ERS33 Pathology Of Breast Cancer Flashcards
Clinical presentations of breast cancer
- ***Presence of lump / thickening
- Change in size / shape
- ***Nipple retraction
- ***Blood nipple discharge
Unusual presentations (distinguish from benign lesion):
- ***Rash on nipple / surrounding area (Paget’s disease of breast)
- ***Dimpling of skin / skin appear inflamed (Inflammatory breast cancer)
What to feel for during breast exam
Best time to check: a few days ***after period (after Estrogen ↓ —> any potential fluid retention / cysts gone —> not obscure real lump)
- Lump (hard / immovable / lemon seed)
- LN (axilla, soft bean)
Paget’s disease of breast
***ALWAYS have underlying Intraductal / Invasive carcinoma
Clinical presentation:
Eczema, Rashes, ***Erosion of nipple + areola
—> Red, weeping
—> Dry, scaly, psoriatic (occasionally)
(may be mistaken with skin lesion)
Histology:
Invasion of epidermis by ***Paget’s cells (Carcinoma cells with Large, Round/oval nuclei, Pale cytoplasm, Mucin-containing)
Inflammatory breast cancer
Clinical presentation:
- **NO single lump / tumour
- Skin appear inflamed (may be ~ mastitis)
—> **Red, Warm, Peau d’orange (Puckering of skin)
—> 1. Blockage of lymph vessel in the skin by cancer cells (Dermal lymphatic spread)
—> 2. Tumour cells infiltrate Fibrous septa + Suspensory ligament
Prognosis:
- Poorer than typical invasive cancer
- Higher chance of metastasis
Histological classification of breast carcinoma
Non-invasive:
- Ductal carcinoma-in-situ (DCIS)
- Lobular carcinoma-in-situ (LCIS)
Invasive:
- Invasive carcinoma of no special type (NST)
- Special subtypes
- Invasive lobular carcinoma
- Tubular carcinoma
- Mucinous carcinoma
- Ductal carcinoma-in-situ (DCIS)
- Confined within Ductal basement membrane
- ***Micro-calcification —> may be detected by Mammography at early stage
- 50% centrally situated —> form palpable mass
Histology:
- ***Cohesive cancer cells (癡埋一齊)
High grade comedo DCIS:
- Large pleomorphic cells
- ***Central comedo necrosis (necrosis of ducts)
- 50% evolve into invasive carcinoma within 5 years
Low grade non-comedo DCIS:
- only 30% evolve into invasive carcinoma within 10-15 years
—> subsequent invasive carcinoma usually in ***same area as initial DCIS (invade into surrounding CT stroma)
- Lobular carcinoma-in-situ (LCIS)
- Cancer cells within Acini
- Confined within Acini basement membrane
- Peri-menopausal women, less common with advancing age
- ***NO distinguishing clinical features —> usually radiologically undetectable / impalpable —> may be missed by Mammography
Gross:
- Multicentric (70%) (i.e. multiple areas of breast)
- Bilateral (20-35%)
- Concentrated within 5cm of nipple in outer / upper inner quadrants
Histology:
- Lobules expanded by cancer cells
- Smaller, ***Discohesive cancer cells (散開)
Prognosis:
- 10x greater chance of developing into invasive carcinoma than general population
- absolute risk 20-25% in 15 years
—> Site of later invasive carcinoma equally divided between **either breast
—> **may be Ductal / Lobular
- Invasive carcinoma of no special type (NST)
Aka:
- Ductal carcinoma (NST)
- Invasive carcinoma (NOS)
- Infiltrating ductal carcinoma
- **MOST common type of breast cancer
- a heterogeneous group of tumours
- fail to exhibit sufficient characteristics to be classified as a specific histological type
- 70% of invasive breast cancer
Gross:
- ***Poorly defined
- Hard, yellow-grey mass
- ***Radiating fibrous trabeculae (Fibrosis)
- ***Gritty sensation and chalky streaks (crab-like, legs of crabs infiltrating)
Histology:
- Clusters of carcinoma cells (poorly differentiated / more differentiated)
- Nuclear pleomorphism
- Special subtypes of invasive carcinoma
- Invasive lobular carcinoma
