Ultrasound of Thyroid Nodules - World Congress on Thyroid Cancer

Ultrasound of Thyroid Nodules
WTC 2013
Advanced Thyroid US course
Susan J Mandel MD MPH
Professor of Medicine and Radiology
Perelman School of Medicine, University of Pennsylvania
Diagnostic thyroid ultrasound
Risk stratification
ATA Guidelines 2009; AACE/AME/ETA Guidelines 2010
What does US tell us?
• Individual US features
• US patterns of nodule
appearance associated with risk
for thyroid cancer
US characteristics of thyroid nodules
1. Echogenicity (hypo*-, hyper-, iso-)
2. Calcifications (micro-*, dense/macro, rim)
3. Margins (irregular, infiltrative*, well-defined
regular)
4. Shape (taller than wide*)
5. Vascularity (intranodular*, peripheral,
absent)
*associated with thyroid cancer
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; Nam-Goong Thyroid 2003; Cappelli Clin Endocrinol 2005; Frates, J Clin
Endocrinol Metab 2006; Kovacevic, J Clin Ultrasound 2007; Moon Radiology 2008; Bonavita AJR 2009;
Ahn AJR 2010
INDIVIDUAL analysis of US predictors
Sensitivity Specificity
Microcalcifications
Hypoechoic
Solid
Absence of halo
Intranodular vascularity
Poorly defined margins
Tall>Wide
44%
81%
86%
66%
62%
55%
48%
89%
53%
18%
54%
77%
79%
92%
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; Nam-Goong Thyroid
2003; Cappelli Clin Endocrinol 2005; Frates, J Clin Endocrinol Metab 2006; Kovacevic, J Clin Ultrasound 2007; Moon
Radiology 2008; Bonavita AJR 2009; Ahn AJR 2010; Cap Clin Endocrinol 1999
MULTIVARIABLE analyses of
sonographic features
Micro
Ca2+
Frates
Cappelli
Nam-Goong
Gul
Popowicz
Salmaslioglu
Papini
Kwak
Moon 2008
Moon 2010
Hypoechoic
Irreg
margins
Tall>
wide
Solid
Vascularity
Trees then
Forest . . .
US Prediction of Thyroid Cancer
Echogenicity
• Normal thyroid is homogeneously
hyperechoic compared to the strap
muscles
• Nodule echogenicity is defined relative to
the normal thyroid (?Hashi’s background)
–
–
–
–
1Kim
Isoechoic
Hyperechoic
Hypoechoic Sensitivity 81%, Specificity 53%
marked hypoechogenicity, defined as relative
to strap muscles1
et al, AJR 2002
Normal thyroid
trachea
Hypoechoic nodules
Iso/Hyperechoic nodules
sagittal
Hyperplastic nodule
transverse
Follicular carcinoma
If associated with minute cystic spaces  hyperplastic
If uniformly solid or associated with an irregular halo
 concerning for a neoplasm often a follicular or
Hurthle cell adenoma or carcinoma
Hyperechoic area in thyroiditis
• Hashimoto’s
thyroiditis is often
asymmetric
• Hyperechoic masses
are usually benign
(Hurthle cell
aggregates)
• “white knight”
Takashima S et al, Radiology 1992;185:125-130; Bonavita AJR 2009; 193:207-13
Completely cystic: Colloid cysts
cyst fluid is ANechoic
Comet-tail artifact
In pure cystic nodules,
comet artifact indicates
a benign cyst
US Prediction of Thyroid Cancer
Calcifications (present in about 30%)
• Dense calcifications: hyperechoic spots
with acoustic shadowing
• Microcalcifications: hyperechoic spots
<1mm without acoustic shadowing
(thought to represent psammoma bodies)
Sensitivity 44%, Specificity 89%
• interrupted linear calcifications
Calcifications
Microcalcifications
(psammomatous) in papillary
thyroid cancer
Coarse calcifications in
follicular thyroid cancer
Microcalcifications—the impact of
post acquisition image processing
Coarse
Ca2+
Coarse calcifications
• Larger than 1mm
• Coarse calcifications common in lymphocytic
thyroiditis secondary to dystrophic calcifications
Present in PARENCHYMA WITHOUT associated nodule
• Concerning for malignancy if mixed with
microcalcifications or present in a SOLID
nodule
Khoo ML, Arch Oto Head Neck Surg 2002; Bonavita AJR 2009
Peripheral calcification
Complete, regular
or “eggshell”
Interrupted
Usually benign
Nam-Goong Thyroid 2003; Lee J Ultrasound Med 2009
Papillary cancer
Follicular cancer
Association of Calcifications with
Malignancy c/w with Absence of
Calcifications
• Micro calcifications3x risk
• Central coarse calcifications - 2x risk
• Peripheral calcifications 2x risk
Frates MC et al, J Clin Endo Metab 2006; 91:3411-3417
US Prediction of Thyroid Cancer
Margins
• Well-defined and regular
• IRREGULAR--Infiltrative, spiculated,
microlobulated1
– Sensitivity 55%, Specificity 79%
– some malignant nodules have a predominately
regular border but are irregular in only small
portion requiring high-resolution technique
• Remember POORLY DEFINED is NOT the
same as DEFINED BUT IRREGULAR
1Kim
et al, AJR 2002
What defines the margins of a nodule?
