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