Ultrasonography (USG) is a non-invasive and widely available diagnostic tool in the evaluation of focal thyroid lesions. The main limitation associated with the modality is the subjectivity of assessment of ultrasound features and the fact that it is impossible to visualise structures located retrosternally(1). It is characterised by relatively low diagnostic sensitivity for particular ultrasound features in estimating the malignant potential of focal lesions (27–63%), with high specificity reported for features including microcalcifications (87.8%), central vascularisation (78%), irregular margins (83.2%), shape higher than wider (96%), use of elastography (86.2%)(2). In 2009, Horvath
The TIRADS classification is intended to have a high sensitivity and thus exclude low-risk lesions from biopsy and minimise the proportion of false-negative lesions. However, it should be noted that in addition to sensitivity, it is important to obtain the highest possible level of specificity, in order to eliminate over-diagnosing and treating patients who do not actually need it. Unfortunately, there is no perfect tool with sensitivity and specificity levels equal to 100%, so it is essential to compare different classifications and adapt the best one to the diagnostic needs in a given population.
In this publication, the authors present a review of the literature based on meta-analyses on the most frequently cited TIRADS classifications.
The EU-TIRADS classification was introduced in 2017 and presented as a guideline by the European Thyroid Association (ETA)(4). This scoring system is derived from the French classification, which was prospectively validated before its introduction, and its high diagnostic value was confirmed by Yoon
EU-TIRADS 1, normal parenchyma (cross-section of the right lobe)
EU-TIRADS 2, spongiform lesion
EU-TIRADS 4, solid hypoechogenic lesion. CD imaging shows marginal and central vascularisation
EU-TIRADS 2, simple cyst
EU-TIRADS 3, solid isoechogenic lesion with hypoechogenic halo
EU-TIRADS 5, solid hypoechogenic lesion with bright echoes (microcalcifications), uneven margins, irregular in shape
EU-TIRADS classification according to the recommendations of the European Thyroid Association (2017)
Category EU-TIRADS | Type of change | Risk of malignancy | Indications for biopsy |
---|---|---|---|
1 | without focal changes | close to 0% | not recommended |
2 | anechogenic mixed solid-cystic with spongiform structure | close to 0% | not recommended (exception: therapeutic biopsy in symptomatic patients, e.g. cyst emptying) |
3 | oval shape isoechogenic regular or margins hyperechogenic without high-risk ultrasound features | 2–4% | >20 mm |
4 | oval shape slightly regular hypoechogenic margins without high-risk ultrasound features | 6–17% | >15 mm |
5 | deeply hypoechogenic shape irregular other margins than oval microcalcifications | 26–87% | >10 mm |
The actual performance of the EU-TIRADS classification has also been tested on the Polish population. It was first
evaluated by Skowrońska
Another study conducted to verify the diagnostic efficacy of the EU-TIRADS RSS (Risk Stratification Scale) in the Polish setting was a multi-centre study published by Dobruch-Sobczak
A recently published paper including 80 patients supported the idea of active surveillance of TN <1 cm classified as EU-TIRADS 5(11). Sixteen (20.0%) of these patients underwent surgery after a median follow-up of 57.2 months, which confirmed the diagnosis of PTC in 15 out of 16 cases, and all were in remission after a follow-up of 6–12 months. The results suggest good accuracy of the EU-TIRADS 5 category in the classification of malignant TNs even <1 cm in diameter, and the possibility of careful monitoring for TNs classified as EU-TIRADS 5(11).
The largest published multi-centre study undertaken to date with a view to evaluating the diagnostic performance of EU-TIRADS with respect to histopathology was that conducted by Trimboli
One recent study by Kovatcheva
In conclusion, the EU-TIRADS system is a simple and valuable RSS with a very good level of sensitivity, easy to incorporate into clinical practice. Its main strength lies in very high NPV, which contributes to reducing the number of FNABs.
In 2017, the American College of Radiology (ACR), in collaboration with the American Association of Clinical Endocrinologists (AAEC) and the American Thyroid Association (ATA), developed a practical ultrasound system for assessing the malignancy risk of thyroid nodules, called the ACR Thyroid Imaging, Reporting and Data System (ACR-TIRADS)(17). The concept is based on the commonly and widely used BIRADS system for the assessment of focal breast lesions(18). The primary goal of the ACR-TIRADS classification, as well as other ultrasound RSSs, is to identify among TNs those which, based on the ultrasound findings, raise suspicion of neoplastic lesion and thus require deeper diagnostics and additional
procedures, most often using FNAB. Additionally, the classification helps to standardise the conclusions arising from the interpretation of ultrasound images, thus improving and streamlining communication between ultrasound technologists and clinicians, while contributing to a reduction in over-performed FNAB.
