CSSO presentation 2012, Utility of FNAC in a symptomatic breast population

1. Myles Smith, Cynthia Heffron, Barbara Loftus, Michael Jeffers, Jane
Rothwell, James Geraghty
Departments of Surgery and Histopathology, AMNCH, Dublin, Ireland

2.  There is controversy surrounding the optimal tissue biopsy methodology in
the diagnosis of symptomatic breast cancer and the identification of benign
disease
 Kocjan et al concluded that the use of core biopsy (CB) has increased for
various reasons
 However, it has been suggested that fine needle aspiration cytology (FNAC)
should be used in the diagnosis of symptomatic, and benign lesions

3.  Advantages:
◦ Highly accurate in experienced hand
◦ Cost effective
◦ May be used for small lesions not amenable to CB
◦ Complementary to core biopsy practice
◦ Complete sensitivity 93% CB vs 82% FNAC...but for FNAC+CB 98%
◦ Benign disease: early discharge and reassurance

4.  Potential disadvantages:
◦ ER and PR receptor status
◦ Tumour grade
◦ LVI
 Jayaram G et al Acta Cytol 2005
 Future potential:
◦ FNAC + gene expression technology:
◦ Improve diagnostic accuracy and classification
◦ ?obviate the need for CB
 Uzan C et al Cancer Cytopathol 2009
 Raza M et a; Bioinformation 2006

5.  Younger
◦ 27% triaged as
low risk were,
<35
◦ No increase in
cancer
diagnosis
10:1 17:1
Benign:malignant ratio
Patient referrals to Cancer
Centres (HIQA)
2006 2009

6.  Media priority
 Screening
centres
GP General
Surgeon,
+/-SI in
Breast
Breast
Cancer
Specialist
GP General
Surgeon
Breast
Specialist
Patient

7.  “One-stop” triple assessment Rapid Assessment Breast Clinic (RABC)
potentially allows:
◦ Reduction in time to diagnosis and treatment of breast cancer
◦ Immediate reassurance and discharge of those with benign
disease
◦ Developed also as a response to high volumes….

8.  We aimed to assess the utility of fine needle aspiration
cytology (FNAC) in the context of a “one-stop” symptomatic
breast triple assessment clinic (RABC)
 We specifically wished to assess:
◦ The diagnostic accuracy of FNAC in breast cancer
◦ Identify the proportion of patients who were diagnosed with benign
disease and hence discharged

9.  We analysed prospective data collected at our
RABC, over a 4 year period
◦ 2004-2007 (inclusive)
 RABC commenced in 2002
 We chose the years 2004-2007 to avoid any
variability in data
◦ Learning curve
 Clinical system
 Computerisation

10. •FNAC only
Palpable
Lump<35
•Mammogram
•FNAC
Palpable
Lump>35
Results
<4 hours
Benign
Malignant
Discordant/
Inadequate/
Atypical FNAC
 FNAC findings were classified in
accordance with the British National
Co-ordinating Committee for Breast
Cancer Screening

11. Concordant
Benign
(C2)
High Risk:
FRAC Genetic
risk/profiling (10%)
Fibroadenoma
>3cm excised
(Phyllodes)
Malignant
(C4/C5)
Surgery as
appropriate
Low Risk:
Reassured and
discharged
LABC
Neoadjuvant
Rx
1° Endocrine

12. DiagnosisAssessmentStainingFixationSampling
Pathologist
Air dried MGG
Definitive
Staining
Inadequate:
Repeat FNAC
ETOH Papanicolau
Residual
Saline/Hank‟s
Adequate

13.  C5: Malignant
◦ High nuclear to cytoplasmic ratio
 Variable shape
 C4: Suspicious for malignancy
 Atypical cells with a high nuclear to cytoplasmic ratio and moderate
pleomorphism
 benign groups and bipolar bare nuclei in the background
 C3: Atypical
◦ Mild anisonucleosis and nuclear crowding may represent hyperplastic
change
 differential includes an atypical ductal or low grade in situ lesion
 C2: Benign
◦ Benign group of ductal epithelial cells
 C1: Inadequate
◦ Low cellularity specimen with blood and fragments of adipose tissue
 At least 6 epithelial cell groups are required for C2 classification

