8. Epithelial component
2 cell types – line ducts &
lobules.
1. Contractile
MYOEPITHELIAL CELLS
lie on the BM assist in milk
ejection during lactation &
provides structural support to
the lobules
2. EPITHELIAL CELLS
Luminal – produce milk.
Epithelial & Myoepithelial
cells lie on the basement
membrane.
20. First month of breast feeding
Cracks / fissures in the nipple
portal of entry of bacteria.
Breast
erythematous,painful,fever
MORPHOLOGY: Staph. Inf.
localized area of inflammation.
Strep. Inf. Diffuse, spreading.
HPE: Involved breast tissue –
necrotic, neutrophil infiltration.
Treated with antibiotics,
continuous milk expression.
Rarely surgical drainage.
21.
22. Recurrent subareolar abscess/
Squamous metaplasia of lactiferous
ducts/ Zuska disease.
Painful erythematous subareolar mass.
90% cases – assoc. with smoking
Vit.A def./toxic substances in smoke –
alters epithelial differentiation.
Recurrent cases – fistula occurs.
HPE : Keratinizing squamous
metaplasia of ducts. Keratin shed from
the cellsplugs the ductal system
dilation & rupture of duct.
Periductal tissue keratin spill
chronic granulomatous inflammatory
response.
Treatment: En bloc surgical removal of
the involved duct, fistula. Antibiotics
for secondary bacterial infection.
23. 5th – 6th decade, multiparous women.
Cl.features: Poorly palpable periareolar
mass, thick white secretions from nipple,
skin retraction.
HPE: Dilated ducts filled by granular
debris numerous lipid-laden
macrophages, inspissation of breast
secretions, marked periductal and
interductal ( dense )infiltrate of
lymphocytes and macrophages, and
variable numbers of plasma cells.
Eventual fibrosis skin & nipple
retraction. Principal significance
produces an irregular palpable mass -
mimics the mammographic appearance
of carcinoma.
24. Dilated duct with
surrounding fibrosis
and chronic
inflammation. Lumen
of the duct
eosinophilic secretion
& markedly attenuated
epithelium.
25. Cl.features: H/o breast trauma / prior
surgery.
Painless palpable mass, skin thickening
or retraction, a mammographic density,
or calcifications.
Acute lesions hemorrhagic + central
areas of liquefactive fat necrosis.
Subacute lesions - areas of fat necrosis
ill-defined, firm, gray-white nodules
containing small chalky-white foci or
dark hemorrhagic debris.Central region
of necrotic fat cells intense
neutrophilic infiltrate + macrophages.
Proliferating fibroblasts + new vessels +
chronic inflammatory cells surround the
injured area Giant cells, calcifications,
and hemosiderin appear focus -
replaced by scar tissue.
26. Rare
CAUSES:
1. Systemic granulomatous ds.
Sarcoidosis,Wegener’s.
2. Granulomatous inf. d/t
Mycobacteria, Fungi.
GRANULOMATOUS LOBULAR
MASTITIS – Parous women,
confined to lobules, d/t
hypersensitivity reactions to the
antigens – expressed by the
lobular epithelium during
lactation.
27.
28. Detected by mammography/incidental
findings in surgical specimen
Based on the risk of developing Breast Cancer
– 3 groups:
NON PROLIFERATIVE
BREAST CHANGES
(FIBROCYSTIC
CHANGES)
PROLIFERATIVE
BREAST
DISEASE
ATYPICAL
HYPERPLASIA
29.
30. Most common benign
breast condition.
Primarily affects terminal
duct–lobular unit (TDLU).
Pathogenesis Obscure –
hormones (estrogen) -play a
role.
Clinical features
Incidence: 10 – 20 % of
adult women.
Age : 25 – 45 yrs.
Usually bilateral.
Vague ‘lumpy’
‘3 principle changes’
Cystic change
with apocrine
metaplasia
AdenosisFibrosis
31. Dilation & unfolding of
lobules small cysts – coalesce
large cysts.
Unopened cysts turbid ,semi
translucent fluid brown/blue
colour BLUE – DOME CYSTS.
Lined by flattened atrophic
epithelium/metaplastic apocrine
cells (Abundant granular
eosinophilic cytoplasm + round
nuclei).
Calcification – common.
“MILK OF CALCIUM” –
Mammographers
Diagnosis – confirmed –
disappearance of the cyst after
FNAC.
