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clinical pathology > L4 - Breast Pathology > Flashcards

L4 - Breast Pathology Flashcards

- Classify common diseases of breast - Describe risk factors for breast cancers - Explain different common types of breast cancers and their prognostic and therapeutic significance including the difference between in-situ and invasive tumours. - Understand the different diagnostic tools and treatment modalities for breast cancers - Explain the breast cancer screening program and role of histopathologists in diagnosis and management of breast cancer

1
Q

What is a breast

A

a modified sweat glad covered by skin and subcutaneous tissue

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2
Q

what does the breast rest on

A

Pectoralis muscle from which it is separated by a fascia

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3
Q

What holds the breast upwards

A

the Cooper’s ligament ( dense connective tissue which extends from the underlying pectoralis fascia to the skin of the breast)

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4
Q

What is the breast divided into

A

two elements ( like any gland) :
1. parenchyma, which is the functional part of the gland
2. stroma/ connective tissue, which supports the parenchyma

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5
Q

what is the parenchyma divided into

A

again into two more elements:
1. terminal duct lobular units (TDLU)
2. branching duct system

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6
Q

What is a terminal duct lobular unit (TDLU)

A

a structural and functional unit of the breast made up of multiple acini grouped together and the terminal duct. it is the primary site for many breast pathologies e.g. fibroadenoma, lobular cancer or invasive ductal carcinoma

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7
Q

Acini vs acinus

A
  • Acinus is the single functional unit of globular tissue, often sac shaped and responsible for secretion e.g. milk during lactation periods and enzymes
  • acini is the plural of acinus and refers to clusters of the sac like cells that form the lobule.
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8
Q

Where do secretions made by the acini need to be drained to

A

the nipple through the terminal duct (ductal system)

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9
Q

What are interlobular ducts

A

Interlobular ducts are located between the acini lobules. They collect and transport secretions (e.g., milk or enzymes) from smaller ducts within the lobules (intralobular ducts) to a larger lactiferous duct which drains into the nipple

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10
Q

What are interlobular ducts lined by in the breast

A

by epithelial cells and surrounded by connective tissue

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11
Q

how many terminal duct lobular units are there on each side of the breast

A

around 15-20

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12
Q

Where is milk stored

A

in the lactiferous sinus (and then upon suckling it is released onto the nipple)

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13
Q

What are the two cell types that line the entire ductal lobular system

A
  • the inner epithelial cells
  • the outer myoepithelial cells
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14
Q

what characteristic gives myoepithelial cells its name

A

the fact that it has dual characteristics of both muscle and epithelial cells

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15
Q

what is the normal function of myoepithelial cells

A

to squeeze the secretion forward by contracting (mycin and actin filaments)

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16
Q

how can the outer myoepthlial cells be used to differentiate between in situ and invasive malignancy in pathology

A

Malignant invasive carcinomas invade the stroma and produce their own basement membrane, which can stain positive for collagen and laminin, potentially mimicking non-invasive tumours. To differentiate, the absence of myoepithelial cells is key, as invasive carcinomas destroy these cells when invading the basement membrane. Although they can create basement membrane components, they cannot regenerate myoepithelial cells

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17
Q

what do you do just to make sure that the tumour is benign when you see the two cell types that line the entire ductal lobular system are intact

A

you stain and use various markers because the inner epithelium and outer myoepithelial layers have distinctive ultrastructural and immunohistochemical characteristics

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18
Q

what are some example markers used to identify myoepithelial cells

A

SMM, p63 and ck5/6

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19
Q

Why do we classify diseases

A

helps group diseases with common features, enabling effective communication across disciplines, understanding of their characteristics, and guiding appropriate treatment strategies.

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20
Q

What does it significy if a disease ends with itis

A

that it is typically an inflammatory disease

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21
Q

what are some examples of inflammatory conditions

A
  • Acute mastitis
  • chronic mastitis
  • mammary duct ectasia
  • fat necrosis
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22
Q

When does acute mastitis occur

A

During lactation, bacteria accumulate when it isn’t looked after properly.

