Ultrasound Evaluation of Thyroid Nodules. October 2016

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1 Ultrasound Evaluation of Thyroid Nodules October 2016

2 Thyroid Nodules Primary goal is to determine if a nodule is malignant and needs surgery, or is benign and does not need surgery.

3 Concerning Clinical Features High clinical suspicion Rapid tumor growth Very firm nodule (rock hard) Fixation to adjacent structures Vocal cord paresis Enlarged regional lymph nodes Family history of PTC or MEN 2 Distant metastases High FDG on PET scan Hot on Sestamibi scan History of radiation exposure to the head/neck Positive Predictive Value (PPV) high, clinically useful Negative Predictive Value (NPV) low, not helpful Hamming JF., et al. Arch Int Med 1990; 150:1088 Rago T., et al. Clin Endo 2007; 66:13

4 Tests for Thyroid Nodules I-123 scan Thyroid ultrasound FNA biopsy

5 Brander, J Clin Ultrasound 1992; Tan, Arch Intern Med 1995; Marqusee, Ann Intern Med 2000 Palpation is NOT accurate in up to 30% of patients with solitary palpable nodules 16% will have no corresponding nodule on US 15% have an additional nonpalpable nodule >1cm on US

6 What nodules can t we feel? Ultrasound vs. Palpation # Nodules found by US % 50% 42% < 1cm 1-2cm >2cm Nodule size by US Nodules MISSED by palpat ion Nodules FOUND by palpat ion Brander, J Clin Ultrasound 1992

7 Neck Ultrasound All guidelines recommend US (after TSH) for nodule evaluation Is the palpable abnormality a thyroid nodule? Are other nodules present? Size and location? Suspicious features? > 50% cystic? Associated abnormal lymph nodes? Note: Increased incidence of thyroid cancer associated with increased use of US (1) 1 Udelsman Thyroid 2014;24:472

8 Volume = p/6( W X D X L ) Width Depth Length Transverse Longitudinal

9 US Appearance of Nodules Composition (solid/cystic) Echogenicity (darkness on US) Margins Presence of calcifications Shape Vascularity Hardness elastography

10 Which Nodules need FNA?? 0.8cm 2.0 cm

11 Frates MC et al, Radiology 2005 Which to FNA?

12 ATA 2015: Nodule Sonographic Pattern Risk of Malignancy High Suspicion 70-90% Intermediate Suspicion 10-20% Low Suspicion 5-10% Very low Suspicion <3% Benign <1% Haugen et al. Thyroid; October 2015 (epub)

13 AACE 2016 Nodule Guidelines Gharib et al. Endocrine Practice. May 2016

14 Characteristics Suggesting Low Risk Nodules Hyperechoic nodule (especially in autoimmune thyroiditis) Pure cyst without a solid component Thin Halo or a smooth margin Colloid within nodule comet tails Spongiform Echotexture

15 % Hyperechoic iate on % The brightness of this nodule on ultrasound represents greater sound reflection from within the tissue. ion Most hyperechoic nodules are benign; However FNA may be required to rule out malignancy.

16 Hyperechoic Nodule With background Hashimoto s WHITE KNIGHT Bonavita AJR 2009; 193:207-13

17 Hyperechoic with background of Hashi s Nodule

18 Hyperechoic with background of Hashi s

19 White Knight

20 Giraffe Pattern in Hashimoto s Bonavita AJR 2009; 193:207-13

21 Giraffe Pattern

22 Halo Halo Edge Artifact

23 No Halo, but a Smooth Margin

24 Halo irregular Follicular adenoma Yokozawa T

25 Halo Thin Halo Benign Follicular Adenoma Thick, Irregular Halo Follicular CA

26 Subtle differences in halo Isoechoic Nodules Irregular halo Thinner halo

27 Colloid within Nodule with Comet Tails

28 Colloid Within Nodule Cat s Eye (Comet Tail, Stepladder or Ringdown artifact)

29 Spongiform nodules aggregation of multiple microcystic components in more than 50% of the volume of the nodule honeycomb of internal cystic spaces Only 1 in 360 spongiform nodules malignant 99.7% Specificity (Moon) Moon Radiology 2008; 247: Bonavita AJR 2009; 193:207-13

30 Spongiform echotexture

31 Spongiform Echotexture Note: Bright Linear Reflectors all posterior to the microcystic areas

32 Thin-walled Cyst Enhancement

33 Thin-walled Cyst Complex cyst

34 Partially Cystic, No Suspicious Features

35 NOT DOPPLER? Suspicious Sonographic Features Hypoechoic Microcalcifications Infiltrative margins Taller than wide on transverse view Abnormal cervical lymph nodes

