The document discusses several benign breast conditions that can present as lumps, including cysts, fibroadenomas, fat necrosis, and sclerosing adenosis. It also covers various benign and rare breast tumors such as fibroadenomas, nipple adenomas, pleomorphic adenomas, adenomyoepitheliomas, papillomas, granular cell tumors, and lactating adenomas. The cytological features of fine needle aspirates for many of these conditions are provided. Additionally, radiation-induced changes in breast tissue and cytology samples are described.

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2. Introduction
• There are many possible causes of non-
cancerous (benign) breast lumps.
• Two of the most common causes of benign
single breast lumps are cysts and
fibroadenomas.
• In addition, several other conditions can
present themselves as lumps, such as fat
necrosis and sclerosing adenosis
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3. Cont’
• The breast can be the site of acute and chronic
inflammatory diseases.
• These diseases can be infectious in etiology
(acute mastitis, breast abscess, and tuberculosis,
among others), others are related to local
changes in the nipple and breast (subareolar
abscess and duct ectasia), some have
posttraumatic causes (fat necrosis), and there are
inflammatory processes related to
hypersensitivity reaction (granulomatous
mastitis) or even idiopathic.
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4. Cont’
• The clinical presentation of all of these entities
is quite variable, and in many situations the
diagnosis is clinical with immediate treatment
(antibiotics in infectious cases), but otherwise,
these lesions can cause tumorlike nodules that
need to be sampled by fine-needle aspiration
for definitive diagnosis.
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5. Benign Neoplasms
Fibroadenoma
• The fibroadenoma is the most common benign
breast neoplasm that usually occurs in young
women of child-bearing age, though it can occur
at any age.
• It often presents as a localized tumor which can
be clinically palpable as a mobile rounded and
rubbery lump, but asymptomatic lesion has been
detected by mammography where it is seen as a
well-defined mass.
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6. Cytologic Findings
• Aspirates from the fibroadenoma are usually cellular
with antler- or staghorn-shaped epithelial clusters and
honeycomb monolayered sheets, set within a clean
background with many naked bipolar nuclei, giving an
appearance of “sesame seeds strewn among epithelial
fragments”.
• The bimorphic or bimodal epithelial clusters feature
ductal epithelial cells with generally bland and banal
vesicular nuclei with smooth nuclear contours, often
accompanied by a second population of myoepithelial
cells with their angular small dark nuclei interspersed
among the ductal epithelial cells or inconspicuously
punctuating the periphery of epithelial sheets.
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7. Cont’
• Presence of usual ductal hyperplasia within
the fibroadenoma can lead to the presence of
larger branched proliferative epithelial
aggregates in the aspirates
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8. Aspirates are cellular with antler- or staghorn-shaped epithelial
clusters in monolayered sheets, set within a clean background
with many naked bipolar nuclei
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9. Fibroadenoma.
A closer view of the bimodal epithelial aggregate with small dark
nuclei of myoepithelial cells at the periphery of the cluster, as
well as intermixed among the ductal epithelial cells
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10. Adenoma of the Nipple
• Nipple adenoma, also known as papillary
adenoma, florid papillomatosis, or erosive
adenomatosis, is a rare and benign tumor
involving the terminal portion of the
lactiferous ducts of the nipple.
• Nipple adenoma consists of a dual cell
population (epithelial and myoepithelial cells)
arranged in papillary clusters associated with
dense stroma.
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11. Cont’
• The tumor occurs commonly in women in the
fourth and fifth decades of life and includes a
series of clinical manifestations, such as small,
circumscribed, unilateral nodules; itching,
redness, erosions, and crusts in the papillae; and
serous or bloody nipple discharge.
• The main clinical differential diagnosis is Paget
disease .
• Cytologic features of single cases have been
reported
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12. Cont’
Cytologic features
• Cellular smears
• Various epithelial cells in monolayer groups or in
tight papillary clusters, with or without
fibrovascular stroma
• Isolated epithelial cells without atypia
• Naked bipolar nuclei and histiocytes with
hemosiderin granules
• Myoepithelial cells overlapping epithelial groups
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13. Pleomorphic Adenoma
• Pleomorphic adenoma of the breast (benign
mixed tumor) is a very rare tumor that occurs in
women from the second to ninth decades of life.
• About one third of cases occur in the subareolar
region.
• Occasionally, the tumor is multifocal.
• Clinical and mammographic findings may raise
the suspicion of a breast carcinoma.
• Two elements are commonly present in smears:
myoepithelial cells and stroma
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14. Pleomorphic adenoma.
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(a) Myoepithelial cells in loose clusters or as single cells in a background of
fibromyxoid stroma.
(b)Myoepithelial cells with a plasmacytoid morphology embedded in a fibrillar and
metachromatic fibromyxoid stroma

