Transcript FNA of BREAST - IAP-AD

FNA of BREAST
The 6th Arab-British School of Pathology
Nina S Shabb, M.D.
American University of Beirut Medical center,
Beirut Lebanon
Objectives
• Overview of breast FNA
• AUBMC data 2003-200
• CNB vs FNA of palpable and non palpable
lesions
Status of breast FNA
•
•
•
•
•
1930: Introduced
1980-90: ↑ ↑ ↑
Late 90’s-now: ↓
Non palpable masses: Replaced CNB
Palpable masses: CNB = FNA ? (institution
dependent)
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
Trend of FNA of breast at AUBMC
250
200
150
Number of breast
FNAs
100
50
0
1997
1999
Total number: 1794
2001
2003
2005
2007
AUBMC data
• All breast FNAs with corresponding
surgical pathology material were reviewed
over 5 years (Jan 2003 - Dec 2007)
• FNA reports were categorized C1-C5
• Palpable and non palpable masses were
segregated
• Data analyzed
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
“Triple test”
• FNA results
• Clinical findings
• Radiologic findings
Combining these 3 tests improves false negative and
false positive results
FNA/Pathology correlation, AUBMC,
2003-2007
PATHOLOGY
FNA
Negative
Positive
Total
C1
4
5
9
C2
56
1
57
C3
9
0
9
C4
0
13
13
C5
1
92
93
Total
70
111
181
FN: 6. FP: 1. Unsatisfactory:5%
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
Complications of FNA
• Very rare
– Pain
– Bleeding/hematoma: Pressure
– Infection: Proper cleaning
– Pneumothorax: Tangential aspirate
– Vasovagal reaction: Legs up
– Needle tract seeding? No
C1
Unsatisfactory
FNA/Pathology correlation, AUBMC,
2003-2007
PATHOLOGY
FNA
Negative
Positive
Total
C1
4
5
9
C2
56
1
57
C3
9
0
9
C4
0
13
13
C5
1
92
93
Total
70
111
181
C1: 5%
C1 palpable vs non palpable
PATHOLOGY
PATHOLOGY
Total
FNA non
palpable
Negative
Positive
Total
2
5
C1
1
3
4
35
1
36
C2
21
0
21
C3
6
0
6
C3
3
0
3
C4
0
12
12
C4
0
1
1
C5
0
73
73
C5
1
19
20
Total
44
88
132
Total
26
23
49
FNA
Palpable
Negative
Positive
C1
3
C2
C1: 3.5% (2.3%pos)
C1: 8%
C1 (Unsatisfactory)
• When FNA does not explain the mass
• Lesions responsible for C1
– Small
– Fibrotic
– Hypocellular benign and malignant
• Operator dependent
• Range in literature: 0.7-47% (5%)
• CNB: advantage
C1
• Management: More tissue
C2
Benign
C2 benign
• FNA: Adequate and representative
material of benign disease
– FCC (cysts)
– Abscess
– Fat necrosis
– Fibroadenoma
– Other
FNA/Pathology correlation, AUBMC,
2003-2007
PATHOLOGY
FNA
Negative
Positive
Total
C1
4
5
9
C2
56
1
57
C3
9
0
9
C4
0
13
13
C5
1
92
93
Total
70
111
181
FN: 1
FNA/pathology correlation of
palpable masses
PATHOLOGY
FNA
p
Negative
Positive
FCC
FA
Other
Total neg
IDC
ILC
DCIS
Other
Total pos
Total
C1
2
1
0
3
2
0
0
0
2
5
C2
16
18
1 PT
35
0
0
1 crib pap
0
1
36
C3
4
2
0
6
0
0
0
0
0
6
C4
0
0
0
0
7
2
2
1 tubular
12
12
C5
0
0
0
0
69
3 (2 Pleo)
1 comedo
0
73
73
Total
22
21
1
44
78
5
4
1
88
132
44
88
FNA/pathology correlation of
non palpable masses
PATHOLOGY
FNA
n
p
Negative
Positive
FCC
FA
Other
Total neg
IDC
ILC
DCIS
Other
Total pos
Total
C1
0
1
0
1
2
0
1
0
3
4
C2
15
5
1 LN
21
0
0
0
0
0
21
C3
1
2
0
3
0
0
0
0
0
3
C4
0
0
0
0
1
0
0
0
1
1
C5
0
0
1 (ame)
1
16
1
2
0
19
20
Total
16
8
2
26
19
1
3
0
23
49
26
23
C2 (benign)
• 1 False negative: (1%)
DCIS Cribriform and micropapillary.
