Sonographic Features of Thyroid Nodules & Guidelines for Management

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Sonographic Features of Thyroid Nodules & Guidelines for Management Mark A. Lupo, MD, FACE, ECNU Thyroid & Endocrine Center of Florida Assistant Clinical Professor of Medicine Florida State University, College of Medicine Sarasota, Florida

Objectives Review ultrasound imaging characteristics for assessment of risk of malignancy in thyroid nodules Discuss current guidelines for UGFNA of thyroid nodules Incorporate clinical status into thyroid nodule FNA decision making

Goals of Thyroid Nodule Evaluation Identify and treat the small group of patients with malignancy while avoiding unnecessary procedures in the majority with benign nodules Evaluate for compressive symptoms of dysphagia, dysphonia and dyspnea Identify nodules that impact thyroid function

How common are nodules? Ultrasound/Autopsy Ultrasound/Autopsy Palpation Mazzaferri, NEJM 1993

Epidemic of Nodules Can no longer FNA all nodules >1cm Current ATA, AACE and Korean guidelines rely on recognition of sonographic features of lowrisk and high-risk nodules

Thyroid Ultrasound R2 Thyroid sonography should be performed in all patients with known or suspected thyroid nodules (A) ATA guidelines, Cooper DS, Thyroid, 2009 Is the palpable abnormality a thyroid nodule? Are other nodules present? Size? Suspicious features? > 50% cystic? Posterior? Associated abnormal lymph nodes?

Which Nodules need FNA?? 0.8cm 2.0 cm

Which to FNA? Frates MC et al, Radiology 2005

2009 ATA Guidelines Microcalcifications, hypoechoic, increased vascularity, infiltrative margins, AP > transverse Cooper, et al, Thyroid 19(11), 2009

NCCN Version 2.2013 US Findings Solid Nodule With Suspicious Features Without Suspicious Features Mixed Solid-Cystic Nodule Threshold for FNA Solid Nodule With Suspicious Features Without Suspicious Features Spongiform Simple Cyst Suspicious Lymph Node Mixed Solid Cystic 1.0cm 1.5cm 1.5 2.0cm 2.0cm 2.0 cm Not Indicated FNA LN and/or Nodule Also recommend lowering thresholds with high risk clinical history. Allow for informed patient Decision making for surgery in patients with nodules >4 cm and/or high risk history.

High Risk History History of thyroid cancer in one or more first degree relatives History of external beam radiation as a child Exposure to ionizing radiation in childhood or adolescence Prior hemithyroidectomy with discovery of thyroid cancer 18-FDG avidity on PET scanning MEN2/FMTC-associated RET protooncogene mutation Calcitonin >100 pg/ml.

AACE / AME Guidelines 2010 >1 cm solid and hypoechoic. US-FNA nodules any size if radiation, FH of MEN/MCT, history of thyroid cancer, or elevated calcitonin (>100) US-FNA nodules of any size with either marked hypoechogenicity, irregular or microlobulated margins, taller than wide shape, microcalcifications, or chaotic arrangement or intranodular vascular images (sic). FNA independent of size if US suggestive of metastatic node or extracapsular growth. FNA (solid component) of complex cystic nodules Do not biopsy nodules hot on scintigraphy.

Korean Endocrine Society 2011 Divides nodules into three categories: Probably benign Suspicious for malignancy Any feature present Spongiform Completely cystic or predominately cystic with comet tails Taller than wide, irregular Marked hypoechoic Calcifications microcalcifications or macrocalcifications Extracapsular extension (spiculated margin) Indeterminate Neither benign or suspicious features Iso, hypo or hyperechogenic Ovoid to round or irregular shape Smooth or ill-defined margin Rim calcification

Korean Endocrine Society 2011 Biopsy based on category (and size) Probably benign < 1cm - no f/u US needed > 1 cm f/u US 2 y and 3-5 y > 2cm Selective FNA biopsy Suspicious for malignancy Any feature present FNA biopsy all < 5mm Selective FNA based on risk factors and experience > 5mm All if feasible Indeterminate Neither benign or suspicious features < 1 cm f/u US > 1 cm FNA biopsy Growth (20% diam or 50% volume) FNA biopsy

Korean Guidelines 2011 Moon et al, Korean J Radiology 2011 *** ***

INITIAL FNA BENIGN What next? Kwak. Radiology: Volume 254: Number 1 January 2010

*** ***

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, B et al: 2015 ATA Nodule and Cancer Guidelines DRAFT Not formally accepted for publication at the present time. As presented by Dr. Susan Mandel June 20, 2014, Chicago. Material used with permission of Dr. Haugen.