ACR-TIRADS, unlike other scales, is based on a unique scoring classification. Of the five categories of ultrasound features, individual elements – morphology, echogenicity, shape, margins, and microcalcifications – are evaluated and assigned a value of 0 to 3 points, with a higher score being associated with a higher risk of malignancy (Tab. 2). The total score determines the TIRADS malignancy risk (TR) divided into the following categories: TR1 – benign (0 point), TR2 – not suspicious (2 points), TR3 – slightly suspicious (3 points), TR4 – moderately suspicious (4–6 points) and TR5 – highly suspicious (≥7 points). The combined assessment of TR grade and maximum lesion diameter determines further management, which may be invasive (FNAB) or observation. The estimated risk of malignancy in each group is: <2% for TR1 and TR2, <5% for TR3, ranging from 5.1% to 20% for TR4 and >20% for TR5. In addition, ACR-TIRADS is part of a new interactive online algorithm, called TNAPP (Thyroid Nodule App), which was presented at the American Association for Clinical Endocrinology annual conference in 2021(19). The innovation of TNAPP is based on combining clinical factors, ultrasound and FNAB features and provide clear suggestions for further management of TNs.
ACR TI-RADS classification – ultrasound features and their score values
Ultrasound features | Ultrasound scoring characteristics |
---|---|
Morphology | cystic = 0 |
spongiform = 0 | |
mixed cystix and solid = 1 | |
solid = 2 | |
indeterminate = 2 | |
Echogenicity | anechogenic = 0 |
isoechogenic = 1 | |
hyperechogenic = 1 | |
heterogeneous = 1 | |
hypoechogenic = 2 | |
deeply hypoechogenic = 3 | |
Shape | wider than tall = 0 |
taller and wide = 3 | |
Margins/borders | smooth = 0 |
ill-defined = 0 | |
cannot be determined = 0 | |
lobulated or irregular = 2 | |
extra-thyroidal extension = 3 | |
Hyperechogenic | none = 0 |
areas | comet tail artefacts = 0 |
macrocalcifications = 1 | |
peripheral (rim) calcifications = 2 | |
punctate echogenic foci (microcalcifications) = 3 |
The diagnostic value of ACR-TIRADS has been confirmed in a number of recent studies. In a meta-analysis published by Li
In conclusion, ACR-TIRADS is a well-established, valuable tool used in the assessment of TN malignancy risk that provides extensive and detailed lesion characterisation with clear management recommendations, thus avoiding unnecessary FNABs. The main disadvantage of this system when used in daily clinical practice is that it is quite time-consuming to use, particularly for novice clinicians.
In 2016, the Korean Society of Thyroid Radiology (KSThR) presented the K-TIRADS classification and recommendations, describing the terminology and symptomatology of ultrasound imaging of focal thyroid lesions(21). These ultrasound image features were used to develop the K-TIRADS classification and recommendations for each category. In addition to the B-mode image, the authors also detailed the vascularisation types of focal lesions and the potential role of sonoelastography in the differential diagnosis of TNs, but did not include them in the classification itself due to the divergent results presented in the literature. The classification itself is based on the ultrasonographic features of the B-mode image. The following were considered suspicious features: microcalcifications, vertical shape of the lesion, spiculated/microlobulated margins(21). K-TIRADS 1 corresponds to healthy thyroid parenchyma without focal lesions. K-TIRADS 2 should be assigned to cysts, partially cystic lesions with comet tail artefacts present, and spongiform nodules. Partially cystic lesions that are iso-, hyperechogenic or of mixed echogenicity (iso-/hyper-) without any of the ultrasound suspicious features are assigned to category “3”, while lesions with any of the suspicious features present are assigned to category “4”. Similarly, category 4 is assigned to solid, hypoechogenic lesions without suspicious features. K-TIRADS 5 refers to solid hypoechogenic lesions with at least one suspicious feature present. Further management of focal lesions depends on their size (referring to the largest dimension)(21):
Category 2:
spongiform lesions, FNAB ≥2 cm (risk of malignancy, RA <3%), partially cystic lesions with comet tail artefacts present, FNAB not recommended (RA <1%),
Category 3: FNAB ≥1.5 cm (RA 3–15%),
Category 4: FNAB ≥1 cm (RA 15–30%),
solid hypoechogenic focal lesion without suspicious features, partially cystic or iso-/hyperechogenic lesion with any suspicious feature present,
Category 5: FNAB ≥1 cm or selectively lesions >5 mm (RA >60%).
