2. FNA of BREAST The 6th Arab-British School of Pathology
Nina S Shabb, M.D.
American University of Beirut Medical center, Beirut Lebanon

3. Objectives Overview of breast FNA AUBMC data 2003-200
CNB vs FNA of palpable and non palpable lesions

4. Status of breast FNA 1930: Introduced 1980-90: ↑ ↑ ↑ Late 90’s-now: ↓
Non palpable masses: Replaced CNB
Palpable masses: CNB = FNA ? (institution dependent)

5. Reasons for ↓ popularity
Lack of experienced cytopathologists
↑ Diagnostic errors
↑ Insufficient samples
False positives
False negatives
Medico legal issues
Inability to distinguish In situ from invasive carcinoma

6. Trend of FNA of breast at AUBMC
Total number: 1794

7. AUBMC data
All breast FNAs with corresponding surgical pathology material were reviewed over 5 years (Jan Dec 2007)
FNA reports were categorized C1-C5
Palpable and non palpable masses were segregated
Data analyzed

8. Diagnostic categories
C1: Unsatisfactory
C2: Benign lesion
C3: Atypical, probably benign
C4: Suspicious for malignancy
C5: Malignant
The uniform approach to breast FNA. NCI recommendations

9. “Triple test” FNA results Clinical findings Radiologic findings
Combining these 3 tests improves false negative and false positive results

10. FNA/Pathology correlation, AUBMC, 2003-2007
PATHOLOGY
FNA
Negative
Positive
Total C1 4 5 9 C2 56 1 57 C3 C4 13 C5 92 93 70
111
181
FN: 6. FP: 1. Unsatisfactory:5%

11. Who should perform the FNA?
The person who is going to read it! (pathologist adequately trained)
Gleans information from gross findings and feel of the needle
Less unsatisfactory results (multiple passes as needed)
Less interpretative errors
Highest sensitivity and specificity

24. Complications of FNA Very rare Pain Bleeding/hematoma: Pressure
Infection: Proper cleaning
Pneumothorax: Tangential aspirate
Vasovagal reaction: Legs up
Needle tract seeding? No

25. C1
Unsatisfactory

26. FNA/Pathology correlation, AUBMC, 2003-2007
PATHOLOGY
FNA
Negative
Positive
Total C1 4 5 9 C2 56 1 57 C3 C4 13 C5 92 93 70
111
181
C1: 5%

27. C1 palpable vs non palpable
PATHOLOGY
FNA Palpable
Negative
Positive
Total C1 3 2 5 C2 35 1 36 C3 6 C4 12 C5 73 44 88
132
PATHOLOGY
FNA non palpable
Negative
Positive
Total C1 1 3 4 C2 21 C3 C4 C5 19 20 26 23 49
C1: 3.5% (2.3%pos)
C1: 8%

28. C1 (Unsatisfactory) When FNA does not explain the mass
Lesions responsible for C1
Small
Fibrotic
Hypocellular benign and malignant
Operator dependent
Range in literature: % (5%)
CNB: advantage

29. C1
Management: More tissue

30. C2
Benign

31. C2 benign FNA: Adequate and representative material of benign disease
FCC (cysts)
Abscess
Fat necrosis
Fibroadenoma
Other

32. FNA/Pathology correlation, AUBMC, 2003-2007
PATHOLOGY
FNA
Negative
Positive
Total C1 4 5 9 C2 56 1 57 C3 C4 13 C5 92 93 70
111
181
FN: 1

33. FNA/pathology correlation of palpable masses
PATHOLOGY
FNA p
Negative
Positive
FCC FA
Other
Total neg
IDC
ILC
DCIS
Total pos
Total C1 2 1 3 5 C2 16 18
1 PT 35
1 crib pap 36 C3 4 6 C4 7
1 tubular 12 C5 69
3 (2 Pleo)
1 comedo 73 22 21 44 78 88
132

34. FNA/pathology correlation of non palpable masses
PATHOLOGY
FNA np
Negative
Positive
FCC FA
Other
Total neg
IDC
ILC
DCIS
Total pos
Total C1 1 2 3 4 C2 15 5
1 LN 21 C3 C4 C5
1 (ame) 16 19 20 8 26 23 49

35. C2 (benign) 1 False negative: (1%)
DCIS Cribriform and micropapillary. Misinterpreted on FNA as FCC

39. FCC Cyst content: Clear, few macrophages Hypocellular
Benign duct epithelial cells
Naked nuclei
Apocrine metaplastic cells

42. Fibroadenoma Pigeon egg, rubbery feel Smears (pattern recognition)
Very cellular
3 components
Staghorn epithelial cohesive honeycombed duct cells
Stromal fragments
Numerous myoepithelial cells (naked bipolar nuclei)

