Received: 25 April 2017
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Revised: 28 July 2017
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Accepted: 14 February 2018
DOI: 10.1002/hed.25160
CLINICAL REVIEW
Investigation of thyroid nodules: A practical algorithm and review of guidelines Jin Soo A. Song MD1
| Adam A. Dmytriw MD, MSc2
| Eugene Yu MD2 |
Reza Forghani MD, PhD3 | Lorne Rotstein MD4 | David Goldstein MD, MSc1 | Colin S. Poon MD, PhD5 1
Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada 2
Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
Abstract Background: High resolution ultrasound has led to early detection of subclinical tumors and drastic increase in incidence of thyroid malignancy. To achieve a balance in appropriate investigation without perpetuating an overdiagnosis phenomenon, a concise set of evidence-based recommendations to stratify risk is required.
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Department of Radiology, Jewish General Hospital and McGill University, Montreal, Quebec, Canada 4 Department of General Surgery, University of Toronto, Toronto, Ontario, Canada
Methods: We sought to assemble an evidence-based diagnostic algorithm and accompanying pictorial review for workup of thyroid nodules that summarizes the most recent guidelines. In addition, we conducted a literature search and analysis of our imaging databases.
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut
Results: Although many imaging features of benign and malignant nodules can be nonspecific, others, such as microcalcifications, lymphadenopathy, and peripheral invasion, are highly suggestive of malignancy. The predictive values of salient imaging characteristics are presented.
Correspondence Adam A. Dmytriw, 263 McCaul Street, 4th Floor, Toronto, Ontario, M5T 1W7, Canada. Email:
[email protected]
Conclusion: Evidence-based guidelines are available such that a cost-effective algorithm for thyroid nodule workup can be devised. Conservative management with a focus on periodic monitoring is the working clinical consensus on the approach to thyroid nodules.
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KEYWORDS fine-needle aspiration (FNA) biopsy, imaging features, thyroid nodule, ultrasound, well differentiated thyroid carcinoma
1 | INTRODUCTION Over the past decade, the incidence of thyroid malignancy has reached epidemic proportions. This is predominantly due to papillary thyroid cancers (PTCs), which comprise 85% of detected thyroid cancers, followed by follicular (11%), medullary (3%), and anaplastic phenotypes (1%).1,2 The incidence of thyroid cancer has risen from 4.9 to 14.3 per 100 000 over 4 decades, with PTC comprising 3.4 to 12.5 per 100 000.3,4 This is largely attributed to advances in imaging modalities, which enable early detection of subclinical tumors, as high resolution ultrasound detects nodules in Head & Neck. 2018;1–13.
19%-68% of randomly selected individuals.1,5 These aptly named incidentalomas are not necessarily life-threatening, as they are discovered in half of thyroid gland autopsy reports and hold the same rate of malignancy as palpable nodules at 4%-12%.1 Despite their alarmingly high rates of discovery, the mortality rate of these endocrine tumors has remained stable. As the majority of thyroid tumors are PTCs, these cancers possess an excellent prognosis, with cancer-specific 5, 10, and 20-year survival rates of 99.8%, 99.7%, and 99.7% in stage I; 98.1%, 95.6%, and 93.7% in stage II; 96.3%, 90.7%, and 60.2% in stage III; and 87.9%, 84.0%, and 76.7% in stage IV of PTC, respectively.6
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Currently, the workup and management practices of these tumors carry an increasingly heavy burden for the healthcare system. It is estimated that by 2019 PTC will become the third-most common cancer in women of all ages at a cost of $18 to $21 billion dollars annually in the United States.7 Hence, therein lies the issue of striking a balance between appropriate rates of detection and intervention to minimize rates of morbidity and mortality, without perpetuating an overdiagnosis phenomenon. Thyroid ultrasound and possible subsequent fine-needle aspiration (FNA) biopsy have become the mainstay in initial management of suspicious thyroid nodules. Given its broad availability, acceptable cost, and immediate visualization, ultrasound has become the primary modality in diagnostic imaging to differentiate suspicious nodules requiring intervention from benign lesions that can be safely monitored. However, as thyroid nodules are a common entity seen by both clinical and surgical specialties, it is necessary to establish consistency in practice guidelines between various agencies. In order to properly stratify risk of malignancy, ultrasound imaging findings should be corroborated by relevant findings on clinical history and examination. Commonly cited clinical features increasing likelihood of cancer include familial history of differentiated thyroid cancer, multiple endocrine neoplasia type II, or medullary thyroid carcinoma, any previous radiation exposure, male