Benign and malignant breast pathology

Dr. Cecily Quinn

Irish National Breast Screening Programme & St. Vincents University Hospital, Dublin 4

Breast Disease
Symptoms

Lump

Smooth, round Hard, irregular

Lumpy area Nipple discharge Breast pain Breast thickening

Breast Disease

Mammographic abnormality
Density
Asymmetry Mass Calcification

Breast Disease Triple assessment

Non-operative breast diagnosis Pathology

Breast: needle core biopsy

B1 normal tissue or non-diagnostic B2 benign B3 - heterogenous group of lesions

Risk concomitant malignancy e.g. radial scar More significant pathology in vicinity

B4 suspicious B5 malignant in situ or invasive

Anatomy of the breast

Benign Breast Disease

Spectrum of lesions
1. 2. 3.

4. 5.

Cysts, duct ectasia, Fibroadenoma Potential for local recurrence Phyllodes tumour Increased incidence of associated malignancy Radial scar, papilloma Atypical lesions
Atypical ductal hyperplasia, lobular neoplasia

Cyst(s)

Pathology

Fluid filled dilated breast gland (acinus) often lined by apocrine epithelium Solitary Multiple +/- other benign change =

fibrocystic disease

Cyst(s)

Clinical

Asymptomatic Mammographic lesion Smooth lump Lumpy area Cyclical pain & nodularity

Management

No treatment Aspiration May be excised if part of a more complex lesion

Duct ectasia

Pathology

Affects breast ducts

Duct dilatation, Accumulation of secretions Periductal inflammation & fibrosis

Periareolar abscess Smoking Hyperprolactinaemia Bacteria

Cause

Duct ectasia

Clinical

Nipple discharge Lump Pain Calcification

Management

Subareolar exploration

Fibroadenoma

Phyllodes tumour

Phyllodes tumour

Potential for local recurrence Clinical

Mammographic lesion Lump Size: 1cm 45cms

Management

Complete excision with 1cm rim of normal tissue note 1

Radial Scar

Pathology

Spiculate lesion Benign tubules in sclerotic stroma Associated benign changes May mimic carcinoma, mammographically and pathologically Associated malignancy in up to 33%

Radial scar

Clinical

Mammographic lesion Lump rare

Management

Complete excision to exclude malignancy

Papilloma

Pathology

Intraductal lesion Solitary or multiple Heterogeneous

Only part represented in needle core biopsy

Papilloma

Clinical

Women in 5th and 6th decades Asymptomatic Mammographic lesion Nipple discharge Lump

Management

Excise in view of heterogeneity

Atypical ductal hyperplasia

Pathology

Proliferation of epithelium lining the ducts and acini Some but not all of the features of DCIS

Atypical ductal hyperplasia

Diagnosis

Needle core biopsy for evaluation of mammographic or symptomatic lesion Excise in entirety to evaluate adjacent tissue for ductal carcinoma in situ Increased (normal x 4) Mammographic surveillance

Management

Risk for malignancy

Lobular neoplasia

Atypical lobular hyperplasia

Risk x 4 normal

Lobular carcinoma in situ

Risk x 11 normal

Lobular neoplasia

Clinical

Traditional teaching

Incidental finding No clinical or mammographic equivalent Risk factor for breast cancer Risk applies equally to both breasts No point in trying to excise Treatment options Mammographic surveillance Bilateral mastectomy

Lobular neoplasia

Recent studies (Molecular analysis

and longitudinal patient studies): Subgroup may act as a precursor lesion (like DCIS) and progress to invasive carcinoma

Treatment approach likely to change in the future

Breast Cancer in Ireland

Affects 1 in 12 women 1800 women newly diagnosed each year 600 women die from the disease each year 12,000 person years of life lost each year due to breast cancer

Breast Cancer

We do not know what actually causes this common disease

We have identified risk factors

Breast Cancer Risk

Family history (20%)