35. Increase in the number of acini
per lobule.
Pregnancy Normal physiologic
adenosis.
Nonpregnant women adenosis
- focal change.
Acini – enlarged,not distorted
Calcifications – occasionally -
within the lumens.
Acini - lined by columnar cells
benign / atypical features (“flat
epithelial atypia”) Earliest
recognizable precursor of
epithelial neoplasia
36. Palpable masses – pregnant/lactating
women.
Normal appearing breast tissue +
physiological adenosis + lactational
changes.
Exagerrated focal response to
hormones.
Gross appearance: Well circumscribed
mass - distinct lobular configuration,
yellowish color, and marked
vascularization.
C/s: Gray / tan. Necrotic changes
frequent.
HPE: Proliferated glands lined by
actively secreting cuboidal cells
37.
38. Mammographic densities, calcifications, or as
incidental findings in specimens from biopsies.
Found alone/assoc. with non prolif. breast changes.
Lesions proliferation of ductal epithelium
and/or stroma without cytologic or
architectural features suggestive of
carcinoma in situ.
39. Normal breast ducts & lobules –
double layer of epithelial cells
luminal & myoepithelial
layers.
Epith.hyperplasia Incidental
finding - > 2 layers – luminal &
myoepithelial cells
fill,distend ducts & lobules.
Irregular lumens – periphery of
the cellular masses.
42. Palpable mass, a radiologic
density, or calcifications.
No. of acini per terminal duct -
increased to double the number
found in uninvolved lobules.
Normal lobular arrangement -
maintained.
Acini - compressed and distorted
in the central portions of the
lesion & characteristically dilated
at the periphery.
Myoepithelial cells - prominent.
NORMAL
ADENOSIS
44. Radial sclerosing lesion (“radial
scar”) - commonly occurring
benign lesion forms - irregular
masses (mimic invasive
carcinoma)mammographically,
grossly, and histologically.
Central nidus of entrapped glands
in a hyalinized stroma with long
radiating projections into stroma.
Radial scar – misnomer (lesions -
not assoc. with prior trauma or
surgery)
45. Multiple branching fibro vascular cores, each
with a connective tissue axis lined by luminal
and myoepithelial cells.
Growth - within a dilated duct.
Epithelial hyperplasia and apocrine metaplasia -
frequently present.
Large duct papillomas - solitary, situated in the
lactiferous sinuses of the nipple.
Small duct papillomas - multiple - located
deeper within the ductal system.
> 80% of large duct papillomas nipple
discharge.
Large papillomas torsion of stalk
infarction bloody discharge.
Intermittent blockage and release of normal
breast secretions or irritation of the duct by the
papilloma Non bloody discharge.
Others + nt as small palpable masses, or as
densities or calcifications seen on mammograms
46. Atypical ductal/lobular hyperplasia
Cellular proliferation - resembles carcinoma
in situ - but lacks sufficient qualitative or
quantitative features for diagnosis as
carcinoma.
47. Found in Bx specimens – done for
calcifications,mammographic
densities,palpable masses.
Relatively monomorphic
proliferation of regularly spaced
cells, sometimes with cribriform
spaces.Limited in extent, only
partially filling ducts.
Duct is filled with a mixed population of
cells oriented columnar cells at the
periphery and more rounded cells within the
central portion. Some of the spaces - round
and regular, the peripheral spaces - irregular
and slitlike Highly Atypical.
49. Proliferation of cells the cells do
not fill or distend more than 50% of
the acini within a lobule.
Atypical lobular hyperplasia also
involves contiguous ducts through
pagetoid spread( discrete
intraepidermal proliferation of cells
occurring singly/ nests at all levels
of the epidermis) in which atypical
lobular cells lie between the ductal
basement membrane and
overlying normal ductal epithelial
cells.
A population of monomorphic small,
round, loosely cohesive cells partially fill
a lobule. Some intracellular lumens can
be seen
50. LESION LIFETIME RISK OF DEVELOPING
INVASIVE CANCER
NON – PROLIFERATIVE BREAST
CHANGES 3 %
PROLIFERATIVE DISEASE
WITHOUT ATYPIA 5 – 7 %
PROLIFERATIVE DISEASEWITH
ATYPIA 13 – 17 %
CARCINOMA IN SITU 25 – 30 %
51.
52.
