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Breast Pathology
Dr. M. GriffinDr. M. Griffin
The Normal Breast
Terminal duct lobular unitTerminal duct lobular unit Segmental DuctsSegmental Ducts Lactiferous ducts and sinusesLactiferous ducts and sinuses Intralobular stromaIntralobular stroma Interlobular stromaInterlobular stroma Nipple areola complexNipple areola complex
Diagram of normal breast
Normal breast tissue
1.1. Large duct on the Large duct on the rightright
2.2. Lobules to the leftLobules to the left
3.3. Collagenous stroma Collagenous stroma extends betweenextends between
4.4. Adipose tissue Adipose tissue admixedadmixed
Terminal duct lobular unit
Pathology of breast
Disorders of development and growthDisorders of development and growth InflammationsInflammations Fibrocystic changeFibrocystic change Proliferative breast diseaseProliferative breast disease TumoursTumours
Disorders of development
Supernumerary nipples/ breastsSupernumerary nipples/ breasts Accessory axillary breast tissueAccessory axillary breast tissue Congenital inversion of nipplesCongenital inversion of nipples MacromastiaMacromastia Failure of growth eg Turners syndromeFailure of growth eg Turners syndrome
Inflammations
Acute mastitisAcute mastitis Periductal mastitisPeriductal mastitis Duct ectasiaDuct ectasia Fat necrosisFat necrosis Granulomatous mastitisGranulomatous mastitis Silicone breast implantsSilicone breast implants
Fibrocystic change/ non proliferative change.
Cyst formation with apocrine metaplasiaCyst formation with apocrine metaplasia
FibrosisFibrosis
Fibrocystic change
White tissue White tissue represents stromal represents stromal fibrosisfibrosis
Multiple cysts are Multiple cysts are present throughout present throughout (arrow)(arrow)
Fibrocystic change
1.Multiple cysts with 1.Multiple cysts with secretionssecretions
2.Arrow indicates 2.Arrow indicates microcalcification in microcalcification in one of the cystsone of the cysts
3.Background fibrotic 3.Background fibrotic stromastroma
Apocrine metaplasia
Proliferative breast Change
Epithelial hyperplasia -Epithelial hyperplasia -
Mild Mild
ModerateModerate
SevereSevere
+/- Atypia+/- Atypia Sclerosing adenosisSclerosing adenosis Multiple intraduct papillomasMultiple intraduct papillomas
Epithelial hyperplasia of usual type
1.1. Duct lumina are Duct lumina are almost completely almost completely filled with filled with proliferating proliferating epitheliumepithelium
2.2. No cytologic atypiaNo cytologic atypia
presentpresent
Atypical Ductal Hyperplasia
1 Ducts are filled with 1 Ducts are filled with markedly atypical markedly atypical cells cells
Proliferative breast disease and risk of CancerAtypical epithelial hyperplasia increases the Atypical epithelial hyperplasia increases the
risk by 4 - 5 times.risk by 4 - 5 times.
Epithelial hyperplasia of usual type increase Epithelial hyperplasia of usual type increase risk by 1.5 -2 times.risk by 1.5 -2 times.
Positive family history doubles these risksPositive family history doubles these risks
Breast Tumours
Benign Benign FibroadenomaFibroadenoma Phyllodes tumourPhyllodes tumour Intraduct papillomaIntraduct papilloma MalignantMalignant CarcinomaCarcinoma Phyllodes tumourPhyllodes tumour Sarcoma/ Lymphoma/ Metastatic tumourSarcoma/ Lymphoma/ Metastatic tumour
Fibroadenoma
1 circumscribed tumour1 circumscribed tumour
2 fibroblastic stoma 2 fibroblastic stoma enclosing glandular enclosing glandular structures lined by structures lined by epitheliumepithelium
Carcinoma of breast Epidemiology and risk factors Geographic factorsGeographic factors Age / SexAge / Sex Genetics and family history Genetics and family history Proliferative breast diseaseProliferative breast disease Radiation exposureRadiation exposure Reproductive/menstrual history Reproductive/menstrual history Obesity/ high fat diet/ Obesity/ high fat diet/
Genetic Predisposition
Positive Family historyPositive Family history 5-10% of cancers related to specific 5-10% of cancers related to specific
inherited gene mutationsinherited gene mutations BRCA1 and BRCA2 gene mutationsBRCA1 and BRCA2 gene mutations Li Fraumeni syndrome –germline mutation Li Fraumeni syndrome –germline mutation
of TP53of TP53 Cowden syndrome -germline mutation in Cowden syndrome -germline mutation in
PTEN.PTEN.
