Breast pathology

Breast cancer
 Malignant tumors of the
breast
Primary:
 Epithelial: breast carcinoma
 Mesenchymal: sarcomas
Secondary

Breast cancer
Breast carcinoma

Breast cancer
 :Epidemiology
It is a disease of developed countries.
It is a very common neoplasm constituting 20%
of cancer death in females. One third of breast
cancer patients die due to the disease.
It is the second most important cancer killer for
females in the USA.
One in every 9 females develops breast
carcinoma in her lifetime.

Breast cancer
Increased incidence of early breast cancer
detection due to mammographic screening ,
leading to detection of small early (and even
non-invasive) breast cancer
Breast cancer
Increased detection of early pre-invasive breast cancer is
balanced by increased incidence of invasive breast cancer.
So mortality is slightly decreased

Breast cancer
 :)Epidemiology )Gharbiah
Breast cancer constituted 37% of cancer in women
in our locality (Al-Gharbiah) in 1999, forming the
most common cancer among females.
After age standardization, breast cancer formed
about 50 per 100,000 per year in Al-Gharbiah
females
The second most common cancer was non-
Hodgkin’s lymphoma forming (8%) of all female
cancers

Breast cancer
 Risk factors
Gender : Females are at higher risk than males.
Race: More common in Caucasian and Jews.
Age: 30-60 years. however, younger and older
ages could be affected.
Family history: There is family history
especially in mothers and sisters (first degree
relative, earlier and of the same pathology).
However, 85% of females with family history of
breast cancer does not develop breast cancer

Past history: Females with previous breast

cancer are at increased risk of developing new
breast cancer Breast cancer
 Risk factors
Menstruation: Early menarche and late
menopause. [increased estrogen exposure]
Pregnancy & lactation: Nulliparous females,
delayed first pregnancy and absence of breast
feeding are important risk factors.[increased
unopposed estrogen exposure]
High fat diet and obesity: Due to local
synthesis of oestrogen. Risk may be decreased
by beta carotene intake

Breast cancer
 Risk factors -Genetic factors
Strong family oncogene (HER2/Neu) is present in
some cases.
25% of familial breast cancer is attributed to
BRCA1 & BRCA2 germline mutations.
Other cases of breast cancer is related to Li-
Fraumini syndrome (germline TP53 mutation) and
cawden syndrome (Germline PTEN mutation).
However, all these mutations accounts for only
30% of familial breast cancer, leaving about two
thirds unexplained.
Breast cancer
 Risk factors
Hormones:
1- Oestrogen exposure (as in late
menopause and in replacement therapy).
2- Prolactin excess (weak evidence).
Viruses:
Bittner milk factor (virus) is incriminated in
the development of breast carcinoma in
mice.
Breast cancer
 :Precancerous lesions

Proliferative changes (especially atypical

hyperplasia) : High risk in patient with
fibrocystic disease particularly those with
marked epitheliosis
Duct papilloma

Breast cancer
Breast cancer
Breast cancer
 Ductography :
injection of contrast
material into one
lactiferous duct,
indicating the complex
branching of a single
lactiferous duct, and
showing a single
breast lobe (or
(segment

Breast cancer
 Classification of breast carcinoma

I- Carcinoma of
ductal origin
II- Carcinoma
of lobular
origin

Each can be
invasive and
non-invasive
Breast cancer
Breast cancer
 I- Carcinoma of ductal origin:
positive for E-Cadherin

1- Ductal carcinoma in situ )DCIS)=Intraduct

carcinoma

2-Infiltrating ductal carcinoma:

a) With prominent intraductal component :
1-Infiltrating papillary carcinoma
2-Infiltrating comedo carcinoma.
3-Infiltrating cribriform carcinoma.
b) Without intraductal foci = Infiltrating Ductal Carcinoma-
Not other wise specified (IDC-NOS) or Infiltrating Duct
Carcinoma of No Special Type (IDC-NST)
Breast cancer
 :c) Special types of IDC
1- Medullary carcinoma
2- Colloid carcinoma.
3- Paget's disease of the nipple
4- Adenoid cystic carcinoma.
5- Tubular carcinoma
6- juvenile (secretory carcinoma).
7- Apocrine carcinoma
8- Carcinoma with neuroendocrine
differentiation.
Breast cancer
 II-CARCINOMA OF LOBULAR ORIGIN:
Negative for E-Cadherin

