This is a presentation on the topic of cytology of the breast, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.

1. CYTOLOGY OF THE
BREAST?!
Dr Ashish Jawarkar, MD

2. Disclaimer
• This presentation is not intended to increase
your knowledge on breast FNA
• Probably this will even further make the scenario
more hazy
• This presentation is meant to discuss the
“probabilistic approach” which makes the
pathologists life easier, say we have found a loop
hole to be safe in an era of medical legislation

3. Introduction
• FNAC is a valuable pre operative tool in
assessment of breast masses as it shows high
accuracy, sensitivity and specificity.
• It is inexpensive and can be performed without
complications
• FNA has significantly contributed to the
reduction of excisional biopsies in assessment
of breast lesions.
• With palpable lesions, FNAC attains a high
positive predictive value of 95–100%

4. Common
disadvantages
operator-dependent
need for extensive training
reality of equivocal results
high expectations from the clinician
no spare material for special technique
morphologic overlap between benign and malignant
(e.g. atypical hyperplasia and carcinoma in situ)

5. Introduction
• However, cyto-histo correlation in breast FNACs has
shown a wide variation, false negative and false
positive reports have been very common.
• To accommodate this, a five tier reporting system
was designed by UK national breast co ordinating
committee.
• This is known as a “PROBABILISTIC APPROACH”

7. Probabilistic approach
• This categorization helps the cytopathologist to define uncertain
areas and clinicians to offer further investigations like excisional
biopsy judiciously
• Let us first see what each category signifies

8. C1 – Inadequate aspirate
• Definition of adequacy
• NCI defines an adequate sample as – The one that led to resolution a problem
presented by lesion in a particular patient’s breast
• This definition is devoid of quantifiable clause, but gives the aspirator full
mandate in deciding whether the cytological features were consistent with
clinical findings and deemed adequate

9. C1 – Inadequate aspirate
• Some authors have suggested a cut off of six epithelial cells clusters as a
criteria for adequacy
• This may help considering that diagnosing malignancy in breast mostly
involves assessment of cytological features of epithelial cells.
• However this renders low cellularity aspirates from cysts / postmastectomy
scars / hardened fibrotic areas as inadequate for assessment
• Hence practical approach would be to consider clinical, radiologic and
cytologic appearances and then judge whether the aspirate is adequate for
assessment or not.

10. C1 – Inadequate
aspirate
• This may either be due to
• Hypocellularity
• Aspiration/smearing/staini
ng errors
• The inadequacy in various
specimens ranges from 0.7 to
25.3 % in different studies as
shown

11. C1 – Inadequate aspirate
• Rate of inadequacy was found to depend on
• The nature of lesion - 68%
• Experience of the aspirator – 32%
• Rate of inadequacy is low if
• A well informed and co operative patient
• And is restricted to clinically and radiologically appropriate scenarios
• If the same person aspirates and interprets the FNAC

12. Inadequate vs Adequate

13. C2 Benign
Bulk of breast FNAs turn out to be benign ranging from 24-77.5% in various studies

14. Benign duct epithelium

16. C2 Benign
• These include usually
• Inflammatory
• Fibroadenomas
• Benign phyllode’s
• Fibrocystic changes
• Lactational changes
• Papillary cystic lesions
• Papillary lesions (intraductal papilloma)

20. Fibroadenomas
• They are the most cause of breast lumps in women under 40 years of
age
• They have characteristic clinical and radiologic appearances
• FNA diagnosis is highly accurate with studies reporting accuracy to be
up to 79.3%
• The aspirates show monolayered sheets with benign looking
epithelial cells mixed with myoepithelial cells – staghorn
configuration, background is composed of naked (bipolar) nuclei with
fibrillar stromal fragments showing myxoid change _
“The diagnostic triad”

25. C2 - Fibroadenoma
• Pitfalls
• Low cellularity with absence of any one of the “triad” components
• VS Phyllode’s - Cellular aspirate, numerous plump spindly nuclei, pronounced
hyper cellularity of stromal fragments over epithelial fragments and nuclear
atypia are some out the soft signs for Phyllode’s
• VS papilloma/fibrocystic changes/duct ectasia – concentrate on overall
cellularity, amount of bipolar nuclei, amount and architecture of epithelial
fragments

