Diagnostic value of 2017 ACR Thyroid Imaging Reporting and Data System (TI-RADS) combined with fine needle aspiration biopsy in thyroid nodules

Abstract

OBJECTIVE:

To evaluate diagnostic value of Thyroid Imaging Reporting and Data System published by American College of Radiology (ACR TI-RADS) in 2017, ultrasound-guided fine-needle aspiration (US-FNA), and the combination of both methods in differentiation between benign and malignant thyroid nodules.

METHODS:

The data of US-FNA and ACR TI-RADS are collected from 159 patients underwent thyroid surgery in our hospital, which include a total of 178 thyroid nodules. A Bethesda System for Reporting Thyroid Cytopathology category of ≥IV and an ACR TI-RADS category ≥4 are regarded as diagnosis standards for malignancy in US-FNA and ACR TI-RADS, respectively. The pathological results after surgery are considered as the gold standard. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the ACR TI-RADS, US-FNA and the combination of both methods for the differential diagnosis of thyroid nodules are calculated, respectively.

RESULTS:

The sensitivity, specificity and accuracy of ACR TI-RADS are 85.4%, 37.5%and 72.5%, respectively. The sensitivity, specificity and accuracy of US-FNA are 70.0%, 100%and 78.1%, respectively. After combining these two methods, the sensitivity, specificity and accuracy increase to 99.23%, 37.50%and 82.58%, respectively. The sensitivity of ACR TI-RADS is higher than that of US-FAN, and the sensitivity of combining these two methods is also higher than that of using ACR TI-RADS and US-FNA alone.

CONCLUSION:

The established ACR TI-RADS can help in selecting the target during nodule puncture, while the combination of ACR TI-RADS and US-FAN can further improve diagnostic ability for detecting malignant thyroid nodules.

Keywords

ACR TI-RADS ultrasound imaging fine-needle aspiration biopsy (FNAB)thyroid nodule differential diagnosis

1 Background

Thyroid nodules can be caused by a variety of reasons, such as thyroid degeneration, inflammation, autoimmunity and formation of neoplasm [1]. In recent years, the detection rate of thyroid diseases has increased year by year. Furthermore, approximately 85%–95%of these are benign, while most of these do not need treatment [2]. However, due to ignorance by patients, its incidence is high. Thus, it is very important to make an effective differential diagnosis of benign and malignant thyroid nodules, which may enable for the early treatment of malignant nodules [3].

The guidelines of the American Thyroid Association recommend that all patients undergoing thyroid surgery needs to undergo a routine ultrasound examination before surgery. Ultrasound is the primary method for distinguishing and diagnosing benign and malignant thyroid nodules [4]. In 2017, the American College of Radiology (ACR) established a new Thyroid Imaging Reporting and Data System (TI-RADS) based on the characteristics of conventional two-dimensional ultrasound, which provides a specific standard for the differentiation between benign and malignant thyroid nodules. This classification system is simple and has strong operability [5]. The scoring methods of ACR TI-RADS in these five aspects do not have high requirements for both ultrasound instruments and doctors. Unlike other imaging modalities like CT and MRI), quality of ultrasound images varies among the clinicians. It will affect the diagnostic results of using ACR TI-RADS. This method provides doctors with a relatively objective scoring index, which is easier to master, and standardizes the treatment of thyroid nodules, in order to prevent excessive medical treatment [6]. Its sensitivity is 77.6%, specificity is 83.0%, accuracy is 82.1%[5].

Ultrasound-guided fine-needle aspiration (US-FNA) is a relatively safe examination method, which can often clarify the pathological nature of nodules [7]. Thyroid needle biopsy (FNA) is an important method to evaluate benign and malignant thyroid nodule preoperatively and to effectively reduce the need for diagnostic surgery. It can effectively increase the rate of malignant tumor in thyroid surgery to 50%[1 –3]. After FNA cytological examination in our unit, the rate of malignant tumors in surgical cases increased to 74.0%[4]. There are currently diagnostic systems in four countries namely, United Kingdom, Italy, United States (USA) and Japan [5]. In 2007, The Bethesda System for Reporting Cytopathology is organized by The National Cancer Institute. It is officially published in 2009. It got its name from the editorial board meeting in Bethesda, USA [1]. However, it is an invasive procedure, and is prone to cause false positivity or false negativity [8].