1-Lobular carcinoma in situ )LCIS)

2- Infiltrating lobular carcinoma

Breast cancer
 Ductal carcinoma in situ )DCIS)
= Intraduct carcinoma
It is non-invasive (early) carcinoma (intact basement
membrane)
Recently increased in incidence [from 5% to 30%
of breast cancer] (i.e. detecteion) by
mammography (microcalcification)
Gross picture:
Most commonly detected as mammographic
calcification, less commonly as area of increased
density (periductal fibrosis).
It may form a palpable small hard mass and may
cause bleeding or serous discharge from the nipple.
Squeezing of the mass yields necrotic pasty-like
material in cases of comedo type
Breast cancer
 Ductal carcinoma in situ )DCIS)
= Intraduct carcinoma
Microscopic picture:

within a single ductal system,

spreading within the duct ,
and when this is extensive , it may involve
an entire segment

Breast cancer
 DCIS- :Microscopic picture

The ducts are enlarged and lined by several

layers of malignant cells without invasion
of the basement membrane.
The pattern of growth of the malignant cells
may be cribriform, papillary,
micropapillary, solid or comedo
Recently, it is comedocarcinoma and non-
comedo DCIS

Breast cancer
The classic cribriform pattern
of intraductal carcinoma of the
breast. they have holes with
sharp margins as though
punched out by a cookie cutter.
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Neoplastic cells are still within the ductules and have not
broken through into the stroma. Note that the two large
lobules in the center contain microcalcifications. Such
microcalcifications can appear on mammography
Breast cancer
Breast cancer
Breast cancer
This mammogram
reveals multiple
clusters of small,
irregular
calcifications in a
segmental
distribution.
Suspicious
calcifications must
be biopsied, as 20%
to 30% will prove
to be due to DCIS.

Breast cancer
 DCIS-:Prognosis
Rarely becomes invasive if not
treated.
The consensus seems to be that many cases
of small, low-grade DCIS, and probably
most cases of high-grade and extensive
DCIS, progress to invasive carcinoma,
emphasizing the importance of proper
diagnosis and appropriate therapy for this
condition
Breast cancer
 PAGET'S DISEASE OF THE
NIPPLE
Malignant cells, referred to as Paget cells,
extend from DCIS within the ductal system
(especially the lactiferous sinuses) into
nipple skin without crossing the basement
membrane .
The tumor cells disrupt the normal epithelial
barrier, and this allows extracellular fluid to
seep out onto the nipple surface.
The Paget’s cells are easily detected by
nipple biopsy or cytologic preparations of the
exudate.
Breast cancer
 PAGET'S DISEASE OF THE
NIPPLE
Gross picture:
- Nipple eczema or ulceration.
- Excoriation of the areola.
-There may or may not be a palpable mass.

Microscopic picture:
- The basal layer of epidermis is infiltrated by large malignant
cells with clear cytoplasm and large hyperchromatic nuclei
(Paget's cells).
- There is an underlying carcinoma which may be intraduct
or invasive carcinoma.

Breast cancer
Breast cancer
Breast cancer
Breast cancer
 INFILTRATING DUCTAL CARCINOMA
)NOT OTHERWISE SPECIFIED )IDC-NOS

It is the most common type of breast carcinoma (80%)

Infiltrating Duct Carcinoma of No Special Type (IDC-NST)

Skin manifestations:
The skin covering of the tumour may simulate the peel of an
orange “peau d’orange” [lymphatic edema].
There may be also nipple retraction and sometimes ulceration.
Dimpling
Tethering
Cancer en cuirase
Skin nodules

Breast cancer
This mastectomy specimen demonstrates the gross findings of "inflammatory"
carcinoma of breast. This is not a specific histologic type of breast cancer, but
rather it implies dermal lymphatic invasion by some type of underlying breast
carcinoma. Such involvement of dermal lymphatics gives the grossly thickened,
erythematous, and rough skin surface with the appearance of an orange peel
.(("peau d'orange" for you francophiles
Breast cancer
 :Gross picture

The tumour is non-capsulated, hard in

consistency, irregular and spiky.
Colour: grayish white
Site: commonly in the upper outer quadrant
of the breast.
The cut surface is chalky and concave.
The tumour gives a gritty sensation during
cutting due to excessive fibrous stroma.

