Week 7 - C - Pathology 2 (malignant) - Lobular, D.C.I.S/Paget's, Invasive carcinoma - Incidence, Risk, Grading/Staging/Hormone, Prognostics Flashcards
What is a breast carcinoma defined as? Where do breast carcinomas arise? What type of carcinoma is the breast carcinoma?
A breast carcinoma is a malignant tumour of breast epithelial tissue arising in the glandular epithelium of the terminal duct lobular unit (TDLU) It is an adenocarcinoma as it arises in the glandular epithelium but is usually just referred to as a breast carcinoma
As stated, breast carcinomas are malignant tumours of the breast epithelial tissue arising from the glandular epithelium of what? What are the two different precursor regions for
The malignant tumours of breast tissue arise from the glandular epithelium of the terminal duct lobular unit (TDLU)- therefore breast carcinomas are technically adenocarcinomas The two different regions they can arise from are the ducal or lobular region of the TDLU
Name some precurosr lesions for breast carcinomas for both the ductal and lobular regions? Clue for ductal - the usual precursor lesions here are from intraductal papillomas
Ductal * Epithelial hyperplasia of usual type * Atypical ductal hyperplsia * Ductal carcinoma in situ * Also columnar cell change Lobular Lobular in situ neoplasia
What is an in situ carcinoma of the breast?
It is a carcinoma of the breast confined within the basement membrane of the acini and ducts
How would an in situ carcinoma be described cytologically?
An in situ carcinoma of the breast is confined to the basement membrane of the acini and ducts It is cytologically malignant but not invascive And carcinoma in situ is classified as either lobular or ductal
Lobular in situ neoplasia can be classified as atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS) What is the difference betwen these two?
Lobular in situ neoplasia:
- Atypical lobular hyperplasia - <50% of the lobule is involved with lobular neoplastic (LN) cells
- Lobular carcinoma in situ - >50% of the lobule is involved with LN cells
Does lobular carcinoma in situ usually present with any symptoms?
Lobular carcinoma in situ (LCIS) is an incidental microscopic finding with characteristic cellular morphology and multifocal tissue patterns.
How would a lobular carcinoma in situ be described under the microscope?
There is the intralobular poliferation of characteristic cells: The nucleus are small-intermediate sized and there is solid proliferation There is also intracytoplasmic lumens/vacuoles in the cells
Lobular Carcinoma In Situ may mimic low grade Ductal Carcinoma In Situ histologically. In these scenarios, pathologists may employ immunohistochemical testing to differentiate between entities What is typically negative on immunohistocehmistry in LCIS? What receptors are typically positive in LCIS?
Typically LCIS is E-cadherin negative on immunohistochemistry Typically it is also oestrogen and progesterone receptor positive
What is the function of E-Cadherin?
E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues.
Are lobular in situ neoplasia typically single, unilateral, multifocal or bilateral? When does incidence of lobular in situ neoplasia decrease?
Lobular in situ-neoplasia is typically multifocal and bilateral in presentation The incidence of its occurrence typically decreases after menopause
How does a lobular in situ neoplasia typically present? ie what does it feel like
It is typically not palpable and not visibile grossly and therefore usually only an incidental finding as it may calcify on mammography
Do in situ lobular neoplasia’s raise the risk of developing invasive carcinoma?
They increase the risk of invasive carcinoma by 8 fold
Having a family history of invasive carcinoma + lobular in situ neoplasia greatly increases the risk The management of lobular in situ neoplasia greatly depends on how it was discovered ie If it were discovered on core biopsy what would you then carry out? If it were discovered on vacuum or excision biopsy what would you then carry out?
If the lobular in situ-neoplasia was discovered on core biopsy, would go on to carry out a vacuum or excision biopsy to rule out higher grade lesion If it were discovered on vacuum or excision biopsy - would follow up to ensure no recurrence Lobular Carcinoma In-situ is both a risk factor and precursor of invasive carcinoma.
What is meant by intraductal proliferation?