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

Suspicious Sonographic Features Hypoechoic Microcalcifications Infiltrative margins Taller than wide on transverse view Abnormal cervical lymph nodes

Hypoechoic Compare to strap muscles and SCM

What About Intranodular Flow? B-Mode Power Doppler NO LONGER CONSIDERED AN INDEPENDENT RISK

Microcalcifications Punctate (<1mm) echogenic lesions without shadowing Differentiate from comet tail ringdown artifact Microcalcifications are felt to be 85% specific for cancer but only 50% sensitive

Microcalcification vs Comet Tail

Comet Tail Artifact Benign Colloid Nodule

Microcalcifications

Diffuse Microcalcifications

Invasion of Strap Muscle

Shape of Nodule Images from Moon et al, Korean J Radiology 2011;12(1):1-14

Taller than Wide (AP > transverse)

INTERMEDIATE Suspicion Pattern 10-20% hypoechoic solid with regular margins Haugen, B et al: 2015 ATA Nodule and Cancer Guidelines DRAFT Not formally accepted for publication at the present time. As presented by Dr. Susan Mandel June 20, 2014, Chicago. Material used with permission of Dr. Haugen.

LOW Suspicion Pattern 5-10% hyperechoic solid reg margins isoechoic solid reg margins partially cystic with eccentric solid areas

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

Subtle differences in halo Irregular halo Thinner halo

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

BENIGN pure cyst

Characteristics Suggesting Low Risk Nodules Spongiform Echotexture Hyperechoic nodule (especially in autoimmune thyroiditis) Pure cyst without a solid component Thin Halo or a smooth margin Thick and Irregular Halo in Follicular Neoplasms Colloid within nodule comet tails Intact eggshell calcifications

Spongiform echotexture

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 Note: Bright Linear Reflectors all posterior to the microcystic areas

The White Knight Hyperechoic with background of Hashi s Bonavita AJR 2009; 193:207-13

Colloid within Nodule with Comet Tails

Small Mural Component Low Risk

Cystic PTC

R8 US Pattern and suggested FNA cutoffs Sonographic Pattern Estimated malignancy risk Consider biopsy Strength of rec Quality of evidence High suspicion >70-90% > 1 cm Strong Moderate Intermediate suspicion Low suspicion 10-20% > 1 cm Strong Low 5-10% > 1.5 cm Weak Low Very low suspicion Benign < 3% > 2 cm Weak Moderate < 1% No biopsy Strong Low Haugen, B et al: 2015 ATA Nodule and Cancer Guidelines DRAFT Not formally accepted for publication at the present time. As presented by Dr. Susan Mandel June 20, 2014, Chicago. Material used with permission of Dr. Haugen.

R8 US Pattern and suggested FNA cutoffs Sonographic Pattern Estimated malignancy risk Consider biopsy Strength of rec Quality of evidence High suspicion >70-90% > 1 cm Strong Moderate Intermediate suspicion Low suspicion 10-20% > 1 cm Strong Low 5-10% > 1.5 cm Weak Low Very low suspicion Benign < 3% > 2 cm Weak Moderate < 1% No biopsy Strong Low FNA is not recommended for nodules that Strong do not meet the above criteria, including all nodules < 1 cm Moderate

R8 US Pattern and suggested FNA cutoffs Estimated Sonographic Consider Strength Quality of Pattern malignancy risk biopsy of rec evidence High suspicion >70-90% > 1 cm Strong Moderate Strong Low Weak Low Modify10-20% cutoffs by> 1 cm Intermediate suspicion patient risk factors Low suspicion 5-10% > 1.5 cm presence of sonographically Very low Weak < 3% > 2 cm suspicion suspicious LNs Benign US FNA Strong < 1% of sono No biopsy susp LNs FNA is not recommended for nodules that Strong do not meet the above criteria, including all nodules < 1 cm Moderate Low Moderate