45. C2 (Benign) Negative triplet: Follow up FNA: Benign Clinical: Benign
Radiologic: Benign

46. C5
Malignant

47. C5 Malignant Primary Metastatic Hematopoetic IDC nos ILC Mucinous
Tubular
Papillary
Other
Metastatic
Hematopoetic

48. FNA/Pathology correlation, AUBMC, 2003-2007
PATHOLOGY
FNA
Negative
Positive
Total C1 4 5 9 C2 56 1 57 C3 C4 13 C5 92 93 70
111
181
False positive: Adenomyoepithelioma

49. FNA/pathology correlation of palpable masses
PATHOLOGY
FNA p
Negative
Positive
FCC FA
Other
Total neg
IDC
ILC
DCIS
Total pos
Total C1 2 1 3 5 C2 16 18
1 PT 35
1 crib pap 36 C3 4 6 C4 7
1 tubular 12 C5 69
3 (2 Pleo)
1 comedo 73 22 21 44 78 88
132

50. FNA/pathology correlation of non palpable masses
PATHOLOGY
FNA np
Negative
Positive
FCC FA
Other
Total neg
IDC
ILC
DCIS
Total pos
Total C1 1 2 3 4 C2 15 5
1 LN 21 C3 C4 C5
1 (ame) 16 19 20 8 26 23 49

51. Adenomyoepithelioma Rare benign tumor, epithelial and ME cells FNA.
Scant. Scattered highly atypical epithelial cells.
Numerous foamy ME cells (histiocytes)
CNB: Interpreted as IDC, Grade 2/3
Single false positive FNA since we started doing FNAs of breast (>3000 cases)
AME has been reported as a cause of false + in literature

52. Diagnostic criteria for malignancy
Tumor cellularity
Discohesion
Cytologic features of malignancy.
Compare neoplastic cells to benign duct cells
↑ N/C ratio
Irregular nuclear contour
Hyperchromasia
Presence of nucleoli

53. Ductal adenocarcinoma nos
Cellular
Necrotic background
Monomorphic cell population
Loss of cell cohesion
Numerous isolated singe cells
Anisonucleosis
Lack of ME cells

57. Tumor grade HISTOLOGY CYTOLOGY Glands Nuclei Mitosis Nuclei Size
Membrane
Chromatin
Nucleoli
Nuclear grade 1-3
Good correlation with histologic
grade

58. Special type carcinomas

62. Lobular carcinoma Low to moderate cellularity
Small chains or groups of cells, single cells
Uniform population, small to medium sized cells
Mild atypia, inconspicuous nucleoli
Occasional signet ring cells
Source of false negative
Feel of the needle in the mass while doing FNA is most helpful

67. Mucinous carcinoma Well circumscribed, soft Thick mucinous material
Cell balls, minimal atypia, few signet rings
Cannot diagnose absolutely on FNA

68. Tubular ca Angular, rigid, bent tubular clusters, sharp borders
Crowded nuclei
Minimal tumor discohesion
Dispersed single cells, minimal atypia
Absence/paucity of ME cells
Peripheral perpendicular cells

69. Other carcinomas Not very good No clinical need
Carcinoma and nuclear grade

70. DCIS FNA cannot distinguish in situ from invasive carcinoma
Cancer cells infiltrating fibrofatty tissue, tubular structures, cytoplasmic lumina, absence of ME cells)
Incidence of DCIS in FNA material ranges 1-18% (palpable vs non palpable)
CNB is more accurate but not infallible (false negative 19-66% )

72. FNA of DCIS DCIS Grade 3: DCIS cribriform DCIS grades 1 and 2:
Pleomorphic carcinoma cells, calcium, necrosis, macrophages
casting Calcification on mammogram
DCIS cribriform
Low grade carcinoma
punched out holes in cell clusters
DCIS grades 1 and 2:
No distinguishing features

73. C5
Management
If the TT is positive then definitive treatment is undertaken

75. C3: Atypical favor benign C4: Suspicious for malignancy
C3 & C4
C3: Atypical favor benign
C4: Suspicious for malignancy

76. C3 (atypical favor benign)
Atypical/indeterminate/favor benign
Lesion is probably benign
Malignancy cannot be excluded entirely TT

77. C4 (Suspicious probably malignant)
Very high probability of malignancy but confirmation is needed prior to definitive therapy
Others are complex lesions
Additional material

78. FNA/Pathology correlation, AUBMC, 2003-2007
PATHOLOGY
FNA
Negative
Positive
Total C1 4 5 9 C2 56 1 57 C3 C4 13 C5 92 93 70
111
181
C3+C4: 11.6%