53. • Incidence increases with age – Peaks at 75
– 80 yrs.Age
• Only 1 % incidence men.
Gender
• Early menarche, Late menopause
increased risk.
Age at menarche &
menopause –
• Nulliparous women /Late pregnancy
proliferation of cells with pre neoplastic
changes.
Age at first live birth -
• Mother,sister increased risk.First-Degree Relatives
with Breast Cancer -
54. • In previous biopsies => increased risk.
Proliferative breast changes without
atypia – smaller risk.
Atypical Hyperplasia
• Non-Hispanic white women highest rates of
breast cancer.Race / Ethnicity
• Increases the risk of breast cancer.Postmenopausal hormone
replacement therapy
• High breast density --d/t less complete involution of
lobules at the end of each menstrual cycle
increases no. of cells potentially susceptible to
neoplastic transformation.
Breast Density
• To chest - d/t cancer therapy, atomic
bomb exposure, or nuclear accidents.Radiation Exposure
55. • 1% of women with breast cancer second contralateral
breast carcinoma / year. Risk - higher for women with
germline mutations in BRCA1 and BRCA2
Carcinoma of the Contralateral
Breast or Endometrium.
• United States and Europe – higher
incidence.
Geographic Influence
• Alcohol consumption higher estrogen levels
and lower folate levels.
Diet
• Postmenopausal obese women increased synthesis of
estrogens in fat depots.Obesity
• The longer women breastfeed, the greater the reduction in
riskBreastfeeding
• Organochlorine pesticides estrogenicEnvironmentalToxins
• Increased risk.Tobacco & cigarette smoking
57. Breast cancers are clonal
proliferations that arise from cells
with multiple genetic aberrations,
acquisition of which is influenced by
hormonal exposures and inherited
susceptibility genes
59. BRCA -1Breast
Cancer 1,Early onset
( Chr.17)
BRCA-2, Breast Cancer
2,Early onset( Chr.13)
p53( Chr.17) CHEK2( Chr. 22)
FUNCTIONS:
1. Transcription
2. DNA Repair of
double stranded
breaks
3. Ubiquitination
4. Transcriptional
regulation.
FUNCTIONS:
1. Stability of
the human genome
2. DNA double strand
break repair.
FUNCTIONS
1. Cell cycle control
2. DNA replication
3. DNA repair
4. Apoptosis.
FUNCTIONS
1. Cell cycle
checkpoint
kinase,
recognition and
repair of DNA
damage.
2. Activates BRCA1
and p53 by
phosphorylation
Germline point
mutations/Deletions
of BRCA1 gene
Hereditary breast &
ovarian cancers.
Mutations 20%
Hereditary breast
cancer, ovarian cancer,
increased cancer risk in
male carriers.
Mutations
Sporadic breast
cancers.
Li Fraumeni
syndrome
Mutations - rare
(<5%).
Li Fraumeni variant
Increase breast
cancer risk after
radiation exposure
60.
61.
62. Member of ErbB protein family.
HER2 is a cell membrane surface-bound receptor
tyrosine kinase - normally involved in signal
transduction pathways cell growth and
differentiation.
Approximately 30 % of breast cancers
amplification of the HER2/neu gene/
overexpression of its protein product.
Overexpression of this receptor in breast cancer
increased disease recurrence and worse
prognosis.
63. Excess Hormonal exposure Sporadic
cancers.
Post menopausal women sporadic
cancers ER positive.
Hormones breast growth during
puberty, menstrual cycles, pregnancy
cycles of proliferation cells at risk for
DNA damage.
If premalignant or malignant cells are
present, hormones - stimulate their
growth + growth of normal epithelial
and stromal cells tumour
development.
Metabolites of estrogen mutations /
generate DNA-damaging free radicals.
64. Approximately 75% of breast tumors
”estrogen dependent.” - predicted by
presence of estrogen receptors in
tumor cells.
Tumors that do not rely on estrogen for
growth "estrogen independent."
The estrogen receptor protein -
detected in breast tumor biopsy
specimens immunohistochemical
staining.
Tumor cells that express estrogen
receptors ER positive- are usually
estrogen dependent.
Tumors that lack estrogen receptors
ER negative-are usually estrogen
independent.
65.
66.
67. > 95 % breast malignancies
ADENOCARCINOMAS
BREASTCARCINOMA
INVASIVE
Penetrated
through the BM
into the stroma.