26. C-2 Fibrocystic changes
• The size of the cysts varies in between consultations giving a hint of
benign nature to the clinicians
• It is important to submit the aspirated cyst fluid for pathological
examination as it gives important clues regarding nature of the lesion
• Mostly the fluid shows macrophages mixed with inflammatory cells
• Ductal epithelial and myoepithelial cells may also be seen, mostly as small
balls and clusters
• If the above findings are mixed with a significant epithelial proliferative
component category of C3 or C4 can be used

29. C-2 Lactational changes
• Aspirates show plenty of proteinaceous fluid with epithelial cells that
are large, with enlarged nuclei, eosinophilic nucleoli and vacuolated
wispy cytoplasm.
• These features though appear worrisome, the clinical history of
lactation helps in assigning the benign category

31. C-2 Papillary cystic lesions
• Papillary apocrine change may cause thickening of the wall of the
cysts with worrisome nuclear and cytoplasmic details
• Apocrine cells lining cavity may exfoliate, showing characteristic
eosinophilic cytoplasm and round nuclei with distinct nucleoli,
sometimes with chromatin clumping and anisonucleosis
• Clinical and especially radiologic features of a well encapsulated cystic
structure will help in assigning a benign diagnosis

33. C-2 PAPILLARY LESIONS
• The accuracy of FNAC in diagnosing papillary lesions is low (benign vs
malignant)
• At the benign end of the spectrum is intraductal papilloma
• Usually presents with nipple discharge, are solitary and present in
subareolar region
• The typical FNA picture shows papillary fronds, cell balls and
columnar cells
• Staghorn clusters may also be seen
• Any deviation from the above or epithelial hyperplasia in a papilloma
makes judging the smear very difficult

37. C3 atypical, mostly benign
• An interpretation of C3 is given when the aspirates show benign
characteristics but have some features not present usually in benign
aspirates.
• These include any or a combination of nuclear pleomorphism, loss of
cell cohesion, nucleocytoplasmic changes resulting from
treatment/hormonal influences and increased cellularity

39. C4 suspicious of malignancy
• C4 category diagnosis is given when the aspirates have cells with
features of malignancy however the material is not very cellular to be
diagnostic, poorly preserved or spread.
• These also include samples showing malignant features of a greater
degree than seen in C3 without the presence of overtly malignant
cells

40. • C3 VS C4

42. C3 – atypical, mostly benign
C4 – suspicious of malignancy
• In categories C3 and C4 in there exists significant interobserver
variation in the diagnosis, as no strict criteria are present for the
diagnosis of these categories.
• Some authors have suggested the use of term “equivocal” for such
inconclusive diagnosis (C3 & C4) on FNAC

43. 77%
86%

44. C3 and C4 – GRAY ZONES – FALSE NEGATIVES
• The major causes of this difference on cyto and histo include
• Technical : low cellularity
• Low grade malignancies (DCIS and Grade I IDC, LCIS and Benign Phyllode’s)

45. Case 1
• 45 years old, vague breast mass for 3 months

50. Moral of the story is…
• Atypical epithelial hyperplasia and low grade carcinoma in situ are
similar entities,
• Quantitatively different (the former being smaller)
• Qualitatively the same (in terms of cellular details)
• Making a diagnosis in FNAC is usually based on qualitative (cellular
and nuclear morphology, background cellular patterns) but not
quantitative (lesion size) parameters of the lesions
• A diagnosis of these should not be made in breast FNAC as the lesion
sizes might not be taken into consideration

51. C3 and C4 – GRAY ZONES – FALSE POSITIVES
• Fibroadenoma
• Commonest cause of false positives and false-negatives
• May show hyper cellularity and nuclear atypia with prominent nucleoli in the
aspirates
• Fibroadenomas are diagnosed cytologically as proliferative breast lesion with
or without atypia in such cases

