Breast

Cytopathology
-Techniques
-Morphology

Jerzy Klijanienko MD
Institut Curie, Paris, France
History of FNA
„ 1926 Martin, Ellis (Memorial Hospital)
„ 1954 Cardozo (Pays Bas)
„ 1954 Zajicek (Karolinska)
„ 1954 Zajdela (Institut Curie)
„ 1972 Rilke (Milan)
„ 1980 USA, Canada
Avantages for the patient
„ Simple
„ No anaesthesia
„ Can be repeated
„ Not time consuming
Avantages for the clinician 1
„ Ambulatory
„ Can be performed during pregnancy
„ Immediate results
„ Can be therapeutic (cyst, abcess)
„ Multiple localisations
„ N (+) or N (-)
Avantages for the clinician 2
„ Can identify a recurrence
„ Can identify non-palpable lesions
„ Can identify metastasis (liver, distant organs)
„ Can determine proliferation index
„ Can identify malignancy for palliative
treatment
„ Procedure explanation to patient is easy
„ Hospital occupation can be planned
Avantages for the laboratory
„ MGG and DQ, fast staining
„ Simple material
„ Low cost
„ Possibility of FCM, Bacteriology, HR
„ Lymphoma, Sarcoma
Complications
„ Distant dissemination: never observed
„ Local dissemination: never observed
„ Hematoma: 40-50% of cases
„ Pneumothorax: 1 in 28 000 cases
„ Infection: 3 in 200 000 cases
Results (1)
„ Exact: M/M, B/B, S/S
„ Suspicious: S/M, S/B
„ False negative: B/M
„ False positive: M/B
„ Non significant: NS/M, NS/B, NS/S
Results (2)
(excluding NS)

„ Sensitivity = VM / VM+FB x 100

„ Specificity = VB / VB+FM x 100

Malignant Tumors
Authors Yr # Exact Susp FB Sensibility
Cases (%) (%) (%) (%)
Zajicek 1970 1068 77 15 8 92

Zajdela 1975 1745 88 3 4 96

Briffod 1981 990 82 9 3 97

Sneige 1993 762 90 5 4 96

Curie 2000 17372 83.7 6.6 6.1 93.2

Benign Tumors
Authors Yr # Exact Susp FP Specificity
Cases (%) (%) (%) (%)
Zajicek 1970 1009 93 7 0.1 93

Zajdela 1975 1027 89 4 0.3 95

Fessia 1987 1449 78 6 0.4 92

Klijanienko 2001 9662 89.2 3.8 0.2 99.7

 False-positive

„ 0.02 % in our series

„ Adenofibroma
„ Ductal ectasia
„ Sclerosing adenosis
„ Papillomas
Why are the results different
between studies?

„ Interpretation
- number of pathologists
- competence
- number of FNA per day
„ Unsatisfactory samples
- multiple localisations
- tumor fibrosis
How to improve
Authors # Clinical Radio FNA All three
Cases (%) (%) (%) (%)
Cornillot 1300 92.1 88.7 87.1 98.8

Briffod 223 88.4 94.2 94.2 98.9

Hermasen 94 80.8 86 80 100

Powles 248 95 81 86 99
Techniques
Sample (1)

„ Material
„ 23 G needles
„ Slides

„ Disinfectant and bandages

„ Microscope + Diff-Quik
Sample (2)

„ Clinicalimpression, tissue resistance

and smearing modality are the THREE
important criteria to provide a high
quality FNA

„ The procedure should be simple and

reproducible
Sample (3)

„ Errors
„ Slow or violent needle introduction
„ Too long or numerous needle passes

„ Use of pistol

„ Bandaging too quickly can cause ulterior

hematoma
Quality control (1)

„ Clinical impression
„ Round, mobile: cysts, FA, mucinous
„ Round with margins: FA, phyllodes tumor

„ Poorly delimited: mastopathia, lobular ca

„ Fixed +/- fossette: carcinomas

„ proximity to scars: fat necrosis, recurrence

Quality control (2)

„ Tissue resistance

„ No resistance: cysts, FA, fat necrosis

„ Fibrous: mastopathia, FA, lobular ca

„ Heterogenous: mastopathia, carcinomas,

necrosis
Quality control (3)

„ Smear macroscopy
„ Color
„ White, pink: galactophotiritis, cysts, FA,
mucinous
„ Gray: carcinoma
„ Adipous: fat necrosis, lipoma, NS

„ Cellularity
„ wet sample, oval, centered on slide
„ Diff-Quik
Non-palpable lesions (1)

„ No microcalcifications
„ US image (FNA) > 2mm < 8mm
„ FNA plus CNB > 8mm
„ Multiple lesions
„ Radio- suspicious lesions (ACR 3-4)
„ Well-trained staff
Non-palpable lesions (2)

