Ultrasound Evaluation of Thyroid Nodules October 2016
Thyroid Nodules Primary goal is to determine if a nodule is malignant and needs surgery, or is benign and does not need surgery.
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
Tests for Thyroid Nodules I-123 scan Thyroid ultrasound FNA biopsy
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
What nodules can t we feel? Ultrasound vs. Palpation # Nodules found by US 35 30 25 20 15 10 5 0 94% 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
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
Volume = p/6( W X D X L ) Width Depth Length Transverse Longitudinal
US Appearance of Nodules Composition (solid/cystic) Echogenicity (darkness on US) Margins Presence of calcifications Shape Vascularity Hardness elastography
Which Nodules need FNA?? 0.8cm 2.0 cm
Frates MC et al, Radiology 2005 Which to FNA?
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)
AACE 2016 Nodule Guidelines Gharib et al. Endocrine Practice. May 2016
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
% 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.
Hyperechoic Nodule With background Hashimoto s WHITE KNIGHT Bonavita AJR 2009; 193:207-13
Hyperechoic with background of Hashi s Nodule
Hyperechoic with background of Hashi s
White Knight
Giraffe Pattern in Hashimoto s Bonavita AJR 2009; 193:207-13
Giraffe Pattern
Halo Halo Edge Artifact
No Halo, but a Smooth Margin
Halo irregular Follicular adenoma Yokozawa T
Halo Thin Halo Benign Follicular Adenoma Thick, Irregular Halo Follicular CA
Subtle differences in halo Isoechoic Nodules Irregular halo Thinner halo
Colloid within Nodule with Comet Tails
Colloid Within Nodule Cat s Eye (Comet Tail, Stepladder or Ringdown artifact)
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: 762-70 Bonavita AJR 2009; 193:207-13
Spongiform echotexture
Spongiform Echotexture Note: Bright Linear Reflectors all posterior to the microcystic areas
Thin-walled Cyst Enhancement
Thin-walled Cyst Complex cyst
Partially Cystic, No Suspicious Features
NOT DOPPLER? Suspicious Sonographic Features Hypoechoic Microcalcifications Infiltrative margins Taller than wide on transverse view Abnormal cervical lymph nodes
Hypoechoic Compare to strap muscles and SCM
Hypoechoic
Hypoechoic
Markedly Hypoechoic Compare to strap muscles and SCM
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
Macrocalcification Patterns Kim et al. J Ultrasound Med 2008, 27:1179
Coarse Macrocalcification in PTC Bonavita AJR 2009; 193:207-13
Eggshell Calcifications with Shadowing Smooth Eggshell Maybe Reassuring Interrupted Eggshell Not reassuring
Eggshell...Intact? next 2 slides are videos Bmode then Harmonics
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.
Amorphous Calcifications with Shadowing In thyroid parenchyma, often Hashi, not in nodule Transverse Longitudinal
Microcalcification vs Comet Tail
Microcalcifications
Microcalcifications Dense and Microcalcifications
Microcalcifications in Papillary Cancer May be confused with comet tails When in doubt - assume the worse
NOT microcalcifications! sagittal sagittal??? Small hyperechoic linear streaks just posterior to small cystic area posterior acoustic enhancement!
Microcalcifications
Calcifications in PTC Transverse Longitudinal
PTC
Similar Appearing? Benign Simple Cyst Nodule with cystic change- PTC
Cystic PTC
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
Cystic PTC - UGFNA 4cm Left Cystic Nodule FNA - PTC
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
Margins Irregular Poorly defined, but not infiltrative (spongiform)
Infiltrative/Irregular Borders
Invasion of Strap Muscle
Invasion of Carotid Sheath
Invasion of Larynx Cystic Papillary carcinoma invading the Larynx. Note the classic intra-cystic Cauliflower appearance.