sex, age under 20 or over 60 years, a firm or fixed nodule, and rapid nodular growth.5,8–12 Physical examination findings that suggest malignancy include vocal cord paralysis, regional lymphadenopathy, dysphonia, and fixation to surrounding tissue.5,9,12,13 Both the American Thyroid Association (ATA) and the American Association of Clinical Endocrinologists (AACE) recommend serum thyroid-stimulating hormone as part of the initial workup.5,14 It was previously believed that nodule size upon presentation was a risk factor for malignancy, however, current literature supported by organizations, including the British Thyroid Association (BTA) and Korean Society of Thyroid Radiology (KSThR), state that size is not a reliable risk factor.10,11 This notion extends to suspicious subcentimeter nodules, which have reported at rates of 19% and with biopsyproven malignancy.15 Conversely, there is an increased risk of false-negative results on FNA biopsy with larger sized nodules.16,17 Hence, it is prudent to consider features beyond size at presentation for determining malignancy. With respect to supplementary imaging, CT or MRI is generally limited to preoperative planning to evaluate substernal extension, airway compression, and bulk of malignancy.14 Additionally, the ATA guidelines recommend selectively incorporating i.v. contrast-enhanced CT or MRI as an adjunct to ultrasound for assessment of clinically evident lymph node involvement in patients with clinical
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suspicion for advanced disease.5 The ineffectiveness of these modalities in initial assessment is illustrated by their decreased capability to capture incidental thyroid nodules, which are seen in 40%-50% of ultrasounds and 16% of CT and MRI studies.18,19 Thyroid scintigraphy aids in further investigation of suppressed thyroid-stimulating hormone in cases of hyperfunctioning or hot nodules with diagnostic uncertainty from cytology or ultrasonography, helping dispel false-positive findings.20–22 Given the increasing phenomenon of overdiagnosis of incidental thyroid malignancy, a more conservative approach toward management is mandated. To amend the workup of thyroid nodules to the changing oncologic epidemiology, it is imperative there is consistency between the various disciplines involved in patient care. The purpose of this study was for us to present the current literature surrounding the main characteristic benign and malignant ultrasound features, describe the predictive values for these imaging findings, and assess the consistency between thyroid nodule ultrasound guidelines in order to present a simple and practical algorithm for workup and initial management.
2 | MATERIALS AND METHODS A literature search using PubMed and the MEDLINE subengine was completed using the terms “thyroid,” “nodule,” “workup,” and “imaging.” Studies reporting on the workup, imaging characteristics, biochemical profile, and clinical history of thyroid patients were included, with relative preference given to those completed between 2003 and 2017. Studies regarding the pediatric population were excluded, as were those including patients who received head and neck radiation therapy due to its possible confounding effect. All societal guidelines publicly available were analyzed, including those of the Society of Radiologists in Ultrasound, the American Thyroid Society, and the Bethesda Classification of thyroid nodules, among others.
3 | RESULTS 3.1 | Features of malignant nodules 3.1.1 | Microcalcifications Calcifications can be present in both benign and malignant nodules, varying in appearance from microcalcifications, macrocalcifications, or rim calcifications.13,23–26 Microcalcifications are cited by both the Society of Radiologists in Ultrasound (SRU) and the ATA as the most specific characteristic of a malignant nodule (see Figure 1), with estimated sensitivity and specificity rates of 26.1%-59.1% and 85.8%95.0%, respectively.5,11,24,25,27 They are formed by
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F I G U R E 1 Surgically proven papillary carcinoma. A, Contrast-enhanced CT demonstrates primarily hypodense nodule with punctate microcalcifications (arrow). B, Ultrasound demonstrates a nodule with hypoechogenicity and punctate echogenic foci consistent with microcalcifications, which correspond with histopathologic psammoma bodies. Both are sonographic features associated with malignancy. Unless these calcifications are clumped, there is usually no posterior shadowing. C, Color Doppler ultrasound demonstrates absence of intranodular flow [Color figure can be viewed at wileyonlinelibrary. com]
