Histopathology - Breast Pathology Flashcards
What are general presenting symptoms of breast cancer?
- Pain (mastalgia/mastodynia)
- Palpable masses
- Nipple discharge
What is the triple assessment for a breast cancer?
- Clinical examination
- Imaging (USS/mammography IF <35yrs)
- Cytology + histology
How is the sample obtained for cytopathology in a breast cancer assessment and how is it coded?
Obtained via FINE NEEDLE ASPIRATION
- Cells spread across a slide, stained + coded
Coding:
- C1 = inadequate sample
- C2 = Benign
- C3 = Atypia
- C4 = Suspicious of malignancy
- C5 = Malignant
How is the sample obtained for histopathology in a breast cancer assessment and how is it coded?
Obtained via CORE BIOPSY
- Intact tissues removed showing architectural + cellular detail + coded
Coding:
- B1 = Normal
- B2 = Benign
- B3 = Uncertain
- B4 = Suspicious
- B5 = Malignant
- B5a = DCIS
- B5b = Invasive carcinoma
What is the gold standard investigation for breast cancer diagnosis?
Histopathology
- Normal breast histology = ductal-lobular system lined by inner glandular epithelium
What are some inflammatory breast conditions?
- Acute mastitis
- Fat necrosis
How does acute mastitis present, what are the different types, features, causes, cytological findings + treatment?
Presentation:
- Painful, red breast
- Hot to touch
- Fever
Types:
- Lactational - most common
- Non-lactational
Causes:
- Lactational = secondary to S. aureus infection (often polymicrobial) via cracks in nipple due to stasis of milk
- Non-lactational = KERATINISING SQUAMOUS METAPLASIA block in lactiferous ducts leading to peri-ductal inflammation + rupture
Cyto (FNA):
- Abundance of neutrophils
Tx:
- Continue milk expression (bilateral), warm compress, analgesia, elevation
- Abx (flucloxacillin PO)
- ?Surgical drainage
How does a breast abscess present and what is its management?
Presentation:
Fluctuant swelling + swinging fevers
Mx:
- IV Abx
- Incision + drainage
What is a fat necrosis, its RFs, causes, presentation and cytological findings?
- Inflammatory reaction to damaged adipose tissue
RFs:
- Obesity
- Middle aged
- Female
Presentation:
- Painless breast mass/skin thickening/mammographic lesion
- May mimic carcinoma displaying skin tethering/nipple retraction
Causes:
- Trauma
- Radiotherapy
- Surgery
- Nodular panniculitis
Cyto:
- Empty fat spaces (damaged fat lobules)
- Histiocytes
- Giant cells
BIG BLOCK OF CHEESE:
- Giant cells
- Recently cut (trauma)
- Full of calcium (calcified)
What are some benign neoplastic conditions?
- Fibroadenoma
- Breast cyst
- Duct ectasia
- Intraductal papilloma
- Radial scar
- Phyllodes tumour
- Fibrocystic disease
What is a fibroadenoma, its epidemiology, appearance, cytology + histology?
Benign neoplasm of a lobule; arising from fibro (stromal) + glandular (adenomal) epithelium
Epi:
- Most common lump in women 20-40yrs
Appearance:
- Size: Single, unilateral 1-5cm + mobile; varies in size during pregnancy + menstrual cycles (oestrogen driven)
- Consistency: Well demarcated, spherical, firm, smooth, rubbery
- Painless
- Mobile, “breast mouse”
Cyto:
- Branching sheet of epithelium
- bare bipolar nuclei + stroma
Histo:
- Multinodular mass of expanded intralobular stroma
What is a breast cyst, its epidemiology and appearance?
Fluid-filled sacs in the breast
Epi:
- Peri-menopausal (50yrs)
Appearance:
- Size: Single/multiple unilateral/bilateral; pain correlates with menstrual cycle
- Consistency: Well demarcated, clear nipple discharge
- Painless, transilluminable
- Fluctuant/mobile
What is a duct ectasia, its epidemiology, appearance, cytology + histology?
