Fine Needle Aspiration Cytology

BREAST
Grace T. McKee, MD

Introduction

The breast is composed of fat and stroma that support glandular tissue, a branching ductal
system that leads to 6-10 main ducts, which open onto the nipple. Both benign and
malignant lesions develop in the breast. In young women fibroadenomas are common
lesions but as women get older, fibrocystic changes tend to be more common. Other benign
lesions include fat necrosis and inflammatory conditions such as breast abscess and
mastitis. Less common benign lesions such as hamartomas and pseudoangiomatous
hyperplasia can occur. Ductal hyperplasia forms part of fibrocystic changes. Atypical ductal
hyperplasia can be difficult to distinguish from low grade ductal carcinoma in situ and these
lesions represent a spectrum of disease that can develop into breast carcinoma. Radiation
changes can produce a mass, which may appear atypical on aspiration cytology. Similarly,
pregnancy and lactational changes can also be mistaken for malignancy on aspirates hence
clinical information is essential for an accurate cytological diagnosis.

Malignancies in the breast may be primary or metastatic Those metastatic to the breast
include lymphoma, malignant melanoma and other secondary tumors such as renal,
bronchial, ovarian or pulmonary carcinomas. Most significant from a diagnostic perspective
is primary breast carcinoma is the ductal type, not otherwise specified (NOS). The second
most common primary mammary neoplasm is lobular carcinoma. Ductal carcinoma in situ
and lobular carcinoma in situ are easily diagnosed on excision biopsies but are more
difficult to diagnose with confidence on cytology.

Breast cytology has a role for both screening and diagnostic purposes. Any lesion detected
on mammographic screening can be sampled with a fine needle, by direct aspiration if
palpable or by stereotactic or ultrasound guidance if non-palpable. If the cytology sample is
unsatisfactory or equivocal, core biopsy or frozen section can be utilized. Palpable breast
masses are easily aspirated and can be quickly processed for a rapid diagnosis.

Fine-needle aspiration cytology is a useful tool in the diagnosis of breast lesions, both
palpable and non-palpable. It is a safe, quick, inexpensive (as compared to core biopsies),
and relatively painless procedure, and can be performed by clinicians as well as
pathologists. In the hands of cytopathologists the inadequacy rate is low as rapid stains can
be performed to evaluate specimen adequacy and the procedure repeated if necessary. Cyto-
histological correlation is excellent in the hands of experienced cytopathologists. One
minor disadvantage of fine-needle aspirates is that it is not always possible to distinguish
between invasive and in situ lesions, but core biopsies too have similar problems in some
cases.
The material aspirated is either smeared on a glass slide or expelled into Cytolyt solution,
and the needle is rinsed with the same solution for each pass made. The fluid can be used to
make several almost identical slides thus enabling the lab to save material for special stains
such as estrogen and progesterone receptors and HER2/neu protein over-expression.

CYTOLOGICAL FEATURES

Benign

Normal breast yields only fat, stroma and a few benign ductal cells. Benign normal breast
is rarely aspirated unless the actual lesion is missed by the needle. In fact, aspirates from
normal breast would not comply with the widely observed criterion for an adequate breast
aspirate: at least five to six clusters of epithelial cells. Exceptions to this rule include fat
necrosis and inflammatory lesions.

Mastitis and breast abscess aspirates contain abundant neutrophils, histiocytes,

multinucleated giant histiocytes, a few degenerating epithelial cells and proteinaceous
material that can mimic necrosis. They are not uncommon findings in lactating women.
Fat necrosis develops after trauma, either because of a direct blow to the breast or
following surgery or radiation therapy. Clinically and mammographically fat necrosis
mimics breast carcinoma, with a hard, irregular mass. However, the aspirate is diagnostic,
as it is composed of degenerating adipocytes with abundant lipophages.

Fibroadenoma presents as a firm, smooth, mobile breast mass. It usually feels rubbery and
grips the needle tip. Aspirates are usually cellular with large branching sheets of benign
ductal cells, with a sprinkling of 'sesame seeds' on the surface myoepithelial cells. In
ThinPrep smears the single background myoepithelial cells tend to accumulate adjacent to
the ductal cells. The ductal cells often show overlapping, suggesting an element of ductal
hyperplasia. Stromal fragments of varying sizes are seen, containing spindled nuclei.

