Endocrinology and Metabolic Disorder Unit Regina Apostolorum Hospital

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2 Enrico Papini Endocrinology and Metabolic Disorder Unit Regina Apostolorum Hospital Albano Laziale, Italy The Following Faculty have provide no information regarding significant relationship with commercial supporters and/or discussion of investigational or non-emea/fda approved (off-label) drugs as of 5 April 2016

3 Thyroid Ultrasonography: Principal Pathologic Findings

4 Learning Objectives To become familiar with ultrasound (US) features predictive of benign or malignant thyroid disease To identify the characteristics of benign and malignant lymph nodes To review the main ultrasound classification systems for the risk of malignancy in thyroid nodules and the indications for fine-needle aspiration (FNA) biopsy.

5 The growing problem of thyroid nodular disease Thyroidnodulesare detectedby ultrasound (US) in up to 50% of women Most are asymptomatic Mainproblemisto ruleout malignancy. Gharib H, Papini E. Endocrinol Metab Clin North Am Sep;36(3):707-35; Hegedus L. Clinical practice. N Engl J Med Oct 21;351(17):

6 Fine NeedleAspiration(FNA) isthe best triage system for malignancy, but..can we perform FNA on all these nodules? We have US features suggestive of malignancy

7 Hypoechoic appearance Irregular margins Papini et al JCEM 2002; Kimet al Radiology2002 Micro-calcifications More tall than wide shape

8 Odds Ratio

9 Differential diagnosis of thyroid nodules Age, sex, size, and single/multiple lesions have marginal impact on risk of malignancy No single US featureisbothsensitive and specific for cancer Part of thyroid malignancies lack suspicious signs at clinical and US examination.

10 US ClassificationSystemsmaybeusedtorate the risk of malignancy and the indication to FNA

11 An US Reporting System for Thyroid Nodules Stratifying Cancer Risk for Clinical Management TIRADS 1: normal thyroid gland TIRADS 2: benign conditions(0% malignancy) TIRADS 3: probably benign nodules(5% malignancy) TIRADS 4: suspiciousnodules(5 80% malignancyrate) 4a (malignancybetween5 and 10%) 4b (malignancy between 10 and 80%). TIRADS 5: probably malignant nodules(malignancy > 80%) TIRADS 6: category included biopsy-proven malignant nodules. Horvath et s. J Clin Endocrinol Metab, May 2009, 90(5):

12 TIRADS Classification Algorithm Modified (Russ) Open Journal of Radiology,

13 TI-RADS2 SIMPLECYST - Anechoic lesion - Thin and regular margins - No vascular signals - No suspicious signs

14 TI-RADS 2 COMET TAIL SIGN Hyperechoic spots within colloid fluid Diameter0.5-2 mm Associated with a comettail aspect Mobile with changes.

15 TI-RADS2 SPONGIFORM NODULE -Tinyfluidareasin > 50% of the nodule - Isoechoic pattern - No suspicious signs

16 TI-RADS2 ISOLATED MACROCALCIFICATION - Posterior shadowing -Isolated - No tissue component - No vascular signals

17 TI-RADS2 'White Knight' Multiple oval/round hyperechoicareasin a hypoechoic gland (usually chronic thyroiditis).

18 TI-RADS2 SUBACUTE THYROIDITIS - Hypoechoic inhomogeneousarea - Blurred margins - Frequently multiple - Scanty vascular signals - Clinical context

19 TI-RADS 3 REGULAR SHAPE Wider than taller Isoechoic pattern Well defined margins Thin and regular halo

20 TI-RADS4A Moderate hypoechogenicity

21 SCORE 4B MARKED HYPOECHOGENICITY More hypoechoic than superficial muscles

22 TI-RADS 4B SPICULATED MARGINS Borders with acute angles and irregular margins

23 TI-RADS 4B LOBULATED MARGINS Ondulated borders At least three small hubs)

24 TI-RADS4B MICROCALCIFICATIONS Hyperechoic spots, round or linear Diameter 1mm No posterior shadowing(unless a cluster is present).

25 TI-RADS 4B "MORE TALL THAN WIDE A-P > TR diameter on transverse scan.

26 TI-RADS5 MULTIPLE SUSPICIOUS SIGNS Extracapsular growth associated with: - marked hypoechogenicity, -irregularmargins, -taller-than-wide shape.

