducts and acini) due to fibrosis
  • some ducts are filled with fluid, therefore also fibrocystic
  • usually only detected radiologically.
  • Can mimic carcinoma both clinically and radiologically.
  • stellar lesion (resembling tubular carcinoma)
35
Q

Breast tumours Types

A

A) BENIGN TUMOURS

  • Intraduct papilloma
  • Fibroadenoma

B) PHYLLOIDES TUMOUR

C) MALIGNANT TUMOURS/BREAST CARCINOMA

  • In-situ carcinoma
  • Invasive carcinoma
36
Q

Fibroadenoma (Composition, epidemiology, features)

A

Composition: It is composed of benign epithelium and made up of glandular breast tissue and stromal tissue

Epidemiology: It is the commonest cause of a palpable lump up to the age of 30; More common in the young but can occur in any age

Features:

  • Clinically it is a well-circumscribed (smooth in outline), firm, painless and mobile (since not fixed to breast tissues) lump [Fig 1]
  • Dubbed “breast mouse” as it is mobile when palpated
  • Is a solid lesion so can differentiate against a cyst via ultrasound
  • proliferation of connective tissue [Stromal overgrowth, see Fig 2] that may compress ducts into slit-like spaces [Fig. 2]
37
Q

Labelling and Identification of Pathology

A

Fibroadenoma

  • stroma compresses the ducts to make them slit-like
  • stroma overgrowth surrounding the ducts
38
Q

Intraductal papilloma (Definition, epidemiology, features)

A

Definition: Benign tumors that grow within the breast ducts.

Epidemiology: Occurs any age

Features:

  • usually within 4 cm of the nipple
  • commonest cause of a bloody nipple discharge (carcinoma being the next most common cause)
  • Can be solitary or multiple
    i) Solitary usually involve large ducts near nipple (Commonest cause of unilateral bloodly nipple discharge)
    ii) Multiple usually involve smaller ducts (and is associated with slight increased risk of breast cancer)
  • Papilloma very fleshy, will cause duct dilation [Fig 1]
  • Still two cell types lining acini -> hence benign [Fig 2]
39
Q

Phylloides tumor (composition, epidemiology, prognosis, features, treatment)

A

Composition: Composed of glandular breast tissue and stromal tissue

Epidemiology: The peak age is 45 years.

Malignancy: Range of clinical behaviour variable - from benign to malignant (majority of phylloides tumours behave in a benign fashion, 3-12% metastasize)

Prognosis:

  • Simple enucleation of the tumour will result in a high frequency of recurrence (Incomplete excision may lead to recurrence)
  • subsequent recurrences may result in development of malignancies therefore follow-ups are essential

Features:

  • Resembles a fibroadenoma, but distinguished by the presence of an “overgrowth” of connective tissue stromal components and a frond-like/leaf-like arrangement [Fig 1] of the fibroepithelial element.
  • Features for distinguishing the malignant form are: (i) increased mitoses (ii) cellular atypia (large pleomorphic nuclei, hyperchromatism; Fig 2), (iii) invasive edge, (iv) stromal overgrowth.

Treatment: The usual treatment for the benign phyllodes tumour is wide excision and for the malignant ones is mastectomy.

40
Q

Labelling and Identification of pathology

A
41
Q

Breast Cancer Epidemiology (statistics)

A

1) 1st leading female cancer in HK
2) 3rd major cause of cancer death in HK
3) at 47.5 per 100,000 for the year 2004
4) Median age at diagnosis = 52 yrs (53)
5) Lifetime risk = 1 in 22 (1/19)
6) Death risk = 1 in 106 (1/102)
7) Although the rate in Hong Kong is lower than that in Caucasians, it is the highest reported in Asian regions
8) Amongst Caucasians, it is one of the commonest malignancies in women, and the 3 leading cause of cancer death
9) its incidence has been steadily rising over the last few decades.
10) incidence of breast cancer rises with age. Past the menopause, a lump in the breast has a higher chance of being a carcinoma.
11) Interestingly however, in Hong Kong there has been an observed marked rising trend affecting the 40-60 years age group, thus breast cancer has become the top cancer in young females in Hong Kong. (stats: top cancer in 20-64 females; 3rd cancer in 65+ females)

42
Q

Aetiology of Breast Carcinoma

A

1) Genetic predisposition
2) Hormonal imbalance
3) Environmental Influences

43
Q

Strongest epidemiological risk factor of breast carcinoma

A

The strongest known epidemiologic risk factor for breast cancer is a positive family history (i.e. genetic predisposition)

[The contribution of hereditary breast cancer however, accounts for only about 5- 10% of all breast cancers. There are other many non-genetic factors that contribute to disease etiology.]