Neoplastic growth within the ductal cells
What are some of the types of intraductal proliferation? Intraductal proliferation and lobular in situ neoplasia can both be a precursor to invasive carcinoma
Epithelial hyperplasia of the usual type Columnar cell change (lesion) Atypical duct hyperplasia Ductal carcinoma in situ
What is the risk of progression to invasive carcinoma with the different intraductal proliferations: * Epithelial proliferation usual type * Atypical ductal hyperplasia * Ductal carcinoma in situ
Epithelial proliferation usual type - 2x increased risk Atypical ductal hyperplasia - 4x increased risk Ductal carcinoma in situ - 10x increased risk
Ducal carcinoma in situ have the greatest risk out of the different types of epithelial proliferations of becoming an invasive malignancy What percentage of breast malignancies are they accountable for? Where do the malignancies arise?
They are accountable for 15-20 of breast malignancies and arise in the ductal part of the terminal duct lobular unit
Characteristically, do ductal carcinomas in situ take up multiple duct systems or just a singular duct system?
Characteristically the ductal carcinoma in situ takes up a single duct system and therefore is known as characteristically unicentric
The DCIS cytologically has malignant cells Histologically how would the DCIS be described? If it involves the lobules what is known as? If it involves the nipple sin what is it known as?
Histologically the DCIS is confined within the basement membrane of the duct and therefore has invaded the breast tissue If the DCIS spreads to the lobule then it known as a DCIS with canceristation of the lobules If the DCIS involes the nipple skin then it is known as pagets disease of the nipple
How does DCIS usually present? How is it usually found?
Ductal carcinoma in situ is usally asymptomatic and is seen as microcalcification on the xray
What is pagets disease of the nipple? Is this invasive cancer
This is a high grade ductal carcinoma in situ that has extended along the ducts to reach the epidermis of the nupple It is still classified as a carcinom in situ and therefore is non-invasive
Paget’s disease of the nipple (breast) is an intrdermal spread of an intraduct cancer How does pagets disease of the breast present and what must be done?
Pagets disease of the breast presents with a nipple that may look like ther eis eczrma on the surface as it appears as a red and scaly lesion - a biopsy must be carried out in this It can sometimes present with an almost weeping discharge
What type of biopsy is taken in pagets disease of the nipple?
The diagnosis is made by histologic tissue biopsy (incisional or punch biopsy).
Ductal carcinoma in situ can be classified based on its cytological grade usually but also by its histological grade How is a DCIS managed?
This is managed by carrying out surgery and adjuvant radiotherapy Ensure sentinel node biopsy is also carried out if high grade
What does a high grade ductal carcinoma in situ show the presence of?
A high grade ductal carcinoma in situ is one where there is the presence of necrosis on the histology
The necrosis usually occurs in the centre of the duct, this is known as a comedocarcinoma
What is a microinvasive carcinoma defined as? How is treated?
A microinvasive carcinoma is defined as a DCIS which is high grade with less than 1mm invasion into the breast A mmicroinvasive carcinoma is treated as a high grade DCIS
What is an invasive breast carcinoma?
This is where the malignant epithelial cells have breached the basement membrane of the acini or ducts and has infiltrated the normal tissue
With invasive breast carcinoma comes the risk of metastases and death The risks are usually linked to age, reproductive history, hormones, history, life-style and genetics Is breast cancer a higher risk at older or younger age? What does reproductive history do for the risk of breast cancer?
Breast cancer risk increases with older age Uninterrupted exposure to oestrogen increases the risk of breast cancer also
What are the different reproductive history risk factors for breast cancer? Remember uninterrupted exposure to breast cancer What are the hormone risk factors for breast cancer?
Reproductive history Age at menarche - early menarche Nullparity Age at first birth >30years old Late menopause Not breastfeeding Hormone risk factors - endogenous Exogenous - Combined oral contraceptive and HRT
What type of cancers does the combined pill affect? what percentages does it reduce the risk of certain cancers?
Decreases the risk of Colorectal Endometrial - 20-50 reduction in this type Ovarian cancer - 20% reduction every 5 years use with a max of 50% reduction after 15 years use Increases the risk of breast and cervical cancer
What were the uninterruped oestrogen exposure again for breast cancer risk factors? Previous breast disease is an obvious risk factor for breast cancer What are lifestyle risk factors for breast cancer?
