Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle...

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Transcript of Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle...

Page 1: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International
Page 2: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Introduction: Ultrasound guided Fine Needle Aspiration:

When and how

Teresa Rago

Unit of Endocrinoloy I

University of Pisa

International Course of Thyroid Ultrasonography and minimally invasive procedure

7-8 October 2016

University of Pisa, Italy

Page 3: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

THYROID NODULE US

DIAGNOSTIC IMPORTANCE

Nodule size and position Suspicious US features Presence of other nodules/lymphnodes Increases FNAC accuracy

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US characteristics

(references)

Sensitivity

(%)

Specificity

(%)

Positive Predictive

Value (%)

Negative

Predicitve Value

(%)

Microcalcifications

(1-5)

26-59 86-95 24-71 42-94

Hypoechogenicity

(2-5)

27-87 43-94 11-68 74-94

Irregular margins or no

halo (2-5)

17-78 39-85 9-60 39-98

Solid

(4-6)

69-75 53-56 16-27 88-92

Frates et al. Radiology 2005

1.Khoo et al. Head Neck 2002

2.Kim et al. Am J Roentgenol 2002

3.Papini et al. J Clin Endocrinol Metab

4.Rago et al. EJE 1998

5.Frates et al. Radiological Society of Noth America 2004

6.Frates et al. J Ultrasound Med 2003

Suspicious US features

Society of Radiologists in Ultrasound Consensus Statement

Page 5: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US features

MALIGNANT BENIGN

Hypoechogenic Absent halo Irregular margins Microcalcificazions

Anechogenic / hyperechogenic Thin Halo Regular margins Egg shell calcifications

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10 US patterns with their malignancy risk and thyroid

imaging reporting and data system (TIRADS) category

Horvath et al., J Clin Endocrinol Metab, 2009

Page 7: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

FNAB TIRADS 2 TIRADS 3 TIRADS 4 TIRADS 5

Benign 100 % 85,9 % 55 % 10,4 %

Cancer 0 % 3,4 % 14 % 86,5 %

Horvath et al, J Clin Endocrinol Metab, 2009

Correlation of TIRADS categories with the risk of cancer determined by FNAB and Histology

TIRADS: thyroid imaging reporting and data system

Page 8: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Haugen B. et al, ATA Guidelines on Thyroid Nodules and DTC, in press

Page 9: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

ECON-ARM

US Features Example Risk Of Malignancy

0-1

Cystic, spongiform, iso-hyperechoic, complete halo sign, macrocalcifications, perinodular vascularization

Low

2-3

iso-hypoechoic with one of US pattern suggestive of malignancy,

Intermediate

4-5

hypoechoic, with 3 or more US pattern suggestive of malignancy, extrathyroid extension, presence of lymph nodes

High

Echographic Classification Of thyroid Nodules According to the Risk of Malignancy (ECON-ARM)

Teresa Rago, Maria Scutari, Francesco Latrofa, Ivo Marchetti, Rossana Romani, Agnese Proietti, Fulvio Basolo, Paolo VittI

Page 10: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

TIR-1 TIR-2 TIR-3 TIR-4 TIR-5 Risk

1 1C A B

ECON-ARM n°

0-1 338 20 16 264 28 10 0 0 Low

2-3 166 13 1 108 29 7 3 6 Intermediate

4-5 18 1 / 0 1 2 3 11 High

Total 522 51 372 58 19 6 17

Low Risk was found in 64,75% : none had TIR 4-5 cytology and 11,2 % TIR 3 cytology.

Intermediate risk was found in 31,8%: 5,4% had TIR 4-5 cytology and 21,7% TIR 3 cytology.

High risk was found in 18%: 78% had TIR 4-5 cytology and 16% TIR 3 cytology.

Conclusions This new US classification of the risk of malignancy in the thyroid nodule allows to establish the strength of the indication to perform FNA in each thyroid nodule.

Echographic Classification Of thyroid Nodules According to the Risk of Malignancy (ECON-ARM)

Teresa Rago, Maria Scutari, Francesco Latrofa, Ivo Marchetti, Rossana Romani, Agnese Proietti, Fulvio Basolo, Paolo VittI

Page 11: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Strength of indication for FNA depending on US features

Cystic

spongiform

Mixed

Solid hypoechogenic

Microcalcificazions Irregular margins

Lymphadenopathy

More suspicious US findings

Ind

icat

ion

Strength of indication for fine-needle aspiration (FNA) biopsy of thyroid nodules on the basis of ultrasonography (US) findings.

Page 12: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Indications for FNA

Which nodules?

3.5.1. Indications for UGFNA

High-US-risk thyroid lesions ≥10 mm

Intermediate-US-risk thyroid lesions >20 mm

Low-US-risk thyroid lesions only when > 20 mm and increasing in size or associated with a risk history and before thyroid surgery or minimally invasive ablation therapy [BEL 2, GRADE A]

3.5.2. UGFNA of multinodular glands

We do not recommend the biopsy of more than 2 nodules when they are selected

on the basis of previously described criteria [BEL 3, GRADE C]

Gharib H. et al, AACE/AME Task Force on Thyroid Nodules, in press

Page 13: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Indications for FNA

US -Guided

Page 14: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

Authors

Patients FNA

Palpation / US

Not diagnostic (%)

FNA

Palpation / US

Cameci 1998

Danese 1998

497 370 / 127

9683 4986 / 4697

16 7

8,7 3,5

Palpation vs US guided FNA

Page 15: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

Page 16: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

US -Guided

necessary

Non palpable Nodules

Mixed / cystic Nodules

Nodules in MG

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US-Guided Fine Needle Aspiration

450 non palpable nodules

94 operated: 20 Ca 8 < 1cm, 12 >1 cm

No correlation size / hystology Ca

Solid–hypoechogenic / hystology Ca p<0.0003

Adequacy of material / size p<0.0001

Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules.

