Introduction
Thyroid disease is one of the most common endocrine diseases, with an estimated prevalence
of approximately 42 million people suffering from thyroid disease in India.[1] The disease processes can be congenital, developmental, inflammatory, or neoplastic,
affecting both children and adults. Thyroid nodules are common in women and the elderly
and are attributed to hormonal, environmental, genetic, and hereditary factors.[2] The incidence of thyroid nodules ranges from 20 to 76%, with increasing diagnosis
of incidental nodules on high-resolution ultrasonography.[2] Fine-needle aspiration cytology (FNAC) is a cost-effective and minimally invasive
test of choice in establishing a definitive diagnosis of these nodules. Malignant
disease is, however, seen in only 5 to 10% of thyroid nodules.[3] Hence, various imaging based TIRADS (Thyroid Imaging Reporting and Data System)
guidelines have been devised for risk stratification of the nodules and reduction
of unnecessary FNACs. This pictorial review gives an overview of ultrasound imaging
techniques, imaging anatomy, developmental, benign, and malignant thyroid pathologies,
and imaging guidelines for reporting of thyroid nodules.
Embryology and Anatomy of Thyroid Gland
The thyroid is a shield-shaped organ in the anterior aspect of the neck (“Thyreos”
means shield in Greek).[4] During the 4th week of intrauterine life, a small diverticulum develops from the
ventral wall of the primitive pharynx in the midline. This primitive gland grows and
migrates to the lower part of the neck coursing anterior to the hyoid and larynx.
The tract between the pharynx and the migrated thyroid, called the thyroglossal duct,
normally involutes at a later stage and only a small pit called foramen cecum remains
in the dorsum of the tongue ([Fig. 1]). The primitive gland gives rise to the follicular cells, which secrete thyroid
hormones. Parafollicular C cells, which secrete calcitonin, arise from the neural
crest cells, which migrate into fourth and fifth pharyngeal pouches forming the ultimobranchial
body. Migration completes by the 7th week of intrauterine life, and the production
of thyroid hormone starts from the 12th week of gestation itself.[4]
[5] The fully developed thyroid gland comprises two lobes, connected by the isthmus
at the level of second and third tracheal rings. It is located in the visceral space
of the neck, related to the trachea and prevertebral space posteriorly, and to the
sternohyoid and sternothyroid muscles anteriorly.
Fig. 1 Schematic diagram of development of the thyroid gland. Embryological location on
the left, and final location after complete development on the right. The primitive
thyroid gland (green) with the thyroglossal duct migrate from the foramen cecum into
the neck. The pharyngeal pouches form the ultimobranchial body (4th and 5th) that
forms the C --cells, superior (4th), inferior parathyroid glands (3rd), and the thymus
(3rd and 4th).
Ultrasound Imaging Techniques in the Evaluation of Thyroid
Being a superficial structure, ultrasound is considered the imaging modality of choice
in the evaluation of thyroid pathologies, characterization of nodules, and calculation
of thyroid volume.[6] High-resolution (7.5–13 MHz) linear array transducers are generally preferred, while
lower frequency transducers can be used for larger nodules and masses. The patient
lies in the supine position, with a pillow under the shoulder to facilitate hyperextension
of the neck. The thyroid is evaluated for nodules, echogenicity, and vascularity.