36 Hypoechoic Compare to strap muscles and SCM

37 Hypoechoic

38 Hypoechoic

39 Markedly Hypoechoic Compare to strap muscles and SCM

40 Calcifications Macrocalcifications: hyperechoic spots with acoustic shadowing ( dense calcifications ) Low-intermediate risk Microcalcifications: hyperechoic spots without acoustic shadowing (thought to represent psammoma bodies) (<1mm) High Risk Rim (eggshell) calcifications: curvi-linear hyperechoic calcification along periphery Higher risk if interrupted

41 Macrocalcification Patterns Kim et al. J Ultrasound Med 2008, 27:1179

42 Coarse Macrocalcification in PTC Bonavita AJR 2009; 193:207-13

43 Eggshell Calcifications with Shadowing Smooth Eggshell Maybe Reassuring Interrupted Eggshell Not reassuring

44 Eggshell...Intact? next 2 slides are videos Bmode then Harmonics

45 PTC in Graves Left lobe showing background heterogeneity and a calcified nodule which proved to be papillary thyroid cancer on FNA biopsy in this patient with Graves Disease.

46 Amorphous Calcifications with Shadowing In thyroid parenchyma, often Hashi, not in nodule Transverse Longitudinal

47 Microcalcification vs Comet Tail

48 Microcalcifications

49 Microcalcifications Dense and Microcalcifications

50 Microcalcifications in Papillary Cancer May be confused with comet tails When in doubt - assume the worse

51 NOT microcalcifications! sagittal sagittal??? Small hyperechoic linear streaks just posterior to small cystic area posterior acoustic enhancement!

52

53 Microcalcifications

54 Calcifications in PTC Transverse Longitudinal

55 PTC

56 Similar Appearing? Benign Simple Cyst Nodule with cystic change- PTC

57 Cystic PTC

58 Cystic change 360 thyroid cancers at Mayo Clinic: Solid or minimally (5%) cystic: 88% <50% cystic: 9% >50% cystic: 3% and another suspicious sonographic feature present 1 microcalcifications Comet tail reverberation artifact Henrichsen et al, RSNA 2005 Cystic papillary cancer

59 Cystic PTC - UGFNA 4cm Left Cystic Nodule FNA - PTC

60 Halos & Margins Halo: sonolucent rim around an iso/hyperechoic nodule representing capsule Thin/regular lower risk Thick/irregular higher risk Hypoechoic Nodules ---- Margins: Smooth and regular Poorly Defined: interface between nodule and surrounding parenchyma is difficult to delineate Lower risk, seen in hyperplastic nodules Irregular: the demarcation between the nodule and parenchyma is clearly visible but demonstrates and irregular, infiltrative or spiculated course. Higher risk

61 Margins Irregular Poorly defined, but not infiltrative (spongiform)

62 Infiltrative/Irregular Borders

63 Invasion of Strap Muscle

64 Invasion of Carotid Sheath

65 Invasion of Larynx Cystic Papillary carcinoma invading the Larynx. Note the classic intra-cystic Cauliflower appearance.

66 PTC with R VC paralysis

67 Taller than wide Nodule is taller than wide on the transverse view Kim AJR 2002; Cappelli Clin Endocrinol 2005; Moon Radiology 2008

68 What About Intranodular Flow? B-Mode Power Doppler NO LONGER CONSIDERED AN INDEPENDENT RISK FACTOR WHEN DECIDING ON FNA

69 Vascularity - What to do? Consider whether features are suspicious for papillary or follicular cancers. Hypoechoic or features of papillary: Vascularity may be less important Iso or hyperechoic with variable thickness halo: Consider intranodular vascularity as potential risk. AACE 2010 and 2016 guidelines do consider vascularity. Korean 2011 and ATA 2015 guidelines do not consider vascularity **Don t be reassured by absence of vascularity.**

70 PTC lack of Doppler

71 Sonographically Suspicious Lymph Nodes Suspicious lymph node features: Rounded Shape (Loss of Hilar Line) Calcifications Cystic Necrosis Peripheral or Chaotic Vascularity Biopsy node for cytology and TG analysis

72 Suspicious Lymph Node Right Lateral Neck

73 Malignant Node

74 US of Thyroid only.. US of Entire Neck reveals.. LEFT Nodule -- PTC LEFT Lateral Neck: Abnl LNs Image from: Sheth, S: Role of Ultrasonography in Thyroid Disease. Otolaryngol Clin N Am 43 (2010)

75 Lymphoma

76 Multinodular Goiter: Characteristics matter more than Size A patient with multinodular thyroid has a similar risk of malignancy as a patient with a single thyroid nodule.