psammoma bodies, or laminar, crystalline calcified deposits, which are particularly common in PTC.11 Calcifications seen in benign nodules tend to be coarse or “eggshell” in appearance. Macrocalcifications occur through fibrosis and degeneration of benign nodules, with estimated rates of sensitivity and specificity at 10% and 96%, respectively.11,25 Benign nodules may also contain inspissated colloid calcifications mimicking the coarse calcifications in medullary thyroid carcinomas but they can be differentiated by the characteristic “ring-down” or reverberating artifact and absence of posterior acoustic shadowing.22 The inverse association between the size of the calcification and the likelihood of malignancy is illustrated in the SRU recommendations: FNA biopsy is recommended for nodules larger than 10 mm and containing microcalcifications but a larger threshold of 15 mm is used for nodules containing macrocalcifications.24 Calcification is also seen in subcentimeter thyroid nodules, with malignant nodules possessing many diffuse calcifications and rim calcifications with 82.1% and 80.6% accuracy, respectively.15
3.1.2 | Marked hypoechogenicity A thyroid nodule can be relatively hypoechoic in relation to the thyroid parenchyma but marked hypoechogenicity is judged when compared with the adjacent strap muscles.11 Marked hypoechogenicity is a fairly reliable finding,11,21–23,25,27,28 with a high diagnostic accuracy. With an estimated specificity for malignant nodules nearing 92.2%-94.0%,11,25,29 it increases the likelihood of malignancy for both purely solid and partially cystic nodules and should prompt FNA.11,25,28,29 However, overall hypoechogenicity relative to surrounding parenchyma is an overlapping feature, occurring within smaller benign nodules at 62.5%.25 Furthermore, a halo or hypoechoic rim surrounding a nodule may reflect benign pseudocapsule formation from fibrous connective tissue, compressed thyroid tissue, and chronic inflammatory change with a 95% specificity.11 Therefore, although nodules appearing both solid and hypoechoic have
a high sensitivity for malignancy at 87%, interpreters should be mindful they are also present in 55% of benign nodules.22 Last, early stages of subacute thyroiditis may also appear markedly hypoechoic, with possible irregular shape and absence of color Doppler flow but will eventually differentiate into isoechogenicity.30
3.1.3 | Spiculated or irregular margins Studies have cited between 56.1% and 71.8% of malignant nodules having irregular margins and shapes, respectively, making them a common appearance for malignancy.22,31 An irregular or spiculated margin, causing a stellate appearance from tissue strands protruding from a poorly defined mass, is a finding that often warrants FNA biopsy. These lesions are more likely follicular neoplasms, with capsular invasion virtually confirming malignancy when present. Although spiculation is more suggestive of malignancy, ill-defined margins can also be seen in benign nodules that are incompletely encapsulated and merge with normal tissue.25 Poorly defined margins also have a high diagnostic indication for thyroiditis, with reported sensitivity and specificity at 87.3% and 80.9%, respectively.32 As an isolated ultrasound finding, spiculated margin is helpful when present, with 48% and 92% sensitivity and specificity, respectively.11,29 Understandably, its absence does not rule out malignancy. Similar to irregular margins, changes in lesion perfusion are common in both thyroiditis and malignancy, illustrating an absence of color flow and intrinsic hypervascularity, respectively.22,30 Hypervascularity and prominent central blood flow has been demonstrated in 69%-74% of malignant thyroid nodules.22,33,34 For this reason, recognition of the difference between peripheral and intranodular flow is essential to rule out thyroiditis nodules with noninternal vascularity.30 Additionally, when marked hypoechogenicity is present without vascularity in a presumed PTC nodule, it is speculated to represent fibrotic regression after spontaneous collapse of a hemorrhagic component of a benign lesion.23
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F I G U R E 2 Pathologically proven papillary thyroid cancer. This taller-than-wide nodule possesses: A, marked hypoechogenicity when compared to strap muscles; B, hyperechoic components with irregular and partly ill-defined margins; and C, peripheral and central vascularity [Color figure can be viewed at wileyonlinelibrary.com]
3.1.4 | Taller than wide A nodule that has a greater anterior-posterior dimension than transverse dimension, or “taller-than-wide,” is a strong predictor of malignancy with an odds ratio (OR) of 8.6 (see Figure 2).5,14 This notion extends to subcentimeter nodules, with taller-than-wide dimensions increasing the OR of malignancy to 8.2.15 Furthermore, meta-analyses have shown taller-than-wide shape, illustrating the disregard for tissue planes and centrifugal growth of thyroid cancers, to be the ultrasound nodule feature with the highest diagnostic OR for PTCs.35 The high specificity of this ultrasound feature has been validated in numerous studies.11,25,35–37 Another feature that is suggestive of malignancies is regional lymphadenopathy, particularly when a morphologically irregular lymph node or intranodular vascularity is present.5,12,14,38 Furthermore, both the recent AACE and ATA explicitly state extrathyroidal extension as an indication of high-risk thyroid nodules.5,14