79. FNA/pathology correlation of palpable masses
PATHOLOGY
FNA p
Negative
Positive
FCC FA
Other
Total neg
IDC
ILC
DCIS
Total pos
Total C1 2 1 3 5 C2 16 18
1 PT 35
1 crib pap 36 C3 4 6 C4 7
1 tubular 12 C5 69
3 (2 Pleo)
1 comedo 73 22 21 44 78 88
132

80. FNA/pathology correlation of non palpable masses
PATHOLOGY
FNA np
Negative
Positive
FCC FA
Other
Total neg
IDC
ILC
DCIS
Total pos
Total C1 1 2 3 4 C2 15 5
1 LN 21 C3 C4 C5
1 (ame) 16 19 20 8 26 23 49

81. C3 and C4 lesions Nature of lesion Technical reasons
Proliferative breast disease with atypia
Low grade carcinoma (in–situ & invasive)
Tubular ca
Papillary lesions
Phyllodes tumor
Technical reasons
Limited cellularity
Poor preservation of cellular features

82. C3 and C4 Number of dx in this category shouldn’t exceed 12% (11.6%)
C3 in literature: 28-52% Malignant (0%)
C4 in literature: 81-97% malignant (100%)

83. N Shabb F Boulous Z Chakhachiro
Inconclusive FNAs of breast with adequate and representative material: A cytologic/histologic study of 18 cases. AUBMC experience
N Shabb
F Boulous
Z Chakhachiro

84. Inconclusive/erroneous cellular and representative FNAs/histology
Patient
Age
Clinical presentation
FNA performed by
Dx 1 Cytologic cancer category
Dx 2 Cytologic cancer category
Final diagnosis 1 58
Hypoechoic mass
Radiologist C5 C4
Adenomyoepithelioma 2 43
6.5cm lump
Clinician
C3-4
DCIS (crib) 3 67
lump
Pathologist C2 C3
DCIS (crib, pap) 4 65
Inv crib 5 40 6 46
4mm U/S
Tubular 7 53
3cm, gritty 8
43f NA 9
44f
Lobular 10
71f
Inv adeno (nos) 1/3 11
50f 12
38f
lump, preg
Inv adeno (nos) 2/3 13
36f
1cm 14
Non palpable 15
73f
3cm 16
66f
15cm hem cyst
ICPC 17
29f FA 18
60f
2cm gritty
PT malignant

85. Papillary lesions
FNA not reliable in distinguishing benign from malignant. Defer to histology

88. False negative FNAs Lesions responsible for false –
Low grade ca/lobular/mucinous/tubular/DCIS
Scirrhous tumors
Hemorrhagic/cystic
Small size
Usually sampling error (5/6)
Can be interpretative error (1/6) TT

89. False positive FNAs Lesions responsible for False +
Fibroadenomas
Epithelial hyperplasia
Pregnancy
Papillary lesions
Reactive atypias
Adenomyoepithelioma
Usually interpretative errors
Poor specimen preparation TT

90. Post triple test recommendations
Benign triplets FU
Malignant triplets
Definitive therapy
Mixed triplets
Histologic evaluation

91. Benefits of the triple test
False negatives: ↓ 10 to 1%
False positives: ↓ 1 to < 0.2%

92. FNA diagnostic accuracy
Literature
Sensitivity: 75-98%
Specificity: %
False positive: 0-2.5%
False negative: %
Insufficient: 4-13% (P), 36% (NP)
AUBMC
Sensitivity: 94.6%
Specificity: 98.6%
False positive: *1%
False negative: 1%
Insufficient: 3.5% (P), 8% (NP)

93. CNB vs FNA preoperative evaluation of breast masses
Special expertise (Performing + interpretation) No
Yes
Feel effect
Safety (chest wall)
Time consuming (pathologist)
In situ/invasive
+/- -
Definitive dx
Better
Good
Cost/TAT/pain/invasiveness
Tumor grade
Prognistic markers
Insufficient rate
↓ experience
False +/-
Inevitable
Palpable
Non palpable
No Good

94. Current issues with FNA of breast
False negative FNAs
High rate in inexperienced hands
Adeverse effect on patient. Delay in proper management
Medico legal problems (10% of MLP in US)
In situ vs invasive
Preoperative chemotherapy
LN dissection (small lesions)

95. Conclusions
Compared to CNB, FNA may not provide all the necessary information in modern management of some cases of breast ca.
Small lesions to determine management of the axilla
Some larger lesions where preoperative chemotherapy is a consideration.