Misinterpreted on FNA as FCC
FCC
• Cyst content: Clear, few macrophages
• Hypocellular
– Benign duct epithelial cells
– Naked nuclei
– Apocrine metaplastic cells
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)
C2 (Benign)
• Negative triplet: Follow up
– FNA: Benign
– Clinical: Benign
– Radiologic: Benign
C5
Malignant
C5 Malignant
• Primary
–
–
–
–
–
–
IDC nos
ILC
Mucinous
Tubular
Papillary
Other
• Metastatic
• Hematopoetic
FNA/Pathology correlation, AUBMC,
2003-2007
PATHOLOGY
FNA
Negative
Positive
Total
C1
4
5
9
C2
56
1
57
C3
9
0
9
C4
0
13
13
C5
1
92
93
Total
70
111
181
False positive: Adenomyoepithelioma
FNA/pathology correlation of
palpable masses
PATHOLOGY
FNA
p
Negative
Positive
FCC
FA
Other
Total neg
IDC
ILC
DCIS
Other
Total pos
Total
C1
2
1
0
3
2
0
0
0
2
5
C2
16
18
1 PT
35
0
0
1 crib pap
0
1
36
C3
4
2
0
6
0
0
0
0
0
6
C4
0
0
0
0
7
2
2
1 tubular
12
12
C5
0
0
0
0
69
3 (2 Pleo)
1 comedo
0
73
73
Total
22
21
1
44
78
5
4
1
88
132
44
88
FNA/pathology correlation of
non palpable masses
PATHOLOGY
FNA
n
p
Negative
Positive
FCC
FA
Other
Total neg
IDC
ILC
DCIS
Other
Total pos
Total
C1
0
1
0
1
2
0
1
0
3
4
C2
15
5
1 LN
21
0
0
0
0
0
21
C3
1
2
0
3
0
0
0
0
0
3
C4
0
0
0
0
1
0
0
0
1
1
C5
0
0
1 (ame)
1
16
1
2
0
19
20
Total
16
8
2
26
19
1
3
0
23
49
26
23
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
Diagnostic criteria for malignancy
1. Tumor cellularity
2. Discohesion
3. Cytologic features of malignancy.
•
Compare neoplastic cells to benign duct
cells
•
•
•
•
↑ N/C ratio
Irregular nuclear contour
Hyperchromasia
Presence of nucleoli
Ductal adenocarcinoma nos
•
•
•
•
•
•
•
Cellular
Necrotic background
Monomorphic cell population
Loss of cell cohesion
Numerous isolated singe cells
Anisonucleosis
Lack of ME cells
Tumor grade
• HISTOLOGY
– Glands
– Nuclei
– Mitosis
• CYTOLOGY
– Nuclei
•
•
•
•
Size
Membrane
Chromatin
Nucleoli
Nuclear grade 1-3
Good correlation with histologic
grade
Special type carcinomas
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
Mucinous carcinoma
•
•
•
•
Well circumscribed, soft
Thick mucinous material
Cell balls, minimal atypia, few signet rings
Cannot diagnose absolutely on FNA
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
Other carcinomas
• Not very good
• No clinical need
• Carcinoma and nuclear grade
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% )
FNA of DCIS
• DCIS Grade 3:
– 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
C5
• Management
• If the TT is positive then definitive
treatment is undertaken
C3 & C4
C3: Atypical favor benign
C4: Suspicious for malignancy
C3 (atypical favor benign)
• Atypical/indeterminate/favor benign
• Lesion is probably benign
• Malignancy cannot be excluded entirely
• TT
C4 (Suspicious probably malignant)
• Very high probability of malignancy but
confirmation is needed prior to definitive
therapy
• Others are complex lesions
• Additional material
FNA/Pathology correlation, AUBMC,
2003-2007
PATHOLOGY
FNA
Negative
Positive
Total
C1
4
5
9
C2
56
1
57
C3
9
0
9
C4
0
13
13
C5
1
92
93
Total
70
111
181
C3+C4: 11.6%
FNA/pathology correlation of
