Pathology of Breast
Anatomy
Modified sweat glands.
Lobes and lobules of gland
in fat tissue stroma.
Ducts emerge from acini of glands
Smaller ducts join to form
lactiferous ducts
Lactiferous ducts merge just
beneath the nipple to form a
lactiferous sinus.
Then individually open on nipple
Anatomy
Lymph Nodes
Lymph node areas adjacent to
breast area
A pectoralis major muscle
B axillary lymph nodes: levels I
C axillary lymph nodes: levels II
D axillary lymph nodes: levels III
E supraclavicular lymph nodes
F internal mammary lymph
nodes
www.breastcancer.org
Structural Anatomy
Normal Breast Histology
Myoepithelial Cells (ipx)
Breast development
Growth begins at the
age of 10
Functional unit of the
breast is the terminal
duct lobular unit
Glandular tissue is
supported by fibrous
stroma
Most benign
conditions and almost
all cancer arise in the
terminal duct lobular
unit
Physiology
Cell Regulation:
Growth development and function under hormone control
Binding of hormone to specific cell receptors trigger effects
Estrogens:
important in development, growth and differentiation.
Normal and most malignant breast cells contain ER
receptors.
Representation of the findings in a series of women
seeking evaluation of apparent breast “lumps”.
Cancer
10%
Fibroadenoma
7%
Fibrocystic
Miscelaneous disease
benign 40%
13%
No disease
30%
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Benign Breast lesions
BENIGN BREAST DISEASES
1. Common benign breast lesions
Fibrocystic change
Non- proliferative fibrocystic change
Proliferative fibrocystic change
Sclerosing adenosis
2. Less common benign breast lesions
Juvenile mammary hypertrophy
Lactational mastitis & abscess
Gynecomastia ( male )
3. Benign breast tumors
Fibroadenoma
Intraductal papilloma
Phyllodes tumor
Fibrocystic Disease
Irregular palpable lumps – mimic ca.
10-50% women
? Hormonal
Periodic discomfort – pain.
Adenosis – hyperplasia - cysts – papillomatosis –
metaplasia – fibrosis.
Fibrocystic change of the breast :
(Fibrocystic disease )
cystic dilatation of terminal ducts
increase in fibrous stroma
variable proliferation of terminal ducts epithelium
Non-proliferative fibrocystic change:
multifocal fibrosis and/or cystic dilatation of terminal
ducts without epithelial hyperplasia
apocrine metaplasia of epithelium
Proliferative fibrocystic change:
Cysts and/or fibrosis with epithelial hyperplasia
fibrocystic change with atypical epithelial hyperplasia
( atypical hyperplasia )
Fibrocytic change
Fibrocystic change
Fibrocystic change
Fibrocystic change
Acute mastitis & Breast abscess
Usually in lactating women
Painful and erythematous
Usually staph and strep
Drainage and antibiotics indicated
Rarely, can aspirate and treat with
antibiotics
Mammary Duct ectasia
Abnormal progressive dilation of large
ducts.
Affects older women.
Firm breast lump mimicking carcinoma.
Blood stained nipple discharge.
Fat necrosis
Usually caused by trauma.
Necrosis with multinucleated giant cells.
May cause lump and calcification
mimicking carcinomas
Benign breast tumors
Fibroadenoma
Intraductal papilloma
Phyllodes tumor
FIBROADENOMA
The most common benign neoplasm of the
breast;
Most frequently in women between the ages
of 20 - 35 years;
Usually solitary ( rarely multiple tumors are
encountered ), firm, freely movable nodule 2
- 4 cm in diameter, sharply demarcated from
surrounding tissue;
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FIBROADENOMA
increased estrogen activity is though to play
a role in its development;
histologically : composed of both fibrous
connective tissue and glandular ( ductal )
elements;
fibroadenomas may enlarge rapidly during
pregnancy and cease after menopause;
Fibroadenom
a
Phylloides Tumor
Old name cystosarcoma phylloides
Mesenchymal tumor: leaf like masses, cellular
with necrosis and hemorrhage
May occur in adolescent (generally benign) or
premenopausal woman (may be malignant)
Treated with excision with margins
Phylloides Tumor
25% risk of local recurrence in 10 years
even with ‘benign” path
Mitotic figure count is the predictor of
malignancy
Metastasis even in “malignant” tumors are
rare
Younger: more likely benign, older women
more likely malignant
Phylloides tumor:
Malignant breast lesions
Breast Carcinoma
20% of all cancers in women
Commonest cause of death - 35-55y
In UK 1 in 10-12 chances
1 in 8 women in US
Less incidence in Asia
Majority of cancers arise in the ducts.
Very rare before age 25
CARCINOMA OF THE BREAST
Epidemiology.