15. Adenomyoepithelioma
• Adenomyoepithelioma is a rare benign breast
tumor characterized by proliferation of ductal
epithelial and myoepithelial cells in different
architectural patterns (lobular, papillary, and
tubular).
• The tumor is solitary, unilateral, and usually larger
than 1 cm and occurs more commonly in women
between the fifth and sixth decades of life.
• Tumors are usually benign but have a propensity
for recurrence and malignant transformation
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16. Adenomyoepithelioma
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(a, b) Clusters of uniform epithelial cells and epithelioid myoepithelial cells with
preserved, clear, and vacuolated cytoplasm .
(c, d) Occasional fragments of fibromyxoid stroma and histiocytes in the background

17. Cytologic features
• Moderately to highly cellular smears.
• Cohesive, three-dimensional, branched clusters of
epithelial and myoepithelial cells.
• Relatively uniform epithelial cells with oval, regular
nuclei and occasional nuclear grooves.
• Variable spindle, epithelioid, and plasmacytoid
appearance of myoepithelial cells.
• Fibromyxoid and metachromatic stroma.
• Occasionally stroma with hyaline globules surrounded
by myoepithelial cells (similar to collagenous
spherulosis), Occasional apocrine cells and histiocytes
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18. Cont’
• Myoepithelial cells are found overlapping the
epithelialclusters or as isolated cells with preserved,
clear, and vacuolated cytoplasm (“soap bubble”
appearance) or in the form of bipolar naked nuclei.
• Apocrine cells and histiocytes are occasionally present
in cytologic smears.
• Adenomyoepithelioma may be confused with
fibroadenoma.
• In general, the epithelial clusters in
adenomyoepithelioma are more three-dimensional
and not monolayers.
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19. Cont’
• In addition to intranuclear inclusions, found in
about one third of cases, cells may show
karyomegaly and prominent nucleoli .
• The presence of mitotic figures and necrosis
raises the possibility of a malignant
adenomyoepithelioma.
• The metachromatic hyaline globules may suggest
the diagnosis of an adenoid cystic carcinoma.
• However, in general, these globules are more
frequent and in greater numbers in adenoid
cystic carcinoma than in adenomyoepithelioma
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20. Papillary Tumors
• Papillomas are solitary or multiple benign breast
lesions that occur in perimenopausal women.
• The solitary papilloma is usually located in the
retroareolar region of the breast.
• Patients may be seen with a palpable nodule or a
serous or bloody nipple discharge.
• The most characteristic findings of a breast
papilloma are the presence of stellate tissue
fragments (branched fragments of stroma with
attached epithelial and myoepithelial cells in the
periphery and meshwork tissue fragments.
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21. Cont’
• Presence of papillary tissue fragments (with
fibrovascular stroma) is uncommon and is not
necessarily required for the cytologic
diagnosis of a papilloma
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22. Cytologic Features
• Moderate to abundant cellularity
• Cuboidal or columnar epithelial cells arranged in
three-dimensional, cohesive, branched groups
and papillary fragments
• Fibrovascular stroma within fragments of
epithelial cells
• Small groups or isolated columnar cells
• No myoepithelial cells overlapping the epithelial
groups
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23. Cont’
• Apocrine cells and histiocytes, occasionally
hemosiderin-loaded
• In general, lower cellularity and
predominantly cohesive groups, sometimes
with a monolayer arrangement, suggest a
papilloma, whereas the presence of numerous
isolated cells (tall columnar cells) favors the
diagnosis of a papillary carcinoma.
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24. Intraductal papilloma
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(a–d) Branched groups and papillary fragments of rounded cuboidal or columnar
epithelial cells with some degree of atypia and with fibrovascular stroma