Low grade phyllodes tumors are also fibroepithelial in composition, with the glandular
element closely mimicking that of fibroadenoma. However, ductal hyperplasia is much
more common in phyllodes tumors. The stromal component tends to be prominent, with
large stromal fragments that are hypercellular. Abundant stromal cell groups may also be
noted. Malignant phyllodes tumors show unequivocal features of malignancy.

Fibrocystic change is a fairly common lesion encompassing cystic change with apocrine
metaplasia, ductal hyperplasia of usual type, and other forms of epitheliosis. Cytological
appearances include sheets and groups of overlapping benign ductal cells with
myoepithelial cells, apocrine metaplasia, foamy macrophages and calcium. The features can
mimic those of fibroadenoma cytologically, but the typical clinical finding is an ill-defined
thickening or ridge rather than the smooth mobile mass of fibroadenoma. Cystic changes
can progress to form palpable cysts which are easily aspirated. The fluid may be clear and
colorless or turbid, brown, green or bloodstained.
Cyst fluids contain proteinaceous material, benign ductal cells that may appear degenerated
or mildly atypical, apocrine metaplastic cells, and foamy macrophages. Brown or green
cyst fluid usually indicates prior bleeding and this is confirmed by the presence of
hemosiderin-laden macrophages on the slide. Apocrine metaplastic cells have abundant
granular cytoplasm, round nuclei and prominent nucleoli. They can be binucleate and may
appear atypical as the nuclear size is variable.

Collagenous spherulosis is a benign lesion that may accompany ductal or lobular

hyperplasia. Aspirates show globules of extracellular material (which stain pale blue with
the Papanicolaou stain and magenta with DiffQuik), benign ductal, apocrine metaplasia and
myoepithelial cells. The differential diagnosis includes adenoid cystic carcinoma.

References

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 IMGENES CITOLGICAS DE MAMA

Figure 1
Breast FNA, Fat.
Fat cells, or adipocytes, are large spherical cells with translucent cytoplasm and small
eccentric nuclei. They are seen in both benign and malignant aspirates. 40x
Figure 2
Breast FNA, Benign ductal cells.
Normal breast aspirates yield benign ductal cells, often accompanied by myoepithelial
cells. 40x

Figure 3
Breast FNA, Abscess.
Fine-needle aspirates of breast abscesses do not usually show epithelial cells. Cellular
debris, lysed red cells and neutrophils are common features. 40x
Figure 4
Breast FNA, Fibroadenoma.
A large stromal fragment is present, containing a few small spindle-shaped nuclei. Stromal
fragments may be seen in aspirates of benign breast tissue as well as in fibroepithelial
lesions such as fibroadenoma. Stromal fragments from phyllodes tumors are much more
cellular. Note the small group of benign ductal cells also present. 40x

Figure 5
Breast FNA, Fibroadenoma.
A large branching sheet of cohesive, uniform benign ductal cells is seen overlying a stromal
fragment. Note the small, somewhat spindled stromal cell nuclei within the stromal
fragment. 20x
Figure 6
Breast FNA, Fibroadenoma.
Typically, fibroadenoma aspirates contain large branching sheets of benign ductal cells as
seen in this illustration. 20x

Figure 7
Breast FNA, Fibroadenoma.
This is another example of the branching appearance of ductal cells in fibroadenoma. 20x
Figure 8
Breast FNA, Fibroadenoma.
In some instances the ductal cell groups have small rounded projections as seen here rather
than the long branches noted in the prior two figures. 20x

Figure 9
Breast FNA, Fibroadenoma.
In this field the edges of the ductal group are not smooth as the previous two images above,
possibly due to the liquid-based processing. Within the group of ductal cells, and at the
upper edge, a few myoepithelial cells are noted. With ThinPrep processing myoepithelial
cells tend to be seen adjacent to the ductal groups rather than scattered in the background as
seen in conventional smears. 40x
Figure 10
Breast FNA, Fibroadenoma.
A branching sheet of benign ductal cells with overlying myoepithelial cells produce the
characteristic 'sesame seed on a bun' appearance. 40x

