Breast Pathology

Dennis Jose S. Carbonell, RMT, MD, DPSP

Anatomic and Clinical Pathologist
Assistant Professor I
 Outline
1. Review normal breast histology
2. Inflammatory and related lesions
3. Benign epithelial lesions
4. Breast carcinoma
5. Histologic types
6. Immunohistochemistry
7. Prognosis and predictive factors
8. Stromal tumors
Review:
BREAST HISTOLOGY
Breast
 Normal Histology

DUCT

ACINI
Breast:
INFLAMMATORY AND RELATED
LESIONS
 Mammary Duct Ectasia
• Ectasia: dilation or distension
of a tubular structure, usually
pathophysiologic

• Seen mostly in perimenopausal

parous women

• Represents a localized
response to different
components of stagnant
colostrum (stale milk mastitis)
 Mammary Duct Ectasia

• Palpable periareolar mass with

thick and cheesy nipple
secretion

• May produce retraction or

inversion of the nipple
simulating invasive carcinoma

• Recurrent abscess/fistula
draining pus
 Mammary Duct
Ectasia
• Dilated ducts containing thick
dark material

• Duct obstruction and fatty

contents (granular material)
• Foamy macrophages in the lumen
• Thinning of lining epithelium
• Periductal inflammation
• Fibrosis and scarring results in
nipple inversion in 30% of cases
simulating carcinoma
 Fat Necrosis
• History of trauma 1-2 weeks
before diagnosis

• Involves superficial
subcutaneous tissue rather
than breast parenchyma itself

• Presents with painless mass

with skin retraction simulating
carcinoma
 Fat Necrosis
• Disruption of fat

• Lipid-laden
macrophages (foamy
macrophages)

• Chronic inflammation

• Foreign-body giant
cell reaction
Fat Necrosis
 Abscess
Formation
• Rupture of mammary ducts
(during lactation)
• Located deep in the
parenchyma or in the
periareolar region
• Central cavity filled with
neutrophils, eventually fibrosis
and obliteration of the lobular
pattern

• Zuska disease – periareolar

abscess associated with
squamous metaplasia of the
lactiferous ducts; associated
with smoking
Breast:
BENIGN EPITHELIAL LESIONS
 Benign Epithelial Lesions

• Classified into 3 groups according to the subsequent risk

of developing breast cancer:

1. Non-proliferative breast changes

2. Proliferative breast disease without atypia
3. Proliferative breast disease with atypia
NON-PROLIFERATIVE BREAST
CHANGES
 Fibrocystic Changes
• “Non-proliferative” – not
associated with an increased
risk of cancer

• Ages of 25 and 45 years

• Most often bilateral, one

breast may be much more
affected

• Primarily affects the TDLU

Fibrocystic Changes
 Basic Morphologic Changes (FCC)
1. Cysts 4. Calcification
• Cloudy or clear yellow fluid • Less common than in duct ectasia
• Bluish cast from outside (blue- and carcinoma
dome cysts) • Ca oxalate or Ca phosphate
• Flattened eipithelium • Coarse and highly irregular
• May rupture - inflammation 5. Chronic inflammation
2. Apocrine metaplasia • Rupture of cyst
• Abundant granular, eosinophilic • Release of secretion to the stroma
cytoplasm • Lymphocytes, plasma cells,
• Round nuclei, prominent nucleoli histiocytes
• Yellow-brown pigment 6. Epithelial hyperplasia
• Resembles apocrine sweat glands • Most important
• Apical snouts • Most troublesome component
3. Fibrosis 7. Adenosis
• After cyst rupture • Increase in the number of acini
• Chronic inflammation per lobule
 Lactating Adenoma
• Localized focus of hyperplasia in the lactating breast

• Not neoplastic

• Exaggerated local response to gestational hormones

• Solitary or multiple
 Lactating Adenoma
Gross appearance

• Well-circumscribed and
lobulated

• Cut surface is gray or tan

or yellowish

• Necrotic changes are

frequent

• Marked vascularization
 Lactating Adenoma
Microscopic feature

• Proliferating
glands are lined
by actively
secreting
cuboidal cells
PROLIFERATIVE BREAST DISEASE
WITHOUT ATYPIA
 Proliferative Breast Disease Without
Atypia
• Associated with a small 1. Epithelial hyperplasia (ductal
increase in the risk of and lobular)
subsequent carcinoma in either 2. Sclerosing adenosis
breast 3. Complex sclerosing lesion
4. Papilloma
• Commonly detected as
mammographic densities,
calcifications, or incidental
findings in biopsies performed
for other reasons
 Epithelial
Hyperplasia