The normal thyroid gland is well-defined, shows uniform homogeneous echotexture, is
more hyperechoic than adjacent muscle, with each lobe measuring approximately 4 to
6 cm craniocaudally (CC) and 1.3 to 1.8 cm in the anteroposterior (AP) and transverse
(T) dimensions.[4]
[7] The volume of each lobe is calculated using the ellipsoid formula (AP × T × CC × 0.52)
and ranges from 10 to 20 mL in adults.[6] Color Doppler imaging, at a low flow setting, is used to assess the vascularity
of the gland as well as nodules. Elastography is a frequently used adjunct technique
which measures the hardness of tissues and, thereby, can help to differentiate benign
and malignant nodules. There are two types of elastography techniques used in routine
practice for thyroid nodules: (1) strain elastography, which depends on the deformation
of tissues in response to mechanical stress (manual compression by the probe or using
carotid artery pulsations as an internal compression source or by focused ultrasound
waves in acoustic radiation force impulse (ARFI) imaging) and (2) shear wave elastography
(SWE), which tracks the attenuation of acoustic pulses called shear waves traveling
perpendicular to the direction of the ultrasound beam.[8] Contrast-enhanced ultrasound (CEUS) is also an additional technique that demonstrates
the tumor microvascularization by intravenous injection of microbubbles (Sulfur Hexafluoride,
SonoVue, 1.2–4.8 mL followed by saline flush). The degree of enhancement (more, less,
or equal to normal thyroid), pattern (centripetal or centrifugal or scattered), homogeneity,
wash-in and wash-out times, and other features like ring enhancement help in the differentiation
of benign and malignant nodules.[9]
Thyroid Pathologies
Congenital and Developmental
Thyroid Dysgenesis
Dysgenesis of the thyroid includes “ectopia” due to abnormal migration of the gland,
“agenesis or athyreosis” where the gland is absent, and “hypoplasia” when it is not
optimally developed. Normal thyroid volume (both lobes) ranges from 0.3 to 4 mL in
neonates and infants to 1.7 to 6.4 mL by 6 to 8 years and 3 to 8.7 mL by 9 to 11 years
of age and is slightly more in girls.[10] Ectopic thyroid tissue can be found anywhere along the course of the thyroglossal
duct, most commonly (90%) at the base of the tongue ([Fig. 2]). Thyroid scintigraphy is the gold standard for the evaluation of children with
congenital hypothyroidism. The thyroid may appear normal on ultrasound in hypoplasia,
but scintigraphy can still show poor uptake.[11] Occasionally, one or more cysts can also be found in the region of the hypoplastic
or absent thyroid ([Fig. 3]). They are hypothesized to be remnants of the ultimobranchial body or the thyroglossal
duct.[12]
Fig. 2 Ectopic lingual thyroid (A and B). Axial contrast-enhanced CT images showing an intensely enhancing lesion at the
base of tongue (black arrow in A) and absence of normal thyroid (white arrows in b). Thyroglossal cyst (C and D). Axial contrast-enhanced CT image shows a thick-walled cystic lesion (asterisk in c) in the midline of neck just anterior to the thyroid cartilage. Longitudinal ultrasound
view (D) shows a cystic lesion (asterisk) anterior to the hyoid (white arrow) and thyroid (thick white arrow) cartilages, with part of the lesion extending between them (arrow head).
Fig. 3 Thyroid dysgenesis. Transverse views of an infant's thyroid (A and B) showing the absence of thyroid tissue with strap muscles filling the thyroid region
(asterisks). Cystic remnants are seen in the right paratracheal region (arrow in B). Similar cystic changes within hypoplastic thyroid tissue are seen in (C) (arrows). Objective evaluation of hypoplasia by measurement of thyroid volume in hypoplasia
in a 6-year-old child (D and E) showing a volume of 0.61 mL, much less than the reference range (1.7–6.4 mL).
Lack of Obliteration of Thyroglossal Duct
Patency of the thyroglossal duct can lead to the formation of cyst, sinus, or fistula.
Thyroglossal duct cyst is the most common congenital neck mass ([Fig. 2]). The thyroglossal duct loops in between the developing hyoid bone and thyroid cartilage.
This creates a tail of the cyst coursing beneath the hyoid, a feature that helps to
differentiate it from other neck cysts. Thyroglossal ducts cysts are seen in the midline,
occasionally paramedian, and can be suprahyoid, at the level of hyoid or commonly
infrahyoid.[13] Thyroglossal fistulas ([Fig. 4]) can open at the foramen cecum above till the lower part of the neck below with
numerous side branches. The persistent tract may also form ramifications within the
hyoid bone or its periosteum.[14]
Fig. 4 Thyroglossal fistula (A–D). Axial unenhanced CT images with injection of contrast into an opening in the left
lateral aspect of neck (D) show a fistulous tract (white arrows) opening into the region of foramen cecum (A). Schematic diagram of thyroglossal duct and related anomalies (E–H). (E) The normal course of the thyroglossal duct (yellow) from foramen cecum to the thyroid, with an inward looping between the hyoid and
thyroid cartilages. The lack of obliteration at various levels give rise to thyroglossal
cyst (F), fistula (G), and ectopic thyroid (H).