IN SITU
Neoplastic cells –
limited within the
ducts,lobules by
BM.
70. Most DCIS detected by
calcifications on
mammography/mammographic
density - periductal fibrosis surrounding
a DCIS/rarely palpable mass/ nipple
discharge/incidental finding on a biopsy
for another lesion.
Spreads through ducts & lobules
extensive lesions entire sector of a
breast.
DCIS – involves lobules – acini
distorted, unfolded appear as small
ducts.
84. Area of invasion
through BM stroma
- > 0.1 cm.
Assoc. with
comedocarcinoma.
Few microinvasion foci
prognosis similar to
DCIS.
85. MASTECTOMY for DCIS –
curative > 95 % pts.
Recurrence – rare – d/t residual
DCIS in ducts in subcutaneous
tissue – not removed during
surgery/ d/t occult foci of
invasion not detected at
diagnosis.
Breast conservation – can be
done but slightly higher risk of
recurrence.
Major risk factors for
recurrence:
1. Grade
2. Size
3. Margins
In ER + ve DCIS Post-
op. radiation +
Tamoxifen recurrence
risk – low.
Death < 2 % DCIS.
86. Incidental biopsy finding -no
calcifications /stromal
reactions mammographic
densities.
Bilateral - 20% to 40% .
Young women.
Loss of expression of E-
cadherin(transmembrane
cell adhesion protein
cohesion of normal breast
epithelial cells).
87. Dyscohesive round cells with
oval or round nuclei and small
nucleoli. Absence of atypia,
pleomorphism, mitoti activity,
necrosis.
Involved acini – recognizable as
lobules.
Mucin-positive signet-ring
cells.
ER and PR +ve.
88.
89. Invasive carcinoma 1% per
year.
Both breasts - increased risk.
Risk - slightly higher in the
ipsilateral breast.
Invasive carcinomas - lobular
type.
Treatment:
1. Bilateral prophylactic
mastectomy.
2. Tamoxifen.
3. Close clinical follow-up.
4. Mammographic screening.
91. Palpable mass.
Axillary lymph node metastases
Fixity to the chest wall / skin
dimpling.
Nipple retraction
Sub dermal 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
92.
93.
94.
95.
96. Majority (70% to 80%).
Gross appearance: Most tumors
- firm to hard ,irregular border .
Less frequently - well-
circumscribed border , softer
consistency.
When cut / scraped
characteristic grating sound d/t
small, central pinpoint foci or
streaks of chalky-white elastotic
stroma and occasional small foci
of calcification.
104. Solid sheets of pleomorphic cells
with high grade hyperchromatic
nuclei.
Areas of central necrosis +nt.
Necrotic cell membranes – calcify
clusters/linear & branching
microcalcifications on
mammography.
Periductal concentric fibrosis &
chronic inflammation.
Extensive lesions – palpable as
vague nodularity.
105. MC - 6th decade.
May closely mimic a benign
lesion clinically and
radiologically/ present as a
rapidly growing mass.
MORPHOLOGY :Well –
circumscribed,soft,fleshy mass -
little desmoplasia more
yielding on palpation and
cutting. (medulla
=>“marrow”).
106. 1. Solid, syncytium-like
sheets of large cells with
vesicular, pleomorphic
nuclei, prominent nucleoli
> 75% of the tumor
2. Frequent mitotic figures;
3. Moderate to marked
lymphoplasmacytic
infiltrate surrounding and
within the tumor.
4. Pushing (noninfiltrative)
border.
Poorly differentiated.
110. Older women (median
age 71) grow slowly -
many years.
Morphology: Tumor –
soft/rubbery .
Consistency &
appearance of pale gray-
gelatinous. Borders -
pushing / circumscribed.
111. Tumor cells - arranged in
clusters and small islands within
large lakes of mucin.
Mucinous carcinomas
diploid, well to moderately
differentiated, and ER positive.
Lymph node metastases -
uncommon.
Overall prognosis is slightly
better.
113. Small irregular mammographic
densities - late 40s.
Uncommon.
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 .
Well differentiated. Excellent
prognosis.
114. Rare - 1% or fewer of all
invasive cancers.
More commonly seen in DCIS.
INVASIVE PAPILLARY CA.
ER positive.
Favorable prognosis.
INVASIVE MICROPAPILLARY
CA.
ER negative,HER2 positive.