44
Q

Breast cancer susceptibility genes

A
  • BRCA-1 and BRCA-2 are the two major breast and ovarian cancer susceptibility genes, thought to account for the majority of hereditary breast and ovarian cancers.
  • they are autosomal dominant genes, transmitted by Mendelian inheritance.
  • BRCA mutation carriers are predisposed to early onset breast cancer, bilateral breast cancer, ovarian cancer and other associated cancers.
45
Q

BRCA1

A
  • autosomal dominant genes, transmitted by Mendelian inheritance.
  • lifelong risk of 85% for breast cancer and 50% for ovarian cancer
  • median age of onset 45 years
  • increased risk for bilateral breast cancer
  • slight increased risk for colon and prostate cancer
46
Q

BRCA2

A
  • autosomal dominant genes, transmitted by Mendelian inheritance.
  • Lifelong risk of 85% for breast cancer and 10% for ovarian cancer
  • male breast cancer risk involved
  • Higher chance of early onset and bilaterality
47
Q

Identification of High risk of genetic predisposition for breast cancer

A
  • Families with 3 or more related individuals with breast and/or ovarian cancer are at highest risk of carrying mutations in either of these genes
  • early onset of breast cancer
  • Bilateral/multifocal breast cancer
  • can be transmitted by both parents
48
Q

Criteria for Assessment of High Risk for Breast cancer

A
  • number of affected relatives
  • presence of ovarian cancer in family
  • relationship of affected relatives
  • age at diagnosis of breast cancer

*** 3 or more members of direct lineage with breast and/or ovarian cancer

49
Q

BRCA gene testing

A

Genetic testing aims at identifying the mutation that predisposes the individual or the family to cancer.

In families where germ-line mutations in BRCA1 and BRCA2 have been identified, estimates for breast cancer risk can be made with greater accuracy. The lifetime risk of cancer in BRCA mutation carriers ranges from 56% to 84%.

50
Q

Limitations and precautions of BRCA testing

A

1) Both BRCA genes are very large with absence of mutational hot-spots, which presents difficulties in genetic testing for germ-line mutations in high risk families. Testing is usually performed on affected individuals. Only if a mutation is identified, can other unaffected members of the family be tested to find out if they have inherited this mutation.
2) A negative result from families where no mutation has been identified cannot exclude the possibility that other genes, as yet unknown, may be involved in that family.
3) Ethical issues such as problems of health insurance and disclosure of information and controversies in options for management of women found to have mutations remain.
4) The potential benefit of knowing one has not inherited a predisposition must be weighed against the possible harm that may result from finding one is at risk.
5) The test may often give unhelpful or uncertain results
6) The benefits and limitations of such testing together with the potential complexities of genetic counselling should be explained clearly to families beforehand.

51
Q

Hormonal imbalance and Breast cancer

A
  • This is thought to play a significant role in the development of carcinoma of breast.
  • The long duration of reproductive life such as early menache (<12 years); late menopause (>54 years); nulliparity; and late age of first pregnancy - all imply increased exposure to oestrogen peaks during the menstrual cycle.
  • Functioning ovarian tumours that elaborate oestrogens are associated with breast carcinoma in postmenopausal women
  • The risk associated with use of oral contraceptives and hormonal replacement therapy, are controversial.
52
Q

Environmental factor and breast cancer

A

1) Obesity (seem to be related to breast carcinoma, particularly after 50 years of age, because they are associated with endogenous hormonal modifications)
2) Diet
- Dietary fat (reason same as obesity)
- Alcohol, folate, anti-oxidants, fruits, vegetables
3) Ionising radiation exposure (may have a limited role, as illustrated by the high incidence among patients who received multiple chest X rays in the course of treatment of pulmonary tuberculosis)