• Increased numbers of both

epithelial and myoepithelial
cell

• Irregular lumens or
fenestration at the periphery
of the cellular masses

• Usually an incidental finding

 Epithelial Hyperplasia

(Microscopic Features)

1. Nuclei – oval, 6. Presence of peripheral

normochromatic, and with a elongated clefts
slight overlap; small, single, 7. Presence of irregularly shaped
indistinct nucleoli; scanty or ridges from opposite walls
no mitotic activity 8. Apocrine metaplasia
2. Cytoplasm – eosinophilic and 9. Presence of foamy
finely granular macrophages
3. Indistinct borders (syncytial) 10. Frequent intaluminal or
4. Streaming effect – oval cells stromal calcifications
arranged in parallel bundles 11. Absence of necrosis
5. “Tufts” and “mounds”
projecting into the lumen
Epithelial Hyperplasia
 Sclerosing Adenosis

• Increased number of acini

that are compressed and
distorted in the central
portion

• Stromal fibrosis creates the

appearance of solid cords of
cells within a dense stroma
(mimics invasive carcinoma)
 Sclerosing Adenosis
• Adenosis with a high likelihood of being misdiagnosed as CA

• Gross: small, multinodular configuration; cuts with increase

resistance; overall gross appearance similar to invasive carcinoma
• Microscopic:
– Round or oval lobular architecture
– More cellular centrally than peripherally
– Elongated and compressed proliferating tubules lined by two cells type
– Pleomorphism and necrosis are absent
– Stroma is dense

• Myoepithelial cells can be demonstrated using

immunohistochemical stains (smooth muscle actin, calponin, p63)
and the presence of basement membrane around the tubules with
stains for laminin and type IV collagen
Sclerosing Adenosis
 Complex Sclerosing Lesion
• Components: sclerosing
adenosis, papillomas,
epithelial hyperplasia

• Radial sclerosing lesion /

“radial scar” – irregular
shape; mimics CA
mammographically, grossly,
and histologically
(conventional or tubular type)
 Radial Sclerosing Lesion / Radial Scar
• Central nidus of entrapped
glands in a hyalinized stroma
surrounded by long radiating
projections
Radial Sclerosing Lesion / Radial Scar
 Radial Sclerosing Lesion / Radial Scar
• A large-scale study has concluded that women with radial scar have
a risk for breast cancer that is almost twice that of women without
scars, regardless of the histologic type of benign breast disease

• The accepted treatment of mammographically detected radial scar

is conservative excision and follow-up
 Intraductal Papilloma
• Small palpable masses,
subareolar location, nipple
discharge

• Arise in large or small ducts

• Large duct papillomas –

lactiferous sinuses of the
nipple; solitary (90%)

• Small duct papillomas – located

deeper; usually multiple;
younger patients
 Intraductal Papilloma

• >80% of large duct papillomas

produce nipple discharge

• Bloody nipple discharge – stalk

undergoes torsion causing
infarction

• Rarely exceeds 3 cm (vs papillary

carcinoma of the breast)

• Grow within dilated ducts and

are composed of multiple
branching fibrovascular cores
 Intraductal
Papilloma
• Complex, cellular, and often
intricately arborescent

• Features of benignancy:
– Well-developed stroma
– Presence of two cell types
– Normochromatic, oval nuclei
– Scanty mitotic activity
– Apocrine metaplasia
– Lack of cribriform or trabecular
pattern
– Nearly absent necrosis
 Intraductal Papilloma
• Solitary papilloma is a benign lesion that is curable by local excision

• Papillomas with foci of atypical hyperplasia (atypical papillomas)

are associated with an increased risk for carcinoma
PROLIFERATIVE BREAST DISEASE
WITH ATYPIA
 Proliferative Breast Disease With Atypia