3.2 | Features of benign nodules 3.2.1 | Simple cystic nodules Approximately 80% of thyroid neoplasms have minimal or no cystic component, making cystic nodule a predominantly benign feature (see Figure 3). Reports have cited that 88% of thyroid cancer is uniformly solid or has minimal cystic change (50%) occurring in only 2.5% of cancers, all of which had numerous other suspicious sonographic findings.39,40 However, elucidating proportions of cystic changes can be difficult as not all nodules progress as anechoic lesions, and markedly hypoechoic fibrosis can present as cyst-like hypoechogenicity.28 Although approximately 90% of thyroid nodules increase 15% or more in volume over 5 years, predominantly cystic nodules exhibit substantially slower growth than their solid counterparts, giving credence to rapid interval growth as a clinically suspicious finding.22
Commonly associated with cystic composition are punctate echogenic foci formed from cholesterol crystals that commonly presents with ring-down artifacts described as “comet tails” (see Figure 4). The majority of cystic nodules have a mixed echogenicity deriving from cystic degeneration of neoplastic and nonneoplastic nodules, as true cysts with epithelial linings are uncommon.23 It is important to differentiate echogenic foci with posterior comet-tail artifacts indicating benignity, from tiny echogenicities representing microcalcifications typical of PTC.24 Previous studies have further differentiated cystic nodules into those with eccentric configurations and either blunt or acute angles between the solid component and cyst wall, with only the latter being associated with malignant PTC nodules.23 In the same study, concentric configuration, smooth margin or microlobulation, peripheral or minimal vascularity, spongiform appearance, and colloid cysts were all indicative of benign nodules.23 Both the AACE and the ATA are in agreement that in nodules with >50% cystic components, there is a 60%-80% probability of requiring repeat FNA biopsies to achieve a diagnostic specimen.5,14 However, a study by Eun et al40 has shown that of 297 nodules with nondiagnostic results on repeat FNA biopsies, none of those with >50% cystic components were malignant. Hence, we do not recommend biopsy of a purely cystic nodule unless aspiration is mandated in cases of therapeutic intervention, endorsed by the ATA guidelines.5 However, a small solid component in a predominantly cystic nodule presenting with suspicious ultrasound features may warrant separate aspiration, as a mural solid component may indicate a PTC.11
3.2.2 | Spongiform Benign nodules may exhibit sponge-like cystic areas, representing solid debris with septations (see Figure 3). These produce the appearance of a heterogeneous nodule, with multiple microcystic spaces separated by thin septae or intervening isoechoic parenchyma. Although spongiform appearance is characteristic of benign thyroid nodules and current
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F I G U R E 3 Ultrasonography of a simple cyst. A, Axial and B, transverse projections. This appearance is classic for a benign nodule and does not require fine-needle aspiration biopsy even with thick septations or internal debris
guidelines recommend FNA biopsy in nodules 2 cm, we propose a more conservative threshold of aspiration in nodules 4 cm. Meta-analysis has shown that spongiform
appearance on ultrasound has the highest diagnostic OR for benign characterization, and in addition to cystic nodules are the only 2 features that can prevent the need for an FNA
F I G U R E 4 Histologically proven multinodular goiter. A, Contrast-enhanced CT demonstrates diffusely enlarged thyroid gland containing multiple cystic nodules. Although the imaging appearance is suggestive of multinodular goiter, it is not specific. B, T1-weighted MRI scan shows some cysts are hyperintense, which may represent colloid or hemorrhage but the imaging appearance remains nonspecific. C, Ultrasound shows primarily cystic nodules that contain solid debris and septations giving a spongiform appearance, and cholesterol crystals with “comet tail” (arrows). D, Ultrasound shows primarily cystic nodules that contain solid debris and septations giving a spongiform appearance, and cholesterol crystals with “comet tail” (arrows) [Color figure can be viewed at wileyonlinelibrary.com]
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T A BL E 1
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Features present in malignant nodules with their reported predictive values
Sonographic features associated with thyroid cancer Features
Sensitivity, %
Specificity %
PPV %
NPV %
Microcalcification
26.1-59.1
85.8-95.0
24.3-70.7
41.8-94.2
Hypoechogenicity
26.5-87.1
43.4-94.3
11.4-68.4
73.5-93.8
Solid
69.0-75.0
52.5-55.9
15.6-27.0
88.0-92.1
Intranodular vascularity
54.3-74.2
78.6-80.8
24.0-41.9
85.7-97.4
Taller-than-wide, AP > side-to-side
32.7
92.5
66.7
74.8
Abbreviations: AP, anterior posterior; NPV, negative predictive value; PPV, positive predictive value. Note: The Korean Society of Thyroid Radiology guidelines (2011) do not advocate for immediate fine-needle aspiration biopsy of lesions with intranodular vascularity.