14. Clinical Examination Mammography Pathology
E1 Normal R1 Normal C1 Inadequate for analysis
E2 Nodularity R2 Probably Benign C2 Benign
E3 Benign R3 Indeterminate C3 Atypia probably benign
E4 Suspicious R4 Probably Malignant C4 Atypia probably malignant
E5 Malignant R5 Malignant C5 Malignant
Key Extra, a module of Order Communications
(Healthcare Management Systems, Tennessee,
USA)

15.  RABC throughput
◦ 2004-2007 inclusive
 Total Attendances=4487
 Mean 22.4 new/week
1572 (35%)
2916 (65%)
FNAC
no FNAC

16. Positive Predictive Values %
PPV (C5) 100
PPV (C4) 95.6
PPV (C3) 18.6
 Positive predictive value of (C5) diagnosis:
◦ The number of correctly identified cancers expressed as a percentage of the total
number of cancers after core biopsy or histology post resection
False negative/positive and inadequate %
False negative rate (excludes C1) 3.85
False positive rate 0.00
Inadequate rate 17.31
Inadequate rate from cancers 2.99
The figures are calculated as per the NHSBP guidelines
1/1572

17. Sensitivity and Specificity %
Absolute Sensitivity 80.77
Complete Sensitivity 94.02
Specificity (full) 77.36
The figures are calculated as per the NHSBP guidelines
 Absolute sensitivity:
 The number of carcinomas diagnosed (C5) expressed as a percentage of the total
number of carcinomas sampled
 Complete sensitivity:
 The number of carcinomas that were not falsely negative or inadequate on FNAC
expressed as a percentage of the total number of carcinomas
 Specificity (full):
 The number of correctly identified benign lesions (the number of C2 results minus
the number of false negatives) expressed as a percentage of the total number of
benign lesions aspirated

18. Invasive
98%
DCIS
1%
Total
benign
0%
No further
histology
1%
Final Histology  Total number C5:
 192
 12.2% total
FNAC
 Comment:
 No False Positives
 1 DCIS diagnosed
post mastectomy
 2 Primary
endocrine
 Hence no
further
histology
IDC 73
ILC 11
Other 5

19.  Total number C4:
◦ 24
 1.5% Total FNAC
 Comment:
◦ DCIS 4
◦ Phyllodes 2
 1 False positive
◦ Discordant; clinical
nodularity and normal
mammogram
◦ CBx2, then excision
◦ Dx: Duct ectasia, apocrine
metaplasia
Invasive
79%
DCIS
17%
Total
benign
4%
No further
histology
0%
Final Histology
IDC 10
ILC 6
Pap 1

20. Invasive
1%
DCIS
0%
Total
benign
12%
No further
histology
87%
Final Histology
 Total C2:
 1041
 66.2% Total FNAC
 Comment
 Discordant triple assessment 137
 Invasive 9 (6.6% of disc TA)
 IDC 6
 ILC 2
 Metaplastic 1
 Benign 128 (93.4%)
 Fibrocystic 84
 Fibroadenoma 35
 Other 9

21. Invasive
19%
DCIS
0%
Total
benign
74%
No further
histology
7%
Final Histology
 Total C3:
 43
 2.7% Total FNAC
 Comment
 3 re-examined and
reclassified as C2
 40 USS and core biopsy
 Invasive 6
 IDC 4
 ILC 2
 Benign 34

22. C1, Inadequate
Invasive
2% DCIS
0%
Total
benign
37%
No further
histology
61%
Final Histology
 Total C1:
 272
 17.3% Total FNAC
 Outcome:
• USS 165
• No further histology
• Reassured and
discharged/FRAC
• Lipoma
• USS+Core biopsy 100
• (if lesion visualised)
• Invasive 7 (2.6% of total )
• IDC 4
• ILC 2
• Primary osteogenic
sarcoma 1

23. 5.8 (85%)
1
FNAC
Benign Malignant
18.3
(95%)
1
RABC Attendance
Benign Malignant

