FNA of BREAST

The 6th Arab-British School of PathologyNina 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

0

50

100

150

200

250

1997 1999 2001 2003 2005 2007

Number of breastFNAs

Total number: 1794

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

  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

FNA/Pathology correlation, AUBMC,2003-2007

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

C1Unsatisfactory

  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

FNA/Pathology correlation, AUBMC,2003-2007

C1: 5%

C1 palpable vs non palpable

  PATHOLOGY

FNA Palpable 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

C1: 3.5% (2.3%pos) C1: 8%

  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

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

C2Benign

C2 benign

• FNA: Adequate and representative material of benign disease– FCC (cysts)– Abscess– Fat necrosis– Fibroadenoma– Other

  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

FNA/Pathology correlation, AUBMC,2003-2007

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 np

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

C5Malignant

C5 Malignant

• Primary– IDC nos– ILC– Mucinous– Tubular– Papillary– Other

• Metastatic• Hematopoetic

  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

FNA/Pathology correlation, AUBMC,2003-2007

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 np

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 1-3Good 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 & C4C3: 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

  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

FNA/Pathology correlation, AUBMC,2003-2007

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 np

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

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

Inconclusive/erroneous cellular and representative FNAs/histology

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: 2.5-

17%– 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

Prognistic markers Yes No

Insufficient rate Better ↓ experience

False +/- Better Inevitable

Palpable Good Good

Non palpable Good No Good

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    

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    

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    

FNA np

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    

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.

2. Chaiwun, B., Thorner, P.Fine needle aspiration for evaluation of breast

masses. 2007 Current Opinion in Obstetrics and Gynecology 19 (1), pp. 48-55.

3. Garg, S., Mohan, H., Bal, A., Attri, A.K., Kochhar, S. A comparative analysis

of core needle biopsy and fine-needle aspiration cytology in the evaluation of palpable and mammographically detected suspicious breast lesions. 2007 Diagnostic Cytopathology 35 (11), pp. 681-689.

4. Barra, A.D.A., Gobbi, H., Rezende, C.A.D.L., Gouve�a, A.P., De Lucena,

C.E�.M., Reis, J.H.P., Silva, S.Z.C. A comparision of aspiration cytology and core needle biopsy according to tumor size of suspicious breast lesions. Diagnostic Cytopathology, 2008, 36 (1), pp. 26-31.

5. How stereotactic core-needle biopsy affected breast fine-needle aspiration

utilization: An 11-year institutional review. Xie, H.B., Salhadar, A., Haara, A., Gabram, S., Selvaggi, S.M., Wojcik, E.M. 2004 Diagnostic Cytopathology 31 (2), pp. 106-110.

6. Lieske, B., Ravichandran, D., Wright, D. Role of fine-needle aspiration

cytology and core biopsy in the preoperative diagnosis of screen-detected breast carcinoma. 2006 British Journal of Cancer 95 (1), pp. 62-66.

7. Pilgrim, S., Ravichandran, D. Fine needle aspiration cytology as an adjunct to

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

of experience reveals that fine-needle aspiration cytology is still a useful method for preoperative diagnosis of breast carcinoma. 2007 Breast 16 (3), 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

• 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)

  PATHOLOGY  

FNA Palpable 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

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 0 21

C3 3 0 3

C4 0 1 1

C5 1 19 20

Total 26 23 49