Figure 11
Breast FNA, Low grade phyllodes tumor.
Phyllodes tumors are, like fibroadenomas, also fibroepithelial lesions. However even the
low grade lesions have the capability of recurring if not excised with a wide margin. The
glandular component is similar to that seen in fibroadenoma although it can be much more
cellular and hyperplastic appearing. This illustration shows a three-dimensional group of
ductal cells showing nuclear overlapping and crowding, suggestive of hyperplastic changes.
40x
Figure 12
Breast FNA, Low grade phyllodes tumor.
This stromal fragment is hypercellular and contains crowded plump spindle cells. Many
single spindled stromal cells may also be seen in the background in this lesion. 60x

Figure 13
Breast FNA, Fibrocystic changes.
This field shows a tight cluster of benign ductal cells with foamy macrophages at each end,
with secretory material in the background. 40x
Figure 14
Breast FNA, Fibrocystic changes.
This small group of benign ductal cells is from an aspirate of fibrocystic changes. 40x

Figure 15
Breast FNA, Fibrocystic changes.
Background secretion, blood and apocrine metaplastic cells are seen in fibrocystic changes.
20x
Figure 16
Breast FNA, Breast cyst.
This cluster of benign ductal cells shows mild atypia in the form of visible nucleoli and
slight nuclear enlargement. Such minimal changes are often noted in breast cyst fluids. 60x

Figure 17
Breast FNA, Breast cyst.
This field shows a small group of benign epithelial cells, one vacuolated, with cyst debris in
the background. 40x
Figure 18
Breast FNA, Breast cyst.
Benign ductal cells in cyst fluid may show degenerative vacuolization as illustrated here.
These changes should not be interpreted as being diagnostic of carcinoma. 60x

Figure 19
Breast FNA, Apocrine metaplasia.
Benign apocrine cells are often seen in flat sheets. They are commonly seen in breast cyst
fluids and in fine-needle aspirates from areas of fibrocystic change. 40x
Figure 20
Breast FNA, Apocrine metaplasia.
Apocrine cells display abundant granular cytoplasm and round nuclei with prominent
nucleoli. Their cytoplasmic borders are usually clearly defined. 60x

Figure 21
Breast FNA, Cystic papillary lesion.
Aspirates from cystic papillary lesions contain epithelial cells as well as foamy
macrophages. The benign ductal cells in this group are uniform in size and shape and
display palisading along one edge. Note the foamy macrophage and single benign ductal
cell above the group. If mild cellular atypia is present it can be difficult to distinguish a
benign lesion from a malignant papillary lesion. 40x
Figure 22
Breast FNA, Cystic papillary lesion. This group of benign ductal cells has a rounded,
palisaded edge, giving the appearance of a papillary structure, although no fibrovascular
core is seen. 40x

Figure 23
Breast FNA, Cystic papillary lesion.
A rounded papillary cluster of degenerating, vacuolated ductal cells is seen in this field,
accompanied by secretory material. This appearance is best reported as atypical as it is not
always possible to distinguish between benign and malignant papillary lesions. The
presence of apocrine metaplastic cells is usually a clue to a benign process. 60x
Figure 24
Breast FNA, Cystic papillary lesion.
Foamy macrophages, as illustrated here, are noted in both benign and malignant cystic
lesions, whether papillary or not. 60x

Figure 25
Breast FNA, Collagenous spherulosis.
This is a benign lesion which is usually an incidental finding in breast biopsies. Rarely does
it form a palpable mass. The aspirate contains evidence of benign ductal hyperplasia,
benign ductal and apocrine metaplastic cells, myoepithelial cells, and globules of
extracellular material surrounded by small benign epithelial cells. A similar picture is seen
in aspirates from adenoid cystic carcinoma of the breast. 60x
Figure 26
Breast FNA, Collagenous spherulosis.
This large globule of hyaline material is surrounded by small epithelial cells. 60x

Figure 27
Breast FNA, Collagenous spherulosis/apocrine metaplasia.
A sheet of apocrine metaplastic cells with relatively abundant cytoplasm was present in the
aspirate of the case pictured above showing collagenous spherulosis. 40x