Specific genetic abnormality

BRCA1 gene 85% risk

Reproductive profile

Uninterrupted oestrogenic stimulation

Exogenous hormones

OCP, HRT

Breast Cancer Risk

Lifestyle

Alcohol, diet, smoking

Environmental

Radiation
Residence in developed countries

Sociodemographic

Breast Cancer Risk

Breast biology
Atypical ductal hyperplasia Lobular carcinoma in situ Ductal carcinoma in situ Cancer in contralateral breast

Breast Cancer
Diagnosis

Non operative 95%

Triple assessment

Clinical assessment Radiology Pathology

Needle core biopsy Fine needle aspirate

Multidisciplinary review

Operative 5%
Open surgical biopsy

Non-operative breast diagnosis Pathology

Breast: needle core biopsy

B1 normal tissue or non-diagnostic B2 benign B3 - heterogenous group of lesions

Risk concomitant malignancy e.g. radial scar More significant pathology in vicinity

B4 suspicious B5 malignant in situ or invasive

fine needle aspirate

Axillary lymph nodes:

Negative Positive

Non-operative breast diagnosis

Guide to surgery

Wide local excision or mastectomy?

Size or extent of lesion

Sentinel node biopsy or axillary clearance?

SNLB invasive carcinoma, high grade DCIS AXCL known positive lymph node

Non-operative breast diagnosis

Guide to non-surgical treatment

Neoadjuvant (Chemo before surgery ) chemotherapy

Extent of disease clinical & radiology Pathology to confirm diagnosis

Hormone treatment only

Exceptional ER and PR receptor status

Pathological evaluation of therapeutic operative breast cancer specimens

he will manage the cure best who has foreseen what is to happen from the current state of matters
Book of Prognostics Hippocrates 400BC

Breast Cancer
Classification

In situ carcinoma

Ductal DCIS Lobular LCIS Ductal Lobular Special types

Invasive carcinoma

Ductal carcinoma in situ

Obligate precursor lesion

Recur if left untreated 50% as invasive carcinoma

20% screen detected cancers

Malignant cells contained within the glandular system of breast

Complete removal should cure

Ductal carcinoma in situ

Old classification

Architectural patterns

Comedo Solid Cribriform Micropapillary

Not reproducible Not clinically relevant

Ductal carcinoma in situ

Nuclear grade

New classification

Nuclear grade

High Intermediate Low

Reproducible Clinically relevant

Ductal carcinoma in situ

Size of lesion
< 15mm
15 40mm > 40mm

Ductal carcinoma in situ

Margin status

> 10mm 1 10mm

< 1mm

Ductal carcinoma in situ

Van Nuys Index

Nuclear grade 1 - 3 Margin status 1 - 3 Lesion size 1-3

35 WLE only 5, 6 WLE & RoRx 8, 9 Mastectomy

Silverstein at al, Lancet 1995

Invasive breast carcinoma

Prognostic parameters

Type Grade Size Margin status Lymphovascular invasion Lymph node status Hormone receptor status Her-2/neu status

Invasive ductal carcinoma

Invasive lobular carcinoma

Tends to infiltrate the breast insidiously Forms irregular lesion Mammogram may be negative Increased multifocality Increased bilaterality E-cadherin negative MRI scan

E cadherin

Invasive breast carcinoma

Special types

Tubular

Mucinous

Basal

Invasive breast carcinoma

Tumour size

Powerful indicator of patient survival WLE vs mastectomy Tumour > 2cm chemotherapy Removal of tumour <15mm alters the clinical course of disease
Tabar et al. Cancer 1999;86:449-462

THE IRISH TIMES

Wednesday, September 1, 2004

North reaps benefit of breast cancer screening

Deaths from breast cancer falling by 4% per annum
Muiris Houston, Medical Correspondent Tumour size is a surrogate marker for monitoring efficacy of screening programmes until improved mortality becomes apparent