Our hypothesis is that ACR TI-RADS can help in selecting the target during nodule puncture; the combination of ACR TI-RADS and US-FAN can improve the diagnostic ability for thyroid malignant nodules. Thus, the present study mainly focuses in discussing the value of ACR TI-RADS, US-FNA and the combination of these two methods in the differential diagnosis of thyroid nodules, with the aim of providing a better method for the differential diagnosis of benign and malignant thyroid nodules, and providing more reference for clinicians.

2 Methods

2.1 Study subjects

From September 2016 to December 2018, 159 patients with thyroid nodules, who underwent thyroid surgery in Shanxi Provincial People’s Hospital, are included in the present study, with a total of 178 thyroid nodules. Among these patients, 139 patients are female and 39 are male, and their age ranged within 18–74 years old, with an average age of 48.09±11.92 years old. The maximum diameter of the nodules ranged within 0.50–0.62 cm. All patients received a conventional ultrasound and US-FNA biopsy to obtain the corresponding pathological results before surgery.

The exclusion criteria are as follows: (1) patients with bleeding tendency, such as abnormal coagulation function; (2) patients allergic to drugs; (3) patients with signs of a pure cystic thyroid nodule by ultrasound; (4) patients with infection at the site of the puncture. The present study is approved by the Ethics Committee of our hospital.

2.2 Apparatus and methods

A GE LOGIQ E9 color Doppler ultrasound diagnostic instrument is used with a linear array probe of 6–15 L and a probe frequency of 6–15 MHZ. The conventional ultrasonic examination methods are as follows: The patient is required to remove the pillow, lie on their back, and keep their neck backwards, in order to fully expose the anterior area of the neck. Then, the selected thyroid nodules are scanned and imaged, and the target nodules are evaluated according to the 2017 ACR TI-RADS. The above-mentioned nodules are graded according to the five sonographic features (the characteristics of structure, echo, shape, edge and local hyperecho), which are graded as 0, 2, 3, 4–6 and ≥7, respectively. A TI-RADS category of ≥4 by conventional ultrasound is regarded as malignant diagnostic criterion. ACR uses 5 scores of the images, including structure, echo, morphology, margin and regional high echo. TI-RADS 1 means the nodule is cystic and horizontal with smooth margin. TI-RADS 2 means the nodule is cystic but has become calcification, and horizontal with smooth margin. TI-RADS 3 means the nodule is solid with high-echo, and horizontal with smooth margin, or the nodule is solid cystic, the solid part has calcificated and smooth margin. TI-RADS 4 means the nodule is solid with low-echo, and horizontal with smooth margin, or the nodule is solid cystic, the solid part has calcificated and smooth margin. TI-RADS 5 means the nodule is solid with low-echo, aspect ratio ≥1, and horizontal with rough margin, and/or invasion to the tissues outside the thyroids.

The methods for US-FNA are as follows: The patient positioned in the supine position, and the neck is fully exposed and covered by a disinfected towel. After local anesthesia with 2%lidocaine, a puncture needle of 23G is inserted under real-time ultrasound guidance. A Bethesda System for Reporting Thyroid Cytopathology category of ≥IV is regarded as the criterion of malignant diagnosis in US-FNA.

Nodules are graded according to their structure, echo, morphology, margin, and focal strong echo as below.

Structure: 0 points for cystic or almost completely cystic nodules, 0 point for spongy structures, 1 point for mixed cystic solid, 2 points for solid or almost completely solid.

Echo: no echo is 0 point, high echo or equal echo is 1 point, low echo is 2 points, and very low echo is 3 points.

