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Y4 Obstetrics and Gynaecology > Breast pathology - malignant > Flashcards

Breast pathology - malignant Flashcards

1
Q

List the 4 main miscellaneous malignant breast tumours

A
  1. Malignant Phyllodes tumour
  2. Angiosarcoma
  3. Lymphoma
  4. Metastatic tumours
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2
Q

What is the malignant change which occurs for a phyllodes tumour to become malignant and how often does this occur?

A
  • Malignant change = stroma becomes sarcomatous (sarcoma)
  • This occurs in 5% of cases
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3
Q

What is an angiosarcoma and what is it associated with occuring after ?

A
  • It is a malignant tumour of the inner lining of blood vessels
  • They have an association of developing post radiotherapy
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4
Q

Can a primary lymphoma occur in the breast ?

A
  • Yes but uncommonly, they occur with diffuse large B-cell lymphoma being the most common

Involvement of the breast in disseminated lymphomas & in myeloid leukaemias is more common e.g. young feales with burkkets lymphoma may develop bilateral breast involvement

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5
Q

What are the common metastatic tumours to the breast ?

A
  1. Carcinomas - bronchial, ovarian serous carcinoma & clear cell carcinoma of the kidney
  2. Malignant melanoma
  3. Soft tissue tumouts - leiomysarcoma
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6
Q

Define what a breast carcinoma is

A

A malignant tumour of breast epithelial cells arising in the glandular epithelium of the terminal duct lobular unit (TDLU)

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7
Q

What are the signs and symptoms of breast cancer ?

A
  • Dimpled or depressed skin
  • Visible/ palpable lump
  • Nipple change e.g. inversion
  • Bloody discharge
  • Texture change
  • Skin change e.g. eczematous
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8
Q

Pathologically what are all types of breast cancer ?

A

An adenocarcinoma

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9
Q

What are the 2 main types of breast carcinomas?

A

Ductal or lobular carcinoma (arising from duct tissue or lobular tissue respectively)

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10
Q

How can ductal & lobular breast cancer be further subdivided ?

A

Based on whether the cancer hasn’t spread beyond the local tissue (described as carcinoma-in-situ) or has spread (described as invasive).

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11
Q

List the 4 main types of breast cancer

A
  1. Invasive ductal carcinoma. (called no special type - NST)
  2. Invasive lobular carcinoma
  3. Ductal carcinoma-in-situ (DCIS)
  4. Lobular carcinoma-in-situ (LCIS)

The other 3 types may be referred to as special types as they are less common

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12
Q

Define what a carcinoma in situ is

A

This is where the cytological changes of malignancy are present in the epithelial cells but the basement membrane remains intact & no invasive is seen

==> invasive once the BM has been breached

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13
Q

What are the 2 subtypes of lobular in situ neoplasia ?

A
  1. Atypical Lobular Hyperplasia (ALH) where <50% of lobule involved
  2. Lobular Carcinoma in situ (LCIS) where >50% of lobule involved
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14
Q

What are the general characteristics of a malignant cell ?

A
  • Increased nuclear size (with increased nuclear/cytoplasmic ratio–N/C ratio).
  • Variation in nuclear or cell size (pleomorphism).
  • Lack of differentiation (anaplasia).
  • Increased nuclear DNA content with subsequent dark staining on H and E slides (hyperchromatism).
  • Prominent nucleoli or irregular chomatin distribution within nuclei.
  • Mitoses (especially irregular or bizarre mitoses).
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15
Q

What are the characterisitc cells seen in lobular in situ neoplasia ?

A
  • Small-intermediate sized nuclei
  • Solid proliferation
  • Intra-cytoplasmic lumens/vacuoles
  • ER positive
  • E-cadherin negative (due to deletion & mutation of CDH1 gene on Chr 16q22.1)
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16
Q

What are the main presenting features of a lobular in situ neoplasia ?

A
  • Frequently multifocal & often bilaterally affecting the breasts
  • Not usually palpable or grossly visible so often incidental finding seen as calcification on mammography
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17
Q

What happens to the incidence of lobular in situ neoplasia following menopause?

A

Its incidence increases

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18
Q

What is the significance of lobular in situ neoplasia in terms of risk of invasive development ?

A

8x increased risk

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19
Q

What is the management of a lobular in situ neoplasia ?

A
  1. If discovered on core biopsy ==> proceed to exicision or vaccum biopsy to exclude higher grade lesion
  2. If discovered on vaccum or excision biopsy ==> follow-up
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20
Q

How do invasive lobular carcinomas typically present ?

A
  • Often not apparent by either palpation or imaging until cancer is at an advanced stage
  • Has typical histological ‘indian file patern’ (infiltrating tumour cells arrnaged in a single file)
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21
Q

What are the ductal carcinoma precusor lesions ?

A
  1. Epithelial hyperplasia of usual type
  2. Columnar cell change
  3. Atypical ductal hyperplasia
  4. Ductal carcinoma in situ
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22
Q

Where does a ductal carcinoma in situ arise ?

A

In the TDLU - characteristically affecting one duct system

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23
Q

How do ductal carcinomas typically present ?

