is the second most common molecular

subtype of invasive breast cancer

Germline TP53 mutations (Li-Fraumeni

syndrome): positive for both ER and HER2

metastasize when small in size and early in

the course, often to viscera and brain

respond completely to antibodies that bind

and block HER2 activity, and such patients
now have an excellent prognosis
 basal-like triple negative carcinoma

approximately 15% of cancers

more common in young premenopausal women

as well as African American and Hispanic
women

majority of carcinomas arising in women with

BRCA1 mutations are of this type

Due to high proliferation and rapid growth, this

type of cancer is particularly likely to present as
a palpable mass in the interval between
mammographic screening

30% completely respond to chemotherapy and

cure may be possible in this chemosensitive
subgroup
 Mammography: calcifications without an associated density are generally < 1 cm in size
Absence of mammography: presents as a mass of at least 2 to 3 cm in size

Less
Theycommonly,
It can
most tumors
be present
imperceptible
commonly present asas deceptively
abeing
hard,comprised wellof
irregular circumscribed
scattered
radiodense
masses
mass composed
neoplastic of or
glands
associated withsheets of tumor
asingle tumor cells
desmoplastic cells with scant
infiltrating
stromal stromal
otherwise
reaction
reaction
unremarkable fibrofatty tissue
 Palpable mass.

Axillary lymph node metastases

Fixity to the chest wall / skin dimpling.

Nipple retraction

Lymphatics - involved - block the local

area of skin drainage
lymphedema, skin thickening.

Tethering of the skin to the breast by

Cooper ligaments peau d'orange.

Mammography Radiodense mass

 Features Well diff. Ca Mod. diff.Ca Poorly diff. Ca.
Tubule formation Prominent Less,solid Ragged nests/solid
clusters/single sheets of cells
infiltrating cells
Nuclei Small,round,monomorphic Greater nuclear Nuclei
pleomorphism enlarged,irregular.
Mitotic figures Rare Present Numerous
Proliferation rate - - High
Tumour necrosis - - Present
 Biallelic loss of expression of CDH1(E-
cadherin) -> Discohesive and often fail to
incite a desmoplastic response

Detection may be difficult because:

Lack of calcification hampers
mammographic detection
Tumor may be poorly defined on palpation
Tumor may be multifocal
 CLINICAL GROSS
palpable mass or a mammographic
Small foci are not visible
density with irregular borders
diffuse infiltrative pattern with
characterstic patterns of metastatic
minimal desmoplasia, difficult to
spread involving
palpate or detect by imaging
Peritoneum
retroperitoneum
Larger tumors appear as
leptomeninges (carcinomatous
indurated, ill-defined masses
meningitis)
gastrointestinal tract
ovaries and uterus
 HISTOLOGY

Morphology:

Histologic hallmark > dyscohesive

infiltrating tumor cells, often arranged in
single file or in loose clusters or sheets
(INDIAN FILE APPEARANCE)

Absent TUBULE Formation

Signet ring cells containing

intracytoplasmic mucin droplet are
common

Minimal or absent desmoplasia

 Mucinous CA usually are diploid, well to
moderately differentiated and ER positive
Occur in Older women
Median age: 71 yo
Grows slowly over a course of many years
ER PR positive, HER2 negative
 GROSS
Well-circumscribed tumor with pushing
margin and typical gelatinous, soft cut
surface
Soft because of mucin
Tumor is soft and rubbery with appearance
of pale gray blue gelatin
 HISTOLOGY

Small clusters of uniform epithelial cells with

mild nuclear atypia float in abundant lakes of
mucus

Delicate bands of fibrovascular connective tissue

are
often present within the mucus lakes.

The cell clusters floating in the mucus may be solid or

micropapillary, or form secondary lumens.

Nuclei is always LOW GRADE: 99% is always Grade 1,

rarely you can see Grade 2
 women in 40s
detected as small irregular mammographic
densities
uncommon, but constitute 10% of tumors
<1cm
a very well-differentiated infiltrating
carcinoma with an
excellent prognosis
 GROSS

Ill-defined firm to hard greyish-white tumor

usually 2 cm or less in diameter.
The tumor is often stellate, and the cut
surface is likely to react (becoming
depressed in relation to the surrounding
breast tissue).
The gross appearance is often similar to that
of a radial scar (complex sclerosing lesion)
 HISTOLOGY

Morphology: Well-formed tubules + nt,

myoepithelial cell layer, BM - nt
tumor cells in direct contact with the
stroma. Apocrine snouts -
typical.Calcifications - within the
lumens.