96. Conclusions
CNB has replaced FNA in non palpable mammographically detected lesions
FNA is highly reliable in palpable masses particularly in the hands of properly trained aspirators and interpreters
FNA needs to be incorporated in the TT

98. Advantages of FNA Easy “painless” office procedure
Quick (dx in minutes)
Inexpensive
Decreases hospital costs
Helps patient plan treatment in case of carcinoma
Helps alleviate anxiety in benign disease

99. Advantages of FNA
Definitive dx in inoperable ca, chest wall recurrence and LN metastases
Useful in pregnant patients
Diagnostic and therapeutic in benign cysts
Helpful in triaging patients for surgery
Decreases time in OR (eliminates need for FS)

100. Disadvantages of FNA False negatives False positives
Special training needed to perform and interpret FNA
In situ vs invasive carcinoma
Complications

101. FNA technique Ljung BM: Techniques of aspiration and smear preparation
Ljung BM: Thin needle aspiration biopsy video. Dept of Pathology UC San Francisco Ca
Koss LG et al: Aspiration biopsy: Cytologic interpretation and Histologic Basis, 2nd ed, NY Igaku-Shoin, 1992.

102. FNA technique Quick aspiration (avoid blood clot)
Quick transfer of material on slides
Proper smearing (avoid crush)
Immediate fixation (avoid air dry)
Papanicoulau stain (fully frosted alcohol fixed)
Romanowsky type stain (frosted tip, air dry)
Cell block (Optional)

103. Pointers while performing FNA
Clinical setting (age, skin and nipple changes, axillary LN)
Gross feel of tumor
Size of tumor. How to direct needle
FNA feel: Gritty or rubbery?
How many passes?
Rapid stain after every pass?
Naked eye inspection of cellularity

104. FNA/pathology correlation of palpable masses
PATHOLOGY
FNA p
Negative
Positive
FCC FA
Other
Total neg
IDC
ILC
DCIS
Total pos
Total C1 2 1 3 5 C2 16 18
1 PT 35
1 crib pap 36 C3 4 6 C4 7
1 tubular 12 C5 69
3 (2 Pleo)
1 comedo 73 22 21 44 78 88
132
Sensitivity: TP/TP+FN = 88/88+1 = 98.8%
Specificity: TN/TN+FP = 44/44+0 = 100%
False negative: 1
False positive: 0

105. FNA/pathology correlation of non palpable masses
PATHOLOGY
FNA np
Negative
Positive
FCC FA
Other
Total neg
IDC
ILC
DCIS
Total pos
Total C1 1 2 3 4 C2 15 5
1 LN 21 C3 C4 C5
1 (ame) 16 19 20 8 26 23 49
Sensitivity: TP/TP+FN = 23/ %
Specificity: TN/TN+FP = 26/26+1 =96%
False negative: 0
False positive: 1

106. Pitfalls Low grade carcinomas (lobular, tubular, low grade ductal)
Apocrine metaplasia and lactational change Have large nuclei and prominent nucleoli

107. Breast FNA report
Precise location (laterality, O’clock, distance from nipple).
Placement of cytologic specimen in one of 5 categories (C1-C5)
Specimen type
Localization technique
Comment of specimen findings
Adequacy
Recommendation of correlation with clinical and radiologic findings

109. Acknowledgments Dr Fuad Boulous Dr Zaher Chakhachiro
Dr Alexis Bousamra
Ms. Nisrine Hashem

110. Benign duct epithelium
Cohesive honeycombed sheets
Regular round/oval evenly spaced nuclei
Evenly distributed chromatin. No nucleoli
Myoepithelial cells (in ductal sheets and in background)
Apocrine cells

113. Papilloma Cellular, bloody background Macrophages
3 dimensional papillary clusters, cell balls
Tall columnar cells, apocrine cells and ME cells

114. Papillary carcinoma Papilloma + Necrotic debris
Atypical cytology High N/C ratio, hyperchromasia, nucleoli
Absence of apocrine cells and ME cells

115. FNA palpable masses 73% FNAs 67% malignant C1: 3.5%
PATHOLOGY
FNA Palpable
Negative
Positive
Total C1 3 2 5 C2 35 1 36 C3 6 C4 12 C5 73 44 88
132
73% FNAs
67% malignant
C1: 3.5%
C2: FCC (16), FA(18), PT (1),
DCIS crib +micropapa (1) FN
C4: IDC (7), ILC (2), DCIS (2), Tubular (1)

116. FNA of non palpable masses
27% FNAs
47% malignant
C1: 8%
C5: 1 FP. Adenomyoepithilioma
The only FP in our 17 year experience (>2500 cases)
PATHOLOGY
FNA non palpable
Negative
Positive
Total C1 1 3 4 C2 21 C3 C4 C5 19 20 26 23 49