Breast Pathology 2 Flashcards
When do most angiosarcomas occur?
Post-radiotherapy
After how many years of radiotherapy do angiosarcomas usually happen?
2-5 years
What are the 3 most common metastatic tumours to the breast?
- Bronchial
- Ovarian serous carcinoma
- Clear cell carcinoma of kidney
Name a soft tissue tumour of the breast.
Leiomysarcoma
What, simply, is a breast carcinoma?
A malignant tumour of the breast epithelial cells
Where in the breast does a carcinoma arise?
Arises in the glandular epithelium of the terminal duct lobular unit (TDLU)
Name 4 ductal precursor lesions in the breast.
- Epithelial hyperplasia of usual type
- Columnar cell change
- Atypical Ductal Hyperplasia
- Ductal Carcinoma in situ
Name a lobular precursor lesion of the breast.
Lobular in situ neoplasia - Atypical lobular hyperplasia or Lobular carcinoma in situ
Where is an in situ carcinoma of the breast confined to?
This is confined to the basement membrane of acini and ducts
What is atypical about breast carcinoma?
They are described as being malignant but are non-invasive
Breast carcinoma can be either _______ or ______
Lobular or ductal
What are the 2 main sub-categories of lobular in situ neoplasia?
- Atypical Lobular Hyperplasia (ALH) - <50% of lobule is involved
- Lobular Carcinoma in situ (LCIS) - >50% of the lobule is involved
ALH is defined as …
<50% of lobule is involved
LCIS is defined as …
> 50% of the lobule is involved
In what is there ‘intralobular proliferation of characteristic cells’?
Lobular in situ neoplasia
List some of the features of cells in lobular in situ neoplasia.
- Small-intermediate sized nuclei
- Solid proliferation
- Intra-cytoplasmic lumens/vacuoles
- Oestrogen receptor positive (ER+)
- E-cadherin negative (deletion and mutation of CDH1 gene on Chr 16q22.1)
What is E cadherin?
E cadherin is a cell adhesion molecule found in the membrane but not in this neoplasia (this process is lost)
Outline the main clinical features of lobular in situ neoplasia.
- Frequently multifocal and bilateral
- Incidence decreases after menopause
- Not palpable or visible grossly
- May calcify – which can be seen on mammography
- Usually an incidental finding
When does the incidence of lobular in situ neoplasia decrease?
After menopause
Lobular in situ neoplasia are not palpable or visible grossly
TRUE
What may a lobular in situ neoplasia do? (hint: it can be seen on mammography)
Calcify
Why is incidence of lobular in situ neoplasia decreased after menopause?
ER (oestrogen receptor) drops
Outline the management of lobular in situ neoplasia.
- Vacuum biopsy
- Excision biopsy – this is less common now
- Follow up
How can you tell what lobular in situ neoplasia will be invasive?
You can’t :(
List the 4 different types of ductal proliferation.
- Epithelial hyperplasia of usual type
- Columnar cell change (lesion)
- Atypical ductal hyperplasia
- Ductal carcinoma in situ
Different intraductal neoplasia’s have different risks of progression to invasive carcinoma. Comment on the different risks.
- Epithelial hyperplasia of usual type – 2x RR
- Atypical Ductal Hyperplasia – 4x RR
- Ductal Carcinoma in situ (low grade) – 10x RR (25% over following 10 years)
15-20% of all breast malignancies are ____
DCIS
DCIS accounts for what % of all breast cancers?
15-20%
Where in the breast does ductal carcinoma in situ arise?
Arises in TDLU (terminal duct lobular unit)
DCIS is characteristically?
Unicentric (single duct system)
What is DCIS a risk factor for?
Risk factor for development of invasive carcinoma !! – a true precursor lesion of invasive carcinoma
What cancers are true precursors of invasive carcinoma?
DICS and LCIS
Cytologically, what is seen in DCIS?
Malignant epithelial cells are seen
Where is DCIS confined to?
** Confined within the basement membrane of a duct !! **
What may DCIS involve?
- May involve lobules (a process known as cancerisation)
* May involve nipple skin (Paget’s)
What is Paget’s disease of the nipple?
High grade DCIS extending along the ducts to reach the epidermis of the nipple
Describe Paget’s disease of the nipple.
- In situ carcinoma
- Non-invasive
*
Explain how in Paget’s disease the cancer can spread from the BM of the duct to the skin but still be in situ.
BM continuous from duct to the epidermis of the skin so this it is still in situ
How is DCIS classified?
- Cytological grade
- Histological type
- Presence of necrosis (comedo)
Outline the management of DCIS.