Benign
Simple or Hemorrhagic Cyst
Cysts are thought to occur due to an ischemic episode that creates necrosis. This
can happen congenitally, developmentally, or due to tumors, most commonly in papillary
thyroid carcinoma. A simple cyst without any septation or solid component is considered
to be benign ([Fig. 5]).[15]
Fig. 5 Benign thyroid nodules. TR1—Completely cystic nodule with dependent colloid (asterisk in A), TR 1—spongiform nodule with more than 50% cystic spaces (B), comet tail artifact (arrow in C), TR 2—solid cystic isoechoic nodule (D), TR3—solid cystic isoechoic nodule with macrocalcification (arrow in E), and TR 3—solid nodule more echogenic than the adjacent parenchyma (asterisk in F). All the nodules were colloid or nodular goiters by FNAC (Bethesda II).
Benign Follicular Nodule
It includes colloid nodules, nodular goiter, hyperplastic nodules, nodules in Grave's
disease, and macrofollicular subtype of follicular adenoma. All such nodules have
a varying composition of follicular cells and colloid within—with more colloid in
colloid nodules and more follicular cells and varying fibrosis in hyperplastic nodules
([Figs. 5] and [6]). Calcification of inspissated colloid is responsible for the comet tail artifacts,
seen on ultrasound.[15]
Fig. 6 Benign thyroid nodules. TR3—Solid isoechoic nodule with peripheral vascularity (A), soft on elastography (B), TR 4—Solid isoechoic nodule with macrocalcifications (arrow in C), TR 4—Solid isoechoic with interrupted rim calcification (arrow in D), TR 4—Solid nodule hypoechoic compared with the adjacent parenchyma (asterisk in E), and TR 4—Solid hypoechoic nodule with rim calcification (arrow in F). FNAC proved them to be nodular goiters (Bethesda II).
Thyroiditis
Diffuse inflammation of the thyroid (thyroiditis) can be classified into acute infectious,
autoimmune (Grave's and Hashimoto), subacute granulomatous (De Quervain's) thyroiditis,
and fibrous (Riedel's) thyroiditis. The thyroid becomes diffusely heterogeneous and
hypoechoic (due to lymphocytes) with increased vascularity and micronodules, particularly
in Hashimoto thyroiditis ([Fig. 7]). There is also an increased risk of primary thyroid lymphoma and papillary carcinoma
in Hashimoto thyroiditis.[16] Occasionally, thyroiditis can itself be focal, accounting to approximately 5.3%
of all thyroid nodules.[17] Differentiation between different types of thyroiditis or nodular thyroiditis from
other follicular nodules on ultrasound is not possible due to overlapping and variable
imaging appearance.[16]
[18]
Fig. 7 Thyroiditis. Transverse ultrasound view showing diffusely heterogeneous echotexture
of the thyroid with rich internal vascularity (A). Solid hypoechoic nodule (TR 4) in a background of thyroiditis seen as diffuse heterogeneous
parenchymal echotexture (asterisk in B). Similar nodule with rich internal vascularity in another patient (C and D). FNAC proved them to be lymphocytic thyroiditis (B) and Hashimoto thyroiditis (C and D).
Follicular Adenoma
It is a benign encapsulated neoplasm made up of follicular cells. Follicular adenomas
and carcinomas cannot usually be differentiated on ultrasound or FNAC; a biopsy is
needed to assess the vascular invasion in carcinomas. However, recent studies suggest
that the presence of nodules within nodule appearance along with calcifications is
more likely in follicular carcinomas.[19]
Malignant
Papillary Carcinoma
It is the most common thyroid malignancy (80%) and includes cells arranged in the
form of papillae or monolayers. Psammoma bodies and cystic changes are typically associated
with them, which correspond to microcalcifications and anechoic areas on ultrasound
in the nodule and their nodal metastases ([Fig. 8]).[7] The follicular variant appears larger and shows more benign sonographic features.[20] It has a very favorable prognosis when treated early, especially in patients who
are below 30 years of age.[15]
Fig. 8 Papillary carcinoma. Punctate echogenic foci (arrows) within hypoechoic (A), isoechoic—almost entirely solid (B) and solid cystic—isoechoic (C) nodules (TR5, TR4, and TR 4, respectively). (D) A very hypoechoic nodule as compared with the strap muscle (asterisk), with lobulated margins (TR5) and figure (E) shows a hypoechoic nodule with irregular margins (arrowheads) and punctate echogenic foci (TR5), which is hard on elastography (F). All the nodules were diagnosed as papillary carcinomas (Bethesda VI) on FNAC.