Lymph node metastases - very
common
Prognosis is poor.
115. 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.
116. Includes a variety of rare types
of breast cancer (<1% of all
cases) matrix-producing
carcinomas, squamous cell
carcinomas, and carcinomas
with a prominent spindle cell
component.
ER-PR-HER2/neu “triple
negative”.
Lymph node metastases -
infrequent.
Prognosis - poor.
118. Palpable mass/ mammographic
density with irregular borders.
Sometimes - tumor infiltrates
the tissue diffusely – little
desmoplasia, not palpable, no
mammographic density.
Metastases – difficult to detect.
Bilateral - 5 – 10 %.
Biallelic loss of expression of
(CDH1, encodes E-
cadherin) d/t mutations.
119. Morphology: Histologic hallmark
dyscohesive infiltrating tumor
cells, often arranged in single file
or in loose clusters or sheets
INDIAN FILE APPEARANCE.
Tubule formation - absent.
Signet-ring cells containing an
intracytoplasmic mucin droplet
are common.
Desmoplasia - minimal or absent
120. Well-differentiated and moderately
differentiated carcinomas diploid,
ER positive, HER2/neu overexpression
- rare
Poorly differentiated carcinomas
aneuploid, lack hormone receptors,
may overexpress HER2/neu.
Different pattern of metastasis than
other breast cancers. Metastasis
peritoneum ,retroperitoneum, the
leptomeninges (carcinoma meningitis),
the gastrointestinal tract, ovaries and
uterus.
123. "Indian file" strands of infiltrating lobular
carcinoma cells are seen in the fibrous stroma
124.
125. Outcome in breast CA –
varies widely.
Prognosis – determined by
pathologic examination of
primary carcinoma &
axillary lymph nodes.
AmericanJoint Committee
on Cancer (AJCC) staging
system divides patients
into five stages (O to IV)
correlated with survival.
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.
126. Stage T: Primary Cancer
Lymph Nodes
(LNs)
M: Distant
Metastasis
5-Year Survival
(%)
0 DCIS or LCIS No metastases Absent 92
I Invasive
carcinoma ≤2 cm
No metastases Absent 87
II Invasive
carcinoma >2 cm
No metastases Absent 75
Invasive
carcinoma <5 cm
1 to 3 positive LNs Absent
III Invasive
carcinoma >5 cm
1 to 3 positive LNs Absent 46
Any size invasive
carcinoma
≥4 positive LNs Absent
Invasive
carcinoma with
skin or chest wall
involvement or
inflammatory
carcinoma
0 to >10 positive
LNs.
Absent
IV Any size invasive
carcinoma
Negative or
positive lymph
nodes
Present 13
137. 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
characteristic mammographic pop corn
appearance.
Small calcifications - clustered -
require biopsy to exclude carcinoma.
GROSS: Spherical, sharply
circumscribed, rubbery, grayish
white, freely movable nodules -
bulge above the surrounding
tissue and contain slitlike spaces.
< 1 cm – large tumors.
138.
139.
140.
141. 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.
142. 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.
145. 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.
149. Fibroadenoma Phyllodes
20-30 yrs Any age
2-3 cms > 5cms
Firm, rubbery, mobile,
painless, well circumscribed
mass
Firm, huge, mobile, painless
Stroma >>> epithelial
component
Invagination of stroma (leaf
like pattern), more cellular,
pleomorphic stroma
Bilateral Unilateral
Slow growing Rapidly growing can turn
malignant
150.
151. Consists of the nipple
and a rudimentary
duct system ending in
terminal buds without
lobule formation.
152. Enlargement of male breast.
Puberty/very aged/hyperestrogens.
Cirrhosis of liver, Increased adrenal
estrogens as androgenic functions of
testis fail in very aged, Drugs – alcohol,
marijuana, heroin,ART, anabolic steroids
used by atheletes & body builders,
Klinefelter syndrome.
D/t imbalance between estrogens,
stimulate breast tissue and androgens
which counteract these effects
Unilateral or bilateral
Button-like subareolar enlargement.
Morphology : Increase in dense
collagenous connective tissue,
marked micropapillary epithelial
hyperplasia of the duct lining.
Individual epithelial cells fairly
regular, columnar to cuboidal cells
with regular nuclei. Lobule
formation is rare.
153.
154.
155. History: 45/ F, school teacher, noticed an odd
change in left breast while showering last week