A
  • Usually as a lump/mass
  • Typically then find stellate (star like) solid mass or pleomorphic casting microcalcifications when investigated
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24
Q

How is definitive diagnosis of a ductal carcinoma made?

A

By image guided tissue core-needle biopsy

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25
Q

How do ductal in situ carcinomas typically present and what is seen on investigation ?

A

Usually present as non-palpable, but seen on screening XRM as malignant calcifications (pleomorphic & of the casting type - stellate)

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26
Q

How is definitive diagnosis of a DCIS made ?

A

By vaccum assisted core-biopsy

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27
Q

What are the pathological features of a ductal carcinoma in situ ?

A
  • Cytologically malignant epithelial cells
  • Confined within basement membrane of duct
  • May involve lobules (cancerisation)
  • May involve nipple skin (Paget’s)
28
Q

Define what pagets disease of the nipple is

A
  • It is a high grade DCIS extending along the ducts to reach the epidermis of the nipple.
  • It is still an in-situ carcinoma i.e. non-invasive as the BM has not been breached.
29
Q

What is the characterisitic appearance of pagets disease of the nipple?

A

Has a characterisitc eczematous appearance but can cause weeping which is percieved as nipple discharge

30
Q

What is a microinvasive breast carcinoma and how are they treated?

A
  • This is a DCIS which has invaded < 1mm
  • Treated as a high grade DCIS
31
Q

Define what an invasive breast carcinoma is

A
  • This is when malignant epithelial cells have breached the BM
  • There is infiltration of normal tissues, with the risk of metastases
32
Q

Appreciate this about breast cancer:

  • It esp affects females
  • Its incidence increases with age
  • It is the 2nd highest cancer cause of death in females
A
33
Q

List the risk factors for breast cancer development

A
  • Increasing age
  • Early menarche ≤ 12
  • Nullipara (never given birth)
  • 1st pregnancy after 30
  • Never breastfed
  • Later menopause > 55
  • Use of OCP or depo
  • Current HRT or used > 5yrs
  • FH - relative < 40 (otherwise not considered increased risk)
  • Previous DCIS/LCIS or breast cancer
  • Smoking & diabetes, increased BMI, alcohol consumption ≥ 1 per day
  • Genetics - BRCA 1/2 and TP53
  • Radiation exposure
34
Q

What are the 2 main mutations which increase the risk of breast cancer ?

A

BRCA 1 and BRCA 2

35
Q

What are the places to which breast cancer commonly invades

A
  • Local invasion (T) - Stroma of breast, Skin, Muscles of chest wall
  • Lymphatics (N) - to the Regional draining lymph nodes
  • Blood-borne (M) - predlictation to the Bone, liver, brain, lungs, abdominal viscera & female genital tract
36
Q

What 3 things are breast cancers classified based on ?

A

Based on:

  1. Morphology - type and grade
  2. Gene expression profiling
  3. Homrone receptor expression - oestrogen receptor (ER), progesterone receptor (PR) & HER2
37
Q

Define what is meant by tumour grade ?

A

This is a measure of tumour differentiation

  • If a tumour is very similar to the original tissue it is described as well differentiated or low grade ==> good prognosis
  • If a tumour is very different to the original tissue it is described as poorly differentiated or high grade ==> poor prognosis
38
Q

Why is the grading of breast cancer important ?

A

Because it indicates prognosis - grade 1 > 2 > 3

39
Q

80% of breast cancers are oestrogen receptor (ER) +ve, what does this mean in terms of treatment options ?

A

It means the cancer may respond to anti-oestrogen therapies which include:

  • Oophorectomy
  • Tamoxifen
  • Aromatase inhibitors (Letrozole)
  • GnRH antagonists - (Goserilin [Zoladex])
40
Q

15% of breast cancers are HER2 +ve what does this mean in terms of treatment options ?

A

HER2 +ve may respond to Transtuzamab treatment (human monoclonal antibody)

41
Q

Referring to hormone receptor expression, what are good prognostic features ?

A
  • If ER +ve rather than -ve
  • If PR +ve rather than -ve
  • If HER2 -ve rather than +ve

These are all associated with increase survival rates

42
Q

How are breast carcinomas staged ?

A

TNM staging:

Direct invasion of adjacent tissues

  • T0 - T4 Local tumour growth (size of tumour and extent of involvement of adjacent structures)

Lymphatic spread

  • N0 - N3 Regional lymph nodes

Blood-borne spread

  • M0 - M1 Distant metastasis
43
Q

State the different levels of local invasion of breast cancers (T component)

A
  • T0 = no evidence of tumour
  • T1 = ≤ 2cm tumour
  • T2 = 2-5cm
  • T3 = > 5cm
  • T4 = a) any sign of tumour invasion into chest wall, b) invasion of skin
44
Q

State the different levels of lymphatic spread of breast cancers (N component)

A
  • N0 = no lymph node involvement
  • N1 = metastases to ipsilateral axillary nodes, but nodes are movable
  • N2 = a) metastases to ipsilateral axillary nodes, but nodes are not movable (stuck), b) metastases to ipsilateral mammary nodes without being in axillary nodes
  • N3 = a) mets in ipsilateral infraclavilcular nodes, b) mets in ipsilateral supraclavilculaar nodes, c) mets in ipsilateral axillary & mammary nodes
45
Q

State the different levels of metastatic spread (blood borne) of breast cancers (M component)

A
  • M0 = no metastatic spread to a diff part of the body
  • M1 = cancer has spread to another part of the body
46
Q

What is used to determine prognosis following surgery for breast cancer?