53
Q

Breast cancer screening

A
  • Emphasis is now being placed on early detection and treatment.
  • Earlier detected carcinomas generally have better prognostic features that are more amenable to treatment and control. Countries that offer mammographic breast cancer screening have claimed a reduction of mortality.
  • especially important for high risk groups
  • Screening methods:
    1) Breast self-examination
    2) Clinical examination (e.g. palpation)
    3) Mamography
54
Q

Breast self-examination

A

Pro: Can be performed frequently at anywhere; very convenient and accessible

Con: Require education; not as effective

55
Q

Mammography (Nature, Functions, Observations, Usage, Limitations)

A

Nature: X-ray

Functions:

1) aims at detecting impalpable cancers
2) also be used to further characterise palpable lesions and to check for bi-laterality

Observations:

1) White spots (i.e. calcium deposits - microcalcification) can be detected against black background -> an early stage of breast carcinoma in-situ [Fig 2, between “horns”]

Usage:

  • baseline for follow up
  • observe size and extent of lesion
  • presence of DCIS (ductal carcinoma in situ)
  • detection of multifocal disease
  • other non palpable abnormalities
  • opposite breast

Limitations:

1) 10-20% of carcinomas may still be undetectable by mammography
2) Not suitable for younger women as they have denser (with less adipose tissue) breast structures -> as a result background more whitish and microcalcification cannot be readily detected due to lack of contrast
3) Lower sensitivity, therefore not a good universal screening method

56
Q

Other modes of radiological detection of breast cancer

A

1) Ultrasonography (not good for screening but good for further grading the lesion or differen solid and cyst, Fig 1)
2) MRI

57
Q

Pre-operative diagnosis methods

A

1) Fine needle aspiration cytology (FNAC) or
2) core biopsies

The above two are now routinely used to arrive at a preoperative diagnosis. This can be used for both clinically palpable (symptomatic) as well as screen detected impalpable lesions (asymptomatic) which will need image-guidance to perform.

58
Q

FNAC Diagnostic categories

A
  • C1 Inadequate
  • C2 Benign
  • C3 Atypia
  • C4 Suspicious of malignancy
  • C5 Malignant
59
Q

Core Biopsies

A
  • May be image guided
  • May be able to provide histologic confirmation
60
Q

multidisciplinary triple approach

A

• Clinical examination

• Imaging – mammography/ultrasound

• FNAC

  • > Cytologic opinion of malignancy in the absence of mammographic and/or clinical evidence of malignancy SHOULD NOT be taken as authority for therapeutic surgery
  • > ALWAYS consider all three and correlate results
  • > multidisciplinary triple approach is now the recommended way of managing breast lesions. The surgeon, radiologist and pathologist work closely as a team to determine the diagnosis, management, treatment and follow up of patients.
61
Q

Unusual clinical presentations of breast cancer

A

1) Inflammtory breast cancer
2) Paget’s disease of the nipple

62
Q

Inflammatory breast cancer

A
  • Usually there is no single lump or tumor but presents with skin of breast appearing inflamed
  • red, warm, peau d’orange appearance of skin due to blockage of lymph vessels in the skin by cancer cells (tumour emboli in lymphatics triggering an inflmmatory reaction)
  • Poorer prognosis than typical invasive cancers, with higher chance of metastatic spread
  • inflammation mimics signs of acute mastitis (swollen, hot, painful)
63
Q

Paget’s disease of the nipple

A
  • Usually presents with erosion of the nipple and areola, which are red and weeping but occasionally dry, scaly and psoriatic [Fig 1]
  • There is always an underlying intraductal or invasive carcinoma
  • It is characterized microscopically by the invasion of the epidermis by Paget’s cells, which are large, round to oval with pale cytoplasm and contain mucin [Fig 2]
64
Q

Male breast pathology

A
  • The most common disease of the male breast is gynaecomastia which is the enlargement of the male breast.
  • The most common cause is cirrhosis of the liver with failure of oestrogen breakdown. It is also seen in Klinefelter’s syndrome, some testicular tumours and as a drug effect.
  • Carcinoma occurs in the male breast with an incidence of one-hundredth that seen in females. Its natural history closely resembles that of the disease in women.