PTC with R VC paralysis
Taller than wide Nodule is taller than wide on the transverse view Kim AJR 2002; Cappelli Clin Endocrinol 2005; Moon Radiology 2008
What About Intranodular Flow? B-Mode Power Doppler NO LONGER CONSIDERED AN INDEPENDENT RISK FACTOR WHEN DECIDING ON FNA
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.**
PTC lack of Doppler
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
Suspicious Lymph Node Right Lateral Neck
Malignant Node
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) 239 255
Lymphoma
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.
Multiplicity Multiple blocks of hyperechogenicity separated by bands of hypoechogenicity with low probability of malignancy Giraffe pattern Bonavita AJR 2009 193:207
Multinodular Goiter Enlarged thyroid with multiple sonographically similar nodules with little or no normal parenchyma
Multiplicity Multiple discreet nodules need to be evaluated individually.
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
Kappa values Interobserver variability of US features 1 0.8 0.6 Kappa values Agreement <0.2 slight 0.21-0.4 fair 0.41-0.6moderate 0.61-0.8 substantial >0.8 ~perfect! 0.4 0.2 0 Microcalc Margin Shape Echogenicity Spongiform Moon Radiology 2008 247:762; Choi Thyroid 2010 20:167
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
US Pattern Recognition While individual features are suggestive, combining features and pattern recognition are the keys to US risk stratification of thyroid nodules
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 4 5-80 4A 4B Solid or mixed hyper/isoechoic with thin capsule Hypoechoic with irreg margins Hyper/iso/hypo with thick capsule 0 5-10 10-80 TIRADS 5 Hypo/Iso nonencapsulated with microcalcs >80
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 3-4 44-73 TIRADS 5 5 88 Suspicious US features: solid marked hypoechogenicity, hypoechogenicity microlobulated or irregular margins microcalcifications taller than wide shape Kwak Radiology 2011;260:892
Kwak 2011 features A hypoechoic, B microca, C Markedely hypoechoic D Irregular Margins
Adapted TI-RADS based on Russ 2011. Russ, Leboulleux, Leenhardt, Hegedus Eur Thyroid J. 2014 Sep;3(3):154-63 Russ 2013
Adapted TI-RADS based on Russ 2011. Russ, Leboulleux, Leenhardt, Hegedus Eur Thyroid J. 2014 Sep;3(3):154-63
Russ 2013 95.7% Sensitivity 61% Specificity Russ, Leboulleux, Leenhardt, Hegedus Eur Thyroid J. 2014 Sep;3(3):154-63
Kappa values TIRADS - Interobserver 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 TIRADS 2-5 TIRADS 4-5 Cheng et al. Russ et al.
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
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
Intermediate Pattern 10-20% HYPOECHOIC BUT WITHOUT OTHER SUSPICIOUS FEATURE
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
2016 AACE Nodule Guidelines
Benign - >1% ROM
Intermediate 10-15% ROM
Suspicious 50-90% ROM
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% 3 0.25% 4b 10-80% 5 >80% 4b 7-38% 4a 6% 4c 44-72% 5 89-98% 4b 69% 5 ~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
Sonographic features: Papillary vs. Follicular thyroid cancer Frequency (%) 100 90 80 70 60 50 40 30 20 10 0 * Hypoechoic * Absent halo * Irregular margins Solid * * M icroca2+ Chan, J Ultrasound Med 2003; Yuan, Clin Imaging 2006; Jeh, Korean J Rad 2007
Ultrasonographic appearance of Follicular Variant Papillary Isoechoic, variable thickness halo
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
Sonographic features: Papillary vs. Follicular Variant of PTC * * * * * Kim J Ultrasound Med 2009
Follicular variant of PTC
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
Isoechoic Nodule Hurthle Cancer w/ bone mets Next 2 slides are real-time clips
Angioinvasive HTC Doppler Grade 3
Other Patterns hyperechoic, microcalcs isoechoic, coarse calc isoechoic, margin lobulated smooth eggshell calc
Heterogeneous -- PTC
Heterogeneous solid - PTC
VERY LOW Suspicion Pattern <3% spongiform partially cystic no suspicious features, note solid areas
BENIGN pure cyst
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
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
Stephanie Lee - AACE 2016 AM
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
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
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