53. C3 and C4 – GRAY ZONES – FALSE POSITIVES
• Papillary lesions
• The cytologic diagnosis of papillary lesions is problematic because to date
there are no well-defined cytological criteria to differentiate between benign
and malignant papillary lesions

57. C3 and C4 – GRAY ZONES – FALSE POSITIVES
• Other common lesions giving a false positive diagnosis for malignancy
include ductal and lobular hyperplasia
• Also, fibrocystic changes and pregnancy related breast masses can
give false positives

58. Case 2
• 45 years old, vague
breast mass for 3
months

59. Case 3
• 80 year old female, long standing breast nodule

63. C5.. When to call
something malignant in
atypical aspirates

64. Parameters that have been evaluated to
predict malignancy include
• Age
• Percentage of bipolar cells
• Cellularity
• Pleomorphism
• N:C ratio
• Stromal fragments
• Histiocytes
• Epithelial clusters
• Single cells

68. In short
• Qualitative parameters useful are
• nuclear pleomorphism
• NC ratio
• epithelial cell atypia
• the presence of necrosis
• Quantitative parameters
• Bipolar nuclei percentage was also an important diagnostic clue
• More bipolar nuclei -associated with benign lesions
• Cellularity was of borderline importance, being higher in malignant lesions

69. In short
• An atypical cytologic diagnosis should prompt histologic evaluation
due to the significant malignancy rate
• Careful assessment of atypical aspirates using the qualitative
parameters may assist the clinicians in stratifying the risk level and
prioritizing histologic assessment of atypical breast aspirates

70. Guess the lesions

71. Case 4

75. Ductal carcinoma in situ

76. Case 5

80. Lobular carcinoma

81. Case 6
• 72 y.o. female with a palpable breast lump, LUOQ

87. Cytological interpretation
• ??????

89. Histology
• Tubular carcinoma

90. Case 7
• 79 year old female
• Right breast mass and bloody nipple discharge

94. Cytological interpretation
• ??????

96. Histological diagnosis
• Ductal carcinoma in situ, low-intermediate grade

97. Case 8
• 67 year old female
• Mass in breast

102. Cytological Diagnosis
• Abnormal
• Moderately cellular specimen consisting of ductal cells with minimal
nuclear atypia. Single cells and small clusters are present in the
background.
• A low grade ductal carcinoma cannot be excluded.

104. Histological diagnosis
• Breast, wide local excision (right) –
• Encapsulated papillary carcinoma, low grade

105. Cytological features
• No single feature distinguishes EPC from papilloma
• Cyst contents may be main finding
• Papillary cores covered by columnar cells are diagnostic of papillary
lesion
• Rounded cell clusters of small hyperchromatic cells with “mulberry-
like” appearance
• Detached columnar cells may be prominent

106. Case 9
• 79 year old female
• Left breast mass

109. Cytological interpretation
• ???

112. Histological diagnosis
• Multifocal invasive ductal carcinoma, NST

113. Case 10
• 86 year old female
• FNA large breast mass

118. Cytological interpretation
• Positive for malignant cells
• Past history very helpful
• Consistent with metastatic renal cell carcinoma

119. Mets to breast
• Main sites of origin: lung (small cell/non-small cell),
ovary/uterus/cervix, melanoma, neuroendocrine tumours, prostate
carcinoma
• Metastases tend to be discrete, round without spiculations,
calcification is uncommon, no DCIS, usually a single lesion (~85%),
may involve ipsilateral axillary LN’s

120. Take home message
• Probabilistic approach - This categorization helps the cytopathologist
to define uncertain areas and clinicians to offer further investigations
like excisional biopsy judiciously
• An adequate sample is the one that led to resolution a problem
presented by lesion in a particular patient’s breast
• In categories C3 and C4 in there exists significant interobserver
variation in the diagnosis, as no strict criteria are present for the
diagnosis of these categories
• Careful assessment of atypical aspirates using the qualitative
parameters may assist the clinicians in stratifying the risk level and
prioritizing histologic assessment of atypical breast aspirates

121. THANK YOU