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23
Q

when does chronic mastitis occur

A

when acute mastitis isnt dealt with or if the inflammation lasts more than two weeks.

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24
Q

what is a type of chronic mastitis

A

chronic lymphocytic lobulitis

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25
Q

What is chronic lymphocytic lobulitis?

A

a condition characterised by a hard breast mass that can easily be mistaken for cancer by clinicians and radiologists. It is most commonly seen in diabetic females over the age of 40.

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26
Q

how can chornic lymphocytic lobulitis be distinguished between cancer

A

through a biopsy and histological analysis, which will show an increased number of large lymphocytes within the lobules and dense fibrotic stroma. This helps reassure the patient that the condition is benign and not cancer.

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27
Q

What are the different stages in mammary duct ectasia

A

periductal inflammation rich in plasma cells which becomes very fibrotic

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28
Q

how does mammary duct ectasia often present itself

A

as bloody nipple discharge which appears cancerous (even though it isn’t )

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29
Q

What are possible reasons for fat necrosis

A

trauma and a cyst rupturing

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30
Q

What is the significance of fat necrosis in the breast

A

fat necrosis will result in saponification and later dystrophic calcification. On a mammogram, the lesion may have an irregular border, density, and calcification, which can mimic the appearance of breast cancer, potentially leading to diagnostic confusion.

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31
Q

what are some examples of proliferative conditions

A
  • Fibrocystic change (most common lesion in the breast)
  • Radial scar
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32
Q

What is the most common lesion in the breast

A

Fibrocystic change

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33
Q

What is radial scarring

A

a stellate lesion in which there is fibrosis in the stroma

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34
Q

What is the appearance of a radial scar

A

has similar morphology to cancer with radiating spikes that invades into the surrounding tissue. However they are lined by two cell layers which shows that they are not malignant

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35
Q

what happens in 0.125% of radial scar cases

A

a radial scar is associated with a carcinoma. therefore it is scored as a B3 lesion for adequate sampling / further investigation.

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36
Q

What are the two main classifications for neoplastic conditions

A
  1. Benign
  2. Malignant
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37
Q

What are the sub classifications of a benign neoplasm

A
  • Adenoma (benign epithelial tumour of glandular differentiation)
  • Fibroadenoma (most common tumour in the breast)
  • Papilloma (benign epithelial tumour showing formation of finger like / papillary structures)
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38
Q

What are the sub classification of a malignant neoplasm

A
  • Carcinoma (malignant tumour of epithelial differentiation)
  • Sarcoma (malignant tumour of mesenchymal differentiation)
  • Paget’s disease
  • Phylloides tumour (malignant tumour of mixed differentiation)
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39
Q

Why is it important to understand how common diseases are

A

Because it makes diagnosis easier if we know what diseases are common for each age group, sex and how they present

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40
Q

What is the most common presentation of breast disease

A

a lump (which can be both benign or malignant)

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41
Q

what were the result of a survey done on 1000 patients attending a clinic with a breast lump

A

10% = CANCER
7 = Fibroadenoma
13% = benign tumour
30% = no disease
40% = fibrocystic change (age related change - not really a disease)
(~70% are normal with no disease)

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42
Q

Where and what are some signs and symptoms for diseases of the breast

A
  • nipples
  • breast pain
  • skin features
  • microcalcification
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43
Q

What are some signs and symptoms of diseases of the breast related to the nipple

A
  1. Discharge which can be milky if pregnant or bloody due to a duct papilloma or carcinoma
  2. Retraction which can be due to an invasive carcinoma
  3. Erythema and scaling which can be due to Paget’s disease or eczema
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44
Q

What is a skin feature of a carcinoma of the breast

A

oedema peu d’orange

45
Q

What happens to cells in the breast in response to oestrogen

A

the epithelial cells of the breast (acini) have receptors and when they associate with estrogen, they multiply (this is to prepare the breasts for pregnancy and lactation) and after they will go back to their normal size

46
Q

What happens if not all the acini go back to their original size in the menstrual cycle.

A

They will continue to grow, forming microcysts that may develop into larger cysts. Over time, the cyst can become so large that it ruptures, causing injury and inflammation in the surrounding tissue. The release of inflammatory mediators can lead to fibrosis in the affected area.