Breast cancer
Breast cancer
Breast cancer
 :Microscopic picture

The tumour is composed of diffuse sheets, well-

defined nests, and cords of somewhat cohesive
malignant cells separated by dense stromal fibrosis
(desmoplastic reaction)

Breast cancer
Breast cancer
Breast cancer
 MEDULLARY )ENCEPHALOID)
CARCINOMA

It is a soft carcinoma less common than

scirrhous carcinoma.
Gross picture: The tumour forms a soft,
fleshy well-circumscribed, large mass. Cut
surface usually bulges and is grayish, red or
yellow with areas of haemorrhage and
necrosis. Skin ulceration may occur.

Breast cancer
 MEDULLARY )ENCEPHALOID) CARCINOMA
Microscopic picture

cells are large, pleomorphic with large

nuclei, prominent nucleoli and numerous
mitoses.
with syncytial or sheet-like appearance.
scanty stroma intensely infiltrated by
lymphocytes.
better prognosis than the scirrhous type.

Breast cancer
MEDULLARY )ENCEPHALOID) CARCINOMA

Breast cancer
COLLOID )MUCINOUS)
CARCINOMA

Breast cancer
This variant of breast cancer is known as colloid, or mucinous, carcinoma. This
variant tends to occur in older women and is slower growing, and if it is the
predominant histologic pattern present, then the prognosis is better than for non-

.mucinous, invasive carcinomas

Breast cancer
Lobular Neoplasia
E-Cadherin Negative

Breast cancer
 LOBULAR CARCINOMAIN SITU
))LCIS
It is composed of (loosely cohesive) neoplastic
lobular cell proliferations that fill one or more lobules
but the basement membrane is intact.
It tends to be mutlifocal , bilateral and usually forms a
palpable mass. [it is usually an incidental finding-no
masses, no calcifications, no stromal reactions]
If present, the risk of invasive carcinoma increases, the
associated invasive carcinoma may be lobular or
ductal.
The management of LCIS is controversial ranging
from follow up to bilateral mastectomy.
Breast cancer
Breast cancer
 INFILTRATING LOBULAR CARCINOMA

It constitutes 10% of infiltrating breast

carcinomas.
It is more frequently bilateral (25%) and
multicentric.
It is more estrogen receptor positive than IDC.
Matched by grade and stage, Its prognosis is
similar to IDC.
loss of a region on chromosome 16 (16q22.1) that includes a cluster of at least eight genes
responsible for cell adhesion.

Breast cancer
 INFILTRATING LOBULAR CARCINOMA

Gross picture:
The tumour forms a poorly circumscribed rubbery to
hard mass, may be diffuse.

Microscopic picture:
The tumour cells are small to medium-sized regular,
and uniform with little cytological abnormalities.
They grow singly in the form of linear cords
(Indian File Pattern) within a dense fibrous
stroma. It may give targetoid appearence

Breast cancer
Breast cancer
 INFILTRATING LOBULAR CARCINOMA
pattern of metastasis
Metastases to
 the peritoneum and retroperitoneum,
 the leptomeninges (carcinomatous meningitis),
 the gastrointestinal tract, and
 the ovaries and uterus.
These carcinomas are less likely to
metastasize to the lungs and pleura.