* Early menarche * Nullparity * Age at first pregnancy >30 years old * Never breastfeeding * Late menopasue
Lifestyle risk factors * Bodyweight - obesity * Physical inactivity - increases risk of breast, endometrial and colorectal mainly * Alcohol consumption and smoking * Diet
Genetics plays a large role in being a risk factor for breast cancer What are the two main mutations which greatly increase the risk of developing breast cancer? What percentage lifetime risk do carries of these mutations have for breast cancer?
These are BRCA1 and BRCA2 mutations BRCA1 mutations - confer a 65% lifetime risk of breast cancer BRCA2 mutations - confer a 40% lifetime risk of breast cancer
What does an affected 1st degree relative do to the risk?
This double the risk fof having breast cancer
We have now gone over different risk factors for breast cancer, the introduction of what in 1988 greatly reduced the mortality of breast cancer sin the UK?
The introduction of breast screening in 1988 greatly reduced the mortality of breast cancer
For invasive breast cancer, how common is this amongst cancers in females? The mortality rates of breast cancer as stated is decreasing, what is happening to the incidence rates?
Breast cancers is the commnest female cancer and the 2nd commonest cause of cancer death in women The incidence of breast cancer is increasing
Once the breast cancer invades the stroma of the breast and skin, it can invade the muscles of the chest wall as well What are the regional draining lymph nodes for breast cancer? Which is the sentinel node?
The regional draining lymph nodes are the axillary nodes The sentinel node would be the anterior axillary lymph nodes
What are the different ways in which an invasive breast carcinoma can be classified?
Can be classified based on the * Type * Grade * Stage * Gene expression * Hormone receptor expression
What are the two most common types of breast cancer histopathologically? What is the tumour grade a measure of?
The most common type is ductal invasive carcinoma of the breast Lobular invasive carcinoma is the next most common type of breast cancer Tumour grade is a measure of the tumour differentiation ie how similar the tumour is to the parent tissue
In cancer, well-differentiated cancer cells look more like normal cells under a microscope and tend to grow and spread more slowly than poorly differentiated or undifferentiated cancer cells. WHat is the difference between low grade and high grade tumours?
Low grade * Very similiar * Well differentiated * This is a good prognosis High grade * Very different * Poorly differentiated * Poor prognosis
There are different “scoring systems” available for determining the grade of a breast cancer. One of these systems is the Nottingham Histologic Score system. There are three factors that the pathologists take into consideration: * Tubular differentiation (the more the tubules change, the less clearly differentiated they are) * the nuclear pleomoprhism(how “ugly” the tumor cells look) * the mitotic activity What is the maximum score from this grading system?
This would be grade 9
The grading from the 3 components – Tubular differentiation (1-3) – Nuclear pleomorphism (1-3) – Mitotic activity (1-3) The grading is added up and split into grad 1-3
WHat score would each grade be?
Grade 1 - Score of 3,4,5
Grade 2 - Score of 6or7
Grade 3 - Score of 8or9
The higher the grade of tumour the worse the survival prognosis
After knowing the type of breast cancer and its grade, important to the know the staging of the breast cancer How is breast cancer staged? Can be stage 1-4 or TNM Just talk about stages 1to4 on this card
Stage 1 -confined to breast and breast is mobile Stage 2 - confined to breast, breast is mobile although lymph nodes in ipsilateral axilla are affected Stage 3 - the tumour is fixed to muscled but not the chest wall, skin involvement, there is ipsilateral nodal involvement and the nodes may be fixed Stage 4 - Complete fixation of tumor to chest wall, distant metastases
Describe the TNM staging of breast cancer? (the T refers to the size of the tumour) N - nodes M - metastases
- T1 - tumour <2cm
- T2 - tumour 2-5cm
- T3 - tumour >5cm
- T4 - Fixed to skin or chest wall
- N0 - no nodal metastases
- N1 - Mobile ipsilateral nodes
- N2 - Ipsilateral nodes affected and fixed
- M0 - no distant metastases
- M1 - distant metastases
Often the breast can be desribed as peau d’orange, what does htis mean? Which score for T in the TNM does the peau d’orange appearance of the breast score?