47
Q

What causes fibrocystic change?

A

hormonal fluctuations (particularly in oestrogen) during the menstrual cycle which lead to increased stimulation of breast tissue, cyst formation, fibrosis and changes in the size and structure of the acini over a persons life time

48
Q

in what age group is fibrocystic change common

A

in people aged 25-45 years old.

49
Q

When can you get cell hyperplasia during fibrocystic change?

A

when there is also an increase in the number of cell layers.

50
Q

What is fibroadenoma

A

the second most common benign condition in the breast. It is a mixed tumour composed of both proliferating ducts (adenoma) and connective tissue stroma (fibro)

51
Q

in what age group do fibroadenomas occur

A

between the ages of 20-35

52
Q

when do fibroadenomas increase and decrease in size

A
  • increase in size during pregnancy because of the increase in oestrogen (have oestrogen receptors)
  • decrease in size with age
53
Q

why are fibroadenomas typically not removed

A

because they are benign tumour that typically don’t cause harm to the patient, however, they may be removed if they grow very large (e.g., over 4 cm) for cosmetic or mental health reasons, or if there is a family history of cancer.

54
Q

how can you distinguish that fibroadenomas are benign tumours

A

they are completely capsulated and don’t invade into the surrounding tissue.

55
Q

what percentage of all cancers in women are carcinomas

A

20%

56
Q

what is the ratio of women that develop breast cancer in the UK

A

1 : 8 (during their lifetime)

57
Q

in what age group are carcinomas the most common cause of death in women

A

women aged 35-55 years old

58
Q

What are risk factors for carinoma (in the breast)

A
  • female sex and age
  • reproductive history
  • obseity
  • family history in 1st degree relative
  • geography (particularly in the west and industrialised countries)
  • atypical hyerplasia
    (oestrogen hormone and age are common similarities)
59
Q

what type of reproductive history increases the risk of carcinomas

A
  • early menarche (1st period under 12yo)
  • late menopause
  • nulliparous women
  • 1st pregnancy after 30 years of age
60
Q

factor increase if 1 vs 2 family relatives have history of carcinomas

A
  • 1.5-2x if 1 relative
  • 4-6 x if 2 relatives
61
Q

what are genes involved / genetic factors that increase someones chances of developing a carcinoma

A
  • BRACA 1 (ch17 - ovary and breast)
  • BRACA 2 (ch13)
62
Q

how common are genetic factors that increase cancer

A

5-10% of people

63
Q

Carcinoma of the breast are broaddly classified on the basis of which two criteria

A
  • invasion of the basement membrane ( in situ vs invasive)
  • morphology (ductal vs lobular)
64
Q

What is the significance of diagnosis of carcinomas in - situ

A

In situ carcinomas cannot metastasise therefore :
- you can potentially cure the patient by complete local excision
- lymph node excision is not required
- better prognosis.

65
Q

each type of carcinoma classification and how often they occur

A
  • In situ carcinoma (5%)
    Ductal carcinoma in situ (DCIS)
    lobular carcinoma in situ (LCIS)
  • Invasive carcinoma
    Invasive ductal carcinoma NST (75-85%)
    invasive lobular carcinoma (10%)
    others (5%)
66
Q

What is the significance of knowing the difference between ductal and lobular carcinomas e.g. DCIS and LCIS

A

because the prognosis and treatment are slightly different.

67
Q

DCIS vs LCIS cancer and treatment

A

DCIS: If left untreated, is likely to progress into an invasive tumor, so treatment involves surgery to prevent development.
LCIS: isn’t considered cancer itself but increases the risk of developing invasive breast cancer in either breast ( tumour may occur in a different breast quadrant). treatment involves close monitor and may include medication to reduce the risk ( rather than getting a bilateral mastectomy without justification - physical and emotional impact)

68
Q

why do many patients with lobular carcinoma diagnosis go through an MRI

A

because it is a more sensitive method for detecting carcinomas than mammograms to make sure there is no other cancer

69
Q

what is the issue with lobular carcinoma in the future

A

lobular carcinomas can come back after many years (after the patient has forgotten which is important when diagnosing an issue that could be related) and can travel to various odd sites of the body

70
Q

ductal carcinomas in situ (DCIS) features

A

appears as dilated ducts filled with neoplastic epithelial cells, with an intact myoepithelial cell layer indicating no basement membrane invasion. It may show central necrosis and calcification, aiding diagnosis on mammograms, and is classified into high, intermediate, or low nuclear grades based on cellular morphology.