palpable masses
PATHOLOGY
FNA
p
Negative
Positive
FCC
FA
Other
Total neg
IDC
ILC
DCIS
Other
Total pos
Total
C1
2
1
0
3
2
0
0
0
2
5
C2
16
18
1 PT
35
0
0
1 crib pap
0
1
36
C3
4
2
0
6
0
0
0
0
0
6
C4
0
0
0
0
7
2
2
1 tubular
12
12
C5
0
0
0
0
69
3 (2 Pleo)
1 comedo
0
73
73
Total
22
21
1
44
78
5
4
1
88
132
44
88
FNA/pathology correlation of
non palpable masses
PATHOLOGY
FNA
n
p
Negative
Positive
FCC
FA
Other
Total neg
IDC
ILC
DCIS
Other
Total pos
Total
C1
0
1
0
1
2
0
1
0
3
4
C2
15
5
1 LN
21
0
0
0
0
0
21
C3
1
2
0
3
0
0
0
0
0
3
C4
0
0
0
0
1
0
0
0
1
1
C5
0
0
1 (ame)
1
16
1
2
0
19
20
Total
16
8
2
26
19
1
3
0
23
49
26
23
C3 and C4 lesions
• Nature of lesion
–
–
–
–
–
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
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%)
Inconclusive FNAs of breast with
adequate and representative material: A
cytologic/histologic study of 18 cases.
AUBMC experience
N Shabb
F Boulous
Z Chakhachiro
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
C4
DCIS (crib)
3
67
lump
Pathologist
C2
C3
DCIS (crib, pap)
4
65
lump
Clinician
C4
C5
Inv crib
5
40
lump
Pathologist
C4
C4
Inv crib
6
46
4mm U/S
Radiologist
C4
C4
Tubular
7
53
3cm, gritty
Pathologist
C3-4
C3-4
Tubular
8
43f
NA
Clinician
C2
C4
Tubular
9
44f
lump
Clinician
C4
C5
Lobular
10
71f
lump
Clinician
C4
C3-4
Inv adeno (nos) 1/3
11
50f
NA
Clinician
C4
C4
Inv adeno (nos) 1/3
12
38f
lump, preg
Pathologist
C4
C5
Inv adeno (nos) 2/3
13
36f
1cm
Pathologist
C4
C5
Inv adeno (nos) 2/3
14
50f
Non
palpable
Radiologist
C4
C5
Inv adeno (nos) 2/3
15
73f
3cm
Pathologist
C4
C4
Inv adeno (nos) 2/3
16
66f
15cm hem
cyst
Clinician
C4
C4
ICPC
17
29f
lump
Radiologist
C3
C3-4
FA
18
60f
2cm gritty
Pathologist
C4
C4
PT malignant
Papillary lesions
• FNA not reliable in distinguishing benign
from malignant. Defer to histology
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
False positive FNAs
• Lesions responsible for False +
–
–
–
–
–
–
Fibroadenomas
Epithelial hyperplasia
Pregnancy
Papillary lesions
Reactive atypias
Adenomyoepithelioma
• Usually interpretative errors
• Poor specimen preparation
• TT
Post triple test recommendations
• Benign triplets
– FU
• Malignant triplets
– Definitive therapy
• Mixed triplets
– Histologic evaluation
Benefits of the triple test
• False negatives: ↓ 10 to 1%
• False positives: ↓ 1 to < 0.2%
FNA diagnostic accuracy
• Literature
–
–
–
–
Sensitivity: 75-98%
Specificity: 60-100%
False positive: 0-2.5%
False negative: 2.517%
– 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)
CNB vs FNA preoperative evaluation of breast masses
CNB
FNA
Special expertise (Performing
+ interpretation)
No
Yes
Feel effect
No
Yes
Safety (chest wall)
No
Yes
Time consuming (pathologist)
No
Yes
In situ/invasive
+/-
-
Definitive dx
Better
Good
Cost/TAT/pain/invasiveness
Good
Better
Tumor grade
Better
Good
Yes
No
Insufficient rate
Better
↓
experience
False +/-
Better
Inevitable
Palpable
Good
Good
Non palpable
Good
No Good
Prognistic markers
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)
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.
