Breast Pathology Flashcards
Describe the normal histology of the breast ducts
Secretory cells lining the inner lumen
Surrounded by myoepithelial cells
Surrounded by basement membrane
Describe the branching structure of the breast ducts
8-10 main ducts up the the nipple
Branch repeatedly in stroma
Terminal part empties into lobule composed of a group of acini
From what part of the breast tissue do most lesions arise?
Epithelium of the terminal duct lobular unit
What features are important on radiology?
Patterns of calcification (present in benign and malignant lesions)
Tissue density
Shape of lesions (many malignancies stellate in shape)
What are the 2 possible types of further investigation into a breast lesion, and what are the benefits and disadvantages of each?
Fine needle aspiration (FNA): collects a sample of cells to look for histological aspects of malignancy
Needle core/tru-cut biopsy: uses a larger needle to obtain a piece of tissue (usually ~1mm across, 1-2cm long), which allows the relationship of the cells to each other, the stroma and the basement membrane to be examined
What are the histological changes that occur with fibrocystic change?
Variable duct dilation +/- cyst formation (1 cyst may predominate) Fibrosis Adenosis (proliferation of acini structures) Apocrine metaplasia (pink, granular epithelial cells)
What is the presentation with fibrocystic change?
Asymptomatic
May produce lumps, discomfort
Bilateral and multifocal on examination/investigation
In what group is fibrocystic change common?
Women of middle to late reproductive years
Almost so common as to be considered physiological
What is fibroadenoma?
A solitary, well circumscribed benign mass, composed of neoplastic or hyperplastic stromal tumour with an epithelial component
In what group is fibroadenoma common?
Younger women
How does fibroadenoma usually present?
As a lump
What is the treatment for fibroadenoma?
Usually removed
What is the relationship between fibroadenoma and malignancy risk?
May be no or only slightly increased risk of malignancy
What is the most common cause of cancer-related death in Australian women?
Lung cancer
What is the most common cancer in Australian women?
Breast cancer
What is the average age of first diagnosis of breast cancer in Australia?
60
List 9 predisposing factors for breast carcinoma
Age (~70% of those diagnosed are over 50) Genetic factors (sporadic or inherited) Increased lifetime oestrogen exposure Less breast feeding Fewer pregnancies Obesity Alcohol Past history of certain breast diseases Other (e.g. ethnicity, radiation)
What type of genetic mutation is most commonly associated with breast carcinoma: sporadic or familial/germline?
Sporadic
List 4 common sporadic genetic abnormalities which predispose to breast carcinoma
p53
HER2
neu
c-erbB-2
What is the role of p53?
Involved in cell cycle arrest and DNA repair
What is HER2?
Proto-oncogene acting as an epidermal GF receptor
How does amplification of HER2 predispose to breast carcinoma?
An excess of HER2 receptors increases the response to GFs, causing increased cell proliferation
In what % of tumours is an amplification of HER2 present?
~20%
What % of breast carcinoma cases have 1 or more affected 1st degree relatives?
15-20%
What is the most common genetic abnormality in familial breast carcinomas?
Multiple low-risk susceptibility genes (cause cancer when they interact with environmental factors)
What % of cases have specific germline mutations in BRCA1, BRCA2 or p53?
5-10%
How are germline mutations in BRCA1, BRCA2 and p53 inherited?
In an AD fashion
What is the effect of germline mutations in BRCA1, BRCA2 and p53 on risk of breast malignancy?
Strongest risk factor - increases risk at least 30%, but up to 90%
Cancer onset is often at a younger age
What is an additional risk (outside of breast carcinoma) with a BRCA1 mutation?
Increased risk of ovarian cancer?
A germline mutation in which gene predisposes to breast cancer in males?
BRCA2
What is the role of BRCA1 and BRCA2?
Involved in cell cycle arrest and initiate mechanisms for DNA repair
List 5 ways lifetime oestrogen exposure might be increased
Early menarche Late menopause Nulliparous or late age of 1st birth HRT Postmenopausal obesity
How does increased oestrogen exposure increase risk of breast carcinoma?
Oestrogen stimulates breast growth, driving cycles of proliferation that increase risk of DNA mutations
List 3 breast diseases which increase risk of breast cancer
Atypical hyperplasia (also hyperplasia without atypia, but risk is less)
In situ carcinoma
Invasive carcinoma
How does hyperplasia increase risk of breast cancer?