• Atypical hyperplasia – a clonal proliferation having some, but not

all, of the histologic features that are required for the diagnosis of
carcinoma in-situ

• Risk for invasive breast carcinoma is 4 to 5 times that of the

general population

• Two forms:
1. Atypical ductal hyperplasia
2. Atypical lobular hyperplasia
 Atypical Ductal Hyperplasia
• Histologic resemblance to
ductal carcinoma in-situ
(DCIS)

• Spaces are round and regular,

the peripheral spaces are
irregular and slitlike

• Mixed population of cells

consisting of oriented
columnar cells at the
periphery and more rounded
cells within the central
portion
 Atypical Lobular Hyperplasia

• Identical to those of
lobular carcinoma in-situ,
but the cells do not fill or
distend more than 50% of
the acini within a lobule

• Also shows loss of E-

cadherin expression –
same with lobular
carcinoma in-situ
Atypical Lobular Hyperplasia
Breast:
CARCINOMA
 Breast Carcinoma
• The most common malignancy in women
• Second only to lung cancer as a cause of cancer deaths
• Almost all breast malignancies are ADENOCARCINOMAS

• Divided into 3 major biologic subgroups based on the expression of

estrogen receptor (ER) and HER2
1. ER-positive, HER2-negative (50% to 65% of tumors)
2. HER2-positive (10% to 20% of tumors; either ER-positive or ER-negative)
3. ER-negative, HER2-negative (10% to 20% of tumors)

• The 3 subgroups present with striking differences in patient

characteristics, pathologic features, treatment response, and
outcome
 Risk Factors
• The common denominator for most of these risk factors is strong
and/or prolonged estrogen stimulation operating on a genetically
susceptible background.

1. Family history
▪ Women who have a 1st-degree relative with breast CA have a 2 or 3 times that
of the general population
▪ Risk is increased if relative was affected at an early age and/or had bilateral
disease

2. Menstrual and reproductive history

▪ Early menarche, nulliparity, late age at first birth, and late menopause
▪ Oophorectomy before age 35 reduces risk to one-third
▪ First child before age 18 have only one-third risk of those delayed until age 30
 Risk Factors
3. Fibrocystic disease and epithelial hyperplasia

4. Exogenous estrogens
▪ 2 to 9 fold increase – newer studies
▪ December 2002, estrogen was declared a known human carcinogen by the US
National Toxicology Program

5. Contraceptive agents
▪ No increase risk, or at most a very low increase among young long-term users
 Risk Factors
6. Ionizing radiation
▪ Increased risk particularly if
exposure occurred at the time of
breast development

7. Breast augmentation
▪ Neither higher nor lower than
that of the general population

8. Others
▪ Peculiar association between
breast CA and meningioma in
some studies
▪ Breast CA has been found to
metastasize within the
meningioma
 Location
• 50% in the upper outer
quadrant
• 15% in the upper inner quadrant
• 10% in the lower outer quadrant
• 5% in the lower inner quadrant
• 17% in the central region (w/ in
1 cm of areola)
• 3% are diffuse (massive or
multifocal)

• Matches closely the amount of

breast parenchyma in each
quadrant
• Multifocal – presence of 2 or
more foci of cancer within the Multifocal vs Multicentric
same breast quadrant
• Multicentric – presence of 2 or
more foci of cancer in different
quadrants of the same breast

• Multicentricity is more common

in lobular than in ductal Ca

• Unifocal and multifocal CA are

similar in frequency of lymph
node involvement
• Multicentric tumors are
associated with a lower survival
rate than unicentric tumors
 Diagnosis
1. Clinical examination
2. Mammography
3. Cytology – fine needle aspiration biopsy
4. Needle core biopsy
5. Open biopsy and frozen section
Clinical Examination
Mammography
 Breast
Biopsies
 Familial Breast Cancer
• 12% of breast cancers occur due to inheritance of an identifiable
susceptibility gene or genes
– Multiple affected 1st degree relatives
– Early onset cancers
– Multiple cancers
– Family members with other specific cancers