biopsy.35 Similarly, reports estimate 10.0% and 99.7% sensitivity and specificity, respectively, for benign disease.11,12,25
3.2.3 | Multiple small nodules The ATA suggests when multiple thyroid nodules >1 cm in size possess suspicious ultrasound features, each nodule carries an independent risk of malignancy and may prompt multiple FNA biopsies.5 This notion is fortified in the KSThR guidelines, which state that the risk of malignancy in patients with multiple thyroid nodules is similar to those with a single thyroid nodule.11 These smaller asymptomatic impalpable nodules are largely responsible for the marked increase in thyroid nodule incidence, as high resolution ultrasound can detect lesions as small as 3 mm.1 Currently, small PTCs account for 90% of cases in countries with rapidly increasing incidences.2 Studies estimate that these microcarcinomas, 80%) Mostly cystic nodules with reverberating artifacts not associated with suspicious US signs Isoechoic spongiform nodules, either confluent or with regular halo
British Thyroid Association (BTA)
Korean Society of Thyroid Radiology (KSThR)
American Association of Clinical Endocrinologists (AACE)
US features of Thyroid Cancer: Microcalcification Hypoechogenecity Irregular margins or no halo Solid composition Intranodular vascularity Taller than wide shape Rapid interval growth Cervical lymphadenopathy
Society of Radiologists in Ultrasound (SRU)
Summary of recommendations from various guidelines stratifying the risk of ultrasound features for thyroid malignancy
Comparison of Guidelines from 2016 AACE/ACE-AME, 2011 KSThR, 2014 BTA, 2005 SRU, 2015 ATA
T AB L E 2
(Continues)
High suspicion: Solid hypoechoic nodule or solid hypoechoic component of partially cystic nodule with 1 or more of following features: Irregular margins (infiltrative, microlobulated) Microcalcification Taller than wide shape Rim calcification with small extrusive soft tissue component Evidence of extrathyroidal extension
Intermediate suspicion: Hypoechoic solid nodule with smooth margin without: Microcalcifications Extrathyroidal extension Taller than wide shape
Benign: Purely cystic nodules Very low suspicion: Spongiform or partially cystic without any US features Low suspicion: Isoechoic or hyperechoic solid nodule, or partially cystic nodule with eccentric solid area without any US features
American Thyroid Association (ATA)
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3.3.2 | Less suspicious (consider fine-needle aspiration biopsy if >2 cm)
American Thyroid Association (ATA)
Cystic nodules with a solid component qualify only at this size, however, features, such as an irregular wall/mural nodule, vascularity, or microcalcifications, are almost invariably present in malignancy. A homogeneously isoechoic or hyperechoic nodule with a smooth or ill-defined margin is also indeterminate. Although most of these nodules are benign, they may uncommonly represent follicular or papillary carcinoma (see Figure 6). We recommend periodic surveillance for low-risk thyroid nodules instead of unnecessary subsequent workup with FNA biopsy.
Malignant: Solid, hypoechoic, lobulated/irregular outline, microcalcification (papillary carcinoma) Solid, hypoechoic, lobulated/irregular outline, globular calcification (medullary carcinoma) Intranodular vascularity Taller than wide shape Characteristic associated lymphadenopathy
British Thyroid Association (BTA) Korean Society of Thyroid Radiology (KSThR) American Association of Clinical Endocrinologists (AACE)
Comparison of Guidelines from 2016 AACE/ACE-AME, 2011 KSThR, 2014 BTA, 2005 SRU, 2015 ATA
T AB L E 2
(Continued)
Society of Radiologists in Ultrasound (SRU)
3.4 | Technologic advances Although FNA biopsy is cited for a sensitivity of 71%-83% and specificity of 96%, between 9.5% and 20.4% of FNA biopsies may return as nondiagnostic even under ultrasound guidance.36,42 Likewise, even in those with an initially benign cytology, the second report may lack the threshold of 6 groups of 10 preserved epithelial cells, thus returning as nondiagnostic or indeterminate in 10%-15% of nodules.2,14 Studies evaluating additional parameters, such as serum thyroglobulin levels, showed no significant difference for malignancy.43 Compared to FNA biopsy, core-needle biopsy has shown higher accuracy of 94%, yet nondiagnostic results still occur in 1.2%-26.0% of cases.40 Even when a successful aspiration is collected, the ambiguous categorization of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) may be reported (see Figure 7). The AUS/FLUS is projected to account for 2 cm, which required fine-needle aspiration biopsy
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F I G U R E 7 Atypia of uncertain significance by pathology. This is a case of A-C, mostly isoechoic solid nodule with D, peripheral and central vascularity. Although >2 cm, this nodule possesses only nonspecific but concerning features. Review of clinical history and endocrine profile could aid the decision to perform fine-needle aspiration biopsy [Color figure can be viewed at wileyonlinelibrary.com]
stiff, as in vitro studies have shown a 10-fold greater stiffness of malignant neoplasms.47 Evidently, this is still subject to the confounding presence of thyroiditis and Hashimoto’s disease, due to increased tissue stiffness from the inflammatory processes.47 This novel method of independent prediction criteria showed 78.17% sensitivity, 50.00% specificity, and 75.24% accuracy in the previous study when combined with B-mode ultrasound.46 A prospective study of real-time elastography categorizing nodule stiffness based on a color scheme revealed those with hard tissue in >50% of the nodule had 81% sensitivity, 62% specificity, PPV 42%, NPV 91%, and OR of 6.9.48 When real-time elastography was combined with the presence of at least 1 traditional ultrasound feature, the results showed 97.0%, 34.0%, 33.0%, 97.0%, and 15.8 for the aforementioned measurements, respectively.48 This high sensitivity of 97.0% was reported in 2 other separate studies assessing tissue elastography.1,29 Ultimately, further studies will need to be conducted to fortify the applicability and efficacy of tissue elastography in assessing thyroid nodules for malignancy but early results show strong promise.