25. Cont’
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(a)Columnar cells in small and loose clusters and in the periphery
(b) of a large three-dimensional cluster

26. Additional case of Intraductal Papilloma.
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(a–d) Smears with fibrovascular stroma with attached fragments of epithelial cells,
occasional apocrine cells, and few myoepithelial cells

27. Granular Cell Tumor
• Granular cell tumor is a rare lesion that,
histogenetically, is related to Schwann cells.
• Granular cell tumor occurs in any age group,
arising most commonly in the skin and
subcutaneous tissue, head and neck, and
especially in the tongue but only occasionally in
the mammary glands in middle-aged women.
• This neoplasm usually shows a benign clinical
behavior (less than 1% are malignant).
• A stellate appearance on mammography may
mimic a breast carcinoma.
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28. Cytologic features
• Polygonal cells with abundant fragile granular
cytoplasm
• A mixture of loose clusters, isolated cells, and often
stripped nuclei due to fragile cytoplasm
• Cytoplasmic granular background
• Small, round to oval nuclei with finely granular
chromatin and small nucleoli
• Occasional moderately pleomorphic cells with nuclei
showing coarse chromatin and macronucleoli
• Tumor cells are positive for S-100 and contain periodic
acid-Schiff (PAS)-positive cytoplasmic material
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29. Granular Cell Tumor
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(a–d) Loose clusters and some isolated cells with abundant granular
cytoplasm and cytoplasmic granular background.
Note occasional moderately pleomorphic cells

30. Benign Lesions During Pregnancy
• The hormonal changes during pregnancy and the
postpartum period may promote the formation
of nonneoplastic breast lesions or highlight the
presence of preexisting breast lumps.
• Such lesions are commonly referred to as
lactating adenomas or lactating nodules.
• These lesions show a benign course and often
regress after cessation of hormonal stimuli
present during pregnancy and lactation.
• Rarely, the nodules may have an ectopic location,
such as the axillary region or vulva.
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31. Cont’
• Because these lesions are not restricted to the
lactational period, some authors propose that
they should be named secretory hyperplastic
nodules.
• Cytologic smears show numerous epithelial cells
in loose clusters or isolated in a “dirty
background” of numerous fat droplets and
cellular debris.
• The cells have abundant, foamy or vacuolated
cytoplasm.
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32. Cont’
• Because of the cytoplasmic fragility, most of
the cells are present as naked nuclei, devoid of
cytoplasm.
• The nuclei exhibit discrete karyomegaly and
prominent nucleoli but regular contours and
delicate chromatin
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33. Lactation adenoma
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(a–d) Loose clusters or isolated cells with abundant, foamy, or vacuolated
cytoplasm and nuclei with discrete karyomegaly and prominent nucleoli but
regular contours and delicate chromatin

34. Lactational change. A totally dissociated population of naked nuclei of lobular
cells admixed with mixed inflammatory cells is present. The presence of
prominent nucleoli is unusual for lobular carcinoma. The observer should
have a much higher threshold for interpreting atypia or cancer when dealing
with a fine-needle aspirate from a young pregnant or lactating patient.
(Smear, Papanicolaou.)
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35. Radiation-Induced Changes
• Radiation-induced changes are not
uncommon because a larger proportion of
patients are undergoing breast conserving
therapies that may include adjuvant radiation.
• The effects of radiation are noted not only in
any residual carcinoma but also in the non
neoplastic mammary tissue.
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36. Cytomorphologic Characteristics
• Smears usually paucicellular
• Small epithelial fragments, often lobular in
nature, with significant cytologic atypia
(vacuolated cytoplasm, enlarged nuclei,
prominent nucleoli) and degenerative changes
• Lymphomononuclear inflammatory cells
• Rarely fat necrosis (in cases of recent
surgery/biopsy)
• If significant atypia, can lead to erroneous false-
positive diagnosis of cancer on aspiration
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37. Partially intact breast lobule with markedly
enlarged, pleomorphic nuclei displaying
macronucleoli.
The patient had a history of radiation
treatment for ductal carcinoma.
Although the morphologic changes are too
bizarre to represent lobular carcinoma, such
cases require a careful interpretation when
patients have previously resected breast cancer.
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Radiation Atypia