• Autosomal dominant trait that is conferred by inheritance of a

defective copy of a tumor suppressor gene
• A single sporadic mutation in the remaining normal allele is all
that is required to completely lose the tumor suppressor function
• The major susceptibility genes: BRCA1, BRCA2, TP53, and CHEK2
(roles in DNA repair and maintenance of the genomic integrity)
 Familial Breast Cancer
• Two high-penetrance susceptibility genes which, when affected by
germline mutations, are associated with a high lifetime risk
1. BRCA1 – on chromosome 17q21
2. BRCA2 – on chromosome 13q12.3

• BRCA1 – DNA repair, cell cycle checkpoint control, and chromatin

remodeling
• BRCA2 – DNA repair, cytokinesis, and meiosis

• Both are essential for accurate repair of DNA double-strand breaks

by homologous recombination repair
 Familial Breast Cancer
BRCA1 mutations
• Markedly increase the risk for ovarian carcinoma (20-40% of
carriers)
• Commonly poorly differentiated with medullary features
• Syncytial growth pattern, high grade, mitotically very active,
pushing margins, lymphocytic response, negativity for hormone
receptors (ER-) and HER2 (“triple negative” or “basal-like”)

BRCA2 mutations
• Smaller risk for ovarian carcinoma (10-20% of carriers)
• More frequently associated with male breast cancer
• Relatively poorly differentiated
• Commonly positive for hormone receptos (ER+)
 Types of Breast Carcinoma
• Almost all (>95%) of breast malignancies are ADENOCARCINOMAS
that first arise in the duct/lobular system as carcinoma in-situ

• Carcinoma in-situ: refers to a neoplastic proliferation of epithelial

cells that is confined to ducts and lobules by basement membrane

• Invasive/infiltrating carcinoma: neoplastic cells have penetrated

through the basement membrane and grows within the stroma

• Lobular: refers to invasice CA biologically related to LCIS

• Ductal: for adenocarcinomas that cannot be classified as a special
histologic type
 Ductal Carcinoma in-situ
• DCIS is a malignant clonal proliferation of epithelial cells limited to
ducts and lobules by the basement membrane

• Myoepithelial cells are preserved, although they may be diminished

in number

• Nuclear grade and necrosis are better predictors of local recurrence

and progression to invasion than architectural type
 Ductal Carcinoma in-situ
2 major architectural subtypes:

• Comedo DCIS
– Two features: tumor cells with pleomophic and high grade
nuclei; and areas of central necrosis

• Noncomedo DCIS
– Lacks either high grade nuclei or central necrosis
– Patterns: Cribriform DCIS, Solid DCIS, and Micropapillary DCIS
Ductal Carcinoma in-situ
 Paget Disease of the Nipple
• A rare manifestation of breast cancer (1-4% of cases)

• Mistaken for eczema

• Malignant cells (Paget cells) extend from DCIS within the ductal
system via lactiferous sinuses into the nipple skin w/o crossing the
basement membrane

• Almost all patients have an underlying invasive carcinoma

• Invasive CA is usually poorly-differentiated, ER(-), and overexpress

HER2
Paget Disease of the Nipple
 Lobular Carcinoma in-situ
• A clonal proliferation of cells within ducts and lobules that grow in
a discohesive fashion, usually due to an acquired loss of the tumor
suppressive adhesion protein E-cadherin

• “Lobular” – cells expand but do not distort involved spaces; lobular

architecture is preserved

• Always an incidental biopsy finding, since it is not associated with

calcifications or stromal reactions seen as mammographic densities

• LCIS is bilateral in 20-40% of cases (DCIS = 10-20%)

 Lobular

Carcinoma in-situ

• Uniform population of cells

with round nuclei and small
nucleoli

• The lack of E-cadherin results

in a rounded shape without
attachment to adjacent cells

• No patterns

• Does not involve nipple skin

• No calcification
 Invasive Carcinoma
I. ER(+), HER2(-) (“luminal”, 50-65% of cancers) is the most
common form of invasive carcinoma

1. ER(+), HER2(-), low proliferation (40-55% of cancers)

– Majority of cancers in older women and men
– Most common type detected by mammographic screening
– Lowest incidence of recurrence; often cured by surgery
– Metastasize after long periods (over 6 years), typically to the
bones
– Respond well to hormonal treatment (long survival with
metastatic disease is possible)
– Incomplete response to chemotherapy (hormone tx is standard
of treatment)
 Invasive Carcinoma
I. ER(+), HER2(-) (“luminal”, 50-65% of cancers) is the most
common form of invasive carcinoma