77 Multiplicity Multiple blocks of hyperechogenicity separated by bands of hypoechogenicity with low probability of malignancy Giraffe pattern Bonavita AJR :207

78 Multinodular Goiter Enlarged thyroid with multiple sonographically similar nodules with little or no normal parenchyma

79 Multiplicity Multiple discreet nodules need to be evaluated individually.

80 US Prediction of Thyroid Cancer Sensitivity Specificity Microcalcifications 45% 85% Absence of halo 66% 46% Poorly defined margins 64% 77% Hypoechoic 80% 45% Increased Doppler flow 67% 81% Taller than Wide 48% 92% MicroCa 2+ + irreg margin 30% 95% MicroCa 2+ + hypoechoic 28% 95% Solid + hypoechoic 73% 69% Brkljacic J Clin Ultrasound 1994; Takashima J Clin Ultrasound 1994; Rago Euro J Endorinol 1998; Cerbone Horm Res 1999; Leenhardt J Clin Endocrinol Metab 1999; Kim AJR 2002; Papini J Clin Endocrinol Metab 2002; Cappelli Clin Endocrinol 2006

81 Kappa values Interobserver variability of US features Kappa values Agreement <0.2 slight fair moderate substantial >0.8 ~perfect! Microcalc Margin Shape Echogenicity Spongiform Moon Radiology :762; Choi Thyroid :167

82 Factors Contributing to Variability of US Reporting US machine properties Probe frequency Gain, power output Use of harmonics or post image acquisition software e.g. smoothing Image interpretation Static vs. real time Use of video Patient factors Depth of nodule

83 US Pattern Recognition While individual features are suggestive, combining features and pattern recognition are the keys to US risk stratification of thyroid nodules

84 Horvath J Clin Endocrinol Metab 2009;90:1748 TIRADS-Horvath 2009 Category US PATTERN MALIGNANCY RISK % TIRADS 1 Normal thyroid gland 0 TIRADS 2 Cyst with or without comet tail Spongiform Mixed cystic/solid with solid portion mixed TIRADS 3 Hashi s pseudonodule <5 TIRADS A 4B Solid or mixed hyper/isoechoic with thin capsule Hypoechoic with irreg margins Hyper/iso/hypo with thick capsule TIRADS 5 Hypo/Iso nonencapsulated with microcalcs >80

85 Category TIRADS-Kwak 2011 Number of suspicious US features TIRADS 3 NONE 1.7 TIRADS 4A 1 3 TIRADS 4B 2 10 CANCER RISK % TIRADS 4C TIRADS Suspicious US features: solid marked hypoechogenicity, hypoechogenicity microlobulated or irregular margins microcalcifications taller than wide shape Kwak Radiology 2011;260:892

86 Kwak 2011 features A hypoechoic, B microca, C Markedely hypoechoic D Irregular Margins

87 Adapted TI-RADS based on Russ Russ, Leboulleux, Leenhardt, Hegedus Eur Thyroid J Sep;3(3): Russ 2013

88 Adapted TI-RADS based on Russ Russ, Leboulleux, Leenhardt, Hegedus Eur Thyroid J Sep;3(3):154-63

89 Russ % Sensitivity 61% Specificity Russ, Leboulleux, Leenhardt, Hegedus Eur Thyroid J Sep;3(3):154-63

90 Kappa values TIRADS - Interobserver TIRADS 2-5 TIRADS 4-5 Cheng et al. Russ et al.

91 ATA 2015: Nodule Sonographic Pattern Risk of Malignancy High Suspicion 70-90% Intermediate Suspicion 10-20% Low Suspicion 5-10% Very low Suspicion <3% Benign <1% Haugen et al. Thyroid; October 2015

92 HIGH Suspicion Pattern 70-90% hypoechoic, microcalcs, irreg margin hypoechoic, irreg margin (microlobulated/spiculated) hypoechoic, irreg margin, taller than wide hypoechoic, irreg margin, extrathyroidal extension hypoechoic, interrupted rim calcification with soft tissue extrusion irregular margins, suspicious left lateral lymph node

93 Intermediate Pattern 10-20% HYPOECHOIC BUT WITHOUT OTHER SUSPICIOUS FEATURE

94 LOW Suspicion Pattern 5-10% hyperechoic solid reg margins isoechoic solid reg margins partially cystic with eccentric solid areas WITHOUT: MicroCa,, Irregular Margin, Taller than Wide or Extra-thyroidal Extension

95 2016 AACE Nodule Guidelines

96 Benign - >1% ROM

97 Intermediate 10-15% ROM

98 Suspicious 50-90% ROM

99 ATA 2015 AACE/AME TIRADS Benign 0% Ultrasound classification systems Very Low Suspicion <3% Low Suspicion 5-10% Intermediate Suspicion 10-20% High Suspicion >70-90% for risk stratification Low Risk <1% Intermediate Risk 5-15% High Risk 50-90% Horvath TIRADS Kwak TIRADS Russ 2 0% 2 0% 2 0% 3 2% 4a 5-10% 4a 3-12% % 4b 10-80% 5 >80% 4b 7-38% 4a 6% 4c 44-72% % 4b 69% 5 ~100%

