1. Cytopathology of breast
• Presenter: Dr. Hayelom k
• Modulators: Dr,Mesele Bezabih
(Pathologist, Epidemiologist, Associate
professor)
Dr.serka addis(year three
resident)
2. OUTLINE OF PRESENTATION
• The normal breast
• Patient approach with breast disease
• Role of FNAC &technical considerations
• Inflammatory conditions
• fibrocystic change & hyperplasia
• Benign tumours and tumour
• Malignant breast tumours
• Other malignant tumours
4. The normal breast
• FNA from normal,
adult breast tissue
will contain variable
amounts of
• ductal epithelial cell
groups,
• small stromal
fragments and
• fatty tissue.
4
5.
6.
7.
8. Breast cells
• 1. Normal epithelial cells /Ductal Cells/
– Small cohesive groups; Often in Monolayer sheets
– The nuclei are relatively uniform, oval to round and
have smooth nuclear membranes.
– The nuclear size is less than twice the diameter of a
RBC
– The chromatin is fine, Evenly distributed;
– Nucleoli are inconspicuous & single
– Scanty cytoplasm
8
9.
10.
11.
12. 2. Myoepithelial cells
– Appear as Naked, bipolar, dense, bland nuclei
– No clearly visible nucleoli
– The length of naked, bipolar nuclei is about the diameter of
an RBC
– at the periphery of ductal sheets and groups or across
the background of the smear
– Is a hallmark of a benign breast aspirate
– Tubular carcinomas and some low-grade ductal carcinomas
are an exception
– How to differentiate from naked epithelial &
stromal cells??
12
13.
14. Foam cells
• They have abundant, multivacuolated cytoplasm and
relatively distinct cell borders.
• The cytoplasm sometimes contains various pigments
or inclusions.
• The nuclei are bland and round to oval.
Multinucleated giant foam cells also occur.
• Foam cells are usually associated with benign breast
lesions and cysts but can also be seen in cancer.
• Origin ? controversy
15.
16. Apocrine Cells
• Apocrine cells represent metaplasia of the
lobular epithelium
• abundant and finely granular cytoplasm
• eccentrically located nuclei with fine
chromatin
17.
18. The breast in pregnancy
• The aspirate may be moderately or
markedly cellular
• The cells are single and well dispersed
• cells and their nuclei are large
• Acinar cells have abundant granular or
vacuolated cytoplasm that is unusually fragile
• Bare nuclei are common
• The nuclei are round and uniform with
active granular or vesicular, but evenly
distributed chromatin.
• Single prominent nucleoli
→ larger than in most malignant breast
tumours
18
19.
20. mass during pregnancy may be due to
– An uneven response to hormonal stimulation or
– Enlargement of a preexisting lesion such as a fibro
adenoma.
– Lactating adenoma and galactocele can also arise de
novo in pregnancy.
– Development of an abscess
• Tumours and tumour-like lesions that occur during
pregnancy and lactation are usually benign.
20
22. Patient approach with breast ds
• The cytological findings should always be
evaluated in conjunction with the clinical and
radiological findings (triple assessment).
– P/E alone is ~ 70% to 90% accurate;
– Mammography alone,~ 85% to 90% accurate;
– FNA biopsy alone, ~ 90% to 99% accurate
• Indication for biopsy after FNA
– Equivocal cytological diagnoses
– Discordant FNA and radiological results
22
23.
24. Clinical Assessment of the Breast
• A firm, painless mass is usually
the major clinical finding in breast
cancer.
• In addition, skin retraction,
edema, peau d'orange,
inflammation, ulceration, fixation
of the mass to surrounding
structures, and
lymphadenopathy, as well as
nipple inversion, crusting, or
discharge, may all be observed.
24
25. Clinical Assessment of the Breast…
• Palpable → at least 1 cm in
diameter
• The average size detected with
self-examination is ~2.5 cm;
about half of these women have
axillary lymph node metastases
• P/E = sensitivity ranges from
~50%-90%, specificity from ~70%-
90%
25
26. Fibro-
adenoma
Cysts Cancer
Usual Age 15-25, usually puberty and
young adulthood, but up to
age 55
30-50, regress after
menopause except with
estrogen therapy
30-90, most common over
age 50
Number Usually single, may be
multiple
Single or multiple Usually single, may coexist
with other nodules
Shape Round, disclike, or lobular Round Irregular or stellate
Consistency May be soft, usually firm Soft to firm, usually
elastic
Firm or hard
Delimitation Well delineated Well delineated Not clearly delineated from
surrounding tissues
Mobility Very mobile Mobile May be fixed to skin or
underlying tissues
Tenderness Usually nontender Often tender Usually nontender
Retraction Signs Absent Absent May be present 26
27. Clinical Assessment of the Breast…
• The risk that a mass is malignant
increases with age
– Breast masses – At age < 40, ~ 10%
are malignant; at > 50 yrs 60% are
malignant
– Mammographic lesion - At age 40, ~
10% are cancer; but at > 50 yrs >
25%.
– Nipple discharge – at age < 60, 7%
are associated with carcinoma; but in
30% of older women
– About 10% of breast cancers present
with noncyclic pain.