Invasive breast carcinoma

Tumour grade

G1

G2

G3

Invasive breast carcinoma

Adequacy of excision

Positive or close margins predict local recurrence further surgery

Invasive breast carcinoma

Lymphovascular invasion

Independent predictor of survival Correlates with lymph node involvement Surrogate marker of lymph node status ? Chemotherapy

Invasive breast carcinoma

Lymph node status

Greatest predictor of patient survival Component of TNM staging system Major factor in patient selection for chemotherapy

Sentinel lymph node biopsy

The lymph node that is most likely to harbour metastases if patient is LN positive

Reliable alternative to axillary lymph node clearance as a staging procedure

Sentinel lymph node biopsy

Removal of one versus 30 LNs allows for enhanced pathological analysis Greater chance of detecting metastases

Axillary lymph node clearance

Positive lymph node fine needle aspirate

One operation Two operations

Positive sentinel lymph node

Number of positive lymph nodes per total lymph node count

Invasive breast carcinoma

Nottingham prognostic index
Tumour size (cms) x 0.2 + Grade (1, 2, 3) + Lymph node status (1, 2, 3)

Three prognostic groups

Invasive breast carcinoma

Effect of NPI on survival
110 100 90 80 70 60 50 40 30 20 10 0 0.0 2.5 5.0 7.5

Percentage survival

NPI 3.4 NPI 3.4-5.4 NPI 5.4

Chemotherapy
10.0 12.5 15.0 17.5

Years

Invasive breast carcinoma

Predictive parameters
Oestrogen receptor

HER2

Immunohistochemistry Fluorescence In Situ Hybridisation

Immunohistochemistry

Molecular classification
Invasive breast carcinoma

Strong ER/PR positive Low proliferation rate Her2 negative Luminal B Weak ER / PR positive High proliferation rate May be Her2 positive HER2 ER & PR negative Her2 positive Triple negative ER, PR & HER2 negative

Luminal A

Gene expression signature predicts survival in breast cancer

295 patients with primary breast cancer Stage I or II < 53 years Lymph node status:

negative = 151; positive = 144

70 gene prognosis profile

Van de Vijver et al NEJM 2002

Gene expression signature predicts survival in breast cancer

Two groups

Good prognosis 115 patients (97% ER positive) Poor prognosis 180 patients

More powerful predictor of outcome than conventional histological criteria

Oncotype Dx test

Multigene expression test Genomic Health Stage 1 or 2 disease Hormone receptor positive [ER or PR] Lymph node negative Predicts response to chemotherapy and likelihood of tumour recurrence

Oncotype Dx test

TNM classification Tumour

T0: No evidence of primary tumor

Tis: Carcinoma in situ T1: Tumor 2.0 cm or less in greatest dimension T2: Tumor more than 2.0 cm but not more than 5.0 cm in greatest dimension T3: Tumor more than 5.0 cm in greatest dimension T4: Tumor of any size with direct extension to

(a) chest wall or (b) skin,

TNM classification Lymph Nodes

NX: Regional lymph nodes cannot be assessed N0: No regional lymph node metastasis N1: Metastasis to movable ipsilateral axillary lymph node(s) N2: Metastasis to ipsilateral axillary lymph node(s) fixed to each other or to other structures N3: Metastasis to ipsilateral internal mammary lymph node(s)

TNM classification Metastases

MX: Presence of distant metastasis cannot be assessed

M0: No distant metastasis M1: Distant metastasis present (includes metastasis to ipsilateral supraclavicular lymph nodes)

Tumour stage AJCC

Stage 0 Stage I Stage IIA Stage IIB Stage IIIA Stage IIIB Stage IV

Tis N0 M0 T1 N0 M0 T0 N1 M0: T1 N1 M0: T2 N0 M0 T2 N1 M0: T3 N0 M0 T0 N2 M0: T1 N2 M0: T2 N2 M0: T3 N1 M0: T3 N2 M0 T4 Any N M0: Any T N3 M0 Any T Any N M1