Compared to ACR-TIRADS, the K-TIRADS classification seems more intuitive, however it should be remembered that ACR-TIR ADS allows (and also requires) a more objective assessment (analysis) of each individual lesion (in contrast to K- and EU-TIRADS). Moreover, it should be noted that focal lesions with suspicious features, with mixed or solid structure and iso-/hyperechogenic in the K-TIRADS classification are in category 4(21) as in ACR-TIRADS(17)classification, whereas in the EU-TIR ADS classification they are assigned to 5(4). K-TIRADS, like EU-TIRADS, do not consider macro-calcifications, annular calcifications and infiltration beyond the thyroid capsule as higher risk features in contrast to ACR-TIRADS, thus omitting quite important TN features considered suspicious in the literature. Another discrepancy among the classification is seen in the cut-off thresholds for the size of nodules referred for FNAB. The authors of K-TIRADS recommend cytological verification in categories 4 and 5 for lesions measuring ≥10 mm, noting the possibility of selective FNAB in category 5 for lesions >5 mm in size. For EU-TIRADS and ACR-TIRADS category 4, FNAB is recommended if the lesion is >15 mm in size and >10 mm in category 5(4,17,21). In the meta-analysis by Kim
Comparison of the diagnostic parameters of the K-, ACR-and EU-TIRADS classifications against the cut-off point for category 5(22)
Category 5 | Sensitivity (%) | Specificity (%) |
---|---|---|
K-TIRADS | 64 | 93 |
ACR-TIRADS | 70 | 89 |
EU-TIRADS | 78 | 89 |
Comparison of diagnostic parameters of the K-, ACR- and EU-TIRADS classification in relation to the cut-off point for category 4 or 5(22)
Category 4 or 5 | Sensitivity (%) | Specificity (%) |
---|---|---|
K-TIRADS | 92 | 61 |
ACR-TIRADS | 95 | 49 |
EU-TIRADS | 96 | 48 |
Comparison of diagnostic parameters of K-, ACR- and EU-TIRADS classification in relation to the cut-off point for category 5(23)
Category 5 | Sensitivity (%) | Specificity (%) |
---|---|---|
K-TIRADS | 55 | 95 |
ACR-TIRADS | 66 | 91 |
EU-TIRADS | 82 | 90 |
Comparison of diagnostic parameters of the K-, ACR- and EU-TIRADS classification in relation to the cut-off point for category 4 or 5(23)
Category 4 or 5 | Sensitivity (%) | Specificity (%) |
---|---|---|
K-TIRADS | 89 | 64 |
ACR-TIRADS | 95 | 55 |
EU-TIRADS | 96 | 52 |
The discussion on the TIRADS classification should also include the problem of fine-needle biopsy and, more specifically, the percentage of unnecessary procedures generated by each classification. This aspect is further discussed in the following meta-analysis(24). In this study, the authors indicate that the K-TIRADS classification is characterised by a high percentage of unnecessary biopsies: 55%. The lowest percentage characterises the ACR-TIRADS classification (25%), significantly lower than for K-TIRADS (
classification and applying them to the K-TIRADS and EU-TIRADS classifications will reduce the proportion of unnecessary FNAB(25). However, it is important to note that a reduction in so-called unnecessary biopsies is not necessarily a desirable solution. It may entail an increase in the percentage of undiagnosed tumours, which may negatively affect the survival curve of patients with thyroid cancer. Based on meta-analyses alone, it is difficult to draw a definitive conclusion on the rate of unnecessary biopsies. The economic element, i.e. the percentage of unnecessary biopsies and thus the possible rate of false positives with their consequences that researchers are willing to accept, may be a factor that facilitates the decision.
The aim of this analysis is to evaluate the application of five major classifications: ACR-TIRADS (American College of Radiology guidelines), ATA (American Thyroid Association guidelines), Kwak-TIR ADS, K-TIR ADS (Korean Thyroid Association/Korean Society of Thyroid Radiology (KTA / KSThR) guidelines) (K-TIR ADS is a development of the Kwak-TIRADS classification), and EU-TIRADS (European Thyroid Association (ETA) guidelines) in estimating the malignancy potential of focal thyroid lesions. Over the last few years, a number of studies have been published comparing the use of the TIRADS classification in the assessment of the malignancy risk of focal thyroid lesions, selected elements of which are presented in the following summary.
