Breast Pathology Dr. M. Griffin

The Normal Breast Terminal duct lobular unit Segmental Ducts Lactiferous ducts and sinuses Intralobular stroma Interlobular stroma Nipple areola complex

Diagram of normal breast

Normal breast tissue Large duct on the right Lobules to the left Collagenous stroma extends between Adipose tissue admixed

Terminal duct lobular unit

Pathology of breast Disorders of development and growth Inflammations Fibrocystic change Proliferative breast disease Tumours

Disorders of development Supernumerary nipples/ breasts Accessory axillary breast tissue Congenital inversion of nipples Macromastia Failure of growth eg Turners syndrome

Inflammations Acute mastitis Periductal mastitis Duct ectasia Fat necrosis Granulomatous mastitis Silicone breast implants

Fibrocystic change/ non proliferative change. Cyst formation with apocrine metaplasia Fibrosis

Fibrocystic change White tissue represents stromal fibrosis Multiple cysts are present throughout (arrow)

Fibrocystic change 1.Multiple cysts with secretions 2.Arrow indicates microcalcification in one of the cysts 3.Background fibrotic stroma

Apocrine metaplasia

Proliferative breast Change Epithelial hyperplasia - Mild Moderate Severe +/- Atypia Sclerosing adenosis Multiple intraduct papillomas

Epithelial hyperplasia of usual type Duct lumina are almost completely filled with proliferating epithelium No cytologic atypia present

Atypical Ductal Hyperplasia 1 Ducts are filled with markedly atypical cells

Proliferative breast disease and risk of Cancer Atypical epithelial hyperplasia increases the risk by 4 - 5 times. Epithelial hyperplasia of usual type increase risk by 1.5 -2 times. Positive family history doubles these risks

Breast Tumours Benign Fibroadenoma Phyllodes tumour Intraduct papilloma Malignant Carcinoma Sarcoma/ Lymphoma/ Metastatic tumour

Fibroadenoma 1 circumscribed tumour 2 fibroblastic stoma enclosing glandular structures lined by epithelium

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/

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.

Carcinoma of breast Etiology and Pathogenesis Age and Sex Genetic factors Hormonal influences Environmental factors Atypical epithelial hyperplasia

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)

Carcinoma of Breast Carcinoma in situ (15-30%) Ductal carcinoma in situ ( including Paget’s disease of the nipple) Lobular carcinoma in situ

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

Ductal carcinoma in situ

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

Lobular carcinoma in situ Neoplastic cells filling the acini are small and uniform

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

Carcinoma of Breast Invasive Carcinoma Ductal carcinoma NOS 79% Lobular carcinoma 10% Tubular/cribriform carcinoma 6% Mucoid carcinoma 2% Medullary carcinoma 2% Papillary carcinoma 1%

Invasive ductal carcinoma- lesion is retracted, infiltrative and stony hard.

Carcinoma of breast Triple approach to diagnosis Clinical examination Imaging – mammogram +/- ultrasound FNA cytology or core biopsy GOAL: Non operative diagnosis of mass

Mammogram showing 2 invasive carcinomas with intervening DCIS

Pre-operative diagnosis Fine needle aspiration cytology Core biopsy

Invasive ductal carcinoma 1 Small nests and cords of neoplastic cells 2.Dense collagenous stroma in between cells

Invasive lobular carcinoma 1.Indian file strands of neoplastic cells 2. Cells are small and uniform 3.Dense stroma

Mucinous carcinoma

Mucinous carcinoma 1. Abundant bluish staining mucin with small groups of carcinoma cells

Tubular carcinoma 1 Normal ducts on the left showing myoepithelial layer (stained brown) 2 Tubular carcinoma on the right, lacking myoepithelail layer

Inflammatory carcinoma- tumour in dermal lymphatics

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

Carcinoma of breast Routes of spread Local -skin, nipple , chest wall Lymphatic- lymph nodes Blood – lungs, liver, bones

Metastatic carcinoma in lymph node and lymphatic

Breast cancer prognosis Stage of disease T –size of primary tumour N – nodal status M - +/_ metastasis

AJCC staging for breast cancer Stage 5 year survival 0 92% 1 87% 2 75% 3 46% 4 13%

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

Prognostic markers Oestrogen receptor positive Her2 protein 3+ positive