Dilatation of milk ducts due to blockage + inflammation
Epi:
- Peri/post-menopausal
- RFs: SMOKING + multiparity
Appearance:
- Size: Sub-areolar mass; nipple inversion
- Consistency: Firm, thick yellow-green-white nipple discharge; may lead to local infection if ducts get infected
- Tender
- Fixed
Cyto:
- Nipple discharge
- Proteinaceous material
- Macrophages
Histo:
- Duct dilatation
- Periductal inflammation
- Proteinaceous material inside duct
What is an intraductal papilloma, how does it present and what is seen on cytology + histology?
Benign papillary tumour arising within the duct system of the breast
- Small terminal ductules cause peripheral papillomas which cause a clinically silent + sub-areolar mass
- Larger lactiferoud ducts cause central papillomas which result in nipple discharge
Presentation:
- Sub-areolar mass
- +/- nipple discharge
- Peri + post-menopausal
- Not seen on mammogram *
Cyto (of nipple discharge):
- Branching papillary groups of epithelium
Histo:
- Papillary mass within a dilatated duct lined by epithelium
What is a radial scar, its causes, presentation and histological features?
Benign sclerosing lesion - central scarring surrounded by proliferating glandular tissue in stellate pattern
Cause:
- Impaired healing, post-injury
Presentation:
- STELLATE MASS (Radial Star) on mammography
- Closely mimics carcinoma
- Lesions >1cm = complex slerosing lesions
Histo:
- Central, fubrous stellate area
What is a phyllodes tumour, its presentation, features + histolgical findings?
Aggressive fibroepithelial neoplasms of breast arising from interlobular stroma (like fibroadenomas) with increased cellularity + mitoses
Presentation:
- >50yrs
- Palpable mass
Features:
- Low grade or high grade lesions
- Mostly relatively benign
- Can be aggressive
- Excised with wide local excision/mastectomy to limit local recurrence
- Mets V Rare
Histo:
- Branching
- Leaf-like fronds
- Artichoke appearance
What is fibrocystic disease, its presentation, features + histological findings?
Fluid-filled sacs in breast
Presentation:
- Changes according to menstrual cycle (hormone responseive)
- Lumpiness in breasts
Features:
- Occurs in 1/3 pre-menopausal women
- No increased risk for breast cancer
- Well-demarcated, fluctuant, transilluminable, clear nipple discharge
Histo:
- Dilated large ducts which may become calcified
What are proliferative breast conditions and three types?
Diverse group of intraductal epithelial proliferations, associated with varying risks of developing invasive breast cancer
- Pre-malignant
- Usually asymptomatic
- Usual epithelial hyperplasia
- Flat epithelial atypia (atypical ductal carcinoma)
- In situ lobular neoplasia
What are some features of usual epithelial hyperplasia + its histological findings?
- Not formally considered precursor lesion to invasive breast carcinoma
- Slightly increased risk (1-2%) of breast cancer
Histo:
- Growth of glandular tissue + epithelial cells forming fronds
What is the carcinoma risk of flat epithelial atypia (atypical ductal carcinoma) + its histological findings?
- 4x risk of developing carcinoma
Histo:
- Multiple layers of epithelial cells
- Lumens more regular + round with punched out areas
What is the carcinoma risk of in situ lobular neoplasia + its histological findings?
- 7-12x risk for developing breast carcinoma
Histo:
- Solid proliferation of aplastic cells
- Little space
- Small residue areas where you can still see lumen
What is the incidence, age and RFs for developing breast carcinoma?
Incidence:
- Most common cancer in women
- Lifetime risk = 1 in 8
Age:
- 75-80yrs
- Younger in Afro-Caribbeans
- Rare <35yrs
RFs:
- Gender
- Susceptibility genes (12%): BRCA1/BRCA2
- Hormone exposure
- Advancing age
- FHx
- Race (Caucasian > Afro-Caribbean > Asian > Hispanic)
- Obesity
- Tobacco
- Alcohol
- Radiation exposure
What is the screening programme for breast carcinoma, and the different types of breast carcinoma?