27
28. Clinical characteristics of lesions sampled by FNA
sensation when the needle enters the lesion and the
Clinical characteristics of lesions:
Soft: fibroadenoma, mucoid carcinoma, medullary
carcinoma
Rubbery: fibrocystic change, lobular carcinoma,
fibroadenoma
Variable resistance with popping sensation: fibrocystic
change
Leathery: dense fibrous change, ancient fibroadenoma
Gritty: carcinoma, partial calcification, a few fibroadenomas
Solid: completely calcified ancient fibroadenomas.
28
29. Use of FNAC & Technical considerations
• Full beast examination including axillary LNDS
should be done before taking specimens.
• Any ulcerative lesions should be accessed
tangentially
• Needles = 23 – 25G in palpable lesions are ideal.
• FNA of non-palpable lesions is performed under
ultrasound guidance, in conjunction with the
radiologists.
• Avoid passing through jell → cell lysis
29
30. Indications of FNAC breast
• Investigation of any clinically palpable lump, clinically benign
or malignant as a guide to clinical management
• As a complement to mammography in the screening
situation
• Diagnosis of simple cysts
• The investigation of suspected recurrence or metastasis in
cases of previously diagnosed cancer
• Confirmation of inoperable, locally advanced cancer
• Preoperative confirmation of clinically suspected cancer
• To obtain tumor cells for special diagnosis
31. Adequacy of smears:
Presence of at least four- six clusters of epithelial cells
in all smears each having 5-10 epithelial cells
? at least 200 well-preserved malignant cells be
present for an unqualified diagnosis of cancer
32. Accuracy and limitations of cyto diagnosis
• Accuracy is operator-dependent:
– Sensitivity for malignancy ranges from 65% to 98%, and
specificity from 34% to 100%
• False negative diagnoses < 5%
– Mainly due to sampling error
– About 70% of the target lesions are < 1cm
• False positive diagnoses
– Are usually interpretation errors (evaluation of rare
lesions, diagnostic pitfalls and look-alikes)
– Should be less than 1%
32
33. Accuracy and limitations of cyto
diagnosis
• FNA Cannot distinguish between an in situ and an invasive
ductal carcinoma.
• It cannot identify the presence of lymphatic or vascular
invasion.
• It is less sensitive in tumors with low-grade cancer histology
(e.g., tubular and lobular), papillary proliferations, and
mucinous lesions.
– Low-grade and lobular carcinomas may be mistaken for a
hyperplastic process
• Impact subsequent tissue biopsies
– Hemo siderosis, hemorrhage, and, rarely, partial necrosis
of breast tissue
33
34. Core Needle biopsy VS FNA
• CNB more often used for mammographically identified
calcifications.
• FNA is preferred In pregnant or postpartum patients, in order
to avoid a draining, nonhealing wound
• FNA is also useful for assessment of recurrent lesions,
nonpalpable lesions with US guidance
• The nondiagnostic rate for FNA is higher, and FNA has a lower
negative predictive value.
• Combination of FNA and CNB may be superior to either alone.
• CNB - more sensitivity and ability to distinguish between
ductal carcinoma in situ and invasive carcinoma.
• CNB - more abundant material for the determination of ER,
PR, and HER2 status.
34
35. Cytological evaluation of the nipple and nipple
secretion
Nipple discharge
– Bloody or serous discharges are most commonly due
to large duct papilloma's and cysts.
• During pregnancy → rapid growth and remodeling
is possibility
– It is associated with carcinoma in 7% of women
younger than age 60 but in 30% of older women.
• Worrisome when it is spontaneous and unilateral.
– Cytology of nipple discharge has a low sensitivity
35
36. • Placing a glass slide tangentially to the nipple in such
a way as to touch the drop of secretion, making sure
not to touch the surrounding skin in order to avoid
contamination.
• Ulceration or eczematous changes on the nipple
– Remove carefully any debris covering the ulceration
– Using the non-cutting edge of a scalpel blade or the edge
of a clean slide scrape cells from the surface.
36
37. Complications of FNA breast
• Are few and seldom serious.
– Formation of a hematoma.
• Minimized by prolonged pressure following aspiration
• As a rule, the radiological investigation should be completed
before FNA is done.
– Pneumothorax
• In the axillary tail of a thin patient.
– Needle tract seeding
• Rare in breast cancer.
– Partial infarction of the lesion, particularly
fibroadenomas,
• hinder histologic confirmation
37
39. Modified reporting categories in breast FNA according
to NHSBSP (National Health Service Breast Screening
Program (UK)) guidelines
Reportig
category
Description
C1 Inadequate. Assessment is based on the presence of a sufficient
number of epithelial cells to provide sample adequate for confident
assessment. E.g. Fat and fibrous tissue only
Aspirates from cysts, abscesses, fat necrosis and nipple discharge should
not be classified as inadequate.
Apart from hypocellularity, crush, air-drying, blood and thickness of
smear could cause inadequate sample.
It is helpful to comment on the cause of inadequate specimens.
C2 Benign. Adequate sample without evidence of atypia, composed of
regular epithelial cells, usually in monolayers; background composed of
dispersed individual or paired nuclei.