Geographic influences - x5 more common in US than in Japan;
Genetic predisposition - well defined.
x5 increased risk with family history of breast cancer
( mother or sister with breast cancer );
Hormonal status - risk increases with early menarche and late
menopause;
Parity - more frequent in nulliparous than in multiparous women;
Age at first child - increased risk when over 30 at time of first
child;
CARCINOMA OF THE BREAST
. ( cont. )
Obesity - higher frequency in obese women.
Increased risk attributed to synthesis or accumulation
of estrogens in fat deposits;
Exogenous estrogens and progesterone -
( oral contraceptives and therapy of menopausal
symptoms ) still controversial;
Fibrocystic changes with atypical epithelial hyperplasia
- increased risk
Risk Factors
Gender
Age History abnormal
breast bx
Genetic (5-10%) History breast
Family history radiation
Personal history of Menstrual history
breast cancer Pregnancy history
HRT
Race
Alcohol
Obesity
Etiology of Breast Carcinoma:
Clinical Features:
Lump / lumps
Characters of lump*
Skin fixation / Skin retraction *
Discharge in many conditions.
Diagnosis:
Mammorgraphy
Ultrasound
Fine Needle Aspiration Biopsy
Core Biopsy
Excision Biopsy
Frozen section
Immunoperoxidase,
Molecular techniques – Gene detection.
CARCINOMA
may arise in the ductal epithelium - DUCTAL CARCINOMA
or within lobular epithelium - LOBULAR CARCINOMA
Both ductal and lobular cancers of the breast are divided into :
NONINFILTRATING ( noninvasive carcinoma or carcinoma
in situ ) - those that have not penetrated beyond basement
membrane of the duct ( ductal carcinoma in situ - DCIS ) or
lobular unit ( lobular carcinoma in situ - LCIS ) ;
and
INFILTRATING ( invasive carcinoma ) - those with
invasion beyond limiting basement membrane into
stroma;
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Intraductal carcinoma ( DCIS )
Invasive ductal ca –w / intraductal
component
Intraductal in-situ Carcinoma
Intraduct Carcinoma
Lobular Carcinoma
Intraduct Carcinoma-in-situ
Pagets Disease
Paget's Disease of Nipple
COMMON HISTOLOGIC TYPES OF
INVASIVE BREAST CARCINOMA
A. Common histologic types.
1. Invasive ductal carcinoma ( 85% )
2. Invasive lobular carcinoma ( 10% )
COMMON HISTOLOGIC TYPES OF
INVASIVE BREAST CARCINOMA (cont.)
B. Less common histologic variants of invasive breast
carcinoma with a better prognosis than regular ductal
carcinoma:
1. Medullary carcinoma
2. Tubular carcinoma
3. Mucinous ( colloid ) carcinoma
4. Secretory carcinoma
5. Adenoid cystic carcinoma
with a worse prognosis than regular ductal carcinoma:
1. Inflammatory carcinoma
C. Unusual presentations
1. Paget’s disease
2. Anaplastic types
Infiltrative ductal carcinoma
The most common type of breast cancer;
Grossly, firm, grayish-white infiltrating mass with irregular
margins;
Fibrosis may be extensive ( desmoplasia ), producing
a hard (scirrhous ) type of cancer;
Microscopically, highly pleomorphic ductal epithelial cells
infiltrate the fibrous stroma.
Lymphatic invasion is common.
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Comedocarcinoma
Infiltrating ductal
Invasive lobular carcinoma
Approximately 10% of all infiltrating breast carcinoma
Differentiated from infiltrating ductal carcinoma by histologic
features only
a different histologic pattern of infiltration :
1. a tendency to form single rows of cells ( “Indian filing” )
and
2. concentric arrangement of cells around ducts ( targetoid
appearance )
More frequently bilateral than infiltrating ductal carcinoma
Prognosis similar to that of infiltrating ductal carcinoma
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Invasive lobular ca
Invasive lobular ca
Invasive lobular ca
Breast
Medullary carcinoma
Medullary ca w/lymphocytic infiltrate
Breast
Colloid carcinoma
Colloid ca
Adenocarcinoma, well differentiated
Adenocarcinoma, moderately
differentiated
Breast - adenocarcinoma, poorly
Breast Carcinoma
Breast Carcinoma
Breast Carcinoma - Schirrous
Infiltrating Duct Carcinoma: small hard
Medullary Carcinoma: Large soft
Spread of Breast
Carcinoma:
Lymphatic spread – Peu-de Orange..