Screening:
- 47Y to 73Y Women
- 3-yearly mammography testing
- Looks for abnormal areas of calcification or mass within breast
Types:
- Non-invasive: Ductal carcinoma in situ (DCIS)
- Invasive: Invasive ductal carcinoma, invasive lobular carcinoma, Paget’s disease of breast
What are some features of gynaecomastia?
- Pubertal boys
- Older men >50yrs
- Idiopathic/ drug associations
- Benign
What are some features of male breast cancer?
- Rare
- Median age = 65yrs
- Most common presentation = palpable lump
- Almost 1/2 = Stage 3/4 + a/w: BRCA2 carriers
What is carcinoma in situ, its prevalence, types, features, histology + general treatment?
Neoplastic epithelial proliferation limited to ducts/lobules by basement membrane
Prevalence = 20%
Types:
- Lobular (LCIS)
- Ductal (DCIS)
Features:
- Inherent but not inevitable risk of progression to invasive breast cancer
Histo:
- Ducts filled with atypical epithelial cells
Tx:
- Surgical excision with clear margins
What are some features of lobular carcinoma in situ (LCIS)?
- Always incidental finding on biopsy
- No microcalcifications/stromal reactions
- 20-40% bilateral
- Cells lack adhesion protein E-cadherin
- RF for subsequent invasive basal carcinomas
What are some features of ductal carcinoma in situ (DCIS)?
- Incidence increased dramatically since development of mamography
- Appear as areas of microcalcification
- 10% present with clinical Sx
- Much increased risk of progression to invasive breast carcinoma
- High, intermediate + low grade
What is invasive breast carcinoma, its prevalence and types (with features)?
Malignant epithelial tumours which infiltrate within breast, capacity to spread to distant sites
Prevalence = 80%
Invasive ductal:
- Carcinoma that can’t be subclassified into another group
- Most common
- Big, pleomorphic cells
- Invasive cells move into stroma
Invasive lobular:
- Cells aligned in single file chains/strands
- Incidental finding
Tubular carcinomas:
- Well-formed tubules
- Low grade nuclei
- Rarely palpable as <1cm
Mucinous carcinomas:
- Cells produce abundant quantities of extracellular mucin
- Mucin dissects into surrounding stroma
How are invasive breast carcinomas graded?
Core needle biopsy + Nottingham Grading System
Graded /3 (/9 total score):
- Nuclear polymorphism
- Tubule formation
- Mitotic activity
Grade 1 = well differentiated (<5/9)
Grade 2 = moderately differentiated (6-7/9)
Grade 3 = poorly differentiated (8-9/9)
What is the most important prognostic factor of breast cancer, as well as other prognostic factors?
Status of axillary lymph nodes - most important
- ER/PR receptor +ve = Good prognosis (response to Tamoxifen)
- HER2 +ve = Bad prognosis
What is Tamoxifen?
Mixed agonist/antagonists of oestrogen at its receptor
What is Herceptin/trastuzumab
Monoclonal Ig to HER2 (direct toxic effect on myocardium, must monitor LVEF)
What are the general receptor statuses of different types of cancers, and which treatments do they receive?
Low grade tumours:
- ER/PR +ve generally
- HER2 -ve generally
- Tx: Tamoxifen
High grade tumours:
- ER/PR -ve generally
- HER2 +ve generally
- Tx: Herceptin
Basal cell carcinomas:
- ER/PR/HER2 -ve
- Triple negative
What is the presentation of basal-like carcinomas, their histological features, associations and spread?
Presentation:
- Breast lump +/- Peau d’orange
- UL DVT
- Nipple retraction
Histo:
- Sheets of markedly atypical cells with lymphocytic infiltrate
- +ve stain for CK5/6/14
Associations:
- BRCA (commonly)
Spread:
- Vascular invasion
- Distant metastatic spread