Benign specific: - Cyst; fibroadenoma; intramammary lymph node.
Benign – non specific diagnosis
39
40. categy Description
C3 Atypia, probably benign. In addition to benign features, certain features not
commonly seen in benign aspirates may be present: nuclear pleomorphism, loss
of cell cohesion, nuclear or cytoplasmic changes (pregnancy, pill, hormone
replacement therapy) and increased cellularity.
C4 Suspicious of malignancy. This category should be used for aspirates with
highly atypical features, that is almost certain that they come from a malignant
lesion, although a confident diagnosis cannot be made due to the following: (a)
specimen is scanty, (b) the sample shows some malignant features in the
absence of overt malignant features, (c) the sample has an overall benign
pattern with large numbers of naked nuclei and/or cohesive sheets of cells but
with occasional cells showing distinct malignant features.
Definitive therapeutic surgery SHOULD NOT be done on based on C3 or C4.
C5 Malignant. Adequate sample containing cells characteristic of carcinoma.
Malignancy should not be diagnosed on the basis of a single criterion.
40
44. • Characteristically manifest by the presence of
pain, redness, swelling & hotness.
• Accounting for less than 1% of breast
symptoms
44
45. Abscess and acute mastitis
• Breast abscesses and acute mastitis occur most
commonly, but not invariably, in the puerperium.
• The diagnosis is usually made clinically
– FNA: - R/O inflammatory carcinoma
• Aspirates contain neutrophils and macrophages in
considerable numbers as well as abundant cell debris.
• Reactive epithelial cells, derived from adjacent
inflamed and possibly lactating breast tissue may also
be found.
45
46.
47. 47
Regenerative epithelial atypia in mastitis
(A) Atypical, reactive/ regenerating epithelial cells with a background of histiocytes,
inflammatory cells and debris (MGG, HP);
48. Sub areolar abscess
• Squamous metaplasia of lactiferous ducts resulting in ductal obstruction
• Keratin shed from metaplastic cells plugs the ductal system,
causing dilation and eventually rupture of the duct.
• There is often a history of the recurrent formation of a tender
mass in the sub areolar region, sinus tract formation and
discharge with partial healing.
• Histologically, inflammatory sinus tract lined by granulation
tissue but often partially by squamous epithelium.
– Squamous Metaplasia of Lactiferous Ducts, recurrent subareolar
abscess, periductal mastitis,
• More than 90% of the afflicted are smokers.
48
49.
50. Epithelial cells stained with Diff-Quik (A) and Pap stain (B). In A, the cells are columnar
or oddly shaped. In B, the cytoplasmic stain suggests squamous derivation. C.
Multinucleated giant cell. D. Tissue section showing squamous metaplasia of a breast
duct surrounded by inflammatory infiltrate
52. Mammary duct ectasia
• Histologically there is dilatation of large or intermediate ducts
that are filled with secretion, and to a variable extent foamy
macrophages, siderophages and cholesterol crystals
– Forming the inspissated, pasty material seen on gross examination
• Epithelial proliferation is not a feature, but reparative changes
in epithelium next to areas of inflammation may give rise to a
spurious impression of atypia both histologically and
cytologically.
• Rupture of the epithelial layer and basement membrane
cause chronic inflammation, fibrosis and scarring of the
surrounding stroma.
52
53. Mammary duct ectasia (plasma cell mastitis)
• Usually in the 5th-6th decade
• Poorly defined periareolar mass with Skin
retraction
• Thick , white nipple secretion
• pain & erythema- uncommon
• May confuse with carcinoma
56. Morphology
• Dilation of ducts with inspissated secretion
with Lipid-laden macrophages
• Marked Periductal & interstitial
granulomatous inflammation
Sometimes plasma cell rich inflammation
‘’ plasma cell mastitis’’
• Fibrosis - skin and nipple retraction
• No epithelial proliferation
57. cytology
• Thick & white aspirate which appear
amorphous granular back ground
• secretory debris and a variable number of
foamy macrophages.
• No other significant finding on cytology
58. Paget’s disease
1-2%
A type of in situ carcinoma that arises in
main excretory ducts of breast and
extends intraepithelially into skin of nipple
Associated with underlying DCIS or invasive
disease (50% have underlying lump or mass)
Gross: skin is fissured, oozing, ulcerated;
resembles eczema
61. cytology
Background of keratin, squamous cells,
inflammatory cells & debris(scrape smears from
nipple)
Large malignant cells, single and in small groups,
closely associated with squamous & inflammatory
cells
Abundant pale cytoplasm with distinct borders
Obvious nuclear features of malignancy
63. Fat necrosis
• Fat necrosis of the breast may be associated with
– Rupture & extravasation of contents in mammary duct
ectasia and fibrocystic changes
– Following surgery and radiotherapy.
– Traumatic fat necrosis – tends to be more superficial
(often in subcutaneous fat),
– history of injury “grandmothers' disease”
• The lesion is often tender on palpation.
63
64. Cytological findings: fat necrosis
• background of granular debris, fat droplets
• Foamy macrophages and multinucleate giant cells
with foamy cytoplasm
• Small irregular groups of (reactive) histiocytic cells
• Fragments of normal as well as degenerate fatty tissue
• Variable numbers of other inflammatory cells but
usually sparse
• Few if any epithelial cells
64
65.
