2 Diseases of The Breast

DISEASES OF THE
BREAST
Lecture Objectives
At the end of the lecture the student should be

able to:
1. Discuss the etiology/pathologic features of

different forms of benign non-neoplastic and
neoplastic breast disease.
2. List the benign breast diseases that increase a

patient’s risk of developing breast cancer and
classify these conditions by the degree of risk.
Lecture Objectives
At the end of the lecture the student should

be able to:
3. Outline other risk factors predisposing to breast

cancer & incidence/prevalence of breast cancer.
4. Classify breast cancer into histologic subtypes

and describe the pathologic features of each.
5. List the prognostic factors for breast cancer.

CLINICAL PRESENTATION
 Palpable lump
 Inflammatory mass
 Nipple discharge
 Non-palpable abnormality
METHODS OF DIAGNOSIS
 FNAC
 Incisional biopsy
 Excisional biopsy
 Image-guided
biopsy
Breast Disease Study
Clinical Findings
5%
15%
80%
Malignant Uncertain Benign

Major classes of breast disease
Normal breast Benign breast disease
Carcinoma in situ Invasive carcinoma

Normal breast
Lobule and duct Lobule

BENIGN BREAST
DISEASE
INFLAMMATION
 Acute Mastitis
 Most clinically important form of
mastitis
 Breast-feeding  cracks/fissures
in the nipples  bacterial infection
(esp. Staph. aureus)
INFLAMMATION
 Acute Mastitis
 Usually unilateral—acute
inflammation in the breast can
lead to abscess formation
 Treatment = surgical drainage

(often under general anesthesia)
and antibiotics
INFLAMMATION
 Mammary Duct Ectasia
 5th and 6th decades

 Affects mainly large ducts
 Periductal chronic inflammation
 destruction and dilation of
the ducts with fibrosis
 The underlying cause is unknown
INFLAMMATION
 Mammary Duct Ectasia

 Poorly defined periareolar mass; can be confused
clinically/radiologically with carcinoma
 Can also present as a thick, cheesy nipple discharge +/- mass
 Periductal fibrosis  skin retraction

INFLAMMATION
 Fat Necrosis
 Uncommon lesion; may be a history

of trauma, prior surgical
intervention or radiation therapy
 Characterized by a central focus of

necrotic fat cells with lipid-laden
macrophages and neutrophils
INFLAMMATION
 Fat Necrosis
  Chronic inflammation with lymphs and multinucleated giant
cells
 Major clinical significance is its possible confusion with

carcinoma (e.g. fibrosis  clinically palpable mass / Ca2+ seen
on mammography)
NON-PROLIFERATIVE
(“FIBROCYSTIC”) CHANGES
 Most common breast disorder
 Alterations present in most women

 No associated risk of progression
or cancer
 ? Due to hormonal imbalances

NON-PROLIFERATIVE
 Pathologic features:
 Cystic change
 Apocrine metaplasia
 Adenosis
 Fibrosis
Benign Breast disease:
Elements of fibrocystic disease
Cyst Ductal hyperplasia
Apocrine metaplasia Sclerosing adenosis

NON-PROLIFERATIVE
 Usually diagnosed 20 to 40 years
 Present as palpable lumps, nipple

discharge or mammographic
densities/calcifications
 Often multifocal and bilateral 

general “lumpiness”
PROLIFERATIVE DISEASE
WITHOUT ATYPIA
 Epithelial Hyperplasia
 ↑ number of layers of cells lining

ducts and acini
 Involved ducts and acini are
filled with overlapping,
proliferating cells
PROLIFERATIVE DISEASE
WITHOUT ATYPIA
 Sclerosing Adenosis
 Characterized by ↑ #acini +
stromal fibrosis within lobules
 Can be assoc with calcifications

which may be detected on
mammography
ATYPICAL HYPERPLASIA
 Epithelial hyperplasia characterized

atypical architectural and/or
cytologic features
 Can affect ducts—atypical ductal

hyperplasia, or lobules—atypical
lobular hyperplasia
ATYPICAL HYPERPLASIA
 Atypical features resemble but fall short of in-situ cancer
 No diagnostic clinical or radiologic features
 ↑ Incidence with ↑use of screening mammography and ↑

