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Breast Pathology Dr. M. Griffin
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The Normal Breast Terminal duct lobular unit Segmental Ducts
Lactiferous ducts and sinuses Intralobular stroma Interlobular stroma Nipple areola complex
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Diagram of normal breast
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Normal breast tissue Large duct on the right Lobules to the left
Collagenous stroma extends between Adipose tissue admixed
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Terminal duct lobular unit
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Pathology of breast Disorders of development and growth Inflammations
Fibrocystic change Proliferative breast disease Tumours
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Disorders of development
Supernumerary nipples/ breasts Accessory axillary breast tissue Congenital inversion of nipples Macromastia Failure of growth eg Turners syndrome
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Inflammations Acute mastitis Periductal mastitis Duct ectasia
Fat necrosis Granulomatous mastitis Silicone breast implants
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Fibrocystic change/ non proliferative change.
Cyst formation with apocrine metaplasia Fibrosis
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Fibrocystic change White tissue represents stromal fibrosis
Multiple cysts are present throughout (arrow)
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Fibrocystic change 1.Multiple cysts with secretions
2.Arrow indicates microcalcification in one of the cysts 3.Background fibrotic stroma
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Apocrine metaplasia
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Proliferative breast Change
Epithelial hyperplasia - Mild Moderate Severe +/- Atypia Sclerosing adenosis Multiple intraduct papillomas
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Epithelial hyperplasia of usual type
Duct lumina are almost completely filled with proliferating epithelium No cytologic atypia present
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Atypical Ductal Hyperplasia
1 Ducts are filled with markedly atypical cells
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Proliferative breast disease and risk of Cancer
Atypical epithelial hyperplasia increases the risk by times. Epithelial hyperplasia of usual type increase risk by times. Positive family history doubles these risks
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Breast Tumours Benign Fibroadenoma Phyllodes tumour
Intraduct papilloma Malignant Carcinoma Sarcoma/ Lymphoma/ Metastatic tumour
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Fibroadenoma 1 circumscribed tumour
2 fibroblastic stoma enclosing glandular structures lined by epithelium
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Carcinoma of breast Epidemiology and risk factors
Geographic factors Age / Sex Genetics and family history Proliferative breast disease Radiation exposure Reproductive/menstrual history Obesity/ high fat diet/
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Genetic Predisposition
Positive Family history 5-10% of cancers related to specific inherited gene mutations BRCA1 and BRCA2 gene mutations Li Fraumeni syndrome –germline mutation of TP53 Cowden syndrome -germline mutation in PTEN.
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Carcinoma of breast Etiology and Pathogenesis Age and Sex
Genetic factors Hormonal influences Environmental factors Atypical epithelial hyperplasia
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Carcinoma of breast Classification
Carcinoma in situ ( carcinoma confined within ducts or acini, may be ductal or lobular) Invasive carcinoma (carcinoma has breached the basement membrane and infiltrated breast stroma)
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Carcinoma of Breast Carcinoma in situ (15-30%)
Ductal carcinoma in situ ( including Paget’s disease of the nipple) Lobular carcinoma in situ
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Microcalcification on mammogram
1 Ductal carcinoma in situ detected by mammography 2 Pleomorphic microcalcifications 3 Localisation wire in situ – to indicate area for excision 4 lesion is nonpalpable in the majority of cases
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Ductal carcinoma in situ
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Paget’s disease of nipple
Large cells in the epidermis represent cancer cells from underlying breast cancer which can be in situ or invasive. The The
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Lobular carcinoma in situ
Neoplastic cells filling the acini are small and uniform
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Carcinoma of Breast Presentation Left breast more often than right
50% affect upper outer quadrant Painless mass Skin dimpling, ulceration, nipple retraction or discharge Peau d’orange/ inflammatory carcinoma Abnormal mammogram- mass/ density/ pleomorphic microcalcifications
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Carcinoma of Breast Invasive Carcinoma Ductal carcinoma NOS 79%
Lobular carcinoma % Tubular/cribriform carcinoma % Mucoid carcinoma % Medullary carcinoma % Papillary carcinoma %
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Invasive ductal carcinoma- lesion is retracted, infiltrative and stony hard.
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Carcinoma of breast Triple approach to diagnosis Clinical examination
Imaging – mammogram +/- ultrasound FNA cytology or core biopsy GOAL: Non operative diagnosis of mass
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Mammogram showing 2 invasive carcinomas with intervening DCIS
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Pre-operative diagnosis
Fine needle aspiration cytology Core biopsy
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Invasive ductal carcinoma
1 Small nests and cords of neoplastic cells 2.Dense collagenous stroma in between cells
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Invasive lobular carcinoma
1.Indian file strands of neoplastic cells 2. Cells are small and uniform 3.Dense stroma
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Mucinous carcinoma
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Mucinous carcinoma 1. Abundant bluish staining mucin with small groups of carcinoma cells
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Tubular carcinoma 1 Normal ducts on the left showing myoepithelial layer (stained brown) 2 Tubular carcinoma on the right, lacking myoepithelail layer
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Inflammatory carcinoma- tumour in dermal lymphatics
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Carcinoma of breast Mass- firm, gritty, scirrhous or gelatinous
Circumscribed or infiltrative margins Microscopy shows a variety of patterns ie glands, cords, or nests of malignant cells infiltrating breast stroma Invasion of breast stroma, fat. lymphatics or blood vessels
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Carcinoma of breast Routes of spread Local -skin, nipple , chest wall
Lymphatic- lymph nodes Blood – lungs, liver, bones
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Metastatic carcinoma in lymph node and lymphatic
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Breast cancer prognosis
Stage of disease T –size of primary tumour N – nodal status M - +/_ metastasis
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AJCC staging for breast cancer
Stage year survival % % % % %
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Carcinoma of breast Prognostic factors
Lymph node status/ Size /Grade (NPI) Histologic type Hormone receptor status Lymphovascular invasion Proliferative rate/ DNA content Oncogene expression eg HER2 NEU Gene expression profiling
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Prognostic markers Oestrogen receptor positive
Her2 protein 3+ positive
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