Follicular Carcinoma
It constitutes 11% of thyroid malignancies. Here, the neoplastic follicular cells
show capsular or vascular invasion and have a propensity for hematogenous spread,
most commonly to bone and lungs ([Fig. 9]). Hurthle cell carcinoma is a variant of follicular carcinoma with oncocytic cells,
which has an aggressive course and poor prognosis.[7]
Fig. 9 Follicular neoplasms. A solid hypoechoic nodule (TR 4) with rich vascularity diagnosed
to be a follicular neoplasm by FNAC (asterisk in A [Bethesda IV]). Another solid hypoechoic nodule with microcalcifications (arrow in B) and lobulated margins (TR 5) diagnosed as follicular variant of papillary carcinoma
on FNAC (Bethesda VI), finally proven to be noninvasive follicular thyroid neoplasm
with papillary features (NIFTP) on histopathology post thyroidectomy. A TR 4 nodule
in left lobe (C) on ultrasound, corresponding to a hypoenhancing nodule (asterisk in D) on CECT, with lytic expansile blow out metastasis of rib and humerus (arrows in E and F), proven to be a follicular carcinoma on histopathological examination.
Medullary Carcinoma
It constitutes 4% of thyroid malignancies with an intermediate prognosis.[7] Arising from the C cells, this tumor produces calcitonin, and it cannot take up
iodine. It is most commonly (80%) sporadic. Twenty percent can be familial—either
related to MEN 2a, MEN 2b, or non-MEN. Compared with papillary carcinomas, they are
larger, more heterogeneous, and vascular on ultrasound ([Fig. 10]).[21]
Fig. 10 Medullary carcinoma (A and B). A solid taller than wide hypoechoic nodule (asterisk in A) with irregular margins, microcalcifications, and extra thyroid extension (arrow in A) into strap muscles (TR5), associated round hypoechoic cervical lymph nodes (arrow in B), proven to be medullary carcinoma on FNAC (Bethesda VI). Lymphoma (C). A heterogeneous very hypoechoic nodule (asterisks) with lobulated margins (TR 5) with thyroiditis changes in the background parenchyma
(arrow in c), proven to be diffuse large B cell lymphoma on biopsy. Anaplastic carcinoma
(D–F). Enlargement of left lobe of thyroid by a large TR 4 nodule (D) with internal cystic change and macrocalcification (arrow in E). Another patient with an ill-defined hypoechoic nodule showing extra thyroid extension
into trachea (arrowheads in F).
Anaplastic Carcinoma
It is a rare thyroid malignancy with aggressive local invasion, amounting to only
up to 2% of the total ([Fig. 10]). The malignant cells are undifferentiated; hence cannot take up iodine and are
unsuitable for radioablation.[7] Most of the patients have a history of long-standing goiter, as the tumor arises
from the transformation of well-defined carcinoma or adenoma. It shows rapid growth
and compressive symptoms.[15]
Lymphoma
Primary lymphoma is rare (1 to 5% of thyroid malignancies). Hashimoto thyroiditis
is a predisposing factor. It can be nodular, diffuse, or mixed ([Fig. 10]). The nondiffuse types are markedly hypoechoic and have been referred to as pseudocysts.
Lesions can be multifocal, hypervascular, and calcification is uncommon.[22]
Metastasis
It is rare and occurs in patients who already have widespread metastasis in other
organs. The most commonly reported tumors metastasizing to the thyroid include lung,
breast, renal malignancies, and melanoma.[23]
Evaluation of Nodules and Risk Stratification
Since 2009, various risk stratification algorithms (TIRADS) have come up for thyroid
nodules, of which the most commonly used one is that of the American College of Radiology
(ACR).[24]
[25] Point scores are given for each morphological feature ([Fig. 11]) and the final score and size are used to decide the need for FNAC or follow-up
([Table 1]).