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

Why use Size Criteria? Numerous studies confirm poor or no correlation between size and malignancy. However, the risk of metastasis (and therefore mortality) does have an association with size. attempts to diagnose and treat all small thyroid cancers in an effort to prevent these rare outcomes would likely cause more harm than good. (ATA 2009 guidelines)

R20 Multiple nodules When multiple nodules >1cm are present, FNA based upon US pattern (R8) Strong recommendation, Moderate quality evidence If multiple sonographically similar low or very low suspicion pattern nodules, the likelihood of malignancy is low and it is reasonable to FNA the largest nodule (>2cm) and observe others Weak recommendation, Low quality evidence

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

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.

Benign Nodule Follow-up ATA 2009 Ultrasound 6 18 months after the initial FNA If same size or smaller, may follow-up @ 3-5 years (C) If increase size by > 50% in volume or >20% in 2 dimension repeat FNA and f/u 6-18mos (B) AACE/AME/ETA 2010 Perform repeated clinical and US examination and TSH measurement in 6 to 18 months (D) Perform repeated UGFNA biopsy in cases of appearance of clinically or US suspicious features (B) Perform repeated UGFNA biopsy in cases of a greater than 50% increase in nodule volume (B) Consider routine repeated UGFNA biopsy in 6 to 18 months, even in patients with initially benign cytological results (D)

ATA 2015 R22 Follow-up of nodules with benign cytology Given the low false negative rate of US FNA cytology and the higher yield of missed malignancies based upon nodule sonographic features rather than growth, the follow up of thyroid nodules with benign cytology diagnoses should be determined by risk stratification based upon sonographic pattern. Haugen, B et al: 2015 ATA Nodule and Cancer Guidelines DRAFT Not formally accepted for publication at the present time. As presented by Dr. Susan Mandel June 20, 2014, Chicago. Material used with permission of Dr. Haugen.

R22 Follow-up of nodules with benign cytology Sonographic Pattern Strength of rec Quality of evidence High suspicion Repeat US and US FNA Strong Moderate Weak Low NO rec Insufficient within 12 months Intermediate/ Repeat US at 12-24m Low suspicion If growth, repeat FNA OR continued observation Very low suspicion Utility of surveillance US and assessment of nodule growth as an indicator for repeat FNA is not known. If repeat US, it should at > 24 months Haugen, B et al: 2015 ATA Nodule and Cancer Guidelines DRAFT Not formally accepted for publication at the present time. As presented by Dr. Susan Mandel June 20, 2014, Chicago. Material used with permission of Dr. Haugen.

R22 Follow-up of nodules with benign cytology Sonographic Pattern Strength of rec Quality of evidence High suspicion Repeat US and US FNA Strong Moderate Weak Low NO rec Insufficient within 12 months Intermediate/ Repeat US at 12-24m Low suspicion If growth, repeat FNA OR continued observation Very low suspicion Utility of surveillance US and assessment of nodule growth as an indicator for repeat FNA is not known. If repeat US, it should at > 24 months IF 2nd US FNA done with benign cyto, US Strong surveillance for continued risk of malignancy is no longer indicated Moderate

R23 Follow-up of nodules that have not undergone FNA Sonographic Pattern Strength of rec Quality of evidence High suspicion Repeat US 6-12 months Weak Low Intermediate/ Repeat US at 12-24m Low suspicion Weak Low NO rec Insufficient Very low suspicion Utility and time interval of repeat US for risk of malignancy is not known. If repeated, do at > 24 months Haugen, BR et al: 2015 ATA Nodule and Cancer Guidelines DRAFT Not formally accepted for publication at the present time. As presented by Dr. Susan Mandel, June 20, 2014, Chicago Material used with permission of Dr. Haugen.

R23 Follow-up of nodules that have not undergone FNA Sonographic Pattern Strength of rec Quality of evidence High suspicion Repeat US 6-12 months Weak Low Intermediate/ Repeat US at 12-24m Low suspicion Weak Low Utility and time interval of repeat US for risk of malignancy is not known. If repeated, do at > 24 months Nodules < 5 mm without high suspicion US pattern do not require routine sonographic FU and if repeated, the US should be performed at 24 months or later NO rec Insufficient Weak Low Very low suspicion