24.  FNAC had a high diagnostic accuracy
◦ Prospectively acquired cohort of 4487, with 1572 FNAC
 Symptomatic disease triple assessment RABC
 We found the complete sensitivity of FNAC
to be 94%
◦ PPV of 100% for a C5
◦ PPV of 95.65% for a C4
 The specificity was 77% - correct
identification of benign disease

25. False negative rateFalse positive rate
 Small:
◦ 3.85%
 Negligible:
◦ Only one case being
classified as
suspicious (C4) with
a discordant triple
assessment and final
diagnosis of benign
disease,
◦ 5 cases of C4/C5
being DCIS

26.  Small proportion of indeterminate (C3) cases (n=43, 2.7%),
which had a poor PPV for cancer (18.6%)
◦ The majority of these were ultimately diagnosed with
benign disease (75%)
◦ Much lower than reported in the literature 18.6 vs 55%
 Bulgaresi P et al Breast Cancer Res Treat 2006
 There were 165 cases with an insufficient (C1) report who had
no further histology
◦ Ultrasound did not reveal a suspicious target
◦ Lipomas were historically inappropriately referred for FNAC

27.  The majority (80%) of patients were
immediately and definitively diagnosed:
◦ Benign disease: 66%
 Reassured
◦ Malignant disease: 13.75%
 Therapeutic surgery
 Excluding those who required further diagnostic
tests
◦ Core biopsy
◦ Discordant triple assessment

28.  We found FNAC to be highly accurate in diagnosing
breast cancer in this population, with the benefit of
rapid diagnosis and discharge of those with benign
disease
 We found the complete sensitivity of FNAC
to be 94%
◦ PPV of 100% for a C5
◦ PPV of 95.65% for a C4
 Benign disease was accurately identified, with the
specificity being 77%

29.  On the basis of our results, we believe that FNAC
remains an important diagnostic modality
especially in the „„one stop‟‟ triple assessment of
symptomatic breast patients
 It may be particularly suited to settings in which
high volumes of benign disease are seen, where
same day diagnosis reassures the patient and
obviates the need for a second visit

30.  AMNCH
◦ Mrs. Terry Hannan
◦ Mr. Eddie O‟Connor
 University of Toronto
◦ Dr. Mark Corrigan

33. FNAC Classification
C5 C4 C3 C2 C1 Total
Histology
Malignant 190 23 8 9 7 232
Invasive 189 19 8 9 7 229
Non-invasive 1 4 0 0 0 5
Total benign 0 1 32 128 100 261
No Histology 2 0 3 904 165 1079
Total FNAC
results
192
(12.2%)
24
(1.5%)
43
(2.7%)
1041
(66.2%)
272
(17.3%)
1572

34. The Health Information and Quality Authority
HIQA
The role of the Authority:
- Setting standards - quality and safety, data and information
- Monitoring compliance with standards
- Investigating serious concerns about the health and welfare
of service users
- Registration and inspection of residential homes for children
and older people
- Advising on the collection and sharing of information
- Evaluating the clinical and cost effectiveness of health
technologies and provide advice to the Minister and HSE
The role of the Authority:
“is to promote safety and quality in the provision of health, and
personal social services for the benefit of the health and welfare of the
public”
(Section 7 of the Health Act 2007).

35.  Relatively pure symptomatic population
 Prospective, real-time capture of robust data
in our rapid breast clinic
 Performance of FNAC in our clinic by 2
pathologists with a special interest in FNAC
 Standardised, audited and quality assured
data
 Data management

37.  Indications:
◦ FNAC report of:
 “inadequate” (C1)
 “atypia probably benign” (C3)
 “suspicious” (C4)
◦ Discordant triple assessment
◦ Locally advanced
 ER/PR/HER2
◦ Elderly/Infirm
 primary endocrine therapy
 Technique:
◦ USS: Toshiba Aplio 80
◦ 1% lignocaine/lidocaine
◦ 14 gauge core biopsy with an automated
disposable Bard Max Core

38.  Weekly multidisciplinary meeting
◦ Tumour Board
 Standardised reporting
 Data manager to ensure integrity of data and database
 Audit and quality assurance
◦ Yearly
 British National Health Service Breast Screening standards
 Irish HIQA (Health Information and Quality Authority)
standards