Table 1
Final scoring and FNAC/follow-up guidelines in ACR—TIRADS[24]
[25]
|
Points
|
TR
|
Risk category
|
FNAC indication
|
Follow-up indication
|
Follow-up time points
|
|
0
|
1
|
Benign
|
No
|
No
|
–
|
|
2
|
2
|
Not suspicious
|
No
|
No
|
–
|
|
3
|
3
|
Mildly suspicious
|
>2.5 cm
|
>1.5 cm
|
1, 3, 5 yr[a]
|
|
4–6
|
4
|
Moderately suspicious
|
>1.5 cm
|
>1 cm
|
1, 2, 3, 5 yr[a]
|
|
≥7
|
5
|
Highly suspicious
|
>1 cm
|
>0.5 cm
|
Annually till 5 yr[a]
|
Abbreviation: FNAC, fine-needle aspiration cytology.
a No further follow up after 5 years if there is no increase in size.
Fig 11 ACR TI–RADS system. Composition (A), echogenicity (B), shape (C), margin (D), and echogenic foci (E). The individual scores (within brackets) are added to give a final score and TIRADS
category, from which FNAC/follow-up is decided based on the category and size (F).
Evaluation of Thyroid Nodules on Ultrasonography
Composition: Nodules can be solid, mixed solid cystic, entirely cystic, or spongiform.
Among these, solid nodules have the highest risk of malignancy.[26] Spongiform nodules, characterized by multiple microcystic areas forming more than
50% of the nodule, have a high negative predictive value for malignancy.[27]
Echogenicity: Nodules are iso, hypo, or hyperechoic if they are equal to, less than,
and more than the echogenicity of the normal thyroid. Nodules are very hypoechoic
if they are less echogenic than the strap muscles.[28]
Margins: They can be smooth, ill-defined (more than 50% contour is not made out),
lobulated, irregular, or can show overt extrathyroid extension ([Fig. 10A]) into strap muscles, trachea, esophagus, or larynx, which has the maximum risk of
malignancy. The presence of only capsular bulge, border abutment, or loss of echogenic
border is considered as minimal extrathyroid extension, the clinical significance
of which is controversial.[24]
Shape: Taller than wide orientation (AP dimension greater than T) happens due to the
nonuniform growth of malignant cells in different directions. When this feature is
combined with solid composition, there is 93% specificity for malignancy.[29]
Calcifications: Dystrophic macrocalcifications with posterior shadowing are commonly
seen with benign multinodular goiters. Punctate echogenic foci, which do not show
posterior shadowing, correspond to Psammoma bodies histologically and are more commonly
seen in malignant nodules.[30] Comet tail artifacts ([Fig. 5C]) are echogenic foci with additional posterior reverberation in a triangular pattern,
which are strongly associated with colloid nodules.
Vascularity: Neoplasms, hyperplasia of follicles, and granulation tissue in colloid
nodules can show vascularity. However, few papillary carcinomas with dense fibrosis
may show poor internal vascularity. Power Doppler, more useful than color Doppler,
is angle independent, reduces the artifacts and can also help in an accurate depiction
of vascularity from small vessels.[31]
Elastography
Strain elastography (SE) by compression: In SE, the stiffness of the tissue is displayed
as a color spectrum from red (soft), green (medium), to blue (hard). Qualitative scores
([Fig. 12]) have been described by Asteria et al (4 points, score 3, or more favoring malignancy)
and Rago and Vitti (5 points, score 4, or more favoring malignancy), in the order
of increasing stiffness of the nodules.[8]
[32]
[33] Semiquantitative evaluation can also be done using strain ratio, comparing the stiffness
between the thyroid nodule and surrounding normal parenchyma or muscle. A strain ratio
of greater than 1.21 has been found to be the best cut-off in differentiating benign
and malignant nodules.[34]
Fig. 12 Schematic representation of the commonly used qualitative SE scores. (A) Asteria et al33 classification—scores: 1 = even elasticity (green) in the entire nodule, 2 = elasticity in most part of the nodule, 3 = stiffness (blue) in most part, 4 = no elasticity); (B) Rago and Vitti et al classification—scores: 1 = Even elasticity (green) in the entire nodule, 2 = elasticity in most part of the nodule, 3 = elasticity
only in the periphery, 4 = no elasticity, 5 = no elasticity in nodule and the surrounding
posterior shadowing).