number of breast biopsies
BENIGN TUMORS
 Fibroadenoma
 Most common benign tumor
 Circumscribed lesion composed

of both proliferating glandular
and stromal elements
BENIGN TUMORS
Fibroadenoma
BENIGN TUMORS
 Fibroadenoma
 Patients usually present < 30 years
 Classic presentation is that of a firm,
mobile lump (“breast mouse”)
 Giant forms can occur, especially in

younger patients
BENIGN TUMOURS
 Fibroadenoma
 Can be associated with proliferative
changes in the adjacent breast tissue
 Approx. 20% of lesions are complex
fibroadenomas —characterized by
certain specific histologic features
BENIGN TUMORS
 Duct Papilloma
 Benign papillary epithelial tumor;

occurs mainly in large ducts
 Papillae are fibrovascular stalks lined

by layers of proliferating epithelial
and myoepithelial cells
 Most patients present with a serous or

bloody nipple discharge
RELATIVE RISK FOR
INVASIVE BREAST
CANCER FOR BENIGN
BREAST LESIONS
RISK FOR INVASIVE BREAST
CANCER
 No Increased Risk (NIR)
 Mastitis
 Fat necrosis
 Mammary duct ectasia
 Non-proliferative
(“fibrocystic”) disease
 Fibroadenoma (simple)
CANCER
 Slightly ↑ Risk (SIR)

= ↑ Risk 1.5-2 Times
 Moderate/florid hyperplasia
 Sclerosing adenosis
 Fibroadenoma (complex)
 Duct papilloma
CANCER
 Moderately ↑Risk (MIR)

= ↑Risk 4-5 Times
 Atypical ductal hyperplasia

 Atypical lobular hyperplasia
CARCINOMA OF
THE BREAST
EPIDEMIOLOGY
Commonest malignancy in women worldwide:
 Breast cancer 18%

 Cervical cancer 15%
 Colonic cancer 9%
 Stomach cancer 8%
RISK FACTORS
 Age
 Incidence of breast cancer ↑ses
with age
 Uncommon before age 25 years;

incidence ↑ses to the time of
menopause and then slows
RISK FACTORS
 Family History
 Approx 10% of breast cancer is due to
inherited genetic predisposition
 A woman whose mother or sister has
had breast cancer is at ↑relative risk 2

to 3 times compared to other women
RISK FACTORS
 Family History
 At least two genes that predispose to
breast cancer have been identified—
BRCA 1 and BRCA 2
 Mutations in these tumour-suppressor

genes also predispose affected women
to ovarian cancer
RISK FACTORS
 Benign Breast Disease

 Certain types of benign breast disease
 History of Other Cancer

 A history of cancer in the other breast
or a history of ovarian or endometrial
cancer
RISK FACTORS
 Hormonal Factors
 ↑ levels of estrogen ↑risk:
Early age at menarche

Late age at menopause
Nulliparity
Late age at first child-birth
Obesity
RISK FACTORS
 Environmental Factors
 High fat intake

 Excess alcohol consumption
 Ionizing radiation
ETIOLOGY
 The etiology of breast cancer in

most women is unknown
 Most likely due to a combination
of risk factors i.e. genetic,
hormonal and environmental
factors
HISTOLOGIC
CLASSIFICATION
Breast Cancer
 
Ductal Lobular
   
DCIS IDC LCIS ILC
(15%) (75%) (5%) (5%)
Ductal Carcinoma In-situ
 ↑sed incidence with ↑sed use of

mammographic screening and
early cancer detection
 50% screen-detected cancers
 Can also produce palpable mass

 Characterized by proliferating
malignant cells within ducts that do

not breach the basement membrane
comedo (central
 Different patterns e.g.
necrosis); cribiform (cells arranged

around “punched-out” spaces);
papillary and solid (cells fill spaces)

distribution of carcinoma in-situ
Ductal carcinoma Lobular carcinoma

Carcinoma in situ
Ductal carcinoma in situ. Lobular carcinoma in situ.