Leenhardt L et al. JCEM, 1998

Page 18: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

Good compliance

Repeatable

Reproducible

Devoid of risk

Accurate Aspiration

21 22 23 Gauge

Thin needle

Capillarity

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US-Guided Fine Needle Aspiration

Drawings: 2-4 in different areas

of the nodule

Page 20: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

Measurement Tg and CT

Immunocytochimistry

Molecular Characterization

Cytological examination

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US-Guided Fine Needle Aspiration

Cytological examination

Adequate: 6 groups of 10-20 cells

Fixation, staining: preservation of nuclei

Hamburger, 1986,1988 Mazzaferri, 1988 Gharib, 2016

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US-Guided Fine Needle Aspiration

Cytological examination

Stain

Papanicolaou

May-Grunwald-Giemsa

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Classification of cytology

Page 24: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Results of cytology

Percentage

Non diagnostic 10-15

Benign 60-80

Indeterminate 10-20

Suspicoius or Malignant 3,5-10%

Page 25: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

Page 26: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

The combination of two or more of these features is

100% specific in detecting papillary thyroid

carcinoma.

Specificity Psammoma bodies: 100% Nuclear grooves: 88% Micronuclei: 86% Pseudo-inclusions: 88% Powdery chromatin: 59%

Cytological features of papillary thyroid tumor on fine-needle aspiration biopsy

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US-Guided Fine Needle Aspiration

Problems

Non Diagnostic

Inderminate

Follicular Nodule / Hurthle cell Nodule

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US-Guided Fine Needle Aspiration

Non Diagnostic Author aa Pz % Repeated FNA

D ND

% %

Tx

Ca

%

Goernell 80-83 1299/6300 20 59 41 118 8

Livolsi 94-97 72/616 11 8 37

Block 81 3/121 2,5 3 33

Burch 95 156/504 31 125 4

Caraway 86-90 9/394 2,28 4 5 5 0

Altavilla 89 392/2433 16 257 12,5

Hing you 97 148/662 22 34 22.9

Page 29: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Predictivity of Cytology

Histology

N° pz 3.406

Benign – N° (%) Malignant– N° (%)

Non diagnostic (TIR 1) 247 165 (67) 82 (33)

Benign (TIR 2) 1295 1271 (98.2) 24 (1.8)

Indeterminate (TIR 3) 969 686 (70.7) 283 (29.3)

Suspicious (TIR4) 391 11 380 (97.2)

Indicative of ca (TIR 5) 504 0 504 (100)

Rago T. et al. EJE - 2010

Page 30: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Results of cytology

THE DILEMMA OF INDETERMINATE

TIR 3 CYTOLOGY RESULT

10-20 %

Page 31: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Follicullar lesions

Increased cellularity,

Small uniform follicule,

Scant watery colloid

Small nuclei

Regular chromatin

Nuclear atipias

Enlarged nuclei

Sparse or irregulary chromatin

Rare prominent nucleoli

Ocasional mitosis

Isolated or arranged in cohesive sheets

Scant colloid

Abundant, dense, finely granular cytoplasm

Eccentrical nuclei granular chromatin

Small single or multiple nuceloli

Hürthle cell nodules

Results of cytology

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0

20

40

60

80

100

Classic Follicular Oxyphylic Tall cell Trabecular

0

20

40

60

80

100

Papillary Follicular Poorly differentiated

n= 308

n= 55

n= 8

n= 239

n= 47

n= 6 n=10 n= 6

Rago et al. JCEM 2013

Histological subtype of CA in 371/1520 (24%) Thy 3 nodules at cytology

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Thyroid US

Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy

in Follicular and Hurthle cell thyroid lesions: results from a series of 505 consecutive patients

Rago et al. Clin Endocrinol, 2006

The only US pattern predictive of carcinoma is the presence of microcalcifications (p=0.0009)

Thyroid follicular neoplasms: can sonography distinguish between adenomas and carcinomas?

Seo HS et al. J Clin Ultrasound. 2009

US…… microcalcifications ……are more common in FC than in FA (p < 0.05 )

Page 34: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Histological subtype of CA in 371/1520 (24%) Thy 3 nodules at cytology

0

25

50

75

100

Thy 3A Thy 3B

Benign

Malignant

227/1170

144/350

p < 0,0001

(Atypias-) (Atypias+)

41%

19%

Page 35: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

Cytologic diagnosis

Measurement of Tg and CT

Immunochemical Examen

Molecular Characterization

Page 36: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

Histochemical Markers

……Many molecular markers have been evaluated to improve diagnostic accuracy for indeterminate nodules (34,35) but none can be recommended because of insufficient data…………

R.8…..the use of specific molecular markers ….. is not recommended.

Page 37: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

US-Guided Fine Needle Aspiration

Conclusions

“Today”: US guided FNA accurate technique, reducing inadequate specimens for cytological examination

“Tomorrow”: Molecular diagnosis will help to improve diagnosis of CA in indeteminate and non diagnostic lesions in conventional cytology

Page 38: Introduction: Ultrasound guided Fine Needle AspirationIntroduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa International

Grazie