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
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
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)
Disadvantages of FNA
• False negatives
• False positives
• Special training needed to perform and
interpret FNA
• In situ vs invasive carcinoma
• Complications
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.
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)
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
FNA/pathology correlation of
palpable masses
PATHOLOGY
Negative
FNA p
Positive
FCC
FA
Other
Total neg
IDC
ILC
DCIS
Other
Total pos
Total
C1
2
1
0
3
2
0
0
0
2
5
C2
16
18
1 PT
35
0
0
1 crib pap
0
1
36
C3
4
2
0
6
0
0
0
0
0
6
C4
0
0
0
0
7
2
2
1 tubular
12
12
C5
0
0
0
0
69
3 (2 Pleo)
1 comedo
0
73
73
Total
22
21
1
44
78
5
4
1
88
132
44
88
Sensitivity: TP/TP+FN = 88/88+1 = 98.8%
Specificity: TN/TN+FP = 44/44+0 = 100%
False negative: 1
False positive: 0
FNA/pathology correlation of
non palpable masses
PATHOLOGY
Negative
FNA
np
Positive
FCC
FA
Other
Total neg
IDC
ILC
DCIS
Other
Total pos
Total
C1
0
1
0
1
2
0
1
0
3
4
C2
15
5
1 LN
21
0
0
0
0
0
21
C3
1
2
0
3
0
0
0
0
0
3
C4
0
0
0
0
1
0
0
0
1
1
C5
0
0
1 (ame)
1
16
1
2
0
19
20
Total
16
8
2
26
19
1
3
0
23
49
26
23
Sensitivity: TP/TP+FN = 23/23+0 +100%
Specificity: TN/TN+FP = 26/26+1 =96%
False negative: 0
False positive: 1
Pitfalls
• Low grade carcinomas (lobular, tubular,
low grade ductal)
• Apocrine metaplasia and lactational
change Have large nuclei and prominent
nucleoli
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
References:
1. Masood, S. Prognostic/predictive factors in breast cancer. 2005 Clinics in
Laboratory Medicine 25 (4), pp. 809-825.
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palpable and mammographically detected suspicious breast lesions. 2007
Diagnostic Cytopathology 35 (11), pp. 681-689.
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core needle biopsy according to tumor size of suspicious breast lesions.
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core biopsy in the assessment of symptomatic breast carcinoma. 2005 Breast
14 (5), pp. 411-414.
8. He, Q., Fan, X., Yuan, T., Kong, L., Du, X., Zhuang, D., Fan, Z. Eleven years
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pp. 303-306
9. Oyama, T., Koibuchi, Y., McKee, G. Core needle biopsy (CNB) as a
diagnostic method for breast lesions: comparison with fine needle aspiration
cytology (FNA). 2004 Breast cancer (Tokyo, Japan) 11 (4), pp. 339-342.
Acknowledgments
•
•
•
•
Dr Fuad Boulous
Dr Zaher Chakhachiro
Dr Alexis Bousamra
Ms. Nisrine Hashem
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
Papilloma
•
•
•
•
Cellular, bloody background
Macrophages
3 dimensional papillary clusters, cell balls
Tall columnar cells, apocrine cells and ME
cells
Papillary carcinoma
• Papilloma +
• Necrotic debris
• Atypical cytology High N/C ratio,
hyperchromasia, nucleoli
• Absence of apocrine cells and ME cells
FNA palpable masses
PATHOLOGY
FNA
Palp
able
Negative
Positive
Total
C1
3
2
5
C2
35
1
36
C3
6
0
6
C4
0
12
12
C5
0
73
73
Total
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)
FNA of non palpable masses
PATHOLOGY
FNA non
palpable
Negative
Positive
Total
C1
1
3
4
C2
21
0
21
C3
3
0
3
C4
0
1
1
C5
1
19
20
Total
26
23
49
•
•
•
•
27% FNAs
47% malignant
C1: 8%
C5: 1 FP.
Adenomyoepithilioma
• The only FP in our 17
year experience
(>2500 cases)