2. ER(+), HER2(-), high proliferation (10% of cancers)

– Most common type associated with BRCA2 germline mutations
– Much higher burden of chromosomal aberrations than low –
grade ER(+) tumors
– About 10% show a complete response to chemotherapy
 Invasive Carcinoma
II. HER2(+) (appoximately 20% of cancers) is the 2nd most common
molecular subtype of invasive breast cancer
– Half are ER(+)
– More common in young women
– Germline mutations in TP53 (Li-Fraumeni syndrome)
– High mutational load
– Can metastasize even when small in size and early in the
course, often to viscera and brain
– Poor clinical outcome (before HER2 targeted therapy)
– Many respond completely to antibodies that bind and block
HER2 activity (trastuzumab or Herceptin)
 Invasive Carcinoma
III. ER(-), HER2(-) tumors (“basal-like” triple negative CA;
approximately 15% of cancers) are the 3rd major molecular
subtype
– More common in young premenopausal women
– Majority arise in patients with BRCA1 mutations
– Can metastasize when small in size, frequently to the viscera
and brain
– High proliferation and rapid growth
– Approximately 30% completely respond to chemotherapy
– Recurrences are generally diagnosed within 5 years of
treatment even after mastectomy
Invasive Carcinoma
 Invasive Carcinoma
• Includes all tumors in which stromal invasion is detectable (whether
in-situ component is present and regardless of the relative
proportion of the two)

• Divided into 2 major categories:

1. Ductal type
2. Lobular type

• Type depends on the appearance of the invasive component (not on

the type of in-situ component)
 Invasive Ductal Carcinoma, NST
• The morphologic variations are innumerable
• Some are distinctive enough to deserve recognition as “special
types”

• Approximately 75% of cases are designated as Invasive Ductal

Carcinoma, No Special Type (NST) or Not Otherwise Specified (NOS)

• The prototypic expression of breast carcinoma

 Invasive Ductal
Carcinoma, NST
• Firm and poorly circumscribed
• Cuts with resistant gritty
sensation
• Yellowish-gray cut surface
• Stellate or crab-like
configuration
• Necrosis, hemorrhage, cystic
degeneration
• May invade overlying skin or
underlying fascia and
pectoralis muscle
 Invasive Ductal
Carcinoma, NST
• Microscopically variable
• Diffuse sheets, well-defined
nests, cords, or as individual cells
• Glandular/tubular differentiation
• Term “adenocarcinoma” is not
advisable

• Tumor cells vary in size and shape

• Prominent nuclei and nucleoli
• Numerous mitotic figures
• Areas of necrosis
• Desmoplasia
Invasive Ductal Carcinoma, NST
Nottingham Histologic Grading
Nottingham Histologic Grading
Nottingham Histologic Grading
 Special Histologic Types

• Types w/c are almost always ER(+) and resembles

luminal cancers
1. Lobular carcinoma
2. Mucinous (colloid) carcinoma
3. Tubular carcinoma
4. Papillary carcinoma
• Types that frequently overexpress HER2
1. Apocrine carcinoma
2. Micropapillary carcinoma
• Types w/c are ER(-) and HER2(-)
1. Medullary carcinoma
2. Secretory carcinoma
 Invasive Lobular Carcinoma
• Classic type is characterized by the presence of small and relatively
uniform tumor cells growing singly, in Indian file, and in a
concentric (pagetoid or target-like growth) fashion around lobules
involved by in-situ lobular neoplasia

• Invasive component should have lobular features (does not depend

on presence of LCIS)

• IHC similar to LCIS: (+) HMW keratins, lack of accumulation of p53,

and decrease or absence of E-cadherin (hallmark feature);
presence of E-cadherin does not preclude diagnosis when
morphologic features are compatible
Invasive Lobular
Carcinoma
 Mucinous Carcinoma
• Mucoid, colloid, or gelatinous
carcinoma