- 5% of all breast tumours
- Multifocal + Bilateral
- Poorly circumscribed mass
- Single cell infiltration
- Single file (Indian filing: 一列隊) / Concentric rings around a duct (Target-like lesion) of ***Small-medium tumour cells (∴ lesion may be impalpable) - Tubular carcinoma
- 90% of tumour composed by **Open tubules lined by **Single layer of cells
- Excellent prognosis
- Distant metastasis unlikely, rarely kill - Mucinous carcinoma
- Older women
- Slow-growing circumscribed mass
- produce Bulky, **soft, gelatinous material
- **Islands of tumour cells floating in ***large lakes of mucin
- Excellent prognosis
Spread of breast carcinoma
- Lymphatic spread
- influenced by location
- Lateral tumours (more common): **Axillary LN (level 1-3 —> Supraclavicular LN)
- Medial / Deep tumours: **Internal mammary LN
Sentinel LN
- 1st LN most likely to spread to
- Sentinel LN biopsy
—> determine whether cancer cells are present
—> -ve result suggest cancer not yet spread to nearly LN / other organs
—> patient spared from further LN surgery
—> ↓ potential SE of LN surgery e.g. lymphoedema (e.g. swelling of arm)
- Haematogenous spread
- Bone (more common), Lung, Liver, Ovaries, Adrenal glands, Brain
Prognosis of breast cancer
Different types of breast cancer —> Differ
Prediction based on statistical probability generated from outcomes of large series of patients
Options of treatment:
- ***Local excision
- Partial mastectomy / ***Mastectomy
- Combinations of **Radiotherapy + **Chemotherapy
- Hormonal therapy SERMs e.g. Tamoxifen
- Targeted therapy e.g. Herceptin
Clinical-pathological prognostic assessment:
- Appropriate clinical decision making
- Predict survival in >= first 5 years
Importance of Pathology report / Pathologist:
- Diagnosis of breast cancer
- Prognostic + Predictive profile of each patient
Pathology examination for stereotactic image guided excision for impalpable lesion
- **Block selection (一階一階) to establish character lesion and size
- superior / inferior / lateral / medial
- need to correlate with specimen X-ray
- embedded blocks in numbered sequence —> allow reconstruction and size assessment
Prognostic / Predictive marker
- Size
- Histological type / grade
- Grade I - III (based on Tubule formation (more the better), Nuclear grade, Mitotic rate) - Presence of DCIS
- assessment of margins, size of lesion, classification of pathological subtype
- low / intermediate / high nuclear grade (comedo necrosis) - Lympho-vascular invasion
- predictor of local recurrence after conservation therapy - LN status (Number + Level of nodal involvement)
- Proliferation rate
- Clearance from resection margins
- Steroid hormone receptor status (nuclear receptor)
- ER +ve tumour are responsive to ***Anti-estrogen treatment - HER2 oncogene overexpression (membrane receptor)
- marker of poor prognosis in LN +ve patients
- predict response to chemotherapy
—> **Doxorubicin-based
—> **Herceptin (Anti-HER2 Ab)
- Immunohistochemical assay widely used but reliability being questioned
—> ***Fluorescent in-situ hybridisation (FISH) gold standard to see whether gene is amplified
—> but expensive + time-consuming
HER-2 breast cancer
HER-2 +ve:
- more aggressive than other types of breast cancer
- less responsive to hormone treatment
- treatments specifically target HER2 are very effective:
1. Trastuzumab (Herceptin)
2. Lapatinib (Tykerb) (Tyrosine kinase inhibitor)
3. Doxorubicin (Adriamycin)
Stages of breast cancer
Determining staging by:
- Pathology - Sentinel LN / LN biopsy
- Imaging - CXR, Bone scan, CT, PET
Revised TNM staging by AJCC:
- pTis - DCIS (including Paget’s disease)
- pT1
- pT1a (<= 5mm)
- pT1b (5-10mm)
- pT1c (10-20mm) - pT2 - 20-50mm
- pT3 - > 50mm
- pT4 - direct extension to skin / chest wall