When the cancers blocks the dermal lymphatics draining causing oedema of the breast and dimpling over the cooper’s ligamenets giving an orange peel like appearance Gives a T score of 4, which also is when it may be fixed to the chest
The breast cancer as said can be graded on its type, grade, stage and gene and hormone receptor expression Lets talk about hormone receptor expression What are the three different examples?
• 80% ER positive • 67% PgR positive • 14% HER2 positive Majority are oestrogen receptor positive then progesterone recepetor positive and finally her2 receptor positive
What does ostreogen receptor positive breast cancers respond to?
Oestrogen receptor positive predicts the cancer response to anti-oestrogen therapy Ie oopherectomy Tamoxifen Aromatase inhibitors GnRH antagonsitis
What type of drug is tamoxifen? What may it increase the risk of? Name an aromatase inhibitor? WHat does it do? When are these drugs used?
Tamoxifen is a selective oestrogen receptor modulator (SERM) May increase the risk of uterine cancer so warn to report vaginal bleeding Aromatase inhibitor ie letrozole or anastrazole - these inhibit peripheral oestrogen syntheseis Aromatase inhibitors only usually given if post menopasual
If pre-menopasual and ER+ve, what drug can be used?
Tamozifen or GnRH receptor antagonist ie goserelin
What does HER 2 stand for? When is the overexpression of the receptor seen? (ie how common in breast cancer) What does HER2 cause?
It stands for human epidermial growth factor receptor 2 (HER2) Overexpression and amplification seen in ~15% of breast cancers If you have too much HER2 expression, it makes the cells in the breast divide in an uncontrollable way.
– HER 2 overexpression or amplification predict response to which drug? Can be given for HER2+ve tumours
This would be trastuzamab (Herceptin) • New class of anti-cancer agents • Humanised mouse monoclonal antibody • Active in HER2 positive disease
What are the breast cancer tumour prognostic factors?
Tumour size, the grade, lymph node status, ER/PgR/HER2 status, presence of vascular invasion
The nottingham prognostic index takes into account the histopathology of the tumour only ie the size, grade and stage How is this score calculated?
Nottingham prognostic index (NPI) - 0.2 x tumour size (in centimetres) x histological grade (1-3) x the nodal status (1-3 nodes involved)
Pathology and Breast Cancer
- * • Breast cancer pathology predicts outcome
- * • Breast cancer pathology predicts response to specific therapies
- * • Pathology aids the rational management of breast cancer
State how the grades are caluculated and the stages
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When assessing tumour invasion, it is important to known its extent of spread into the axilla How is this carried out?
Pretreatment ultrasound evaluation of the axilla should be performed for all patients being investigated for early invasive breast cancer and, if morphologically abnormal lymph nodes are identified, ultrasound-guided needle sampling should be offered. Sentinel lymph node biopsy (SLNB) is the preferred technique.
What is the treatment of breast cancer? Stage 1and2 or Stage 3 and 4
Stage 1 and 2
- * Surgery - removal of tumour by wide local excision or mastectomy +/- breast reconstruction + axillary node sampling
- * Radiotherapy is also recommended for all patients after wide local excision and as is chemotherapy
- * Hormone agents given sometimes also
If stage 3 and 4
- Systemic so would probably use chemotherapy, hormonal therapy and targeted therapy
When would radiotherapy be given after mastectomy?
Usuauly considered if there is 4 or more nodes involved or the tumour is greater than 5cm in size or there are positive surgical margins for cancer after mastectomy Or if it is T4 disease - fixed to skin or chest wall, or when peau d’orange
What would be different about the treatment of breast cancer in women who are pregnant?
During pregnancy, hormonal therapy with trastuzamab or tamoxifen is contraindicated as is radiotherapy unless potentially life saving
What is the treatment for lobular in situ neoplasia? What is the treatment for DCIS?
Lobular in situ neoplasia Always want an excision biopsy (or wide local excision) or vacuum assisted biopsy to take the large sample DCIS Surgery with adjuvant radiotherapy