• Difference in echogenicity from surrounding
thyroid parenchyma, i.e. HYPOechoic nodule
c/w normal thyroid
• Hypoechoic or sonolucent rim surrounding
ISO/HYPERechoic nodule (thought to
represent the compressed perinodular
vessels)—HALO
– Smooth and thin thought to represent
compressed perinodular blood vessels
– Thick or irregular—more suggestive of
CAPSULE of neoplasm (follicular or Hurthle
cell carcinoma or adenoma; encapsulated
papillary cancer)1
1Cerbone
et al, Hormone Res 1999
Smooth halo
sagittal
Thin halo is
compressed blood
vessels
Thick, irregular halo
sagittal
Follicular cancer
Infiltrative margins—difference in
nodule echogenicity
Sagittal
Margins not well-defined,
BUT NOT inflitrative
US Prediction of Thyroid Cancer
Taller than wide
• Nodule is taller than
wide on the
transverse view—
AP > transverse
Sensitivity 48%,
Specificity 92%
CA
trachea
2.5cm
1.6cm
Kim AJR 2002; Cappelli Clin Endocrinol 2005; Moon Radiology 2008
Highest
specificity
> 90%
Highest
sensitivity
~80%
Microcalcifications
Irregular margins
Taller than wide
Hypoechoic solid
Likelihood of
malignancy
What has strongest strength of
association?
Now the Forest . . .
Risk stratification by sonographic
patterns
Pure
cyst
Mixed cystic/
Solid
Spongiform
Iso/hyperechoic,
Hypoechoic,
Microcalcifications
solid
solid, regular Irregular border
Partially cystic, w/
border
Taller>wide shape
eccentric solid area
Metastatic LNs
Extrathyroidal
invasion
HIGH Suspicion >80-90%
Hypoechoic, solid
Irregular margin
microCa2+
extrathyroidal extension
Papillary carcinoma
HIGH Suspicion >80-90%
Micro and coarse
Ca2+
extrathyroidal extension
Medullary carcinoma
Micro Ca2+ in
hyperechoic nodule
Papillary carcinoma
Lymph node
ATA and AACE/AME/ETA
guidelines: US detected
abnormal lymph node
demands FNA of nodule
or lymph node
INTERMEDIATE Suspicion 10-20%:
Hypoechoic nodules, regular smooth margins
Papillary carcinoma
Benign hyperplastic nodule
• 80% of papillary cancers are hypoechoic
• However, since benign nodules are much more
common, most hypoechoic nodules are benign!
LOW Suspicion: 5-10%
Iso- to hyperechoic nodules with regular margins
Benign Hürthle cell
adenoma
Hyperplastic nodule
PTC foll variant
Follicular thyroid cancer
Hyperplastic nodule
20% of all cancers are Iso/hyperechoic:
predominantly follicular/ Hürthle/PTC foll variant
Some caveats . . .