66. Diagnostic pitfalls
• Abnormalities of the macrophage
• Reactive epithelial cells
• Giant cells
• Clinical feature, the background & fat droplets
are important clues
67. . A. Cluster of ductal cells with enlarged nuclei. B. Markedly atypical
macrophages with enlarged, irregular nuclei. (Diff-Quik stain.)
68. Granulomatous mastitis
• Various systemic and local conditions can give rise to
the formation of a granulomatous response in the
breast.
– Tuberculosis – is more common in developing countries.
– Fungal infections,
– Part of the spectrum of duct ectasia.
– Foreign body reaction to implanted silicone and tumours.
– Idiopathic granulomatous mastitis
68
69. Clues to the most probable aetiology of the
granulomatous infiltration may be found from history
and P/E findings
• Special stains (, Ziehl-Neelsen, PAS, methenamine
silver ) is important to identify specific organisms.
69
70. Cytological findings:
• Sheets or clusters of epithelioid cells with abundant
cytoplasm and elongated nuclei
• Multinucleate giant cells associated with epithelioid cells.
The giant cells often have epithelioid cell characteristics.
Langhans type giant cells may be identified
• A variable number of inflammatory cells: lymphocytes,
plasma cells, neutrophilic granulocytes
• In tuberculosis and fungal infections, a mixture of
necrotic debris and inflammatory cells is often the
dominant finding
• Admixture of ductal or lobular epithelial cells which may
be reactive with enlarged nuclei and distinct nucleolus.
70
72. BREAST DISEASE IN MALES
GYNECOMASTIA:
• Enlargement of the male breast due
to hypertrophy and hyperplasia of
glands and stroma, unilateral
(common) or bilateral
• Caused by increase in estrogen to
androgen ratio (liver cirhosis; drugs=
marijuana, steroids, ART; hormone
producing tumors ,puberty ; often
idiopathic
73. Cytological findings:gynaecomastia
• Scanty or moderately
cellular smears
• Small- to medium-sized
epithelial fragments that
may be hyperplastic and
three-dimensional
– Resembles
fibroadenoma
• Small to moderate
numbers of bipolar cells.
73
74. BENIGN EPITHELIAL BREAST LESIONS
Non proliferative breast
disease
Cysts with apocrine
metaplasia
Fibrosis
Adenosis
Proliferative disease
without atypia
Epithelial hyperplasia
Sclerosing adenosis
Complex sclerosing scar
Papillomas
Proliferative disease
with atypia
Atypical ductal hyperplasia
Atypical lobular
hyperplasia
75. Breast cysts
• Cyst – A lesion that contain fluid
• The great majority of cyst fluids are benign; only
about 2% prove to be carcinoma.
• On the other hand, a small number of carcinomas are
cystic and yield fluid that looks grossly that of benign
cysts.
• Fluid types range from thin, clear, straw colored fluid
to thick, opaque, green or brown material
75
76. • Two main forms of
cyst
– Those lined by a
single layer of
cuboidal or
flattened
attenuated
epithelium and,
– More commonly,
those lined by
apocrine
epithelium
76
77. A. Macrophages, some binucleated, with foamy cytoplasm. B. Exceptionally large
“foam” cells. C. Clusters of epithelial cells, some of which have aprocrine features.
78. Fibrocystic change(FCC)
• The most common cause of a palpable breast lump,
• The typical between 30 and 50 years old (rare before 25 and
after menopause)
• Often, fibrocystic lumps shows cyclic change and are more
commonly tender or painful than malignant ones.
• Presents as a mass of variable size that may be ill defined or
well defined; as solitary lesion or bilaterally
78
79. • Basic spectrum of Histologic ‘fibrocystic change’ are:
1. The formation of cysts
2. Apocrine metaplasia of cyst lining cells and of duct
and lobular epithelium
3. Rupture of the cyst lining with extravasation of
contents and associated inflammation
4. Fibrosis of the stroma
5. Chronic inflammation of non-specific type
6. Adinosis ( increase nu of acinai )
7. Fibroadenomatoid change.
79
80. Cytological findings: FCC
• Scanty, often watery smear
• Low or moderate cellularity
• Fat or fibrous stroma in variable
quantities.
• Three-dimensional epithelial
aggregates representing intraductal
hyperplasia
• Macrophages and granular debris form
microscopical cysts
80
81. Cytological findings: FCC
• Sheets or fragments of
ductal epithelium with
bland nuclei arranged in
a honey-comb pattern
with admixed
myoepithelial cells and
dispersed bipolar nuclei
81
82. • Benign Apocrine cells either
dominating the cellular
picture or in variable numbers
– Form large cohesive sheets
or dispersed singly or in
small groups
– Large, round and relatively
hyperchromatic nuclei
– Large and prominent
nucleoli
– Abundant, well-defined
and usually granular
cytoplasm.