„ Material
„ US 7-10 MHz
„ Standard FNA material

„ Needle attached to syringe: aspiration

Non-palpable lesions technique

„ The shortest way

„ Optimal cutaneous point
„ Angular insertion
„ Vertical insertion
„ Aspiration
„ Visualized on screen during aspiration
„ Possibility of completion by US-CNB
Cytology analysis
„ Clinical data: age, size, site, tumor
kinetics, clinics, radiology, N, M,
previous treatment
„ FNA components: cellularity,
distribution, cohesiveness, chromatin,
stroma, necrosis, secretions
„ Simple report, one diagnosis
Cell bloc

cerbB2

ER

PR
References for diagnosis of
breast lesions
Institut Curie, Paris

2008
# patients

# Age Diameter
(mean) (mean)
1981 941 55.9 41.2
1985 982 55.8 36.3
1989 1161 55.7 31.8
1997 1130 56 31.9
1999 1252 56.3 29.5
2001 1767 56 29.2
Diagnostic circumstances

Mammography Palpation
1981 4% 71%
1985 6% 74%
1989 23% 68%
1993 33% 60%
1997 33% 61%
1999 33% 61%
Stage at diagnosis 1
Stage at diagnosis 2

0 I II III
1981 2% 14% 61% 23%
1985 3% 21% 60% 16%
1989 5% 36% 48% 11%
1993 7% 44% 41% 8%
1997 10% 42% 40% 8%
1999 14% 40% 38% 8%
Initial surgical treatment

1981: 19%
1985: 30%
1989: 41%
1993: 52%
1997: 60%
1999: 62%
Diagnosis

„ Anamnesis
„ Clinical
examination
„ Radiology
„ Mammography
„ US

„ CT-scan and IRM (if necessary)

„ Pathology report
But also ….
„ FCM for DNA ploidy and SPhase
„ Ki-67, c-erbB2, p53, ….
„ HR using ICC
„ Microbiology
„ FCM for lymphoma membrane markers
„ Cell and tissue banks – molecular profile
Pathology report

„ To obtain the diagnosis in order to

inform the patient about treatment
modalities
„ To indicate Sentinel LN
„ To avoid successive interventions
„ To know prognostic parameters and to
predict prognosis
(HR, SPh, MI, EE grade, cerbB2, E+)
Breast lesions
Lésion non palpable

Microcalcifications Nodule échographique Nodule échographique

ACR 4 Suspect Indéterminé
ACR 5

Mammotome Suspect < 7mm Suspect > 7mm Cytoponction

Microbiopsie

Cytoponction Microbiopsie
+/- Cytoponction
DRILL-BIOPSIE, 11G
MICRO-BIOPSIE AU PISTOLET 22mm, 14G
FNA vs CNB vs Surgical Specimen
FNA:M FNA:B FNA:M Mean size
MB:M MB:M MB:B
SS:M SS:M SS:M

88% 2.8% 9.2% 31 mm

The drawbacks
„ The procedure may be painful
„ Impossible to sample MCA
„ Infiltration features are seen in only
90% of carcinomas
„ Procedure needs well-trained staff
Morphology
Histology
(Benign tumors)

Inflammation specific and non-specific

Adenosis Increased number
Hyperplasia Increased number
Cyst Pathological dilatation
Metaplasia i.e. oncocytic metapl
Papilloma Tumor vs hyperplasia
Fibroadenoma Double composition
Histology (Malignant tumors)
„ NON INFILTRATIVE „ INFILTRATIVE
„ Ductal in situ „ Ductal
„ DIC with in situ pred.
„ Lobular in situ
„ Lobular
„ Mucinous
„ Medullary
„ Papillary
„ Tubular
„ Ad Cystic Ca
„ Apocrine
„ Metaplastic
„ Paget disease
„ Others: MM, Lymph, Sarc
Breast Pathology
in FNA
- Benign
- Malignant
Inflammatory cytology
„ Acute inflammation
„ Chronic inflammation
„ Non-specific granuloma
„ Foreign body granuloma
„ TBC/sarcoidosis
„ Fat necrosis
Acute Inflammation
„ Purulent collection
„ Painful FNA
„ Fever
„ +/- Dermatitis
„ Malignant clinical aspect
„ Microbiology
„ No CNB
Granulomas

„ TBC or Sarcoidosis
„ Microbiology (liquid, PCR, smears)
„ Foreign body granuloma
„ Frequent post-surgical complication
„ Haematoma
„ Sebaceous cyst
Fat necrosis
„ Different chronology:
„ Initial: lipophages
„ Advances: fibroblastic reparation

„ May be a problem of diagnosis

„ Possibility of FP !!
Benign Tumors (1)
Cysts
„ Different types
„ Apocrine metaplasia
„ « Old » cyst

„ Possibility of atypical cells

„ Differential diagnosis
„ Apocrine carcinoma
„ Papilloma

„ Papillary carcinoma
Benign Tumors (2)
Breast dystrophia
„ Breast dystrophia
„ Benign cytology
„ Variable

