Thyroid Nodules: US Risk Stratification and FNA Guidelines

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Thyroid Nodules: US Risk Stratification and FNA Guidelines Mark A. Lupo, MD, FACE, ECNU Thyroid & Endocrine Center of Florida Assistant Clinical Professor of Medicine Florida State University, College of Medicine Sarasota, Florida

Which of the following is true? A. All echogenic foci represent microcalcifications B. Hypervascularity of any nodule is an independent risk factor for thyroid cancer C. A thin hypoechoic, regular halo surrounding an isoechoic nodule is generally suggestive of a low risk process D. In a multinodular thyroid gland the largest nodule is the most concerning for malignancy E. Spongiform nodules have an intermediate risk of malignancy

Objectives Review features of benign and malignant nodules Highlight importance of pattern recognition for risk of malignancy assessment Introduce ACR TIRADs System Discuss current guidelines for nodule FNA

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

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) Pseudonodules in Hashimoto s Pure cyst without a solid component Colloid within nodule comet tails Spongiform Echotexture

Hyperechoic with background of Hashi s Nodule

Hyperechoic with background of Hashi s

Nodule? CLEFT SIGN Due to Fibrosis

Cleft Sign Right Transverse Right Sagittal Thick hyperechoic fibrotic band separates the posterior and anterior components of the lobe in transverse view creating the appearance of a hypoechoic nodule (arrow) with hyperechoic halo (note: true halos are only hypoechoic) In Sagittal view, it is evident that there is no discrete nodule.

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

What is the best description of this right lobe finding? A) It s a cyst because there is posterior acoustic enhancement B) It is ATA very low risk C) It could be a solid nodule, turn on Doppler to check D) It has an irregular halo

Thin-walled Cyst Enhancement

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

Halo Halo Edge Artifact

No Halo, but a Smooth Margin

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

Margins Irregular Poorly defined, but not infiltrative (spongiform)

Infiltrative/Irregular Borders

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

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.

Microcalcification vs Comet Tail

Microcalcifications

Microcalcifications Dense and Microcalcifications

Microcalcifications in Papillary Cancer May be confused with comet tails If in doubt - assume microcalcifications

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

Microcalcifications

Calcifications in PTC Transverse Longitudinal

PTC

Does this nodule have microcalcifications? A. Yes B. No

Cystic PTC

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

Invasion of Strap Muscle

Invasion of Carotid Sheath

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

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

PTC lack of Doppler Don t be re-assured by lack of Doppler flow!

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

Interobserver variability of US features Kappa values Agreement <0.2 slight 0.21-0.4 fair 0.41-0.6moderate 0.61-0.8 substantial >0.8 ~perfect! 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

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

Which of the following statements regarding FNA is most accurate? A. All nodules greater than 1-1.5cm should undergo FNA B. A high suspicion nodule with benign initial does not require repeat FNA C. FNA may be indicated for some nodules <1cm depending on location and US features D. Size is more important than characteristics when considering a nodule for FNA

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

Micronodules Concerning for PTC

Sonographic appearance of micro PTC and risk 50% 14% 2% 30% <5% Risk of invasion starts at >= 7mm Ito World J Surg 2016;40:523 528; Miyauchi World J Surg 2016 40:516 522

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

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

ATA May Have Limitations in Thyroid Nodule Classification Compared with TIRADS -Comparison ATA 2015 with TIRADS 2011-3.4% of 1,293 nodules without ATA Classification -18.2% of not specified ATA nodules malignant Yoon et a. Radiology 2016; 278: 917-924

ACR TI-RADS 2017 Point based system Composition Echogenicity Shape Margins Echogenic Foci Leave no nodule behind Tessler et al; J ACR 2017

Tessler et al; J ACR 2017

Cystic or almost completely cystic almost universally benign Spongiform composition 0 points Colloid cyst No FNA Mixed Cystic-Solid -- 2 points (w/ no suspicious features) Russ G. Ulttasonography 2016; 35: 25-38 Moon WJ Radiology 2008; 247: 762-770 Lee et al. Thyroid 2009; 19(4): 341-346

ACR TI-RADS System FNA Indications TIRADS 3-5 Consider FNA

2016 AACE Nodule Guidelines

Benign - <1% ROM

Intermediate 10-15% ROM

Suspicious 50-90% ROM

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

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