• Usually in post-menopausal
women

• Well-circumscribed and formed

by a currant jelly-like mass
held together by delicate septa

• Frequent foci of hemorrhage

 Mucinous Carcinoma
• Small clusters of tumor cells
“floating in a sea of mucin”
• Clusters may be solid, exhibit
acinar formations, or form
micropapillary structures
• Mucin is almost entirely
extracellular, and may be of
acid or neutral type
• Hormone receptors are always
positive (ER+) and almost
always HER2(-)
• Pure mucinous CA is associated
with a very low incidence
(2-4%) of nodal metastases
 Tubular Carcinoma
• Considered as a well-
differentiated carcinoma

• Average age of patient is 50

years

• Poorly circumscribed margins

• Hard consistency

• Small, with a mean diameter

of about 1.0 cm.
 Tubular Carcinoma
• Simulates a benign condition (eg.
radial scar) because of the well-
differentiated nature of the
glands, absence of necrosis or
mitoses, and scanty pleomorphism
• Clues: haphazard arrangement of
glands, frequent invasion of fat at
the periphery, cellular stroma,
irregular and angulated contours of
the glands

• Metastases to axillary nodes in 10%

of cases
• Prognosis is excellent
 Papillary
Carcinoma

• Occurs commonly in
postmenopausal women
• True papillae, fronds of
fibrovascular tissue lined by
tumor cells
• Rare entity as a whole
 Apocrine
Carcinoma
• Very rare form of breast
malignancy (1-4% of cases)
• Large tumor cells with
abundant granular cytoplasm
• Contain eosinophilic or golden
brown granules
• Vesicular nuclei and prominent
nucleoli
• Luminal portion of the tumor
has a characteristic bulbous
expansion (apocrine snouts)
• Prominent mitochondria
ultrastructurally
 Micropapillary
Carcinoma
• Misnomer
• Hollow balls of cells that float
within intercellular fluid
• Mimic the appearance of true
papillae
• Formation of pseudopapillary
structures lacking fibrovascular
core floating in clear spaces
• Nuclear grade is typically high
• Lymph metastases is the rule
• High local recurrence
• Survival rate lower than NST
 Medullary Carcinoma
• Have features that are characteristic of BRCA1-associated
carcinomas

• BRCA1 carriers: 13% are of medullary type and up to 60% have

medullary features

• Relatively good prognosis compared to other poorly differentiated

carcinomas

• Presence of lymphocytic infiltrates is associated with higher

survival rates and greater response to chemotherapy

• ER-negative and HER2-negative tumor

 Medullary
Carcinoma
• Solid, syncytium-like sheets of
large cells with pleomorphic
nuclei and prominent nucleoli
(75% of tumor mass)

• Frequent mitotic figures

• Lymphoplasmacytic infiltrate
surrounding and w/in the
tumor

• Pushing margin
 Secretory
Carcinoma
• Rare form of breast carcinoma
that can be seen in children
• Well-circumscribed, usually
small
• Mimics lactating breast by
forming dilated spaces filled
with eosinophilic-PAS positive
secretions
• Tumor cells contain numerous
membrane-bound
intracytoplasmic secretory
vacuoles
• Excellent overall prognosis
 Metaplastic Carcinoma
• <1% of all cases
• Includes conventional
adenocarcinoma with
chondroid stroma,
squamous cell
carcinomas and
carcinomas with a
prominent spindle cell
component
• ER-PR and HER2
negative
• Lymph node metastasis
is infrequent but
prognosis is poor
ER/PR Scoring
HER2 Scoring
 Prognosis and Predictive Factors
• Outcome depends on the biologic features of the carcinoma
(molecular and histologic type) and the extent to which the cancer
has spread

• Prognosis is also determined by pathologic examination of the

primary carcinoma and axillary lymph nodes

• Important in counseling patients about the likely outcome of their

disease, choosing appropriate treatment, and design of clinical trials

• Prognostic factors fall into two groups:

1. Those related to the extent of carcinoma (tumor burden or
stage)
2. Those related to the underlying biology of the cancer
 Prognosis and Predictive Factors
1. Invasive carcinoma versus carcinoma in-situ
– CIS has excellent prognosis