100 Iso/Hyperechoic Nodules Low Suspicion pattern if no microcalcifications, thick/irregular halo (margin), extrathyroidal extension or taller than wide shape ~20% of cancers are Iso/Hyperechoic Usually FTC or Follicular Variant PTC

101 Sonographic features: Papillary vs. Follicular thyroid cancer Frequency (%) * Hypoechoic * Absent halo * Irregular margins Solid * * M icroca2+ Chan, J Ultrasound Med 2003; Yuan, Clin Imaging 2006; Jeh, Korean J Rad 2007

102 Ultrasonographic appearance of Follicular Variant Papillary Isoechoic, variable thickness halo

103 Sonographic Features of Follicular Variant Papillary Cancer versus Conventional Papillary Cancer FEATURE FOLLICULAR VARIANT (n=44) CONVENTIONAL PAPILLARY (n=74) Size (mean) 17 mm 10.5 mm Ovoid to round shape 95% 73% Isoechoic 52% 8% Halo 25% 3% Taller than Wide 5% 22% Marked Hypoechogenicity 5% 38% Microcalcifications 3% 24% FNAB Dx of Papillary CA 28% 56% FNAB Indeterminate 46% 19% Kim DS et al. J Ultrasound Med 2009, 28:1685

104 Sonographic features: Papillary vs. Follicular Variant of PTC * * * * * Kim J Ultrasound Med 2009

105 Follicular variant of PTC

106 Isoechoic/Hyperechoic and Solid Benign Hürthle cell adenoma PTC foll variant Follicular thyroid cancer Hyperplastic nodule Hyperplastic nodule ~20% of all cancers are Iso/hyperechoic: predominantly follicular/ Hürthle

107 Isoechoic Nodule Hurthle Cancer w/ bone mets Next 2 slides are real-time clips

108

109

110 Angioinvasive HTC Doppler Grade 3

111 Other Patterns hyperechoic, microcalcs isoechoic, coarse calc isoechoic, margin lobulated smooth eggshell calc

112 Heterogeneous -- PTC

113 Heterogeneous solid - PTC

114 VERY LOW Suspicion Pattern <3% spongiform partially cystic no suspicious features, note solid areas

115 BENIGN pure cyst

116 R8 US Pattern and suggested FNA cutoffs Sonographic Pattern Estimated malignancy risk FNA size cutoff Strength of rec Quality of evidence High suspicion >70-90% > 1 cm Strong Moderate Intermediate 10-20% > 1 cm Strong Low suspicion Low suspicion 5-10% > 1.5 cm Weak Low Very low suspicion < 3% > 2 cm Weak Moderate One option is surveillance Benign < 1% No biopsy Strong Moderate FNA is not recommended for nodules that do not meet the above criteria, including all nodules < 1 cm Strong Moderate Haugen et al. Thyroid; January 2016

117 R23 Follow-up of nodules with benign cytology Sonographic Pattern High suspicion Intermediate/ Low suspicion Very low suspicion Repeat US and US FNA within 12 months Repeat US at 12-24m If growth or new suspicious US feature, repeat FNA OR continued observation Utility of surveillance US and assessment of nodule growth as an indicator for repeat FNA is not known. If repeated, US should at > 24 months IF 2 nd US FNA done with benign cytology, US surveillance for continued risk of malignancy is no longer indicated Strength of rec Strong Weak Weak Strong Quality of evidence Moderate Low Low Moderate Haugen et al. Thyroid; January 2016

118 Stephanie Lee - AACE 2016 AM

119

120

121 US Risk and suggested FNA cutoffs Sonographic Pattern Estimated malignancy risk FNA size cutoff AACE Level of Evidence AACE Strength of Rec High Risk US Intermediate Risk US 50-90% > 1 cm 2 A 5-15% > 2 cm 2 A Low Risk US <1% > 2 cm or growing 2 A

122 R24 Recommended follow-up of nodules that have not undergone FNA Sonographic Pattern Strength of rec Quality of evidence High suspicion Intermediate/ Low suspicion Very low suspicion Repeat US 6-12 months Weak Low Repeat US at 12-24m Weak Low > 1cm: Utility and time interval of repeat US for risk of malignancy is not known. If repeated, do at > 24 months <1cm: Do not require routine US surveillance NO rec Weak Insufficient Low Haugen et al. Thyroid; January 2016

123 Conclusions Ultrasound is the cornerstone of thyroid nodule evaluation and always includes evaluation of the regional lymph nodes Pattern recognition is more valuable than individual suspicious features FNA decision making is based on the risk stratification of the nodule pattern

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