82
85. Proliferative Breast Diseases without atypia
• They rarely form palpable mass
• More commonly, detected as a mammographic
densities or incidental finding in biopsies
• characterized by proliferation of ductal epithelium or
stroma without cellular abnormalities suggestive of
malignancy
• slightly increased risk (1.5 - 2 x normal) for breast
carcinoma
86. • Histologically, the basic appearances described as fibrocystic
changes frequently include epithelial proliferative changes of
various types.
• Cytologically, this may be suspected when an aspirate,
otherwise typical of ‘ simple ’ fibrocystic change, is cellular
with the additional cells being non-apocrine type
• It is preferable to report the cytological
findings in this category of lesions as
consistent with ‘proliferative fibrocystic
change’ with or without atypia.
87. The following entities are included
Moderate or florid epithelial hyperplasia
Sclerosing adenosis
Papilloma
Complex Sclerosing lesions(Radial scar)
Fibroadenoma with complex features
88. Epithelial hyperplasia
presence of more than two cell layers
Hyperplasia is moderate to florid when there are
more than four cell layers
Usual ductal hyperplasia and lobular hyperplasia
89.
90. Cytological findings: epithelial
hyperplasia
• Low or moderate cellularity with small epithelial
groups
• Nuclei may be enlarged, but the chromatin pattern is
fine and nucleoli inconspicuous
• The epithelial groups contain the smaller darker
ovoid nuclei of myoepithelial cells
• An absence of nuclear atypia, widespread loss of cell
cohesion or necrotic debris
90
92. number of acini per terminal duct is increased
to at least 2x the number found in uninvolved
lobules
• the acini are compressed & distorted in
central portion & dilated at periphery
accompanied by prominent stromal fibrosis
• There is hyperplasia of both epithelial and
myoepithelial cells with distortion of the lobular
structure
Sclerosing adenosis
93.
94.
95. Cytological findings
• Moderate to high
cellularity
• Small groups of
uniform epithelial cells
and myoepithelial cells
• The relationship of
sclerosing stroma and
microacinar epithelium
may be preserved.
95
96. Papillomas
• can be large duct or small duct
• LDP is a papillary benign growth within the major
lactiferous duct
• commonly present with serous or bloody breast
discharge
• Usually soft on palpation; rarely exceed 30mm
• small mass may be felt in the region of the nipple
97. - Small duct papilloma(SDP)- are commonly
multiple & located deeper within the ductal
system
- SDP-increased risk of Ca than LDP
- Epithelial hyperplasia & apocrine metaplasia
are frequently present
98.
99. Cytological findings:
• Variable cellularity with a basic benign pattern
• The epithelial cells are often dispersed or in small groups
• Complex, folded three-dimensional epithelial aggregates
• Papillary clusters may be preserved
• Papillary stromal fragments may be present
• Rows of palisaded columnar epithelial cells,
• Small numbers of bipolar cells
• Apocrine cells may be present
• A small amount of debris and macrophages may be present.
99
102. Lactating adenoma and lactational change
in benign mass lesions
• Lactating adenoma occurs more commonly
during rather than after pregnancy.
• Regard as a fibroadenoma or tubular adenoma
modified by the hormonal influences of
pregnancy.
• Foci of lactational change may occasionally be
seen within fibroadenomas and other benign
breast changes outside of the context of
pregnancy.
102
103. Cytological findings:
• Moderately cellular aspirates composed of
dispersed cells singly or in small groups in a foamy
background containing cell fragments and lipid
droplets
• The cytoplasm is vacuolated or wispy and
stripped epithelial nuclei may be present
• The nuclei are uniform, round or ovoid with a
smooth nuclear membrane and show fine,
stippled chromatin and a prominent nucleolus.
103
104. (Proliferative DS) Hyperplasia with atypia
• There is correlation between the degree of
hyperplasia and the risk of subsequent development
of invasive carcinoma. 5x increased risk
• Atypical ductal hyperplasia (ADH) has been defined
as being less than 3mm in maximum diameter with
low-grade cytology.
• Any atypical ductal proliferation with high-grade
cytology must be called DCIS whatever the size.
104
105. Cytological findings: hyperplasia with atypia
• Increased crowding and overlapping of cells within the groups
• Three-dimensional epithelial aggregates
• Obvious papillary groups
• Decreased cohesion of epithelial cells
• More variation in nuclear size
• More prominence of nucleoli
• Less evidence of cells of apocrine type.
The features used are highly subjective.
Where there is any doubt as to the presence of atypia, the triple
assessment findings should be considered and excision biopsy or
follow-up undertaken, as appropriate.
105
109. Lobular hyperplasias
• Characterised by a proliferation
of small and often loosely
cohesive cells originating in the
TDLU.
• Encompasses LCIS and ALH
• These lesions are usually not
palpable and have no radiologic
appearance.
109
110. Cytological findings:
• Loosely cohesive groups
• Uniform cells with occasional
intracytoplasmic lumina
• Slightly irregular and eccentric
nuclei.
• There are no reliable cytological
criteria that help in
differentiating between lobular
neoplasims and from invasive
lobular carcinoma (ILC)
110
111. Benign tumours and tumour
• Typically present as firm, discrete and highly mobile
lump
• Commonly presents between the ages of 20 and 35
years, though it can be seen in women of any age
• The size usually range from 5–30mm
• On mammograms, fibroadenomas typically present as
round, well-defined lesions.