Morphology: horizontal bit is 0 point (aspect ratio < 1), and vertical bit is 3 points (aspect ratio > 1).

Edge: smooth is 0 point, fuzzy is 1 point, lobulated or irregular is 2 points and external thyroid invasion is 3 points.

Focal strong echo: no or large comet tail is 0 point, coarse calcification is 1 point, marginal calcification is 2 points, and dot strong echo is 3 points.

Grading: 0 points TI-RADS 1 benign, no NEED for FNA; 2 points TI-RADS 2 no suspicious, no NEED for FNA; 3 points TI-RADS 3, nodules ≥2.5 cm in diameter, FNA is recommended; FNA is recommended for 4∼6 points TI-RADS 4 nodules ≥1.5 cm in diameter. FNA is recommended for patients with ≥7 points TI-RADS 5 and nodules≥1.0 cm diameter. (For nodules < 1.0 cm, puncture is performed according to clinical requirements).

US-FNA: According to the standards of the Bethesda reporting System for thyroid cytopathology, the cytological diagnosis results are divided into 6 categories: Category I, where the specimens are undiagnosable or unsatisfactory; Class II, benign lesions; Class III, atypical cellular or follicular lesions of undefined significance; Class IV, follicular tumors or suspected follicular tumors; Class V, suspected malignancy; Class VI, malignant tumor.

2.3 Statistical data analysis

The SPSS 20.0 software is used for the statistical analysis. Counting data are expressed in percentage, and measurement data is presented as x±standard deviation (SD). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of ACR TI-RADS, US-FNA and the combination of both methods for the differential diagnosis of thyroid nodules are respectively calculated. Paired chi-square test is used for comparisons. P < 0.05 is considered statistically significant.

3 Results

3.1 Pathological results of thyroid nodules after surgery

Among the 178 thyroid nodules, 48 nodules are benign. These included 35 nodular goiters, nine nodular goiters with adenomatous nodules, and four nodular goiters with cystic nodules. The remaining 130 nodules are malignant nodules. These included 126 papillary carcinomas, three medullary carcinomas and one thyroid follicular carcinoma. TI-RADS 1 (< 2%of all subjects); TI-RADS 2 (< 2%of all subjects); TI-RADS 3 (< 5%of all subjects); TI-RADS 4 (5%–20%of all subjects); TI-RADS 5 (> 20%of all subjects) (Figs. 1 –5).

Fig. 1

ACR TI-RADS score is 4 points, US-FNA Bethesda classification is grade II, and the surgical pathology is thyroid adenoma. Both US-FNA and ACR TI-RADS scores are true.

Fig. 2

ACR TI-RADS score is 8, US-FNA Bethesda classification is V, surgical pathology is papillary thyroid carcinoma, both US-FNA and ACR TI-RADS scores are true.

Fig. 3

ACR TI-RADS score is 9 points, and the US-FNA Bethesda classification is grade III. The surgical pathology is micropapillary thyroid carcinoma, and the US-FNA is false negative for the nodules, which is corrected by ACR TI-RADS score in combination.

Fig. 4

ACR TI-RADS score is 6 points, and the US-FNA Bethesda classification is grade III. The surgical pathology is nodular goiter, and ACR TI-RAD score of the nodule is too high, which is corrected by us-FNA combined.

Fig. 5

ACR TI-RADS score is 4, US-FNA Bethesda classification is V, surgical pathology is medullary thyroid carcinoma, the nodules had low ACR TI-RAD score, which is corrected by us-FNA combined.

3.2 The diagnostic value of the combination of the ACR TI-RADS by conventional ultrasound and US-FNA for thyroid nodules

The sensitivity of the ACR TI-RADS, US-FNA and the combination of both methods is 85.38%, 70.00%and 99.23%, respectively. The sensitivity of ACR TI-RADS is higher than that of US-FNA, and the difference is statistically significant (P = 0.011). The sensitivity of the combination of both methods is higher than that of the former two, and the difference is statistically significant (P < 0.001). A total of 129 malignant nodules are diagnosed by the combination of these two methods. As shown in Tables 1 2, the positive predictive value, negative predictive value, sensitivity, specificity and accuracy of the combination of ACR TI-RADS and US-FNA for diagnosing thyroid nodules is 81.13%, 94.74%, 99.23%, 37.50% and 82.58%, respectively.