2. Distant metastases
– Once present, cure is unlikely
– Tumor type influences timing and location of metastases

3. Lymph node metastases

– The most important prognostic factor for invasive carcinoma in the absence of
distant metastases
– Biopsy is necessary for accurate assesment
– No nodal involvement (70-80% disease-free survival)
– One to three LN (35-40% disease-free survival)
– Ten LN (10-15% disease-free survival)
 Prognosis and Predictive Factors
4. Tumor size
– The risk of axillary LN mets increases with the size of the primary tumor, but
both are independent prognostic factors
– Node-negative CA less than 1 cm in size have a 10-year survival rate of more
than 90%
– Survival drops to 77% for cancers greater than 2 cm
– Size however, is less important for HER2(+) and ER(-) CA as they can
metastasize even when small

5. Locally advanced disease

– Those invading the skin or skeletal muscle are usually large and difficult to
treat surgically
 Prognosis and Predictive Factors
6. Lymphovascular space
invasion
– Tumor cells are present within
vascular spaces (either
lymphatics or small capillaries)
– Strongly associated with the
presence of LN metastases
– Poor prognostic factor
– Risk factor for local recurrence
 Ten-year survival according to
AJCC depending on the extent of
tumor at time of diagnosis
 Prognosis and Predictive Factors
1. Molecular subtype
– Determined by expression of ER and HER2 as well as proliferation rate

2. Special histologic subtype

– Survival rate of women with some special types (tubular, mucinous, lobular,
papillary) is greater than that of women with ductal carcinoma of no special
type (NST)
– Women with metaplastic CA or micropapillary CA have a poorer prognosis

3. Histologic grade
– Nottingham histologic grade – nuclear grade, tubule formation, and mitotic
rate
– Correlates well with disease free and overall survival
 Prognosis and Predictive Factors
4. Proliferative rate
– Measured by mitotic counts (part of histologic grading)
– By IHC detection of proteins that are specifically expressed by actively dividing
cells (Ki-67)
– Primarily important in ER(+), HER2(-) carcinomas
– CA with high proliferation rates have a poorer prognosis but may respond
better to chemotherapy
5. Estrogen and progesterone receptors
– 80% of CA that are both ER(+) and PR(+) respond to hormonal therapy
– Strongly ER(+) cancers are less likely to respond to chemotherapy
– CA that fail to express either ER or PR have a less than 10% likelihood of
responding to hormonal therapy but are more likely to respond to
chemotherapy
6. HER2
– Associated with poorer survival
– Predictor of response to agents that target the receptor
Histopathology Report
Histopathology Report
Histopathology Report
Immunohistochemistry Report
Breast:
STROMAL TUMORS
 Fibroadenoma
• Common; typically occurs in patients
between ages 20 and 35 years

• Palpable mass in younger patients and

mammographic densities in older
patients

• Increases in size during pregnancy

(hormonally responsive) and tends to
regress as the age of the patient
increases

• Usually single; multiple lesions in the

same breast or bilaterally in 20% of
cases
 Fibroadenoma
Gross appearance

• Sharply demarcated firm

mass
• Usually not more than 3
cm in diameter
• Cut surface is solid,
grayish-white, and
bulging
• Whorl-like pattern and
slit-like spaces
• Necrosis is absent
 Fibroadenoma
Microscopic appearance
• Glands – cuboidal to low
columnar cells with round
uniform nuclei resting on
myoepithelial cell layer
• Stroma – loose myxoid
connective tissue or dense
fibrous tissue
• Intracanalicular – stroma
invaginates into the grandular
spaces (misnomer)
• Pericanalicular – round or oval
glandular configuration is
maintained
 Phyllodes Tumor
• Arise from intralobular stroma like FA but are less common

• Most present at 6th decade

• Majority are detected as palpable masses

• Associated with clonal acquired chromosomal changes, with gains in

chromosome 1q being the most frequent

• Increased numbers of chromosomal aberrations are associated with

higher tumor grade and more aggressive behavior
 Phyllodes Tumor
• Vary in size from a few
centimeters to massive
lesions involving the entire
breast

• Larger lesions have bulbous

protrusions (phyllodes is
Greek for “leaflike”)
 Phyllodes
Tumor
• Nodules of proliferating
stroma covered by
epithelium

• Differentiated from FA:

– Higher cellularity
– Higher mitotic rate
– Nuclear pleomorphism
– Stromal overgrowth
– Infiltrative borders
Phyllodes Tumor
Thank you!

END