SE by Acoustic radiation force: Qualitative ARFI imaging ([Figs. 13D] and [13F]) displays tissue stiffness in the form of a grayscale, darker the nodule, more the
stiffness. They have been classified into six grades (grade 4 or more favoring malignancy)
based on the increasing proportion of darker/blacker areas by Xu et al.[8]
[35] It was also observed that malignant nodules, owing to their infiltrative margins,
show larger areas on elastography images than conventional ultrasound. Nodules were
more frequently malignant when the area ratio (area on elastography to that in conventional
ultrasound) was greater than 1.09.[36]
Fig. 13 Elastography of thyroid nodules. Benign nodular goiters showing a qualitative strain
elastography score of 2 (A and B), appearing soft on SWE with elasticity of 3.61 kPa (C). Another benign nodular goiter evaluated by qualitative virtual touch imaging (VTi,
Siemens), appearing similar to the background parenchyma (asterisk) on gray scale, with mean shear wave velocity of 1.8 m/s on point SWE (D and E). Biopsy-proven medullary thyroid carcinoma, appearing blacker than the background
thyroid parenchyma (asterisk) on VTi (F), with an area of involvement larger than that in the gray scale image, and mean
shear wave velocity values X.XX suggesting that it is higher than the highest possible
value of 8.4 m/s (G).
Point SWE: In point SWE, the stiffness of tissues is depicted in m/s of the shear
wave speed inside a region of interest (ROI) of fixed size ([Figs. 13E] and [13G]). The median shear wave velocity of normal thyroid parenchyma ranges between 1.2
and 3.6 m/s.[37] The cut-off between benign and malignant nodules with the best diagnostic efficacy
ranges between 2.48 and 2.55 m/s.[38] Diffuse thyroid diseases like Hashimoto or Grave's disease may also show high shear
wave values of 2.68 ± 0.5 m/s.[8] However, the range of elasticity values that can be depicted is narrow in m/s (usually
0.5–8.4 m/s or 0–10 m/s, depending on the manufacturer) and hence, very hard or very
soft tissues are expressed as nonmeasurable (“X.XX m/s”).
Two-dimensional SWE: This is available in single shot or real time modes ([Figs. 6B, ]
[8F, and ]
[13C]) by different vendors. It provides tissue stiffness information in a larger area
of user selected box and allows quantitative assessment from multiple ROIs drawn within
it. Values are expressed either in m/s (shear wave velocity) or kPa (elasticity),
and the color scale is graded from blue (soft) to red (hard).[8] The elasticity values for normal thyroid parenchyma ranges between 10 and 40 kPa.
An elasticity value of 65 and 66 kPa in the nodule or an elasticity ratio between
the nodule and surrounding normal thyroid of more than 3.7 is considered as the cut-off
for malignancy.[37] The values are higher in papillary carcinomas due to their calcifications and fibrous
component compared with follicular carcinoma which has more cellular components.[38]
A few pitfalls of elastography include lower stiffness in malignancies with necrosis,
cystic areas, and smaller sizes, higher stiffness in benign nodules with calcifications
or thyroiditis with more fibrous components, dependence on the application of adequate
probe compression, need for including adjacent normal thyroid parenchyma in the field
for strain or elasticity ratios which may not be possible in large nodules and varying
cut-off values of elastography parameters by different studies to distinguish benign
and malignant nodules.
Contrast-Enhanced Ultrasonography
Benign nodules: The patterns of enhancement described in benign nodules ([Figs. 14] and [15]) include (1) uniform homogeneous or scattered enhancement; (2) iso or hyperenhancement
compared with surrounding normal parenchyma; (3) fast wash-in and slow wash-out; (4)
complete hyper- or hypo-enhancing peripheral ring; and (5) no enhancement in cysts.[39]
[40]
[41] The first three features are related to the homogeneous architecture of benign nodules
with a relative lack of necrosis or calcifications as well as preserved vascularity
within them. Follicular adenomas can show hyperenhancement due to their rich vascularity.
A hyper or hypoenhancing rim can be seen due to compression of surrounding thyroid
parenchyma and interstitial edema, inflammatory exudates, or the presence of cystic
areas within the nodule decompressing the pressure on adjacent parenchyma. Benign
nodules with necrosis or a higher proportion of cystic areas, however, may show heterogeneous
enhancement.[39]
[40]
[41]
Fig. 14 CEUS enhancement patterns in thyroid nodules. (A and B) Biopsy-proven papillary carcinoma thyroid seen as a solid hypoechoic nodule with
microcalcifications (TR5), with heterogeneous centripetal hypoenhancement pattern
on CEUS. An incomplete irregular hyperenhancing ring is seen along part of the nodule
(arrowheads in B). (C and D) Solid hypoechoic nodule (TR 4) with intranodular vascularity (C), showing homogeneous iso enhancement and a complete regular hyperenhacing ring (arrowheads in D). It was proven to be a nodular goiter by FNAC.