Breast cancer
 Spread of breast cancer
1) Direct spread: To the overlying skin and chest wall
2) Lymphatic spread: Two methods
a- lymphatic emboli:
The outer part: To the axillary lymph nodes, which may extend to
supraclavicular lymph nodes
The inner part: To the internal mammary lymph nodes, then to the
contralateral axilla.
The lower part to the peritonium, falciform ligamnt, porta hepatis
and umbilicus (sister Joseph nodule of mayo
clinic)
b- lymphatic permeation: It leads to lymphoedema -Skin
nodularity
-Cancer en cuirasse
-Peau d’orange.
3) Blood spread: To the lung, liver, bone, adrenals and ovaries
Breast cancer
 )Staging of breast cancer )TNM staging

Tumour )T) Lymph node )N) Metastases )M)

Tis: )carcinoma in N0: No lymph node metastases M0: No distant metastases

situ )

T1: Tumour 2 cm N1: Metastases to movable ipsilateral M1:Distant metastases

or less axillary nodes

T2: Tumour 2-5 N2: Metastases to fixed ipsilateral

cm axillary nodes

T3: Tumour more N3: Metastases to ipsilateral

than 5 cm supraclavicular or infraclavicular
lymph nodes or metastases to internal
mammary nodes in the presence of
axillary nodes.
T4: Tumour of any
size with invasion of
skin or chest wall.

Breast cancer
 Clinical staging
0 Tis N0 M0

I T1 No M0

II A T1 N1 M0
T2 N0 M0

II B T2 N1 M0
T3 N0 M0

III A T1 N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0

III B T4 Any N M0
Any T N3 M0

IV Any T Any N M1
Breast cancer
 Prognostic factors in breast cancer

1- Tumour size
2- Lymph node status and number
3) Histologic grade
4) Histological type
(1) Non (2) uncommonly (3) commonly
metastasizing metastasizing metastasizing
- Carcinoma in situ 1) colloid - IDC-NOS
2) Medullary - ILC
3) Papillary
4) Tubular
5) Adenoid cystic
Breast cancer
5) Estrogen and progesterone receptor status
6) Lymphovascular space invasion
7) Proliferation rate by flow cytometry
8) Presence of activated oncogenes e.g.
HER2/Neu, but herceptin changed this view
9) Clinicopathologic stage
10)Ploidy [i.e. DNA contents]

Breast cancer
 Sentinel lymph node
First in cutaneous melanoma, then in the breast,
then in many other cancer
Applied to avoid removal of lymph nodes which
may lead to lymphatic edema and aggressive
angiosarcoma
Injecting a dye or a radioactive substence around
the tumor before the operation, and following it
during the operation to the first node.
This node (the sentinel node)is examined
immediately by frozen sections and if involved,
axillary dissection is cariied out, if not, leave the
axilla alone
Breast cancer
 CAUSES OF BREAST MASS

Inflammatory: Chronic abscess, duct ectasia

and tuberculous mastitis.
Hyperplastic: Fibrocystic disease and
sclerosing adenosis.
Traumatic: Traumatic fat necrosis and
haematoma.
Neoplastic: Different benign and malignant
tumours of the breast.
Breast cancer
 DISEASES OF MALE BREAST
Gynaecomastia: It means enlargement of
male breast which may be unilateral or bilateral,
due to:
a) Oestrogen excess as in liver cirrhosis and fibrosis
due to failure of detoxification of oestrogen, oestrogen
forming tumours e.g. sertoli cell tumour of the testis,
or oestrogen therapy for carcinoma of the prostate.
b) Drugs such as digitalis for a long time.
c) Idiopathic.

Breast cancer
 :Carcinoma of male breast

It is a rare tumour with bad prognosis due to early

invasion if the chest wall
It is stated that 1% of breast cancer occurs in males
However, this disease is common in our locality ,
with prevalence of the atypical proliferative
lesion in cases of gynecomastia (personal
observation, not yet documented)

Breast cancer
 Important subjects

Causes of breast mass

Fibrocystic disease of breast
Benign tumors of the breast
Risk factors of cancer breast
Medullary carcinoma of the breast
Paget’s disease of the breast
Prognostic factors in cancer breast

Breast cancer
Thank
you

Breast cancer