> 95% of all tubular carcinomas -

diploid, ER + ve,HER2/neu ve
 Infiltrating carcinoma with clear-cut papillary
configuration
No myoepithelial cells, present in a desmoplastic
stroma
Produces true papillae fronds of fibrovascular tissue
lined by tumor cells
Infiltrating papillary carcinomas with truly infiltrating
papillary configurations are extremely rare.
Represents 1% of all invasive CA together with invasive
micropapillary CA
Variable ER PR HER2 pattern but can NOT be triple
negative
 GROSS
Usually a well-circumscribed tumor.

It cannot be separated from invasive breast

carcinomas of no special type
 HISTOLOGY
Clear-cut invasive carcinoma showing exclusively or
predominantly a papillary configuration

Neoplastic cells with mild to moderate nuclear atypia

Papillary DCIS (DIN) present in more than 70% of

cases
 A rare but distinctive variant of infiltrating carcinoma composed of small clusters of
tumor cells closely resembling the micropapillary pattern of DIN (DCIS).
It can occur as pure or mixed type.
more likely to be ER (-) and HER2 (+)
over express HER2
Lymph node metastasis common, poor prognosis
shows a characteristic pattern of anchorage independent growth.
Cells are adherent to each other and express Ecadherin
 GROSS
Lobulated outline due
to expansive growth
pattern
 HISTOLOGY

Micropapillary carcinoma forms hollow balls of

cells that float within intercellular fluid, creating
structures that mimic the appearance of true papillae

Micropapillary structures (pseudopapillary structures

lacking a fibrovascular core) are present that closely
resemble the micropapillary pattern of DIN (DCIS)
 Most common in women in 6th decade of life
All are poorly differentiated
Has basal like gene expression profile.
Among CA arising from BRCA1, 13% are medullary type and up to 60% have a
subset of medullary features
67% of these tumors has hypermethylation of the BRCA1 promoter leading to
downregulation of BRCA1 Expression
noted that the presence of lymphocytic infitrates within the tumors is associated
with higher survival rates and a greater response to chemotherapy
 GROSS

A well circumscribed, occasionally encapsulated fleshy

tumor (soft consistency).

The color of the cut surface varies from tan to grayish

white with yellow zones of necrosis and red or brown
hemorrhagic foci.

solid, syncytium-like sheets of large cells with

pleomorphic nuclei, and prominent nucleoli, which
compose more than 75% of the tumor mass
 HISTOLOGY

Microscopic features (5 criteria)

1. A well-delineated tumor with pushing, expansile
margins (smooth, rounded contour)

2. Syncytial growth pattern of tumor cells (solid

clusters of tumor cells without recognized cell
borders), forming anastomosing cords and sheets

3. Diffuse lymphoplasmacytic infiltration of stroma

(the lymphocytic infiltration must involve at least 75%
of the periphery and be present diffusely in the
central portionsof the tumor).

4. Tumor cells with severe nuclear atypia and easily

recognizable mitotic figures. No significant
desmosplastic stromal change. (Grade 3 atypia)

5. No glandular (tubular) formation.

 Tumors swollen,
erythematous breast - caused by
extensive invasion and
obstruction of dermal
lymphatics by tumor cells.

Underlying carcinoma -
diffusely infiltrative - does not
form a discrete palpable mass
confusion with true
inflammatory conditions a
delay in diagnosis.

Many patients metastases at

diagnosis / recur rapidly.

Overall prognosis poor.

 increasing age
first-degree relatives with breast cancer
exposure to exogenous estrogens or ionizing
radiation,
Infertility
Obesity
prior benign breast disease
And residency in Western countries

3% to 8%: associated with Klinefelter syndrome

and decreased testicular function

60 years old: The typical age at diagnosis and 70

years.

4% to 14% attributed to germline BRCA2 mutations.