38. Collagenous Spherulosis
• Collagenous spherulosis is an uncommon lesion, first
described in 1987, characterized by the presence of
distinct globules of amorphous material that resemble
adenoid cystic carcinoma histologically and
cytologically.
Cytomorphologic Characteristics
• Metachromatic “hyaline” globules (on Diff-Quik stain),
pale green and vaguely translucent (on Papanicolaou
stain), usually well formed, surrounded by
monomorphic ductal epithelial cells
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39. Cont’
• Higher magnification reveals fibrillar
structures of the globules, which often vary in
size
• Smears are moderately cellular with
monolayered fragments of epithelium, often
with a focal branching papillary architecture
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40. Collagenous spherulosis.
Cellular smear with
hyperchromatic and crowded
ductal epithelium.
Two well-defined pale green
globular structures are present.
Branching cords of pale green
cylindrical structures lined by
proliferative ductal epithelium.
Note the presence of stromal nuclei
within the pale green substance, a
feature helpful in distinguishing
collagenous spherulosis from
adenoid cystic carcinoma.
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41. Collagenous spherulosis. High magnification of a
hyperchromatic crowded ductal epithelial fragment and
juxtaposed pale green sharply defined globular structure.
A morphologic distinction from adenoid cystic carcinoma can be
extremely difficult.
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42. Gynecomastia
• Male breast masses are uncommon pathologic
findings.
• They are rarely aspirated, resulting in limited
cytopathologic experience (male breast FNAs account
for 1.4%–7.3% of all breast FNAs).
• However, male breast FNA is considered to be a highly
sensitive (95.3%) and specific (100%) diagnostic
procedure.
• Gynecomastia is defined as male breast enlargement
caused by both hypertrophy and hyperplasia of the
ductal epithelial and stromal components.
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43. Cont’
• Although the etiologic factors may vary, the
condition is essentially caused by a relative
increase in estrogenic activity, a decrease in
androgenic activity, or a combination of both.
Cytomorphologic Characteristics
• Variable cellularity, most often moderate
(however, cellularity can often be low because of
the fibrous nature of the lesion, and the
discomfort that the patient experiences at the
time of aspiration is due to an often extreme
tenderness)
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44. Cont’
• Large cohesive ductal epithelial fragments, often
papillaryl ike or flat and monolayered; often a
prominent cribriform architecture is seen
• Focal to confluent epithelial atypia, sometimes
quite significant with cellular crowding, nuclear
enlargement, and prominent nucleoli
• Small amount of scattered background
myoepithelial nuclei
• Atypical single epithelial cells rarely observed
(useful feature when distinguishing gynecomastia
from a male breast ductal carcinoma)
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45. Cont’
• Occasional fragments of metachromatic
stromal/fibrous tissue (may appear falsely
biphasic resembling a fibroadenoma)
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46. Gynecomastia.
A large fragment of hyperplastic ductal epithelium with a vague
papillary and cribriform architecture is seen.
Note the presence of numerous naked myoepithelial cells in the
background. (Smear, Papanicolaou.)
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47. Thank You
The End
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48. References
• Gupta RK, McHutchison AG, Dowle CS, Simpson JS: Fine-needle
aspiration cytodiagnosis of breast masses in pregnant and lactating
women and its impact on management. Diagn Cytopathol 1993,
9:156–159.
• Jain S, Kumar N, Sodhani P, Gupta S: Cytology of collagenous
spherulosis of the breast: a diagnostic dilemma–report of three
cases. Cytopathology 2002, 13:116–120.
• Jayaram G, Sthaneshwar P: Fine-needle aspiration cytology of
phyllodes tumors. Diagn Cytopathol 2002, 26:222–227.
• Lopez-Ferrer P, Jimenez-Heffernan JA, Vicandi B, Ortega L, Viguer
JM: Fine needle aspiration cytology of breast fibroadenoma. A
cytohistologic correlation study of 405 cases. Acta Cytol 1999,
43:579–586.
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