DCIS LCIS
 Different grades i.e. low, intermediate

and high grade—comedo DCIS is
classically high grade
 Often multifocal—malignant
population can spread widely through
the duct system
 Women with DCIS are at risk of:
 Recurrent DCIS following Rx
 Invasive cancer (rel. risk 8 to 10

times) especially in the same
breast
Lobular Carcinoma In-situ
 Relatively uncommon lesion
 Malignant proliferation of small,

uniform epithelial cells within
the lobules
 Also at marked ↑sed relative risk

for invasive cancer (8 to 10 times)
in either breast
Invasive Ductal Carcinoma
 Commonest form of breast cancer especially in poorer
populations
 ↑sing incidence of screen–detected

cancer in developed countries
(usually smaller; much better
prognosis)
 Clinical presentation:
 Hard, irregular palpable lump
 Peau d’orange (lymphatic obstruction

 thickening/dimpling of the skin)
 Paget’s disease of the nipple

(ulceration/inflammation due to
intraductal spread to the nipple)
 Clinical presentation:
 Tethering of the skin
 Retraction of the nipple
 Axillary mass (spread to regional

lymph nodes)
 Distant mets (lung, brain, bone)

 Different histologic types exist
 The most common is scirrhous

carcinoma (IDC of no special type)
 This type is characterized grossly by an

irregular, hard mass
 Histology shows infiltrating clusters of

malignant cells in a dense, fibrous stroma
 Special histologic types of IDC:
 Medullary carcinoma = circumscribed

tumour; sheets of malignant cells in
dense lymphoid stroma
 Tubular carcinoma = infiltrating

tubular structures on histology
 Special histologic types of IDC:
 Mucinous/colloid carcinoma =
malignant cells in pools of mucin
 Papillary carcinoma = papillary

formations like papilloma +
invasion
Invasive Lobular Carcinoma
 Much less common than IDC
 Can present with similar features
 More likely to be bilateral and/or

multicentric (multiple lesions
within the same breast)
Invasive Lobular Carcinoma
 Classic histology = small, uniform cells arranged as:
 Strands/columns within a fibrous stroma (“Indian-file”)
 Around uninvolved ducts ( “bull’s-eye” pattern)
 Metastasize more frequently to CSF, serosal surfaces and pelvic

organs
PROGNOSIS
 Stage
 Staging systems inc.TNM and the
Manchester classification
 Tumour size and axillary node status

are important parameters
 10-year survival rate for lymph node

neg disease is 80% vs 35% for tumours
with positive nodes
PROGNOSIS
 Tumour Grade
 Different grading systems exist
 ↑tumour grade = worse prognosis
 Histologic Subtypes
PROGNOSIS
 Hormone Receptors
 Estrogen receptors
 Progesterone receptors
 Molecular Markers
 Inc. c-erb-B2, c-myc and p53
TREATMENT OPTIONS
 Surgery
 Mastectomy
 Breast conservation
 +/- Axillary dissection
 Radiation therapy (local control)

 Chemotherapy (systemic control)
 Hormonal Rx (systemic control)
PHYLLODES TUMOUR
 Stromal tumour arising from the

intralobular stroma
 Range in size from a few cm to

massive lesions
 Classically have a “leaf-like”

configuration
PHYLLODES TUMOUR
 Most are low-grade lesions that can

recur locally but do not metastasize
 Others are of high-grade and exhibit

aggressive clinical behaviour e.g.
spread to distant sites (cystosarcoma
phyllodes)
THE MALE BREAST
 Gynecomastia
 Enlargement of the male breast due to

hormonal imbalance (rel.↑estrogens):
 Physiologic; seen at puberty or old age

 Pathologic; associated with cirrhosis,
functional testicular tumours, certain
drugs (alcohol, marijuana and anabolic
steroids)
Gynecomastia
THE MALE BREAST
 Gynecomastia
 Can be unilateral/bilateral; present as
diffuse enlargement /defined mass
 Most important clinically as a marker
of hyperestrinism
 Neoplasia needs to be excluded in
certain cases
THE MALE BREAST
 Carcinoma
 Very rare occurrence; female cancer
to male cancer ratio approx 100:1
 Pathology and behavior is similar to
cancers seen in women although with

less breast tissue, skin involvement is
more frequent
Histopathologic Report
The pathology report include:
 The definite diagnosis