4 | DISCUSSION With the rising incidence but unchanged mortality rates of thyroid cancer, conservative management with greater emphasis on monitoring is the working clinical consensus on approach to the management of thyroid nodules. To successfully and safely achieve this, a high level of mutual understanding and continuity between the affiliated clinical and surgical experts, as well as a more rigorous risk stratification approach is needed. Table 2 illustrates these principles through a high consensus for suspicious ultrasound criteria between several major associations. However, these imaging features of malignant and benign thyroid diseases are often nonspecific. Microcalcifications, hypoechogenicity, irregular margins, taller-than-wide, extrathyroidal extension, and lymphadenopathy are independent features highly suggestive of malignancies. As only a limited number of findings is often seen, collaboration between specialties and corroboration of imaging, clinical, and endocrine features is required to avoid unnecessary FNA biopsies. Given the possible imaging and growth similarities between indolent thyroid
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F I G U R E 8 Suggested nodule management algorithm based on summary of current practice guidelines. FNA, fine-needle aspiration biopsy [Color figure can be viewed at wileyonlinelibrary.com]
cancer and benign disease, investigators should be mindful of insidious malignancies. Figure 8 illustrates an algorithmic approach to the initial investigation of thyroid nodules. As both multiple and small nodules have been shown to carry independent risks for malignancy, we feel both solid nodules and solid component of a cystic nodule >1 cm with malignant features warrants an FNA biopsy. Table 2 illustrates the high degree of continuity in malignant sonographic features, which we have incorporated as required stipulations for biopsy. For patients with nodules that do not possess any malignant sonographic features but contain a solid component, biopsy is suggested for any nodules >2 cm regardless of echogenicity. This is a more conservative threshold relative to the recent ATA guidelines. Given the increasing incidence and highly favorable prognosis of thyroid malignancy, in conjunction with burgeoning literature suggesting no difference in mortality from delayed diagnosis, we believe this approach will sufficiently capture suspicious thyroid nodules without overlooking large groups of insidious malignancies. Similarly, our more
conservative approach extends to low-risk thyroid nodules, as we feel an FNA biopsy is merited in spongiform nodules >4 cm. This is a more lenient threshold to the ATA recommendations of biopsy consideration, as aforementioned meta-analyses have shown particularly high ORs and specificity for benign characterization with this feature. Furthermore, as there is an increased likelihood of false-negative FNA biopsy results in larger thyroid nodules, we believe even purely cystic nodules >4 cm size warrant investigation. Patients who fulfill sonographic criteria but not size criteria for biopsy may be appropriately managed through risk-based serial observation for clinical, biochemical, or sonographic changes suggestive of malignancy. Of course, in any patients with indeterminate or ambiguous radiographic features, a more thorough review of clinical and endocrine background will help dictate the need for biopsy. Ultimately, through adaptation of contemporary investigation to reflect a greater understanding of thyroid malignancy incidence and prognosis, as well as an evidence-based appreciation of benign and malignant sonographic traits, the optimal goal of judicious management without
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overburdening healthcare providers and patients alike can be achieved. As evidence-based guidelines are available for workup of thyroid nodules, we believe this simple and practical algorithm can augment their management. O R CI D Jin Soo A. Song MD http://orcid.org/0000-0001-5416-7525 Adam A. Dmytriw MD http://orcid.org/0000-0003-0131-5699 R EF ERE NC ES [1] Aspinall SR, Ong SG, Wilson MS, Lennard TW. How shall we manage the incidentally found thyroid nodule? Surgeon. 2013; 11:96-104. [2] Brito JP, Morris JC, Montori VM. Thyroid cancer: zealous imaging has increased detection and treatment of low risk tumours. BMJ. 2013;347:f4706. [3] Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014;140: 317-322. [4] Morris LG, Tuttle RM, Davies L. Changing trends in the incidence of thyroid cancer in the United States. JAMA Otolaryngol Head Neck Surg. 2016;142:709-711. [5] Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016; 26:1-133. [6] Kulstad R. Do all thyroid nodules >4 cm need to be removed? An evaluation of thyroid fine-needle aspiration biopsy in large thyroid nodules. Endocr Pract. 2016;22:791-798.
