Introduction: Ultrasound guided Fine Needle Aspiration: When and how

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2 International Course of Thyroid Ultrasonography and minimally invasive procedure 7-8 October 2016 University of Pisa, Italy Introduction: Ultrasound guided Fine Needle Aspiration: When and how Teresa Rago Unit of Endocrinoloy I University of Pisa

3 THYROID NODULE US DIAGNOSTIC IMPORTANCE Nodule size and position Suspicious US features Presence of other nodules/lymphnodes Increases FNAC accuracy

4 Suspicious US features Society of Radiologists in Ultrasound Consensus Statement Frates et al. Radiology 2005 US characteristics (references) Sensitivity (%) Specificity (%) Positive Predictive Value (%) Negative Predicitve Value (%) Microcalcifications (1-5) Hypoechogenicity (2-5) Irregular margins or no halo (2-5) Solid (4-6) Khoo et al. Head Neck Kim et al. Am J Roentgenol Papini et al. J Clin Endocrinol Metab 4.Rago et al. EJE Frates et al. Radiological Society of Noth America Frates et al. J Ultrasound Med 2003

5 US features BENIGN MALIGNANT Anechogenic / hyperechogenic Thin Halo Regular margins Egg shell calcifications Hypoechogenic Absent halo Irregular margins Microcalcificazions

6 10 US patterns with their malignancy risk and thyroid imaging reporting and data system (TIRADS) category Horvath et al., J Clin Endocrinol Metab, 2009

7 Correlation of TIRADS categories with the risk of cancer determined by FNAB and Histology TIRADS: thyroid imaging reporting and data system 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

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

9 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 ECON- ARM US Features Example Risk Of Malignancy 0-1 Cystic, spongiform, isohyperechoic, 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

10 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 TIR-1 TIR-2 TIR-3 TIR-4 TIR-5 Risk 1 1C A B ECON-ARM n Low Intermedia te / High Total 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.

11 Strength of indication for FNA depending on US features Indication More suspicious US findings Microcalcificazions Irregular margins Lymphadenopathy Solid hypoechogenic Mixed spongiform Cystic Strength of indication for fine-needle aspiration (FNA) biopsy of thyroid nodules on the basis of ultrasonography (US) findings.

12 Indications for FNA Indications for UGFNA High-US-risk thyroid lesions 10 mm Intermediate-US-risk thyroid lesions >20 mm Which nodules? 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] 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

13 Indications for FNA US -Guided

14 US-Guided Fine Needle Aspiration Palpation vs US guided FNA Authors Patients FNA Palpation / US Not diagnostic (%) FNA Palpation / US Cameci 1998 Danese / / ,7 3,5

15 US-Guided Fine Needle Aspiration

16 US-Guided Fine Needle Aspiration US -Guided necessary Non palpable Nodules Mixed / cystic Nodules Nodules in MG

17 US-Guided Fine Needle Aspiration Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules. 450 non palpable nodules 94 operated: 20 Ca 8 < 1cm, 12 >1 cm No correlation size / hystology Ca Solid hypoechogenic / hystology Ca p< Adequacy of material / size p< Leenhardt L et al. JCEM, 1998

18 US-Guided Fine Needle Aspiration Thin needle Good compliance Repeatable Reproducible Devoid of risk Accurate Gauge Capillarity Aspiration

19 US-Guided Fine Needle Aspiration Drawings: 2-4 in different areas of the nodule

20 US-Guided Fine Needle Aspiration Cytological examination Measurement Tg and CT Immunocytochimistry Molecular Characterization

21 US-Guided Fine Needle Aspiration Cytological examination Adequate: 6 groups of cells Fixation, staining: preservation of nuclei Hamburger, 1986,1988 Mazzaferri, 1988 Gharib, 2016

22 US-Guided Fine Needle Aspiration Cytological examination Stain Papanicolaou May-Grunwald-Giemsa

23 Classification of cytology

24 Results of cytology Percentage Non diagnostic Benign Indeterminate Suspicoius or Malignant 3,5-10%

25 US-Guided Fine Needle Aspiration

26 US-Guided Fine Needle Aspiration Cytological features of papillary thyroid tumor on fine-needle aspiration biopsy Specificity Psammoma bodies: 100% Nuclear grooves: 88% Micronuclei: 86% Pseudo-inclusions: 88% Powdery chromatin: 59% The combination of two or more of these features is 100% specific in detecting papillary thyroid carcinoma.

27 US-Guided Fine Needle Aspiration Problems Non Diagnostic Inderminate Follicular Nodule / Hurthle cell Nodule

28 US-Guided Fine Needle Aspiration Non Diagnostic Author aa Pz % Repeated FNA D ND % % Tx N Ca % Goernell / Livolsi / Block 81 3/121 2, Burch / Caraway /394 2, Altavilla / ,5 Hing you /

29 Predictivity of Cytology Histology N pz Benign N (%) Malignant N (%) Non diagnostic (TIR 1) (67) 82 (33) Benign (TIR 2) (98.2) 24 (1.8) Indeterminate (TIR 3) (70.7) 283 (29.3) Suspicious (TIR4) (97.2) Indicative of ca (TIR 5) (100) Rago T. et al. EJE

30 Results of cytology THE DILEMMA OF INDETERMINATE TIR 3 CYTOLOGY RESULT %

31 Results of cytology Follicullar lesions Hürthle cell nodules 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

32 Histological subtype of CA in 371/1520 (24%) Thy 3 nodules at cytology n= n= n= 47 n= 6 n=10 n= Classic Follicular Oxyphylic Tall cell Trabecular n= 55 n= 8 0 Papillary Follicular Poorly differentiated Rago et al. JCEM 2013

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

34 Histological subtype of CA in 371/1520 (24%) Thy 3 nodules at cytology 100 Benign /1170 p < 0, /350 Malignant 25 41% 0 Thy 3A (Atypias-) 19% Thy 3B (Atypias+)

35 US-Guided Fine Needle Aspiration Cytologic diagnosis Measurement of Tg and CT Immunochemical Examen Molecular Characterization

36 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.

37 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

38 Grazie