• Fibroadenoma result from both stromal and glandular
proliferation.
• Malignant change is exceedingly uncommon
111
112. Cytological findings: Fibroadenoma
The cytologic studies of fibroadenoma characteristically
display a triad of numerous epithelial cells, naked oval
nuclei, and stromal fragments
• Moderate or high cellularity
• large sheets or LP = three-dimensional clusters with
antler- or staghorn-shaped epithelial groups.
• Some loss of epithelial cohesion
114. Cytological findings: Fibroadenoma
Epithelium : -
• Have regular nuclear spacing
• Approximately one or two
erythrocytes sized, round or slightly
ovoid, nucleus with finely granular
chromatin pattern
• Small, 1-2, round nucleolus &
• A few nuclear atypia
• Generally
– Best visualized by papanicolaou
stained smear
– In air-dried preparations –
sometimes satisfactory close
examination is possible only at the
edge of the epithelial group
114
115. Cytological findings: Fibroadenoma
• Many naked bipolar cell
nuclei in the background
• If apocrine or foamy cells
are present they are few.
• Fibrillar stromal fragments
– Bluish-gray with the
Papanicolaou stain
– Magnita with a
Romanowsky-type stain
115
116.
117. Cytological findings: Fibroadenoma
• Aspirate in different variants of fibroadenomas may
lead to
– Scant cellularity in older or fibrotic lesions or
– Abundant cellular stroma that merge with phyllodes
tumours
– Highly myxoid stroma on smears, that can mimic the
pattern mucinous carcinoma.
– Occurrence of apocrine metaplasia, haemorrhagic
infarction, especially during pregnancy, squamous
metaplasia (more common in phyllodes tumour) and
stromal metaplasias, including the formation of smooth
muscle, cartilage, bone or dystrophic calcification.
117
118. Cytological findings: Fibroadenoma
• Bare nuclei in the background could be
– Stripped epithelial nuclei
– Myoepithelial nuclei,
– Some stromal cells nuclei – more spindly nuclei and a
strand of pale blue cytoplasm at each pole
118
119. Tubular adenoma
• Are part of fibroepithelial
neoplasms.
• The clinically indistinguishable
from fibroadenoma
• Histologically: -densely packed
benign tubular structures with a
double layer of epithelial and
myoepithelial cells but with very
little stroma.
• Softer than the average
fibroadenoma.
• Relatively rare 119
120. Cytological findings: tubular adenoma
• Moderate to highly cellular aspirate with a basic
benign pattern
• No large antler-like groups are seen
• The epithelial cells are cytologically benign and in
small groups, some displaying a microacinar
arrangement
• Bipolar cells are fewer than seen in fibroadenomas.
120
121. Lactating adenoma and lactational change
in benign mass lesions
• Lactating adenoma occurs more commonly
during rather than after pregnancy.
• Regard as a fibroadenoma or tubular adenoma
modified by the hormonal influences of
pregnancy.
• Foci of lactational change may occasionally be
seen within fibroadenomas and
121
122. Cytological findings: lactating adenoma and
lactational change in benign mass lesions
• Moderately cellular aspirates
• dispersed cells singly or in small groups in a
foamy background containing cell fragments and
lipid droplets
• The cytoplasm is vacuolated
• The nuclei are uniform, round or ovoid with a
smooth nuclear membrane and show fine,
stippled chromatin and a prominent nucleolus.
122
123. Phyllodes tumour
• fibroepithelial tumors from benign with a strong
resemblance to fibroadenomas, through borderline
with notable stromal overgrowth and proliferation to
malignant, in which the stroma is frankly sarcomatous.
• Accounting for less than 1% of all breast tumors.
• The enucleation that would be adequate for a
fibroadenoma may result in a local recurrence if
applied to a phyllodes.
• A margin of normal tissue around a known or suspected
phyllodes tumour is removed.
123
124. Count….
Histologic distinction among phylodes is based on the
degree of;
• cellular atypia of stromal cells
• mitotic activity of the stromal cells and
• the appearance of the margin of the tumour
This classification is highly subjective and the important
is to DX this tumor
125. Benign phyllodes tumour
• There is considerable overlap with fibroadenoma.
• The differentiation between giant fibroadenoma and
benign phyllodes tumour depends entirely on the
histological appearance of the stroma. and the
distinction is frequently impossible cytologically.
• Tend to be larger on presentation
• Majority of phyllodes tumors are benign (>60%)
125
126. Count….
• On examination, these tumours are softer, less
mobile and less well-defined than
fibroadenomas.
• The smears are usually very cellular and the
differentiation from a cellular fibro adenoma
can be impossible.
• The clinical features are of assistance in
balancing the probabilities.
128. Cytological findings: benign phyllodes tumour
• Cellular smears with occasional large sheets of benign
epithelium
• Numerous plump & single stromal cells
• little cellular pleomorphism
• The prominence and number of bipolar cells are usually
greater than in fibroadenomas
• Obvious stromal fragments, some large and with high
cellularity
128
130. Borderline phyllodes tumours
• Often present with a large tumour that has grown
rapidly.
