Breast pathology - malignant Flashcards
List the 4 main miscellaneous malignant breast tumours
- Malignant Phyllodes tumour
- Angiosarcoma
- Lymphoma
- Metastatic tumours
What is the malignant change which occurs for a phyllodes tumour to become malignant and how often does this occur?
- Malignant change = stroma becomes sarcomatous (sarcoma)
- This occurs in 5% of cases
What is an angiosarcoma and what is it associated with occuring after ?
- It is a malignant tumour of the inner lining of blood vessels
- They have an association of developing post radiotherapy
Can a primary lymphoma occur in the breast ?
- 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
What are the common metastatic tumours to the breast ?
- Carcinomas - bronchial, ovarian serous carcinoma & clear cell carcinoma of the kidney
- Malignant melanoma
- Soft tissue tumouts - leiomysarcoma
Define what a breast carcinoma is
A malignant tumour of breast epithelial cells arising in the glandular epithelium of the terminal duct lobular unit (TDLU)
What are the signs and symptoms of breast cancer ?
- Dimpled or depressed skin
- Visible/ palpable lump
- Nipple change e.g. inversion
- Bloody discharge
- Texture change
- Skin change e.g. eczematous
Pathologically what are all types of breast cancer ?
An adenocarcinoma
What are the 2 main types of breast carcinomas?
Ductal or lobular carcinoma (arising from duct tissue or lobular tissue respectively)
How can ductal & lobular breast cancer be further subdivided ?
Based on whether the cancer hasn’t spread beyond the local tissue (described as carcinoma-in-situ) or has spread (described as invasive).
List the 4 main types of breast cancer
- Invasive ductal carcinoma. (called no special type - NST)
- Invasive lobular carcinoma
- Ductal carcinoma-in-situ (DCIS)
- Lobular carcinoma-in-situ (LCIS)
The other 3 types may be referred to as special types as they are less common
Define what a carcinoma in situ is
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
What are the 2 subtypes of lobular in situ neoplasia ?
- Atypical Lobular Hyperplasia (ALH) where <50% of lobule involved
- Lobular Carcinoma in situ (LCIS) where >50% of lobule involved
What are the general characteristics of a malignant cell ?
- 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).
What are the characterisitc cells seen in lobular in situ neoplasia ?
- 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)
What are the main presenting features of a lobular in situ neoplasia ?
- Frequently multifocal & often bilaterally affecting the breasts
- Not usually palpable or grossly visible so often incidental finding seen as calcification on mammography
What happens to the incidence of lobular in situ neoplasia following menopause?
Its incidence increases
What is the significance of lobular in situ neoplasia in terms of risk of invasive development ?
8x increased risk
What is the management of a lobular in situ neoplasia ?
- If discovered on core biopsy ==> proceed to exicision or vaccum biopsy to exclude higher grade lesion
- If discovered on vaccum or excision biopsy ==> follow-up
How do invasive lobular carcinomas typically present ?
- 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)
What are the ductal carcinoma precusor lesions ?
- Epithelial hyperplasia of usual type
- Columnar cell change
- Atypical ductal hyperplasia
- Ductal carcinoma in situ
Where does a ductal carcinoma in situ arise ?
In the TDLU - characteristically affecting one duct system
How do ductal carcinomas typically present ?
- Usually as a lump/mass
- Typically then find stellate (star like) solid mass or pleomorphic casting microcalcifications when investigated
How is definitive diagnosis of a ductal carcinoma made?
By image guided tissue core-needle biopsy
How do ductal in situ carcinomas typically present and what is seen on investigation ?
Usually present as non-palpable, but seen on screening XRM as malignant calcifications (pleomorphic & of the casting type - stellate)
How is definitive diagnosis of a DCIS made ?
By vaccum assisted core-biopsy
What are the pathological features of a ductal carcinoma in situ ?
- Cytologically malignant epithelial cells
- Confined within basement membrane of duct
- May involve lobules (cancerisation)
- May involve nipple skin (Paget’s)
Define what pagets disease of the nipple is
- 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.
What is the characterisitic appearance of pagets disease of the nipple?
Has a characterisitc eczematous appearance but can cause weeping which is percieved as nipple discharge
What is a microinvasive breast carcinoma and how are they treated?