Table 1
The pathological results after surgery for thyroid nodules and the diagnostic value of the combination of ACR TI-RADS and FNA in evaluating benign and malignant thyroid nodules

Methods of examination Surgical pathology Sensitivity Specificity Accuracy Positive predictive value Negative predictive value

Malignant Benign

ACR Positive 111 30 85.38% 37.50% 72.47% 78.72% 48.65%

Negative 19 18

Cytodiagnosis Positive 91 0 70.00% 100.00% 78.09% 100.00% 55.17%

Negative 39 48

Combination of the above two Positive 129 30 99.23% 37.50% 82.58% 81.13% 94.74%

Negative 1 18

Methods of examination		Surgical pathology	Sensitivity	Specificity	Accuracy	Positive predictive value	Negative predictive value
ACR	Positive	111	30	85.38%	37.50%	72.47%	78.72%	48.65%
	Negative	19	18
Cytodiagnosis	Positive	91	0	70.00%	100.00%	78.09%	100.00%	55.17%
	Negative	39	48
Combination of the above two	Positive	129	30	99.23%	37.50%	82.58%	81.13%	94.74%
	Negative	1	18

Table 2

The diagnostic rate of the combination of ACR TI-RADS and FNA in evaluating benign and malignant thyroid nodules

Sensitivity Cytodiagnosis				Specificity Cytodiagnosis
		+	–			+	–
ACR	+	73	38	ACR	+	0	26
	–	18	1		–	0	22
ACR	+	111	0	ACR	+	26	0
	–	18	1		–	0	22
Cytodiagnosis	+	91	0	Cytodiagnosis	+	0	0
	–	38	1		–	26	22

ACR: American College of Radiology.

4 Discussion

In the new TI-RADS published by ACR in 2017, further guidance is provided for US-FNA: fine-needle aspiration (FNA) is recommended for nodules of TI-RADS category 3, with a maximum nodule diameter of ≥2.5 cm; FNA is recommended for nodules of TI-RADS category 4, with a maximum nodule diameter of ≥1.5 cm; FNA is recommended for nodules of TI-RADS category 5, with a nodule diameter of ≥1.0 cm [9 –11]. In the present study, 81 nodules are classified into four categories, according to the ACR TI-RADS, and nodules with a score ranging within 4–6 are categorized as category 4.

A study revealed that the sensitivity and specificity of US-FNA in the differential diagnosis of thyroid nodules ranged within 65%–98%and 72–100%, respectively [12]. The results of the present study are consistent with the reports of the above literature. In the present study, nine cases had small nodules, and the puncture needle entered the surrounding normal thyroid gland tissue by mistake, resulting in a small number of positive cells, and the pathological result is a large number of tissue cells. In three cases, there are many calcifications in the nodules. This affected the routes of puncture or prevented the needle from entering the nodule. Hence, the positive cells are not enough for the analysis. Two cases are cystic solid nodules. Due to the viscosity of the cystic part, it is difficult to distinguish the cystic and solid part on the ultrasound image. Furthermore, although the cystic liquid is extracted, the cell content is still not adequate. Thyroid follicular carcinoma is diagnosed in two cases by post-operative pathology. The thyroid cell pathology is classified as Bethesda III. The diagnosis in one case might have been affected by the atypical cytology, and the other case is misdiagnosed due to too few positive cells through punctures. A definite diagnosis is not obtained in 20 cases, which may be correlated to the nature of the nodule itself. The small blood vessels are injured in the nodules with rich blood supply during the puncture, which resulted in more blood components and unsatisfactory diagnostic results. The needle could not be repositioned and moved when thick nodules are punctured, causing the lack of positive cell components. The reason might also be correlated to the experience of the puncture operator. The repeated lifting and insertion of the needles can lead to more blood components in the puncture needle. Thus, US-FNA also needs to be combined with other examinations, in order to obtain a more accurate diagnosis, and make a comprehensive judgment of the thyroid nodules.