• Partially cystic nodules
Partially cystic nodules
• 30% of nodules have
cystic change
• Thyroid cancer more
likely to be solid
360 thyroid cancers at
Mayo Clinic:
Solid: 78%
<50% cystic: 19%
>50% cystic: 3% and
another suspicious
sonographic feature
present1
Henrichsen TL et al, J Clin Ultrasound. 2010 Sep;38(7):361-6
Cystic papillary cancer
Partially cystic nodules
• 30% of nodules have
cystic change
• Thyroid cancer more
likely to be solid
360 thyroid cancers at
Mayo Clinic:
Solid: 78%
<50% cystic: 19%
>50% cystic: 3% and
another suspicious
sonographic feature
present1
Henrichsen TL et al, J Clin Ultrasound. 2010 Sep;38(7):361-6
microcalcifications
Comet tail
reverberation
artifact
Cystic papillary cancer
Partially cystic nodules—the solid part
Uniformly solid area, abutting one side of cyst
Kim Am J Neuroradiol 2010 31:1961
Can we define sonographically
nonsuspicious nodules?
Given that 7-9% of nodules are cancers,
for every 1000 nodules that LACK:
Taller than wide shape
Irregular margin
Hypoechogenicity
Microcalcifications
Macrocalcifications
Only 9 are cancer!!!!*
*by Bayes’ theorem
VERY LOW Suspicion <3%:
“Spongiform”
Transverse
Sagittal
Only 1 of 360
cancers had this
appearance
specificity 99.7%
Moon
Moon, Radiology 2008; 247:762-770,
Bonavita AJR 2009 193:207-13.
peripheral vascularity
Hyperplastic nodule
• Area of the thyroid that is stimulated to
undergo follicular hyperplasia and
accumulation of colloid
• Composed of follicles of various sizes and
age, colloid, macrophages
Hyperplastic
nodule
Normal
thyroid
Common pitfall:
Not microcalcifications
Small hyperechoic linear streaks
just posterior to small cystic area 
posterior acoustic enhancement!
BENIGN <1%:
Pure cystic nodule
Benign cyst
Comet tail
artifact
Frates, J Clin Endocrinol Metab 2006
Why isn’t US 100% accurate?
• Interobserver variation
Kappa values
Agreement
<0.2 slight
0.21-0.4 fair
0.41-0.6moderate
0.61-0.8 substantial
>0.8 ~perfect!
Kappa values
1
0.8
0.6
0.4
0.2
0
Microcalc
Margin
Shape
Echogenicity
Spongiform
• Not all thyroid cancers are the same
Moon Radiology 2008 247:762; Choi Thyroid 2010 20:167
Sonographic features of Papillary
thyroid cancer
100
n=259 pts
Frequency (%)
90
80
70
60
50
40
30
20
10
0
Hypoechoic
Irregular
margins
Solid
MicroCa2+
Chan, J Ultrasound Med 2003; Yuan, Clin Imaging 2006; Jeh, Korean J Rad 2007
Sonographic features:
Papillary vs. Follicular thyroid cancer
100
*
Frequency (%)
90
80
70
*
60
50
40
*
30
20
*
10
0
Hypoechoic
Irregular
margins
Solid
MicroCa2+
Chan, J Ultrasound Med 2003; Yuan, Clin Imaging 2006; Jeh, Korean J Rad 2007
Summary of Ultrasound appearance
• With the exception of suspicious
lymphadenopathy, no single US feature
or combination is adequately SENSITIVE
to identify all malignant nodules
• However, certain combination of features
(PATTERNS) have high POSITIVE
PREDICTIVE value to indicate if a nodule
is likely to be malignant and the ABSENCE
of these features has high NEGATIVE
PREDICTIVE VALUE
• RISK stratification for detection of thyroid
cancer
How to use sonographic features
for clinical decision-making?
Risk assessment based upon:
Size, sonographic features and clinical history
– American Thyroid Association 2009
(www.thyroid.org/professionals/publications/guidelines.html)
– AACE/AME/ETA 2010
(www.aace.com/pub/guidelines)
How can you do the best
thyroid US?
•Experience of the operator
•Equipment
Thyroid US: Summary
Palpable nodule
–
–
–
–
Assess if corresponding nodule
Assess US characteristics to determine if FNA is
indicated
Assess the presence and US characteristics of
other nonpalpable nodules to determine if FNA
indicated
Guide FNA for complex and posterior nodules
Nonpalpable nodule
–
Detect and assess the US characteristics and
guide FNA
Multiples nodules
–
Select the nodule(s) to be submitted to FNA
All nodules
–
Assess lymph nodes