Carcinoma of breast
Etiology and Pathogenesis Etiology and Pathogenesis
Age and SexAge and Sex Genetic factorsGenetic factors Hormonal influencesHormonal influences Environmental factorsEnvironmental factors Atypical epithelial hyperplasiaAtypical epithelial hyperplasia
Carcinoma of breast
ClassificationClassification Carcinoma in situ ( carcinoma confined Carcinoma in situ ( carcinoma confined
within ducts or acini, may be ductal or within ducts or acini, may be ductal or lobular)lobular)
Invasive carcinoma (carcinoma has Invasive carcinoma (carcinoma has breached the basement membrane and breached the basement membrane and infiltrated breast stroma)infiltrated breast stroma)
Carcinoma of Breast
Carcinoma in situ (15-30%Carcinoma in situ (15-30%))
Ductal carcinoma in situ Ductal carcinoma in situ
( including Paget’s disease of the nipple)( including Paget’s disease of the nipple)
Lobular carcinoma in situLobular carcinoma in situ
Microcalcification on mammogram
1 Ductal carcinoma in situ 1 Ductal carcinoma in situ detected by detected by mammographymammography
2 Pleomorphic 2 Pleomorphic microcalcificationsmicrocalcifications
3 Localisation wire in situ – 3 Localisation wire in situ – to indicate area for to indicate area for excisionexcision
4 lesion is nonpalpable in the 4 lesion is nonpalpable in the majority of casesmajority of cases
Ductal carcinoma in situ
Paget’s disease of nipple
The The
Large cells in the epidermis represent cancer cells from underlying breast cancer which can be in situ or invasive.
Lobular carcinoma in situ
Neoplastic cells filling the acini are small and uniform
Carcinoma of Breast
PresentationPresentation Left breast more often than rightLeft breast more often than right 50% affect upper outer quadrant50% affect upper outer quadrant Painless massPainless mass Skin dimpling, ulceration, nipple retraction or Skin dimpling, ulceration, nipple retraction or
dischargedischarge Peau d’orange/ inflammatory carcinomaPeau d’orange/ inflammatory carcinoma Abnormal mammogram- mass/ density/ Abnormal mammogram- mass/ density/
pleomorphic microcalcificationspleomorphic microcalcifications
Carcinoma of Breast
Invasive CarcinomaInvasive Carcinoma
Ductal carcinoma NOS 79%Ductal carcinoma NOS 79%
Lobular carcinoma 10%Lobular carcinoma 10%
Tubular/cribriform carcinoma 6%Tubular/cribriform carcinoma 6%
Mucoid carcinoma 2%Mucoid carcinoma 2%
Medullary carcinoma 2%Medullary carcinoma 2%
Papillary carcinoma 1%Papillary carcinoma 1%
Invasive
Invasive ductal carcinoma- lesion is retracted, infiltrative and stony hard.
Invasive ductal carcinoma- lesion is retracted, infiltrative and stony hard.
Carcinoma of breast
Triple approach to diagnosisTriple approach to diagnosis
Clinical examination Clinical examination
Imaging – mammogram +/- ultrasoundImaging – mammogram +/- ultrasound
FNA cytology or core biopsyFNA cytology or core biopsy
GOAL: Non operative diagnosis of massGOAL: 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 1 Small nests and cords of neoplastic cellsof neoplastic cells
2.Dense collagenous 2.Dense collagenous stroma in between stroma in between cellscells
Invasive lobular carcinoma
1.Indian file strands of 1.Indian file strands of neoplastic cells neoplastic cells
2. Cells are small and 2. Cells are small and uniformuniform
3.Dense stroma3.Dense stroma
Mucinous carcinoma
Mucinous carcinoma
1. Abundant bluish 1. Abundant bluish staining mucin with staining mucin with small groups of small groups of carcinoma cells carcinoma cells
Tubular carcinoma
1 Normal ducts on the 1 Normal ducts on the left showing left showing myoepithelial layer myoepithelial layer (stained brown)(stained brown)
2 Tubular carcinoma on 2 Tubular carcinoma on the right, lacking the right, lacking myoepithelail layer myoepithelail layer
Inflammatory carcinoma- tumour in dermal lymphatics
Carcinoma of breast
Mass- firm, gritty, scirrhous or gelatinousMass- firm, gritty, scirrhous or gelatinous Circumscribed or infiltrative marginsCircumscribed or infiltrative margins Microscopy shows a variety of patterns ie Microscopy shows a variety of patterns ie
glands, cords, or nests of malignant cells glands, cords, or nests of malignant cells infiltrating breast stromainfiltrating breast stroma
Invasion of breast stroma, fat. lymphatics or Invasion of breast stroma, fat. lymphatics or blood vesselsblood vessels
Carcinoma of breast
Routes of spreadRoutes of spread
Local -skin, nipple , chest wallLocal -skin, nipple , chest wall
Lymphatic- lymph nodesLymphatic- lymph nodes
Blood – lungs, liver, bonesBlood – lungs, liver, bones
Metastatic carcinoma in lymph node and lymphatic
Breast cancer prognosis
Stage of diseaseStage of disease T –size of primary tumourT –size of primary tumour N – nodal statusN – nodal status M - +/_ metastasisM - +/_ metastasis
AJCC staging for breast cancer
Stage 5 year survivalStage 5 year survival 0 92%0 92% 1 87%1 87% 2 75%2 75% 3 46%3 46% 4 13%4 13%
Carcinoma of breast
Prognostic factorsPrognostic factors
Lymph node status/ Size /Grade (NPI)Lymph node status/ Size /Grade (NPI)
Histologic typeHistologic type
Hormone receptor statusHormone receptor status
Lymphovascular invasionLymphovascular invasion
Proliferative rate/ DNA contentProliferative rate/ DNA content
Oncogene expression eg HER2 NEUOncogene expression eg HER2 NEU
Gene expression profilingGene expression profiling
Prognostic markers
Oestrogen receptor positive Her2 protein 3+ positive
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