In the present study, the diagnostic accuracy for nodules with ACR TI-RADS category 4 is 69.5%(48/69). Most of these nodules are characterized by solid hypoechoic sonography, which is common in clinic. The diagnostic accuracy for nodules with ACR TI-RADS category 5 is 71.4%(5/7), and these nodules are solid hypoechoic nodules with coarse calcifications. There have been different opinions on the degree of malignant risk of such nodules, especially for nodules without malignant signs [13, 14]. The diagnosis for nodules with ACR TI-RADS category 6 is 100%(5/5). Among the six cases, three cases are cystic solid with microcalcifications, while two cases are hypoechoic solid nodules with peripheral calcification. Some researchers have suggested that a ring calcification or an arc calcification has a higher correlation with the degree of malignancy, when compared to a coarse calcification. If the calcification ring around the nodule is damaged or interrupted, and the tissue could infiltrate outward at the broken part, the nodule would be highly suspected to be malignant. The pathological manifestation is that the tumor has infiltrative growth, which destroyed the calcification ring [15 –17]. In the present study, 11 cases of thyroid nodules are categorized as US-FNA cellular pathology Bethesda category IV and ACR TI-RADS category 5, which are highly suspicious of malignancy. The postoperative pathological results revealed that all these nodules are malignant. The false negativity in the diagnosis of thyroid nodules is corrected by the combination of these two methods. If some small nodules are punctured, the needle might penetrate into the surrounding normal thyroid tissues by mistake, resulting in unsatisfactory results or a wrong diagnosis, and thereby increasing the false negativity [18 –22]. In combination with the characteristics of the ultrasound image and the ACR TI-RADS category, the re-evaluation of thyroid nodules can improve the sensitivity and reduce the false negativity.

There are some limitations in the present study. First, all nodules in the present study are treated by thyroidectomy and the number of benign cases is small. Thus, there is a selection bias. Second, there are few pathological types of malignant nodules, and almost all of these are papillary thyroid carcinoma. In addition, the sample size of the present study is small. Hence, there is a need to increase the sample size, and other pathological types should be included for future research. In addition, since the malignancy rate is 73%, the patient population is not representative of nodules seen in most practices, which should be avoided in future studies. And the specificity of ACR TI-RADS (37.5%) is lower than in many other papers, so we should further improve it in future studies.

5 Conclusion

The ACR TI-RADS is merely a method for evaluating thyroid nodules and is far from meeting clinical needs. Hence, it is necessary to make a comprehensive judgment during the differential diagnosis of benign and malignant nodules. Combining this method with FNA biopsy can help to further clarify the nature of the nodule and thus help guide the next step in the clinical therapy.

Declarations

Ethics approval and consent to participate.

The authors confirm that we have read the Editorial Policy pages. This study is conducted with approval from the Ethics Committee of Shanxi Provincial People’s Hospital (0351-4960079). This study is conducted in accordance with the declaration of Helsinki.

Availability of data and materials

We declared that materials described in the manuscript, including all relevant raw data, will be freely available to any scientist wishing to use them for non-commercial purposes, without breaching participant confidentiality.

Competing interests

The authors declare that they have no competing interests.

Funding

None.

Authors’ contributions

Conception and design of the research: Zhang C. Acquisition of data: Zhang C, Huang YQ. Analysis and interpretation of the data: Liu ZL. Statistical data analysis: Huang YQ. Obtaining financing: None. Writing of the manuscript: Zhang C. Critical revision of the manuscript for intellectual content: Liu ZL.

Footnotes

Acknowledgments

We would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study.

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