- This is a DCIS which has invaded < 1mm
- Treated as a high grade DCIS
Define what an invasive breast carcinoma is
- This is when malignant epithelial cells have breached the BM
- There is infiltration of normal tissues, with the risk of metastases
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
List the risk factors for breast cancer development
- 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
What are the 2 main mutations which increase the risk of breast cancer ?
BRCA 1 and BRCA 2
What are the places to which breast cancer commonly invades
- 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
What 3 things are breast cancers classified based on ?
Based on:
- Morphology - type and grade
- Gene expression profiling
- Homrone receptor expression - oestrogen receptor (ER), progesterone receptor (PR) & HER2
Define what is meant by tumour grade ?
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
Why is the grading of breast cancer important ?
Because it indicates prognosis - grade 1 > 2 > 3
80% of breast cancers are oestrogen receptor (ER) +ve, what does this mean in terms of treatment options ?
It means the cancer may respond to anti-oestrogen therapies which include:
- Oophorectomy
- Tamoxifen
- Aromatase inhibitors (Letrozole)
- GnRH antagonists - (Goserilin [Zoladex])
15% of breast cancers are HER2 +ve what does this mean in terms of treatment options ?
HER2 +ve may respond to Transtuzamab treatment (human monoclonal antibody)
Referring to hormone receptor expression, what are good prognostic features ?
- 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
How are breast carcinomas staged ?
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
State the different levels of local invasion of breast cancers (T component)
- 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
State the different levels of lymphatic spread of breast cancers (N component)
- 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
State the different levels of metastatic spread (blood borne) of breast cancers (M component)
- M0 = no metastatic spread to a diff part of the body
- M1 = cancer has spread to another part of the body
What is used to determine prognosis following surgery for breast cancer?
Nottingham prognostic index
Prior to surgery for any breast cancer (including DICS & pagets) what should be assessed?
Prior to surgery, the presence/absence of axillary lymphadenopathy:
- 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
- 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
What can axillary lymph node clearance lead to ?
Arm lymphedema and functional arm impairment
What is the initial treatment of breast cancer?
Surgery + radiotherapy +/- adjuvant systemic therapy (hormonal, biological or chemo)
Surgery is either:
- 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)
- Modified radical Masectomy - multifocal or central tumour, large lesion in small breast, DICS > 4cm, pagets not localised
What does modified radical masectomy involve ?
- 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
What should women be offered alongside surgery for breast cancer regardless of the type of operation they undergo?
Breast reconstruction to achieve a cosmetically suitable result regardless of the type of operation they have.
What should always be discussed prior to masectomy ?
Breast reconstruction options and if they would like it done immediately, delayed or not at all following the surgery
When is adjuvant radiotherapy offered to a women with breast cancer alongside surgery ?
- 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
- 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.
When is adjuvant chemotherapy used in breast cancer treatment ?
- 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
Post-operatively what should be assessed to determine adjuvant treatment of breast cancer ?
Assess ER & HER2 status (PR status not routinley done)
Who should be considered for adjuvant systemic therapy in breast cancer treatment ?
All those with early invasive breast cancer following surgery
How soon after surgical treatment should adjuvant chemo or radiotherapy be initiated?
Within 3 days
What should be offered for those <50 with tripple -ve breast cancer (hormone receptors), but no family history of breast/ovarian cancer
BRCA 1/2 genetic testing
What hormonal therapy should be used following surgery for ER +ve breast cancers ?
- Tamoxifen is still used in pre- and peri-menopausal women.
- In post-menopausal women, aromatase inhibitors such as anastrozole, letrozole
When should hormonal therapy not be given for ER+ve early invasive breast cancer following surgery?
Do not give it for DICS following BCS (WLE)
What targeted therapy is given for HER2+ve early invasive breast cancers following surgery?
Herceptin (Trastuzumab, TZ)
When is the use of Trastuzumab contraindictated for use in HER2+ve breast cancer?
Cannot be used in patients with a history of heart disorders.
What extra investigations should be done for advanced breast cancer?
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
What is the treatment of advanced ER+ve breast cancer ?
- 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
What is used for advanced breast cancer if HER2+ve ?
Herceptin (Trastuzumab, TZ)
What is the 1st line treatment of metastatic breast cancer ?
Biological therapy - bevacizumab