71
Q

Why do you sometime see central necrosis in ductal carcinomas in -situ

A

Rapid tumour growth outpaces the blood supply, creating a hypoxic environment (low oxygen levels) and insufficient nutrition in the centre. This leads to cell death and necrosis, often visible on mammograms as calcifications (necrosis results in dystrophic calcification)

72
Q

lobular carcinomas in situ (LCIS) characteristics

A

features lobules with distended acini filled with round, regular neoplastic epithelial cells. The myoepithelial cell layer remains intact, and E-cadherin immunostaining is negative, which helps differentiate LCIS from low-grade DCIS.

73
Q

What are the characteristics of invasive lobular carcinoma with LCIS?

A

cells arranged in a single-file pattern, infiltrating the stroma. The invasive component lacks a myoepithelial cell layer. These tumours can be deceptive clinically, radiologically, and histologically, and may be multifocal or multicentric.

74
Q

What are the charcteristics of invasive ductal carcinoma with DCIS

A

the invasive tumour consists of small tubular structures lacking a myoepithelial cell layer meaning cells have invaded into the basement membrane

75
Q

what are some treatment strategies for breast carcinomas

A
  • Surgery
  • Chemotherapy
  • Radiotherapy
  • Hormonal treatment
    (sometimes a therapy / treatment is given prior to the surgery)
76
Q

how is treatment for an individual patient decided

A

there are interdespilinary team meetings (around 5h long) discussing each breast cancer case individually (discuss ~30 cancer cases per week)

77
Q

around how many breast cancer cases are here in Bristol

A

~1,500 (one of the largest centres in the country)

78
Q

What is it called if surgery is given after treatment e.g. chemotherapy, radiotherapy or hormonal treatment

A

Adjuvent treatment (used to remove any tumour remaining after the primary treatment e.g. tumour has shrunk which makes surgery more effective)

79
Q

What is it called if surgery is performed before other treatments like chemotherapy, radiotherapy, or hormonal therapy

A

neoadjuvent

80
Q

When is a mastectomy offered instead of breast conserving

A

If the tumour is too large relative to the size of the breast, if there are multiple tumours in different areas of the breast, the patient has had previous radiotherapy treatment, if there are no clear margins for the tumour ….

81
Q

Why can’t radiotherapy be given to the same patient multiple times

A

because this is a carcinogen

82
Q

What type of mastectomies are there

A
  • Simple mastectomy
  • Skin spring mastectomy
  • Sub cutaneous mastectomy
    ( different types are offered depending upon the individual situation as well)
83
Q

On top of removal of the carcinoma in the breast, what else is removed if the tumour is invasive

A

the lymph nodes

84
Q

When is a sentinel lymph node biopsy (SLNB) performed in breast cancer cases, and what does it involve?

A

Performed in early-stage, clinically node-negative breast cancer. A dye or radioactive substance is used to identify the first lymph nodes likely to be affected by cancer (sentinel nodes). Only these nodes are removed for testing.

85
Q

When are axillary nodes sampled

A

When there is suspician of lymph node involvement. only a sample of the lymph node is removed.

86
Q

What is axillary lymph node clearance (ALNC) and what are the differences between Level 1, Level 2, and Level 3 lymph node dissection in breast cancer surgery?

A

Performed when cancer has spread to multiple lymph nodes, requiring removal of a larger number of nodes from the axilla.
Level 1: Removal of the first group of nodes closest to the tumour (near the armpit).
Level 2 : Removal of deeper nodes in the axillary chain.
Level 3 : Removal of nodes near the collarbone and under the pectoral muscle, if cancer has spread extensively.