Does not directly progress to cancer, just indicates future risk
What is in situ carcinoma?
Malignant population of cells confined to ducts and/or acini, with no invasion through the basement membrane
What are the 2 types of in situ carcinoma?
Ductal carcinoma in situ (DCIS)
Lobular carcinoma in situ
Which of the 2 types of in situ carcinoma is more common?
DCIS
What are some of the possible histological findings with DCIS?
Associated calcification (seen on mammogram) Various architectural types (can be graded) Large atypical nuclei, pleomorphism, areas of necrosis which can undergo calcification
How does DCIS present?
May produce a mass or can be an incidental finding on biopsy
Usually asymptomatic
How does lobular carcinoma in situ present?
Incidental finding on biopsy
Usually asymptomatic
What is a possible complication of DCIS?
Paget’s disease of the nipple (where malignant cells extend up ducts to the nipple, causing inflammation, erthyma, and exudate of the nipple)
What are some possible presentations of invasive carcinoma?
Lump
Discomfort
Nipple changes (e.g. retraction due to underlying scarring) or discharge
Change in shape/texture of breast (e.g. peau d’orange due to invasion of skin lymphatics by tumour)
Skin tethering
Screening detection
What are the 2 main types of invasive carcinoma?
Invasive ductal carcinoma
Invasive lobular carcinoma
What is the most common type of invasive carcinoma?
Invasive ductal carcinoma (70-80%)
What is the most common site for invasive ductal carcinoma?
Upper outer quadrant of breast (50%)
What is the typical appearance of an invasive ductal carcinoma?
“Schirrous” firm stellate mass
What are the typical histological hallmarks of an invasive ductal carcinoma?
Malignant duct-forming cells (infiltrating parenchyma)
Irregular margin
Areas of scarring and fibrosis
Abnormalities of cell junction proteins
List 4 possible sites of local spread of invasive carcinoma
Skin
Nipple
Underlying muscle/chest wall
Pleura
List 7 common sites of metastatic spread of invasive carcinoma and their routes of spread
Lymphatic: axillary (most common), supraclavicular, internal mammary nodes
Blood: lungs, bones, liver, brain
List 5 possible treatment approaches for breast cancer
Surgery Radiotherapy Chemotherapy Anti-oestrogen drugs Herceptin/transtuzumab NB: a combination is usually used, based on the characteristics of the primary tumour and the stage
What types of surgery are usually used in the management of breast cancer?
Usually breast-conserving surgery (wide local excision) with axillary LN sampling or sentinal node biopsy
Quadrantectomy
Complete mastectomy (less common)
What will happen if all draining LNs around the breast are removed?
Oedema
List 9 prognostic/predictive factors when assessing the excised tumour histologically
Tumour type Grade Size and local extent Lymphovascular invasion Presence and extent of DCIS Surgical margins Nodal involvement ER/PR HER2
What is the prognosis for the most common type (duct) of breast carcinoma?
Poor (<50% 10 year survival)
How are breast cancers graded?
Using Bloom and Richardson system, which takes into account acinar/tubule formation, nuclear pleomorphism and mitotic index, and applies a grade of 1-3 (1 being low grade, 3 being high grade)
What does presence of lymphovascular space invasion (LSI) indicate?
Likelihood of nodal metastases
Higher risk of local recurrance
What is the relevance of measuring surgical margins histologically?
Assess distance from margins of invasive tumour and DCIS to determine whether the tumour has been fully excised, and whether further surgery is required
When is tamoxifen used?
In tumours with a high % of ERs
When is herceptin/transtuzamab used?
Only in tumours with HER2 amplification
What is the criteria for a TNM stage 4 breast cancer? What is the prognosis?
Invasive carcinoma any size with distant metastases
10% 10 year survival with optimal treatment
What is a new tool used for classification and what is the basis of this method? Give 3 examples of types of tumour under this classification system
Molecular classification
Based on molecular subtype (distinguished by changes in DNA, mRNA and protein expression) and reflects the behaviour of the tumour
E.g. luminal, basal-like, HER2 positive
What is gynaecomastia?
Increase in size of male breast tissue due to proliferation of ducts and stroma
What causes gynaecomastia?
Relative or real increase in oestrogen
E.g. at puberty, in cirrhosis, with certain drugs, due to testicular atrophy
What is the incidence of breast carcinoma in males compared with females?
~1% of incidence in women