• histologicallycharacterised by
• modest stromal hypercellularity,
• moderate cellular pleomorphism, an
• intermediate number of mitoses with
• heterogeneous stromal expansion .
130
131. Cytological findings:
• Cellular smears
• Numerous plump, single stromal cells with
moderate cellular pleomorphism
(Predominant)
• Occasionally bizarre, degenerative type
nuclear abnormalities
• Occasional mitoses.
131
132.
133. high-grade malignant phyllodes tumour :
Cytological findings:
• abundantly cellular
• Large atypical stromal cells, often in cohesive
groups
• obvious mitoses are seen
• The epithelial content sparse
• epithelial content is benign but may demonstrate
hyperplasia and mild atypia.
133
134.
135.
136.
137. Criterion Benign Malignant
Cellularity Poor or moderate Usually high
Cell-to-cell
cohesion
Good, with large defined
clusters of cells
Dissociated cells
Cell arrangement Even, usually in flat sheets Irregular, overlapping,
often three-
dimensional
Cell types Mixture of epithelial,
myoepithelial and other
cells, e.g. stromal
Usually uniform cell
population
Bipolar (elliptical)
bare nuclei
Present Not conspicuous
Background Generally clean Occasionally with
necrosis and
macrophages 137
138. Criterion Benign Malignant
Nuclear characteristics
Size (in relation to
RBCs)
Small Variable, often large,
depending on tumour type
and grade
Pleomorphism Rare Common
Nuclear membranes
(PAP)
Smooth Irregular with indentations
Nucleoli (PAP) Indistinct or small
and single
Variable, may be prominent
Chromatin Smooth or fine Clumped, may be irregular
Additional features Apocrine metaplasia,
foamy macrophages
Mucin, intracytoplasmic
lumina 138
139.
140.
141.
142.
143.
144.
145. Histopathology
Classification of Primary Breast Cancer :-
A. Non Invasive Epithelial Cancers :-
I. Ductal Carcinoma In Situ (DCIS) :-
1. Papillary
2. Cribriform
3. Solid &
4. Comedo types
II. Lobular Carcinoma In Situ (LCIS)
B. Invasive Cancers :-
I. Invasive Ductal Carcinoma :-
II. Invasive Lobular Carcinoma
147. I. Ductal Carcinoma In Situ (DCIS) :-
• Dx has increased dramatically with the introduction of
mammography
• neoplastic population of cells limited to ducts by basement
membrane
• Mastectomy for DCIS is curative in 95% of cases!
• Categorized by :-
The size of the lesion
Nuclear grade
The presence & extent of comedo necrosis
148. 1. Papillary DCIS
• Papillary growth within ductal lumina
• Lined by Tall Columnar cells.
149. 2. Cribriform DCIS
• Malignant looking cells surrounding free spaces
• Spaces are evenly distributed & regular in shape
• Lumen filled with calcifying material.
150. 3. Solid DCIS
• Pleomorphic cancer cells proliferate, obliterate the lumina,
distend the duct.
151. 4. Comedo DCIS
• The cells outstrip their blood supply
• X-ized by large central zone of necrosis with calcified debris.
153. II. Lobular Carcinoma In Situ (LCIS) :-
• The true incidence in the general population is unknown, due to
the lack of clinical & mammographic signs.
• 80 – 90% of cases occur in premenopausal women
• LCIS cells have a higher level of estrogen receptor (ER) positivity
• Multicentricty identified in 60 – 80% &
• Bilateral disease is present in 23 – 35%.
155. • Histological grading is an integral part of the
histopathology report on all breast carcinomas.
• Preoperative (cytological) grading is possible, but
is not commonly done.
• cytological grading based on nuclear futures.
– show a good correlation with both histological
grading and ploidy.
159
Cytological grading of
invasive breast carcinoma and DCIS
157. DCIS cytology
Specific diagnosis or classification of DCIS
cannot be made on FNAC
Epithelial cells mainly cohesive forming large
sheets,often with holes or papillary fragments
bipolar nuclei absent
Variable ,mild to moderate epithelial atypia
Necrotic debris
Macrophages
158. • more heterogeneous in appearance than
high-grade DCIS both histologically and
cytologically.
• The criteria overlap with criteria for epithelial
hyperplasia.
• A diagnosis or suggestion of a low-grade/non-
high-grade DCIS should lead to a local excision
only.
162
Low- and intermediate-grade DCIS
159. • Very large three-dimensional epithelial
aggregates, cribriform and solid,
• often more cohesive than high-grade lesions
• Cell monotony with moderate atipia
• Micropapillary groups or true papillary structures
• Monolayer sheets
• Variable number of single cells usually few,
• Recognizable myoepithelial cell nuclei in
epithelial aggregates and sheets not rare (!).
163
Cytological findings: low- and intermediate
grade DCIS
160.
161. • Usually cell-rich smears,
• Solid or cribriform, three-dimensional aggregates of
epithelial cells with high-grade nuclear atypia
• structures as well as monolayer sheets
• Variable number of single cells; occasional cases may
present as an almost exclusively single cell population
• Microcalcifications (without a tumor)
• Comedo type necrosis.