Fig. 15 Schematic diagram of common CEUS enhancement patterns in thyroid nodules. Malignant
nodules (A) show heterogeneous centripetal hypoenhancement, irregular hypo- or hyper ring enhancement,
and sometimes no enhancement in smaller nodules. Benign nodules (B) show scattered or equal homogeneous enhancement in all areas, which is equal or
more than the background parenchyma, hyper- or hypoenhancing complete regular ring,
and no enhancement in cysts.
Malignant nodules: In malignancy, necrosis and tumor embolus formation happens within
vessels when the growth of the tumor tissue exceeds the vascular supply, which causes
hypoenhancement. They also have a heterogeneous composition with varying areas of
fibrosis, necrosis, and calcifications within. The enhancement patterns described
in CEUS in malignant nodules include ([Figs. 14] & [15]): (1) hypo-enhancement with nodule to peri-nodule peak intensity ratio less than
0.9,[9]
[39] (2) heterogeneous enhancement, (3) centripetal enhancement attributed to predominant
fibrosis in the central parts, (4) slow wash-in, rapid wash-out ratios and time to
peak intensities, although follicular carcinomas with rich vascularity show faster
wash-in and slow wash-out times just like follicular adenomas, (5) ill-defined enhancement
borders, (6) irregular or incomplete ring enhancement (usually hypo- or sometimes
hyperenhancing due to peritumoral immune response), (7) no enhancement, particularly
in nodules less than 1 cm, and (8) enhancement area smaller or larger than grayscale
image.[39]
[40]
[41]
Besides aiding in the differentiation of benign and malignant nodules, they can also
help in the follow-up of patients postablation or postradioactive iodine therapy by
identifying enhancing viable tissue.[39]
[42]
Associated Cervical Lymph Nodes
Features of malignant lymph nodal metastasis ([Figs. 16] and [17]) from the thyroid include[43] hyperechogenicity, round shape, microcalcifications, and cystic change. The presence
of cystic areas on ultrasonography is more specific for papillary carcinoma of the
thyroid. Echogenic foci can be seen in lymph nodes in both medullary carcinoma (due
to amyloid) and papillary carcinoma (due to Psammoma bodies).[44] Metastatic lymph nodes are harder with higher elasticity scores on SWE.[45] On CEUS, malignant lymph nodes show poor vascularization/enhancement areas and perfusion
deficits due to necrosis, with centripetal enhancement, while benign nodes show iso
and centrifugal enhancement.[42]
Fig. 16 Schematic diagram of lymph node evaluation in suspected thyroid malignancy. Suspicious
features (A–D), intermediate suspicion (E) when there is loss of echogenic hilum and hilar vascularity, and benign (F) when there is the presence of echogenic hilum and hilar vascularity.
Fig. 17 Lymph node metastasis from papillary carcinoma. Longitudinal views of ultrasound
show cystic change (asterisk in A), hyperechogenicity (arrow in B), rich vascularity with lost fatty hilum (C), and microcalcifications (arrows in D). Contrast-enhanced CT images show cystic changes within a large left level V lymph
node (arrow in E). Another patient showing calcification within a metastatic node (arrow in F).
Thyroid Nodule Mimic
Parathyroid adenomas commonly occur along the inferior poles of the thyroid, separated
from it by an echogenic capsule, and appear as hypoechoic solid lesions with feeding
polar vessels[46] ([Fig. 18]). In approximately 1 to 7% cases, they can be completely or partially intrathyroid
and can be confused with a thyroid nodule.[47] Four-dimensional computerized tomography can help to differentiate between thyroid
nodules and parathyroid lesions, as the latter show arterial hyperenhancement, washout,
and polar vessels.[48]
Fig. 18 Parathyroid adenoma. Ultrasound shows a circumscribed hypoechoic lesion (asterisk) with rich peripheral vascularity (A), separated from the thyroid parenchyma by an echogenic capsule (arrowheads in B). On contrast-enhanced 4D CT, the lesion (arrow and arrow heads) is hypodense on unenhanced section (C), intensely enhancing with cystic change and well delineated in the arterial phase
(D), showing washout in the delayed phase (E).