 The local/regional extent of the disease
 Data relevant to prognosis
 Data relevant for the choice of treatment
The Pathology report, Carcinoma resection
MAIN DIAGNOSIS:
 Local resection (lumpectomy) of breast with invasive ductal carcinoma
OTHER FEATURES:
 TUMOR SIZE: 3 cm
 LOCATION: Upper inner quadrant, right breast
 TUMOR GRADE: 2
 RESECTION MARGINS, MINIMUM DISTANCE TO TUMOR: 4 mm from dorsal margin, 32 mm from
ventral margin
 TUMOR INVASION OF SKIN, MUSCLE, PAGET’S DISEASE OF THE NIPPLE: Absent.
 VASCULAR INVASION: Present
 DCIS: Present
DCIS GRADE: 3
DCIS MIN. DIST. TO RESECTION MARGIN:
1 mm to dorsal margin
 NO. OF LYMPH NODES EXAMINED: 13
 NO. OF LYMPH NODES WITH TUMOR: 5
 HORMONE RECEPTOR STATUS:
Positive for estrogen receptor
Negative for progesteron receptor
 Her-2 STATUS:
Negative (2+ by immunohistochemistry, negative by FISH)
 pTNM CLASSIFICATION: pT1N2Mx
 EXTRA-TUMORAL BREAST: Fibrocystic disease
MAIN DIAGNOSIS:
• Local resection (lumpectomy) of breast
with invasive ductal carcinoma
OTHER FEATURES:
• TUMOR SIZE: 3 cm
• LOCATION: Upper inner quadrant, right breast
• TUMOR GRADE: 2
• RESECTION MARGINS, MINIMUM DISTANCE TO TUMOR: 4 mm from dorsal margin, 32 mm from ventral margin
• TUMOR INVASION OF SKIN, MUSCLE, PAGET’S DISEASE OF THE NIPPLE: Absent.
• VASCULAR INVASION: Present
• DCIS: Present
DCIS GRADE: 3
• NO. OF LYMPH NODES EXAMINED: 13
• NO. OF LYMPH NODES WITH TUMOR: 5
• HORMONE RECEPTOR STATUS:
• Her-2 STATUS:
• pTNM CLASSIFICATION: pT1N2Mx
• EXTRA-TUMORAL BREAST: Fibrocystic disease
Types of Invasive Carcinoma
Ductal Ductal Lobular
Tubular Mucinous Medullary

Inflammatory carcinoma
• The diagnosis is based on clinical features:
Diffuse erythema, peau d’orange, tenderness,

induration, warmth, enlargement
• And carcinoma confirmed by biopsy:
In most cases an invasive ductal carcinoma

grade 3 with tumor in dermal lymphatics
MAIN DIAGNOSIS:
• Local resection (lumpectomy) of breast with invasive ductal carcinoma
OTHER FEATURES:
• TUMOR GRADE (1-3): 2

• RESECTION MARGINS, MINIMUM DISTANCE TO TUMOR: 4 mm from dorsal margin, 32 mm from
ventral margin
• DCIS: Present
DCIS GRADE: 3
• Her-2 STATUS:
Tumor Grading
Feature Score
Tubule formation 1-3
Nuclear atypia 1-3
Number of mitoses 1-3
Grade Sum of scores

Grade 1 3-5
Grade 2 6-7
Grade 3 8-9
Tumor Grades
Grade 1 Grade 3
MAIN DIAGNOSIS:
OTHER FEATURES:
• TUMOR GRADE: 2
• RESECTION MARGINS, MINIMUM DISTANCE

TO TUMOR: 4 mm from dorsal margin, 32
mm from ventral margin
• DCIS: Present
DCIS GRADE: 3
• Her-2 STATUS:
Orientation of the Specimen
Inking of resection margins
inked surface as seen in the microscopic slide
Examination of resection margin
Skin
Section 1 Inked
Section 2 margin
MAIN DIAGNOSIS:
OTHER FEATURES:
• TUMOR GRADE: 2
ventral margin