27 TI-RADS5 MULTIPLE SUSPICIOUS SIGNS Pathologic lymph node associated with: - marked hypoechogenicity - microlobulatedmargins - microcalcifications, - taller-than-wide shape

28 The ATA 2015 Thyroid Nodule and Cancer Guidelines recommendan US ClassificationSystem with 5 major US patterns Each class is related to different risk of malignancy with increasing indication to FNA. HaugenB et al. Thyroid, January2016; 26: 1-133

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31 British Thyroid Association Guidelines for the Management of Thyroid Cancer The practitioner should identify signs that allow differentiation of thyroid nodules: benign(u2) equivocal/indeterminate(u3) suspicious(u4) malignant(u5)

32 Interobserver Agreement in Assessing the US Features of Thyroid Nodules AJR:193, November 2009

33 Stiffness at Elastography

34 Intranodular vascular signals

35 Classifications may be false friends Minimally Invasive Follicular Carcinoma Hyperplastic Nodule

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37 2016 AACE/AME/ETA Guidelines US criteria for US-FNA Microcalcifications, Irregular margins Abnormal neck lymph nodes or extracapsular invasion Mixed cystic / solid Solid, deeply hypoechoic Stiffness at elastography Purely cystic Hyperechoic Spongiform Announced: May 2016

38 2016 AACE-AME US Classification Low-riskUS lesion(us class1) Intermediate-risk US lesion(us class 2) High-riskUS lesion(us class3) Endocrine Practice 2016 (announced: May 2016)

39 Low-Risk nodules(us class 1) A B C A. Thyroid cyst(fluid component > 80%, regular margins) B. Mostlycysticnodulewith reverberatingartifacts, no suspicious signs C: Iso-echoic spongiform nodule, regular margins.

40 A Intermediate-risk nodules(us class 2) B C D Slightly hypo- or iso-echoic nodules with smooth margins or halo. May be present: A. intranodularvascularization: B. elevatedstiffnessatelastography; C. coarse or rim calcifications; D. indeterminate hyperechoic spots.

41 High-Risk Nodules (US class 3) A B D E C F A. Marked hypoechogenicity; B. Spiculated or lobulated margins; C. More tall than wide shape; D. Microcalcifications; E. Extracapsular growth; F. Pathologic adenopathy.

42 Lymph-node Structure hilum

43 Presence of hilum Long & flat aspect (L/S > 2) No suspicious changes Benign Lymph-Nodes

44 From a benign to a malignant lymph node Normal lymph node: Central vascularization Malignant node : Peripheral vascularization Courtesy of Sato

45 Roundedappearanceand short axis> 5 mm unsatisfactory(aspecific) predictive criteria

46 Pathologic lymph nodes Micro-calcifications

47 Pathologic lymph nodes Cystic Changes

48 Pathologic lymph nodes Lymph-nodes «like thyroid tissue»

49 Vascular Architecture of Benign Nodes hilar and longitudinal peripherical from longitudinal vessels intranodular «fern» spots

50 Vascular Architecture of Malignant Nodes displacement of longitudinal vessels and aberrant vessels focal absence of perfusion subcapsular vessels(non hilar)

51 Normal Hilus Ovoid shape Absent or hilar vascularity Courtesy of L. Leenhardt US Characterization of LNS ETA 2013 Indeterminate Absent hilus AND 1 of the following Round shape Increased central vascularization Suspicious 1 of the following Microcalcifications Cystic Peripheral or diffuse vascularity Hyperechoic

52 Thyroid US: Conclusions US is a sensitive exam and may be specific for thyroid carcinoma (particularly papillary) elastography and other techniques may provide diagnostic information In many cases no single US feature is diagnostic for malignancy US signs should be used in summation to determine whether FNA should be performed.

53 Thyroid US: Conclusion(2) US classification systems should be used for assessing risk of malignancy and guiding actions Indication for FNA should be evaluated in the context of patient s clinical picture.

54 Indicationsfor US-GuidedFNA High-risklesions: nodules>10 mm Intermediate-risk lesions: nodules >20 mm Low-risk lesions: nodules > 20mm AND increasing in size symptomatic associated with clinical risk factors.

55 Indicationsfor US-GuidedFNA (2) In high-risknoduleswith a major diameter5-10 consider either UGFNA sampling or watchful waiting on the basisof: US pattern clinical setting patientpreference.

56 ThankYou