- Diagnosis
- Surgery – trials of mammographic follow-up in low risk DCIS)
- Adjuvant radiotherapy
- Chemoprevention (trial)
Microinvasive carcinoma is common
FALSE - very rare
What is micro invasive carcinoma?
DCIS (high grade) with invasion of <1mm
How is micro invasive carcinoma treated?
As a high grade DCIS
What are the characteristics of INVASIVE breast carcinoma?
- Malignant epithelial cells which have BREACHED the BM
- Infiltration of normal tissues
- Risk of metastasis and death
Outline all the risk factors you can think of for invasive breast carcinoma.
- Age
- Age at menarche (earlier is worse)
- Age at first birth (<30 years is protective)
- Parity (greater parity is protective)
- Breastfeeding (protective)
- Age at menopause (late menopause is worse)
- Hormones – HRT, OCP
- Previous breast disease
- Lifestyle – bodyweight, physical activity (protective), alcohol conumption, diet, NSAID (lower risk), smoking
- Genetics
- Family history – an affected first degree relative doubles your risk
Puberty starting at an older age is protective
True
What % of breast cancers have increased oestrogen as a risk?
80%
Greater parity is protective against breast cancer
TRUE
An affected first degree relative doubles your risk of having breast cancer
True
What is the most common breast cancer mutation?
BRCA 1 and BRCA 2
How many women carry BRCA1/2?
1 in 450
What is the commonest female cancer?
Invasive breast carcinoma
2nd commonest cause of cancer death in women is?
Invasive breast cancer
How many women will develop breast cancer?
1 in 8
What are the 3 things used to assess progression of breast cancer?
- Local invasion
- Lymphatics
- Blood borne
Where are the 3 most common sites of local invasion of breast cancer?
- Stroma of breast
- Skin
- Muscles of chest wall
What lymph nodes are commonly invaded in breast cancer?
- Axillary
- Parasternal
- Sub-clavicular
- Intramammary nodes
When breast cancer invades the blood, where is the most common site for mets?
Bone, liver, brain, lungs, abdominal viscera, female genital tract
What 3 factors are used in the classification of invasive breast carcinoma?
- Morphology
- Gene expression profiling
- Hormone receptor expression
What are the different hormones that can be expressed in invasive breast cancer?
- Oestrogen receptor (ER)
- Progesterone receptor (PR)
- HER2
What is tumour grade a measure of?
Grade is a measure of tumour differentiation
Very similar to parent tissue =
Well differentiated = Low grade = Good prognosis
Very different to parent tissue =
Poorly differentiated = High grade = Poor prognosis
In breast cancer grading, what is there an objective assessment of?
Tubular differentiation – scored from 1-3
Nuclear pleomorphism – scored from 1-3
Mitotic activity – scored from 1-3
Min score - 3
Max score - 9
In breast cancer grading, what is there an objective assessment of? Also outline the different scores.
Tubular differentiation – scored from 1-3
Nuclear pleomorphism – scored from 1-3
Mitotic activity – scored from 1-3
Min score - 3
Max score - 9
Score 3, 4 or 5 = grade 1
Score 6 or 7 = grade 2
Score 8 or 9 = grade 3
80% of breast carcinomas are oestrogen receptor (ER) positive
True
67% of breast carcinomas are progesterone receptor positive
True
14% of breast carcinomas are HER2 receptor positive
True
What does oestrogen receptor predict?
This predicts the response of the carcinoma to anti-oestrogen therapy
Give examples of anti-oestrogen receptor drugs.
- Oophorectomy
- Tamoxifen
- Aromatase inhibitors (letrozole)
- GnRH antagonists (Goserilin (Zoladex))
What does HER2 stand for?
Human Epidermal growth factor Receptor 2
HER 2 overexpression or amplification predict response to __________?
Trastuzamab
HER 2 overexpression or amplification predict response to __________?
Trastuzamab
What is Trastuzamab good for?
HER2 active disease
What 3 factors would infer the worst prognosis for an invasive breast cancer?
- Tumour size >50 mm
- 3+ nodes
- Lymphovascular invasion
Outline the features of the Nottingham Prognostic Index.
- 0.2 x tumour diameter (cm)
- Tumour grade (1-3)
- Lymph node status (1-3)
Small tumours have a better prognosis than big
True
Describe the TNM staging of breast cancer.
Direct invasion of adjacent tissues:
T0 - T4 – Local tumour growth (size of tumour and extent of involvement of adjacent structures)
Lymphatic spread:
N0 – N – Regional lymph nodes
Blood-borne spread:
M0 - M1 – Distant metastasis