87
Q

What type of breast cancer gets chemotherapy

A

the aggresive kind (not all) e.g.
- large grade 3 tumours with nodal metastasis
- Triple negative or Her2 positive tumours
- Borderline cases have further genetic tests e.g. Oncotype DX to divide chemotherapy
- Adjuvent vs neo-adjuvent chemotherapy

88
Q

What does it mean if a patient is triple negative

A

refers to a type of breast cancer that does not express three key receptors that commonly found on cancer cells which makes it more difficult to treat with hormone or HER2 targeted therapies. They also tend to be more aggressive and high risk of recurrence.
Receptors :
Estrogen receptor (ER)
Progesterone receptor (PR)
Human epidermal growth factor receptor 2 (HER2)

89
Q

what is Her2

A

an EGFR receptor

90
Q

What is a targeted therapy used to treat HER2 positive breast cancer

A

Herceptin
(when it was on trial mid 2010s, they found a significant response in those who reciped herceptin particularly combined with chemotherapy. studies found that after 1 year of taking herceptin there were improved survival and reduced recurrence rates)

91
Q

what is oncotype DX

A

a genetic test usesd to assess the risk of breast cancer and help guide cases where chemotherapy would be beneficial. It is available on NHS and costs ~ £5k

92
Q

When is radiotherapy to the breast given

A

after conservative surgery in all caess except certain circumstances

93
Q

When is raditiotherapy to the breast not given

A

in patients older than 85, when the tumour is less than 2cm in size or if it is a grad 1 tumour that is ER+ve and HER2 negative

94
Q

When can radiotheray be given to the chest wall (mastectomy)

A

when the tumour is larger than 5cm, it is a grade 3 tumour with positive margins or 4 or more lymoh nodes involved

95
Q

When can radiotherapy be given to the axilla

A

if the central lymph node is positive but the remaining lymph node isn’t going to be taken out

96
Q

what percentage of breast cancers are positive for oestrogen receptors (ER)

A

~80%

97
Q

What is the significance of the fact that ~80% of breast cancers are oestrogen receptor (ER) positive

A

this means that they can be given hormone therapy

98
Q

how long is hormone therapy given for

A

5 years

99
Q

what type of hormone therapy is given to premenopausal women

A

Tamoxifen

100
Q

What type of hormone therapy is given to post-menopausal women

A

Aromatase inhibitors (AI)

101
Q

What is the risk factor if Tamoxifen is given to post-menopausal women

A

It can cause endometrial cancer

102
Q

What are the parameters used to make an educated prognosis (“Dr how much time do I have left”) / identify how the tumour is going to behave

A
  • Size of the tumour
  • Grade of the tumour
  • Histological type of tumour
  • Vascular invasion
  • Stage of the tumour (nodal status)
  • Receptor status of the tumour.
103
Q

What is an example of a scenario when it is almost certain that a tumour will behave “nicely”

A

If the tumour was of smaller size, of low grade and tubular like carcinoma with no vascular invasion, T1 tumour with no nodule metastasis

104
Q

What is the criteria for breast cancer screening programme

A
  • Age group : All women aged between 48-69 years
  • Eligibility: Names listed on the Family Practitioner Committee register.
  • Screening frequency: Every 3 years.
  • Technique: Mammography with two views (craniocaudal [CC] and oblique).
105
Q

Why are cancer screenings not typically done before the age of 48

A

Younger women often have denser breast tissue which reduces mammogram accuracy and it isn’t cost effective with it being less common in women under 48

106
Q

Why do we need a breast cancer screening programme

A

Breast cancer is highly prevalent in the Western world, with women in high-risk areas having a 1 in 8 lifetime risk. Early detection through screening significantly improves outcomes, as the 5-year survival rate is ~84% for stage I (<2 cm lesion) compared to ~18% for stage IV (>5 cm lesion)

107
Q

Where do we see microcalcification gistologically

A

usually asssociated with DCIS mostly high grade with central necrosis (microcalcification isn’t always malignant and can also be associated with benign fibrocystic change)

108
Q
A

clinical pathology (5 decks)

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