A

Nottingham prognostic index

47
Q

Prior to surgery for any breast cancer (including DICS & pagets) what should be assessed?

A

Prior to surgery, the presence/absence of axillary lymphadenopathy:

  1. women with no palpable axillary lymphadenopathy at presentation should have a pre-operative axillary U/S before their primary surgery. If positive then they should have SLNB to assess the nodal burden
  2. In patients with breast cancer who present with clinically palpable lymphadenopathy or ≥ 4 +ve nodes on SLNB, axillary node clearance (ALND) is indicated at primary surgery, if this cant be done then adjuvant radiotherapy to axilla done
48
Q

What can axillary lymph node clearance lead to ?

A

Arm lymphedema and functional arm impairment

49
Q

What is the initial treatment of breast cancer?

A

Surgery + radiotherapy +/- adjuvant systemic therapy (hormonal, biological or chemo)

Surgery is either:

  1. WLE (breast conserving surgery) - solitary lesion, peripheral tumour, small lesion in large breast, DICS < 4cm, pagets assessed as localised (also has removal of nipple-areloar complex)
  2. Modified radical Masectomy - multifocal or central tumour, large lesion in small breast, DICS > 4cm, pagets not localised
50
Q

What does modified radical masectomy involve ?

A
  • This is removal of the entire breast inclduing the overlying skin & axillary lymph nodes.
  • The pectoralis major muscle is preserved however as this fascilitates improved wound healing & potentially allows for reconstruction surgery
51
Q

What should women be offered alongside surgery for breast cancer regardless of the type of operation they undergo?

A

Breast reconstruction to achieve a cosmetically suitable result regardless of the type of operation they have.

52
Q

What should always be discussed prior to masectomy ?

A

Breast reconstruction options and if they would like it done immediately, delayed or not at all following the surgery

53
Q

When is adjuvant radiotherapy offered to a women with breast cancer alongside surgery ?

A
  1. Whole breast radiotherapy (3-6 weeks) + a boost dose targeted at the tumour bed is recommended after a woman has had a wide-local excision
  2. For women who’ve had a mastectomy radiotherapy is offered for T3-T4 tumours and for those with three or more positive axillary nodes, positive surgical margins and/or tumors > 5 cm.
54
Q

When is adjuvant chemotherapy used in breast cancer treatment ?

A
  • Cytotoxic therapy may be used either prior to surgery (‘neoadjuvanant’ chemotherapy) to downstage a primary lesion or after surgery depending on the stage of the tumour, for example, if there is axillary node disease - FEC-D is used in this situation.
  • It should be considered for all patients with breast cancer where the benefit outweighs the risk
55
Q

Post-operatively what should be assessed to determine adjuvant treatment of breast cancer ?

A

Assess ER & HER2 status (PR status not routinley done)

56
Q

Who should be considered for adjuvant systemic therapy in breast cancer treatment ?

A

All those with early invasive breast cancer following surgery

57
Q

How soon after surgical treatment should adjuvant chemo or radiotherapy be initiated?

A

Within 3 days

58
Q

What should be offered for those <50 with tripple -ve breast cancer (hormone receptors), but no family history of breast/ovarian cancer

A

BRCA 1/2 genetic testing

59
Q

What hormonal therapy should be used following surgery for ER +ve breast cancers ?

A
  1. Tamoxifen is still used in pre- and peri-menopausal women.
  2. In post-menopausal women, aromatase inhibitors such as anastrozole, letrozole
60
Q

When should hormonal therapy not be given for ER+ve early invasive breast cancer following surgery?

A

Do not give it for DICS following BCS (WLE)

61
Q

What targeted therapy is given for HER2+ve early invasive breast cancers following surgery?

A

Herceptin (Trastuzumab, TZ)

62
Q

When is the use of Trastuzumab contraindictated for use in HER2+ve breast cancer?

A

Cannot be used in patients with a history of heart disorders.

63
Q

What extra investigations should be done for advanced breast cancer?

A

Assessment for the presence or extent of metastases should be made using a combination of: (advanced means locally advanced so more likely to have metastases than early invasive)

X-rays, U/S, CT & MRI

64
Q

What is the treatment of advanced ER+ve breast cancer ?

A
  • 1st line = hormonal therapy (depending on if theyve undergone menopause or not)
  • Offer chemo 1st line if disease is immenitley life threatening or requires early relief of symptoms because of sig visceral ogran involvement, then followed by hormonal therapy
65
Q

What is used for advanced breast cancer if HER2+ve ?

A

Herceptin (Trastuzumab, TZ)

66
Q

What is the 1st line treatment of metastatic breast cancer ?

A

Biological therapy - bevacizumab

Y4 Obstetrics and Gynaecology (63 decks)

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