Yang
Sensitivity, specificity, LR(+), LR(-), DOR, AUC for individual TIRADS qualifications
TIRADS classification | Number of tests | Sensitivity (95% CI) | Specificity (95% CI) | LR(+) (95% CI) | LR(-) (95% CI) | DOR (95% CI) | AUC |
---|---|---|---|---|---|---|---|
ACR-TIRADS | 13 | 0.85 (0.84–0.86) | 0.68 (0.6–0.69) | 2.98 (2.37–3.75) | 0.22 (0.16–0.29) | 15.23 | 0.8553 |
EU-TIRADS | 4 | 0.85 (0.83–0.87) | 0.61 (0.59–0.62) | 2.84 (1.43–5.64) | 0.21 (0.13–0.34) | 13.18 | 0.8810 |
K-TIRADS | 4 | 0.85 (0.83–0.86) | 0.47 (0.46–0.48) | 2.60 (1.2–5.57) | 0.18 (0.08–0.39) | 14.57 | 0.9022 |
Kwak-TIRADS | 6 | 0.94 (0.94–0.95) | 0.62 (0.6–0.63) | 3.23(0.90–11.61) | 0.08 (0.04–0.16) | 43.15 | 0.9101 |
CI – confidence interval; LR(+) – positive likelihood ratio; LR(-) – negative likelihood ratio; DOR – diagnostic odds ratio; AUC – area under the ROC curve
In contrast, the head-to-head comparison method yielded relative diagnostic odds ratio RDOR values of 1.57 (ACR vs ATA), 1.37 (ACR vs EU), 1.8 (ACR vs Kwak), 1.74 (ARC vs K), which distinguishes ACR-TIRADS in the analysis (Tab. 8). The authors of the study further highlighted the differences in the TIRADS classification system. ACR and Kwak-TIRADS are based on point classification, whereas the others categorise focal lesions based on sonographic patterns, which in clinical practice seems to be a more intuitive procedure, but associated with lower test accuracy. For example, the EU-TIRADS category 5 or 4 may correspond to ACR-TIRADS TR4/3 or K-TIRADS TR4/3, whereas focal lesions classified as K-TIRADS TR3 and EU-TIRADS category 3 (low risk of malignancy) may be categorised as ACR-TIRADS TR2, meaning no suspicion of malignancy. These differences in eligibility criteria,
Head-to-head comparison of relative diagnostic odds ratio (RDOR) with CI 95%
ACR-TIRADS | EU-TIRADS | K-TIRADS | Kwak-TIRADS | |
---|---|---|---|---|
ACR-TIRADS | - | 0.7308 (0.3000–1.7803) | 0.5734 (0.2759–1.1919) | 0.5564 (0.2552–1.2131) |
EU-TIRADS | 1.3683 (0.5617–3.3332) | - | 0.7846 (0.3075–2.0020) | 0.7614 (0.2498–2.3208) |
K-TIRADS | 1.7439 (0.8390–3.6247) | 1.2745 (0.4995–3.2518) | - | 0.9703 (0.3697–2.5466) |
Kwak-TIRADS | 1.7972 (0.8243–3.9183) | 1.3138 (0.4309–4.0035) | 1.0306 (0.3927–2.7048) | - |
RDOR – relative diagnostic odds ratio; CI – confidence interval
which also take into account the size of the lesion, lead to differences in the specificity of the methods used. On the basis of the meta-analysis performed for ACR-TIRADS, the highest diagnostic accuracy in estimating the risk of malignancy and related limitation of indications to perform FNAB were noted(26). The authors point out certain limitations of the meta-analysis, including the lack of histopathological verification for each analysed focal lesion. Another limitation of the study was the numerical difference of lesions with malignant potential qualified for the analysis, moreover, there were no sufficient data related to the comparative analysis using K-TIRADS and EU-TIRADS. Also noteworthy is the limitation due to the incompatibility of ultrasound results obtained by different investigators and by the same investigator (inter-observer and intra-observer variability)(27). Conclusions from the presented meta-analysis emphasize the clinical usefulness and confirm the validity of recommending the use of TIRADS classification in estimating the malignancy potential of focal thyroid lesions, with an emphasis on the highest accuracy of the method for ACR-TIRADS.
Similar results on the benefits of using the ACR-TIRADS classification were obtained by Castellana
In a subsequent study by Kim
In a subsequent meta-analysis of 29 papers evaluating a total of 33,748 focal thyroid lesions, Kim
Kim
The presented findings of the meta-analyses prove the diagnostic utility of the TIRADS classification in estimating the risk of malignancy of focal thyroid lesions and confirm the validity of recommending its applications in clinical practice. A head-to-head statistical analysis of the available data provides evidence for the superiority of the ACR-TIRADS classification, which also translates into minimising the number of unnecessary FNAB. However, in order to draw more far-reaching conclusions, it is necessary to conduct more studies using individual TIRADS classifications (including EU-TIRADS, K-TIRADS), taking into account the limitations presented above related to the heterogeneity of the groups subjected to the analysis. An advantage of the EU-TIRADS scale is that it includes only the most important ultrasound features, so its use is not time-consuming, and the scale is easy to apply in clinical practice. The application of the system would facilitate reporting of the thyroid ultrasound result and could improve TN qualification for FNAB.