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and Associazione Medici Endocrinologi Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules–2016 update. Endocr Pract. 2016;22:622-639. [15] Sharma A, Gabriel H, Nemcek AA, Nayar R, Du H, Nikolaidis P. Subcentimeter thyroid nodules: utility of sonographic characterization and ultrasound-guided needle biopsy. AJR Am J Roentgenol. 2011;197:W1123-W1128. [16] Pinchot SN, Al-Wagih H, Schaefer S, Sippel R, Chen H. Accuracy of fine-needle aspiration biopsy for predicting neoplasm or carcinoma in thyroid nodules 4 cm or larger. Arch Surg. 2009; 144:649-655. [17] Bomeli SR, LeBeau SO, Ferris RL. Evaluation of a thyroid nodule. Otolaryngol Clin North Am. 2010;43:229-238. [18] Hoang JK, Grady AT, Nguyen XV. What to do with incidental thyroid nodules identified on imaging studies? Review of current evidence and recommendations. Curr Opin Oncol. 2015;27:8-14. [19] Nishimori H, Tabah R, Hickeson M, How J. Incidental thyroid “PETomas”: clinical significance and novel description of the self-resolving variant of focal FDG-PET thyroid uptake. Can J Surg. 2011;54:83-88. [20] Lacout A, Thariat J, Chevenet C, Marcy PY. Management of thyroid nodules on US with benign or atypical cytological features. Diagn Interv Imaging. 2015;96:507-509. [21] Paschke R, Heged€us L, Alexander E, Valcavi R, Papini E, Gharib H. Thyroid nodule guidelines: agreement, disagreement and need for future research. Nat Rev Endocrinol. 2011;7:354361. [22] Hoang JK, Lee WK, Lee M, Johnson D, Farrell S. US Features of thyroid malignancy: pearls and pitfalls. Radiographics. 2007; 27:847-860; discussion 861-865. [23] Kim DW, Lee EJ, In HS, Kim SJ. Sonographic differentiation of partially cystic thyroid nodules: a prospective study. AJNR Am J Neuroradiol. 2010;31:1961-1966.
[7] Aschebrook-Kilfoy B, Schechter RB, Shih YC, et al. The clinical and economic burden of a sustained increase in thyroid cancer incidence. Cancer Epidemiol Biomarkers Prev. 2013;22: 1252-1259.
[24] Frates MC, Benson CB, Charboneau JW, et al. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Ultrasound Q. 2006;22: 231-238; discussion 239-240.
[8] Ito Y, Kakudo K, Hirokawa M, et al. Biological behavior and prognosis of familial papillary thyroid carcinoma. Surgery. 2009; 145:100-105.
[25] Moon WJ, Jung SL, Lee JH, et al. Benign and malignant thyroid nodules: US differentiation–multicenter retrospective study. Radiology. 2008;247:762-770.
[9] Burman KD, Wartofsky L. Thyroid nodules. N Engl J Med. 2016;374:1294-1295.
[26] Lee YS, Kim HK, Chang H, et al. Diagnostic thyroidectomy may be preferable in patients with suspicious ultrasonography features after cytopathology diagnosis of AUS/FLUS in the Bethesda System. Medicine (Baltimore). 2015;94:e2183.
[10] Kanona H, Virk JS, Offiah C, Stimpson P. Ultrasound-guided assessment of thyroid nodules based on the 2014 British Thyroid Association guidelines for the management of thyroid cancer how we do it. Clin Otolaryngol. 2017;42:723-727. [11] Moon WJ, Baek JH, Jung SL, et al. Ultrasonography and the ultrasound-based management of thyroid nodules: consensus statement and recommendations. Korean J Radiol. 2011;12:1-14. [12] Xie C, Cox P, Taylor N, LaPorte S. Ultrasonography of thyroid nodules: a pictorial review. Insights Imaging. 2016;7:77-86.
[27] Lim KJ, Choi CS, Yoon DY, et al. Computer-aided diagnosis for the differentiation of malignant from benign thyroid nodules on ultrasonography. Acad Radiol. 2008;15:853-858. [28] Na DG, Kim JH, Kim DS, Kim SJ. Thyroid nodules with minimal cystic changes have a low risk of malignancy. Ultrasonography. 2016;35:153-158.
[13] Chen AY, Bernet VJ, Carty SE, et al. American Thyroid Association statement on optimal surgical management of goiter. Thyroid. 2014;24:181-189.