PATHOLOGIC PARAMETERS USEFUL
IN PREDICTING INVASIVE BREAST CANCER
PROGNOSIS W.B.J. 10/06
PATHOLOGIC PARAMETERS USEFUL IN PREDICTING
INVASIVE BREAST CANCER PROGNOSIS
I. HISTOLOGIC TYPE OF TUMOR
II. HISTOLOGIC GRADE OF TUMOR
1. degree of gland formation
2. nuclear atypia
3. mitotic rate
III. TUMOR SIZE
PATHOLOGIC PARAMETERS USEFULIN PREDICTING
INVASIVE BREAST CANCER PROGNOSIS
IV. AXILLARY LYMPH NODE STATUS
V. THE CLINICOPATHOLOGIC STAGE
Staging of breast carcinoma is based on defined criteria
relating to:
- the primary tumor ( T )
- lymph nodes (N) and
- distant metastases ( M )
Staging is the most important predictor of prognosis.
CLINICOPATHOLOGIC STAGING
OF BREAST CANCER
( as defined by American Joint Committeeon Cancer Staging )
Stage O ( Tis ) - In situ cancer
Stage I. - Tumor 2 cm or less in greatest diameter and without
evidence of regional or distant spread;
Stage II. - Tumor more than 2 cm but not more than 5 cm
in greatest dimension, but without distant spread;
Stage III (A) - Tumor of up to and more than 5cm in diameter
with or without homolateral regional (local) spread
that may or may not be fixed, but without distant spread;
Stage III (B) - Tumor up 5cm or >5cm with homolateral metastatic
supraclavicular and infraclavicular nodes
Stage IV. - Tumor of any size with or without regional spread
but with evidence of distant metastases.
W.B.J. 10/06
PATHOLOGIC PARAMETERS USEFUL IN
PREDICTING INVASIVE
BREAST CANCER PROGNOSIS
VI. THE ESTROGEN AND PROGESTERONE RECEPTORS.
- Women with cancers which express high levels of estrogen
and progesterone receptors have a better prognosis
than those with intermediate levels or no receptors.
PATHOLOGIC PARAMETERS USEFUL IN PREDICTING
INVASIVE BREAST CANCER PROGNOSIS
VII. ONCOGENE AMPLIFICATION AND EXPRESSION.
- It has been reported that amplification of HER-2 ( c-erb-2
or NEU ) proto-oncogene correlates with tumor recurrence
and a shorter survival of patients.
- Amplification of other proto-oncogenes, such as c-myc,
Ha-ras, or int-2 oncogene, and
- deletions of tumor suppressor genes, such as Rb, NM23
and p53, have been also found. The clinical utility of these
findings is still unproven.
W.B.J. 10/06
PATHOLOGIC PARAMETERS USEFUL IN PREDICTING
INVASIVE BREAST CANCER PROGNOSIS
VIII. THE PROLIFERATIVE ACTIVITY AND DNA PLOIDY.
- High proliferative activity which can be measured as:
1. mitotic index;
2. S-phase fraction of the cell cycle estimated by flow
cytometry; or
3. expression of proliferation antigens (PCNA or Ki67)
is associated with poorer prognosis.
- Presence of aneuploid DNA content of cancer cells,
as measured by flow cytometry, has also been associated
with poorer prognosis.
W.B.J. 10/06
Estrogen receptor (ER) in nuclei
Immunoperoxidase Positivity
Neg 1+
2+ 3+
Breast Cancer Staging SuperSimplified
T1a 0.1-0.5, T1b 0.6-1.0, T1c 1.1-2.0
T2 2.1-5cm
T3 >5 cm
T4 skin or CW involvement
N1 ipsilat axillary nodes mobile
N2 ipsilateral matted, fixed axillary nodes
N3 ipsilateral infraclav/Supraclav, IM
nodes
DISEASES OF THE MALE BREAST
Pathologic lesions of the rudimentary male breast are relatively
uncommon. Only two disorders occur with sufficient frequency to
merit consideration.
I. GYNECOMASTIA - an uncommon benign condition
characterized by proliferation of the ducts and stroma
of the male breast. Most cases are idiopathic, but in few
cases a cause may be identified:
1. testicular atrophy or destruction;
2. estrogen-secreting tumors of the testis
3. cirrhosis of the liver
4. increased prolactin levels, as in diseases of the hypothalamo-
pituitary axis
5. increased gonadotropin levels as in choriocarcinoma of the
testis
6. certain drugs, most commonly digoxin.
Male breast; gynaecomatsia
Gynecomastia
Male Breast carcinoma
is extremely rare.
histologically identical to infiltrating ductal carcinoma
of the female.
diagnosis of male breast carcinoma is usually delayed
50% of patients have axillary lymph node metastases
at the time of diagnosis,
as a results, male breast cancer has a worse overall
prognosis.
W.B.J. 10/06
Male breast carcinoma