• DCIS: Present
DCIS GRADE: 3
• Her-2 STATUS:
Vascular Invasion
Tumor tissue
Lymph vessel
MAIN DIAGNOSIS:
OTHER FEATURES:
• TUMOR GRADE: 2
• RESECTION MARGINS, MINIMUM DISTANCE TO TUMOR: 4 mm from dorsal margin, 32 mm from ventral margin
• DCIS: Present
DCIS GRADE (1-3): 3
DCIS MINIMUM DISTANCE TO
RESECTION MARGIN:
• Her-2 STATUS:
MAIN DIAGNOSIS:
OTHER FEATURES:
• TUMOR GRADE: 2
• RESECTION MARGINS, MINIMUM DISTANCE TO TUMOR: 4 mm from dorsal margin, 32 mm from ventral
margin
• DCIS: Present
DCIS GRADE: 3

• Her-2 STATUS:
Axillary Lymph Nodes
Breast cancer
spreads through
lymphatic channels
to axillary lymph
nodes.
When axillary
content is
removed, all nodes
are searched and
embedded for
microscopy
Micrometastasis
Micrometastasis spotted in otherwise negative

sentinel node
Tumor deposits in lymph node
Size Designated pTNM

class
> 2 mm Metastasis pN1
≤ 2 mm; > 0.2 Micrometastasis pN1(mi)
mm
≤ 0.2 mm Isolated tumor pN0 (i+)
cells
MAIN DIAGNOSIS:
OTHER FEATURES:
• TUMOR GRADE: 2
margin
• DCIS: Present
DCIS GRADE: 3

• Her-2 STATUS:
Immunohistochemistry:
Estrogen receptor
Negative: No benefit from Positive: Will benefit from

hormone therapy hormone therapy
MAIN DIAGNOSIS:
OTHER FEATURES:
• TUMOR GRADE: 2
margin
• DCIS: Present
DCIS GRADE: 3
• Her-2 STATUS: Negative

Immunohistochemistry
Her-2
Her-2 positive. Will benefit from Herceptin therapy

MAIN DIAGNOSIS:
OTHER FEATURES:
• TUMOR GRADE: 2
margin
• DCIS: Present
DCIS GRADE: 3
• Her-2 STATUS:

MAIN DIAGNOSIS:
OTHER FEATURES:
• TUMOR GRADE: 2
ventral margin
• DCIS: Present
DCIS GRADE: 3
• Her-2 STATUS:

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DISEASES OF THE

At the end of the lecture the student should be

1. Discuss the etiology/pathologic features of

2. List the benign breast diseases that increase a

At the end of the lecture the student should

3. Outline other risk factors predisposing to breast

4. Classify breast cancer into histologic subtypes

5. List the prognostic factors for breast cancer.

Malignant Uncertain Benign

Normal breast Benign breast disease

Carcinoma in situ Invasive carcinoma

Lobule and duct Lobule

 Treatment = surgical drainage

 Mammary Duct Ectasia

 5th and 6th decades

 Mammary Duct Ectasia

 Can also present as a thick, cheesy nipple discharge +/- mass

 Periductal fibrosis  skin retraction

 Uncommon lesion; may be a history

 Characterized by a central focus of

 Major clinical significance is its possible confusion with

 Most common breast disorder

 Alterations present in most women

 ? Due to hormonal imbalances

Cyst Ductal hyperplasia

Apocrine metaplasia Sclerosing adenosis

 Usually diagnosed 20 to 40 years

 Present as palpable lumps, nipple

 Often multifocal and bilateral 

 ↑ number of layers of cells lining

 Can be assoc with calcifications

 Epithelial hyperplasia characterized

 Can affect ducts—atypical ductal

 Atypical features resemble but fall short of in-situ cancer

 No diagnostic clinical or radiologic features

 ↑ Incidence with ↑use of screening mammography and ↑

 Most common benign tumor

 Circumscribed lesion composed

 Classic presentation is that of a firm,

mobile lump (“breast mouse”)

 Giant forms can occur, especially in

changes in the adjacent breast tissue

 Approx. 20% of lesions are complex

 Benign papillary epithelial tumor;

 Papillae are fibrovascular stalks lined

 Most patients present with a serous or

 Slightly ↑ Risk (SIR)

 Moderately ↑Risk (MIR)

 Atypical ductal hyperplasia

Commonest malignancy in women worldwide:

 Breast cancer 18%

 Uncommon before age 25 years;

inherited genetic predisposition

 A woman whose mother or sister has

had breast cancer is at ↑relative risk 2

 Mutations in these tumour-suppressor

 Benign Breast Disease