PROGRESSION CLINICAL PRESENTATION
usually present as a palpable subareolar
The carcinoma is situated close to the overlying
mass
skin and underlying thoracic wall, and even small
carcinomas can invade these structures and cause 2 to 3 cm in size
ulceration
With or without nipple discharge
Dissemination follows the same pattern as in women,
and axillary lymph node involvement is present in about Most cancers are treated locally with
half of cases at the time of diagnosis mastectomy and axillary node
dissection.
Distant metastases to the lungs, brain, bone, and liver
are common The same systemic treatment guidelines
are used for men and women, and
response rates are similar
 Outcome in breast CA
1. biologic features of the carcinoma (molecular or histologic type)
2. extent to which the cancer has spread (stage) at the time of
diagnosis
Prognosis determined by pathologic examination of primary
carcinoma & axillary lymph nodes.
 Major prognostic factors strongest predictors of death.
1) Invasive vs insitu CA.
2) Distant metastasis
3) Lymph node metastasis
4) Tumour size
5) Locally advanced ds.
6) Inflammatory CA.
 Histologic Gene
expression
Type & Grade profiling
INTRALOBULAR FIBROADENOMA
PHYLLODES TUMOUR
STROMA

LIPOMAS
ANGIOSARCOMAS
INTERLOBULAR PSEUDOANGIOMATOUS
STROMAL HYPERPLASIA
STROMA FIBROUS TUMOURS
MYOFIBROBLASTOMA
 MC benign tumor - 2 nd & 3 rd
decade.Multiple, bilateral.
Young women palpable mass. Older
women mammographic density /
calcifications.
Epithelium hormonally reponsive
increase in size during lactation
complicated by inflammation, infarction
mimics CA.
Stroma - densely hyalinized after menopause
-may calcify. Large lobulated (popcorn)
calcifications characteristic
mammographic appearance. GROSS: Spherical, sharply
circumscribed, rubbery, grayish
Small calcifications - clustered -require
white, freely movable nodules -
biopsy to exclude carcinoma. bulge above the surrounding
tissue and contain slitlike spaces.
< 1 cm large tumors.
 Stroma delicate,
cellular,myxoid-resembles
normal intralobular stroma.
Epithelium - surrounded
by stroma - compressed &
distorted by it.
Risk of malignancy
assoc. with Complex
fibroadenomas cysts >
0.3 cm. in size, sclerosing
adenosis, epithelial
calcifications, papillary
apocrine change.
 INTRACANALICULAR PERICANALICULAR

In pericanalicular histologic pattern, the glands maintain their round or

oval profiles. There is no prognostic or clinical significance attached to
the pericanalicular and intracanalicular patterns. Both may be seen within
the same lesion.
 Arise from intralobular stroma.

Any age, most 6th decade.

Majority palpable masses,

few found by mammography.

Cystosarcoma phyllodes
Misnomer.

MORPHOLOGY : Few cms. to

massive lesions involving the
entire breast Larger lesions
bulbous protrusions d/t the
presence of nodules of
proliferating stroma covered
by epithelium . Some tumors -
protrusions extend into a
cystic space.
 HPE: Greater cellularity,
mitotic rate, nuclear
pleomorphism, stromal
overgrowth, and infiltrative
borders.

Recur locally, rare

metastases.

Majority Low-grade
lesions
Rare High-grade lesions.

Phyllodes tumors - excised

with wide margins /
mastectomy to avoid local
recurrences.
 Composed of stromal cells without an accompanying epithelial component
Uncommon and hence considered brief

MYOFIBROBLASTOMA

Rare benign spindle cell tumor of

mammary stroma composed of
myofibroblasts
May derive from CD34+ vimentin+
fibroblasts of mammary stroma capable
of multidirectional differentiation
 Composed of stromal cells without an accompanying epithelial component
Uncommon and hence considered brief

LIPOMA
Often palpable but can also be detected
mammographically as fat containing lesion
Lipomas are usually solitary masses composed of
mature fat cells (adipocytes)
 Composed of stromal cells without an accompanying epithelial component
Uncommon and hence considered brief

FIBROMATOSIS

Clonal proliferation of fibroblasts and myofibroblasts

Irregular, infiltrating mass that can involve both skin
and muscle
Locally aggressive but doesnt metastasize