• A few myoepithelial cells may be seen
165
Cytological findings: high-grade DCIS
163. • Proliferation of fibroblasts (a
sign of tumor induced
stromal reaction)
• Cell poor elastoid stromal
fragments
• Invasion of single or small
groups of 2 – 3 carcinoma
cells in stromal tissue and
fatty fragments
• Intracytoplasmic vacuoles
• Tubular structures
167
Criteria suggestive of invasive lesion!!
165. Infiltrating duct carcinoma
Cell rich smears, single population of
epithelial cells
no myoepithelial cells,
no single bare bipolar nuclei
Variable loss of cell cohesion irregular
clusters and single cells
Single epithelial cells with intact cytoplasm
166. Count…
Mod to severe nuclear atypia, enlargement,
pleomorphism, irregular nuclear membrane&
chromatin
Fibroblasts & fragments of collagen( stromal
desmoplasia) a/w atypical cells
Intracytoplasmic neolumina in some cases
Necrosis unusual
171. LOBULAR CARCINOMA
• centrally located
• more often bilateral,
greater tendency to be
multicentirc
• Less stromal reaction
• Small sized cells in line
b/c of adhesive
molecule e-cadherin
172. LOBULAR CA…….
Cytological findings
A variable, often poor cell yield
Cells single and in small clusters, single files
characteristic ( Indian file)
Scanty cytoplasm; many naked nuclei; nuclear
moulding in cell clusters
Small hyperchromatic nuclei of relatively uniform size.
Intracytoplasmic lumina/mucin vacuoles/signet ring cells
Few if any naked bipolar nuclei
175. • Common in younger age group and typically under 50
years.
• Soft, fleshy, mobile & well defined mass mimics benign
L.N metastasis common
Prognosis favourable
• Histologically, it is completely circumscribed (pushing
border) composed of large syncytial sheets of high-
grade atypical cells with no glandular structures and
secretion (comprising at least75% of tumor area) and
scant intervening stroma with a prominent
lymphoplasmacytic infiltrate.
179
Medullary carcinoma
176. • cellular smears
• Poorly cohesive large malignant cells with abundant
pale staining cytoplasm, some forming syncytial
aggregates
• Large angular nuclei with coarse chromatin and
prominent nucleoli.
• Mitotic figures are not unusual
• The background of small lymphocytes and plasma cells
is a vital feature but their number is very variable.
• Tumour giant cells are sometimes a feature.
180
Cytological findings:
179. Colloid Carcinoma/Mucinous carcinoma
• well defined, mobile, soft to hard mass mimic fibro
adenoma or cysts .
This is typically a tumor of older post-menopausal
women occurring at an age of 60 years or more.
• Most are low grade, slow growing and
• favourable prognosis with a 5-year survival of up to
86%.
180. Cytological findings
• On spreading, the aspirate is quite glairy, hinting at a high
mucin content
• usually cellular
• The single and agrigates of cells are bathed in mucin of
variable density. This is more obvious in MGG (stains
violet)
• Bipolar cells are absent
• The cells are small, with small, uniform, round nuclei,
smooth nuclear outlines, bland, possibly granular,
chromatin and inconspicuous nucleoli
• Moderate atipia
183. • Generally has a good prognosis.
• very slow growing lesions and having a
significantly collagenous stroma,
• these tumours commonly present when small as
firm and discrete or on screening mammogram.
• average: 50yrs
• On aspiration it can be quite difficult to obtain
smears with adequate cellularity and suboptimal
sampling is a major cause of not reaching a
definite diagnosis of malignancy.
187
Tubular carcinoma
184. • There is slight anisonucleosis and mild
hyperchromasia.
• The chromatin is finely granular and evenly
distributed
• Nucleoli are indistinct or small
• Bipolar nuclei are present in occasional cases (33%)
– May be from surrounding breast tissue
• No apocrine, or foam cells present, rare Necrosis
188
Cytological findings:
185.
186. • Charaterestic features
– open tubular structures,
(straight and ridged, or
angular, twisted or branched)
– Glands with pointed, arrow
head outline
• Predominantly in Cohesive
clusters, Dissociated cells
where present may have a
columnar appearance
190
Cytological findings:
187. • Pure apocrine carcinoma is unusual, forming
only 1 –4% of all breast carcinomas.
• Elderly women
• The tumours may present with all grades of
atypia.
• Aspirates tend to be cellular and the cells
dispersed
191
Apocrine carcinoma
188. • The cells are large with abundant acidophilic cytoplasm
that may be granular but this is less marked than in
benign apocrine epithelium
• The cell borders tend to be indistinct or ragged in
contrast to the well-defined borders of benign apocrine
cells.
• nucleus is large and the chromatin coarse and unevenly
distributed
• nucleolus is very large.
• Multiple nucleoli are also seen in the higher-grade
tumours.
192
Cytological findings:
192. Referances
• Demay,the art and science of cytopathology
• Orell and Sterrett’s fine needle aspiration
cytology,5th edi
• Comprhensive cytopathology,4th ed
• Robins 8th edi
• WHO gaide line of breast Cancer