„ Cystic background

„ No atypia

„ Clinically benign

„ 50% of patients
Benign Tumors (3)
Epithelial hyperplasia

„ Epithelial hyperplasia
„ simple
„ atypical
Benign Tumors (5)
Atypical hyperplasia
„ Atypical hyperplasia
„ 3-D clusters
„ Irregular nuclei

„ Benign/Atypical FNA morphology

Benign Tumors (6)
FIBROADENOMA
„ Usually 20-35 yrs
„ Multiple in 20% of cases
„ Characteristic cytology
„ Epithelial cells
„ Naked nuclei
„ Connective fragments
„ Mucin (+/-)
„ Digitiform clusters (+/-)
Benign Tumors (7)
PHYLLODES Tumor
„ Rare
„ Large size
„ « malignant » or « benign» behaviour
„ FNA: pseudo-FA
„ Abundant connective fragments
„ « normal » epithelial cells
„ Some C/N atypia
„ Mitoses +/-
BENIGN TUMORS (8)
DUCTAL ECTASIA, PAPILLOMA
„ Ductal ectasia
„ Possibility of nipple retraction
„ Pseudo-cystic morphology
„ Central localization
„ Papilloma
„ Cystic background
„ Papillary clusters
„ Vascular structures
„ Macrophages
„ Myoepithelial cells
„ Possibility of FP !!!!
BENIGN TUMORS (9)
RARE CONDITIONS

„ Lipoma
„ Granularcell tumor
„ Intramammary Lymph Node
„ Gynecomastia
MALIGNANT TUMORS (1)
DUCTAL CARCINOMA
- 80-85%
- Polymorphous cells
- Glandular structures.
- Isolated cells with preserved cytoplasm
- Irregular nuclei
- Huge nuclei
- Necrosis
- Mitoses +/-
MALIGNANT TUMORS (2)
LOBULAR CARCINOMA
„ 5%
„ Variable cellularity
„ Monomorphic nuclei
„ Isolated cells
„ Small clusters
„ Cells in indian file
„ Discrete C/N atypia
„ Connective tissue
MALIGNANT TUMORS (3)
MUCINOUS CARCINOMA
„ 2%
„ Mixed variants
„ Characteristic mucin
„ Inconspicious C/N atypia
„ Differential diagnosis:
„ Fibroadenoma
„ Ductal ectasia
MALIGNANT TUMORS (4)
MEDULLARY CARCINOMA
„ Round – clinically benign
„ Variable size of cells
„ Huge nucleoli
„ Lymphocytes
„ Plasma cells +/-
„ Differential diagnosis:
„ Inflammatory carcinoma
MALIGNANT TUMORS (5)
PAPILLARY CARCINOMA
„ Rare (2%)
„ Malignant cells in papillary clusters
„ Isolated cells and naked nuclei
„ Cystic background
„ Necrotic background
„ Differential diagnosis:
„ Papilloma (atypia!)
„ Cystic carcinoma
Actine smooth
MALIGNANT TUMORS (6)
TUBULAR CARCINOMA
„ Super grade I
„ Tubular clusters
„ Differential diagnosis:
„ Atypical hyperplasia
„ Fibroadenoma

„ Possibility of false-negative
MALIGNANT TUMORS (7)
ADENOID CYSTIC CARCINOMA

„ 0.1%
„ Characteristic smears
„ Round cells, « finger-like »
„ Eosinophilic fragments
„ Differential diagnosis:
„ Metaplastic carcinoma
MALIGNANT TUMORS (8)
APOCRINE CARCINOMA
„ 1%
„ Apocrine cells (benign +/- morphology)
„ Important C/N atypia
„ Necrosis
„ Differential diagnosis:
„ Comedocarcinoma
„ Cysts with dystrophic cells
MALIGNANT TUMORS (9)
METAPLASTIC
CARCINOMA
„ SCC
„ Spindlecell carcinoma
„ Chondroid, osseous
„ Mixed
MALIGNANT TUMORS (10)
Specific variants
„ Neuroendocrine carcinoma
„ Paget’s disease
„ Giant cell carcinoma
„ 1° Sarcoma
„ Sarcomas after RT
„ Lymphomas
„ Metastases
Is it possible to
distinguish????

Infiltrative

Not infiltrative
REFERENCES
„Zajdela A, Vielh P, Di Bonito L. Manuel et Atlas
de Cytologie Mammaire. Piccin 1995
„Cytopathologie Mammaire par Monction. Marsan
C coordination, Diebold J editeur, Elsevier 2001
„Klijanienko J et al. Critical clinicopathologic
analysis of 23 cases of fine-needle breast
sampling initially recorded as false-positive. The
44-year experience of the Institut Curie. Cancer
93: 132-139, 2001
Cases
FN
Sa
LMS
Thank you !!!!!!!!
Wouaw

Now it is finished !