The Clinical Utility of Fine Needle Aspiration Cytology in a Symptomatic Breast Population

Myles Smith, Cynthia Heffron, Barbara Loftus, Michael Jeffers, Jane Rothwell, James Geraghty

Departments of Surgery and Histopathology, AMNCH, Dublin, Ireland

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

Introduction

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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

Benefit of FNAC

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

Controversies and Potential of FNAC in Cancer

FNAC in the Irish Context

Younger◦ 27% triaged as

low risk were, <35

◦ No increase in cancer diagnosis

10:1 17:1

Benign:malignant ratioPatient referrals to Cancer Centres (HIQA)

2006 2009

Media priority Screening

centres

Why?GP General

Surgeon, +/-SI in Breast

Breast Cancer Specialist

GP General Surgeon

Breast Specialist

Patient

“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….

FNAC in Context

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

Objectives

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

Methods

Rapid Assessment Breast Clinic

• FNAC onlyPalpable Lump<35

• Mammogram• FNACPalpable

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

Triple Assessment

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

LABCNeoadjuvant Rx

1° Endocrine

FNAC Process

DiagnosisAssessmentStainingFixationSampling

Pathologist

Air dried MGG

Definitive Staining

Inadequate:Repeat FNAC

ETOH Papanicolau

Residual Saline/Hank’s

Adequate

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

Cytological Diagnosis

Closed Field Data Capture: Bespoke EPR

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)

Results RABC throughput

◦ 2004-2007 inclusive Total Attendances=4487

Mean 22.4 new/week

1572 (35%)

2916 (65%)

FNACno FNAC

Positive Predictive Values %

PPV (C5) 100

PPV (C4) 95.6

PPV (C3) 18.6

Diagnostic Accuracy of FNAC

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

Sensitivity and SpecificitySensitivity 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

C5, Malignant cytology

Invasive98%

DCIS1%

No further his-tology

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 73ILC 11Other 5

C4, Suspicious for malignancy

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

In-va-sive79%

DCIS17%

Total benign4%

Final Histology

IDC 10ILC 6Pap 1

C2, Benign

Invasive1%

Total benign12%

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

C3, Atypical

Invasive19%

Total benign74%

No further his-tology

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

C1, Inadequate

Invasive3%

Total benign37%

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

Benign to Malignant Ratios

5.8 (85%)

1

FNAC

Benign Malignant

18.3 (95%)

1

RABC Attendance

Benign Malignant

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

Discussion

AccuracyFalse 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

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

Indeterminate and Insufficient

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

Discussion: Diagnostic Utility

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%

Summary

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

Conclusion

AMNCH◦ Mrs. Terry Hannan◦ Mr. Eddie O’Connor

University of Toronto◦ Dr. Mark Corrigan

Acknowledgements

Outtakes

FNAC ClassificationC5 C4 C3 C2 C1 Total

HistologyMalignant 190 23 8 9 7 232 Invasive 189 19 8 9 7 229 Non-invasive 1 4 0 0 0 5Total benign 0 1 32 128 100 261No Histology 2 0 3 904 165 1079Total FNAC

results192

(12.2%)24

(1.5%)43

(2.7%)1041

(66.2%)272

(17.3%)1572

Definitive Histology of FNAC Samples

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).

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

Advantages

Ratio of benign:malignant disease

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

Core Biopsy

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

Data Quality Assurance