[29] Remonti LR, Kramer CK, Leit~ao CB, Pinto LC, Gross JL. Thyroid ultrasound features and risk of carcinoma: a systematic review and meta-analysis of observational studies. Thyroid. 2015;25:538-550.
[14] Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology,
[30] Pan FS, Wang W, Wang Y, et al. Sonographic features of thyroid nodules that may help distinguish clinically atypical
SONG
ET AL.
|
13
subacute thyroiditis from thyroid malignancy. J Ultrasound Med. 2015;34:689-696.
nodules should be considered for repeat biopsy or surgery rather than follow-up? Ultrasonography. 2016;35:234-243.
[31] Jabiev AA, Ikeda MH, Reis IM, Solorzano CC, Lew JI. Surgeon-performed ultrasound can predict differentiated thyroid cancer in patients with solitary thyroid nodules. Ann Surg Oncol. 2009;16:3140-3145.
[41] Singh B, Shaha AR, Trivedi H, Carew JF, Poluri A, Shah JP. Coexistent Hashimoto’s thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery. 1999;126:1070-1076; discussion 1076-1077.
[32] Bhatki AM, Brewer B, Robinson-Smith T, Nikiforov Y, Steward DL. Adequacy of surgeon-performed ultrasound-guided thyroid fine-needle aspiration biopsy. Otolaryngol Head Neck Surg. 2008;139:27-31.
[42] Park YJ, Kim JA, Son EJ, et al. Thyroid nodules with macrocalcification: sonographic findings predictive of malignancy. Yonsei Med J. 2014;55:339-344.
[33] Chang Y, Paul AK, Kim N, et al. Computer-aided diagnosis for classifying benign versus malignant thyroid nodules based on ultrasound images: a comparison with radiologist-based assessments. Med Phys. 2016;43:554. [34] Bahl M, Sosa JA, Nelson RC, Hobbs HA, Wnuk NM, Hoang JK. Thyroid cancers incidentally detected at imaging in a 10year period: how many cancers would be missed with use of the recommendations from the Society of Radiologists in Ultrasound? Radiology. 2014;271:888-894. [35] Brito JP, Gionfriddo MR, Al Nofal A, et al. The accuracy of thyroid nodule ultrasound to predict thyroid cancer: systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99: 1253-1263.
[43] Lee EK, Chung K-W, Min HS, et al. Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules. J Korean Med Sci. 2012;27:1014-1018. [44] Khoncarly SM, Tamarkin SW, McHenry CR. Can ultrasound be used to predict malignancy in patients with a thyroid nodule and an indeterminate fine-needle aspiration biopsy? Surgery. 2014; 156:967-970. [45] Burch HB, Burman KD, Cooper DS, Hennessey JV, Vietor NO. A 2015 survey of clinical practice patterns in the management of thyroid nodules. J Clin Endocrinol Metab. 2016;101:2853-2862. [46] Migda B, Słapa R, Bierca J, et al. Differentiation of thyroid nodules in multinodular goiter with the application of technical ultrasound advances - initial results. Endokrynol Pol. 2016;67:157-165.
[36] Zhang J, Chen Z, Anil G. Ultrasound-guided thyroid nodule biopsy: outcomes and correlation with imaging features. Clin Imaging. 2015;39:200-206.
[47] Azizi G, Keller J, Lewis M, Puett D, Rivenbark K, Malchoff C. Performance of elastography for the evaluation of thyroid nodules: a prospective study. Thyroid. 2013;23:734-740.
[37] Beech P, Lavender I, Jong I, et al. Ultrasound stratification of the FDG-avid thyroid nodule. Clin Radiol. 2016;71:164-169.
[48] Trimboli P, Guglielmi R, Monti S, et al. Ultrasound sensitivity for thyroid malignancy is increased by real-time elastography: a prospective multicenter study. J Clin Endocrinol Metab. 2012; 97:4524-4530.
[38] Perros P, Boelaert K, Colley S, et al. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf). 2014;81 Suppl 1: 1-122. [39] Henrichsen TL, Reading CC, Charboneau JW, Donovan DJ, Sebo TJ, Hay ID. Cystic change in thyroid carcinoma: prevalence and estimated volume in 360 carcinomas. J Clin Ultrasound. 2010;38:361-366. [40] Eun NL, Yoo MR, Gweon HM, et al. Thyroid nodules with nondiagnostic results on repeat fine-needle aspiration biopsy: which
How to cite this article: Song JSA, Dmytriw AA, Yu E, et al. Investigation of thyroid nodules: A practical algorithm and review of guidelines. Head & Neck. 2018;00:1–13. https://doi.org/10.1002/hed.25160
