European Journal of Radiology

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1 European Journal of Radiology 82 (2013) Contents lists available at SciVerse ScienceDirect European Journal of Radiology jo ur n al hom epage: Ultrasonographic criteria for fine needle aspiration of nonpalpable thyroid nodules 1 2 cm in diameter Ji Yang Kim a,b,, Soo Young Kim b, Ki Ra Yang b a Department of Radiology, University of Louisville, 530 South Jackson Street, Louisville, KY 40242, USA b Department of Healthcare System Gangnam Center, Department of Radiology, Seoul National University Hospital, 737 Star tower, 40 floor, Yeoksam-dong, Gangnam-gu, Seoul , South Korea a r t i c l e i n f o Article history: Received 29 March 2012 Received in revised form 21 October 2012 Accepted 24 October 2012 Keywords: Thyroid carcinoma Thyroid ultrasonography FNA guideline a b s t r a c t Purpose: To investigate the ultrasonographic (US) characteristics for nonpalpable thyroid nodules 1 2 cm in diameter and to evaluate the guideline for fine needle aspiration (FNA) in terms of US findings. Materials and methods: Between June 2005 and November 2006, FNA was performed in 919 thyroid nodules by radiologists. Of these nodules, 51 malignant nodules and 72 benign nodules were finally included. All 123 nodules were analyzed by 3 radiologists if there were the following US characteristics: marked hypoechogenecity, hypoechogenecity, isoechogenecity, hyperechogenecity, microcalcification, coarse calcification, rim calcification, spiculated margin, taller-than-wide shape, irregular shape, hypoechoic rim and honeycomb appearance. The maximum diameters of nodules and thickness of hypoechoic rim were measured. US characteristics relevant as predictors were identified using a Chi-square or Fisher s exact test and odds ratio. We compared the diagnostic efficacy of 3 US criteria for FNA indication. Results: Microcalcification, taller-than-wide shape, marked hypoechogenecity, hypoechogenecity, coarse calcification, irregular shape and spiculated margin were significant characteristics of malignant nodules. Isoechogenecity, hypoechoic rim and honeycomb appearance was significant characteristics of benign nodules. Rim or arc calcification, hyperechogenecity and thickness of hypoechoic rim were insignificant. Among 3 US criteria for FNA indication, NFI showed the highest diagnostic efficacy, 98.0% in sensitivity, 75.0% in specificity and in odds ratio. Conclusion: As for nonpalpable thyroid nodules 1 2 cm in diameter, US characteristics are useful for differentiating between malignant and benign nodules. Malignant US characteristics and honeycombing appearance have significant value in selecting nodules for biopsy and reducing the frequency of the FNA procedure Elsevier Ireland Ltd. All rights reserved. 1. Introduction Thyroid nodules are very common. They are found in 4 7% of adults by means of palpation [1]. During the past 2 decades, wide use of ultrasonography for the evaluation of thyroid and neck diseases has resulted in a dramatic increase in the prevalence of clinically unapparent thyroid diseases, which are estimated to be Abbreviations: PFI (positive FNA indication)-a, if a nodule has 2 or more malignant US features, it is positively indicated for biopsy; PFI (positive FNA indication)-b, if a nodule has 1 or more malignant US features, it is positively indicated for biopsy; NFI (negative FNA indication), if a nodule has honeycomb appearance or has no malignant US feature, it is negatively indicated for biopsy. Corresponding author at: Department of Radiology, University of Louisville, 530 South Jackson Street, Louisville, KY 40242, USA. Tel.: ; fax: address: j0kim040@louisville.edu (J.Y. Kim) % in the general population [2]. Its prevalence is similar to that which was reported in autopsy data to be 50% in patients with no history of thyroid diseases [3]. Many of these nodules are further evaluated by ultrasound-guided fine needle aspiration (FNA). To avoid the inappropriate use of FNA in a large part of the general population, it is essential to determine, on the basis of their ultrasonographic (US) features, which thyroid lesions have malignant potential [4]. However, there is no consensus in the FNA guidelines on which nodule to be aspirated. Society of Radiology in the Ultrasound Consensus Statement and the American Thyroid Association (ATA) suggest same guidelines for the thyroid nodules smaller than 1 cm and larger than 2 cm: All thyroid nodules smaller than 1 cm are not to be aspirated, and all nodules larger than 2 cm are to be aspirated for cytological confirmation [5,6]. On the other hand, for nodules larger than 1 cm and equal to or smaller than 2 cm (1 2 cm), the FNA guidelines of these two societies are different: while the Society of X/$ see front matter 2012 Elsevier Ireland Ltd. All rights reserved.

2 322 J.Y. Kim et al. / European Journal of Radiology 82 (2013) Radiology suggests that aspiration should be performed if a nodule is at least 1 cm with microcalcifications on ultrasound exam, or a nodule is at least 1.5 cm with mainly solid or contains coarse calcifications [5]. ATA recommends that all nodules larger than 1 cm should be aspirated [6]. Many studies have been reported about the US features predicting malignancy which have proven to be valuable for differential diagnosis [7 11]. However, to the best of our knowledge, few previous studies have focused on FNA guidelines of thyroid nodules 1 2 cm in diameter which is controversial. Therefore, this study was conducted to investigate the US characteristics and to evaluate the appropriate guidelines for FNA in nonpalpable thyroid nodules 1 2 cm in diameter. 2. Materials and methods 2.1. Patient population Between June 2005 and November 2006, screening thyroid US was performed on 13,607 self-referred patients without clinical symptoms at the medical screening center of Seoul National University Hospital. Among these patients, FNA was performed on a total of 919 thyroid nodules by board-certified radiologists. The pathologic reports of FNA showed 588 benign nodules, 109 indeterminate nodules, 120 undiagnosed nodules and 102 malignant nodules. In the malignant group, 51 nodules 1 2 cm in 47 patients were included. They were confirmed by total thyroidectomy in our hospital (n = 29) and an outside hospital (n = 12) or only FNA without operation (n = 10). All of twenty-nine malignant nodules that underwent an operation in our hospital were papillary type. There were 20 men (42.6%) and 27 women (57.4%), and their ages ranged from 31 to 77 years (mean age, 52.1 years). In the benign group, 72 thyroid nodules 1 2 cm in 66 patients were included. Benign nodules were confirmed by both FNA and follow-up US or FNA over 12 months. There were 22 men (33.3%) and 44 women (66.6%), and their ages ranged from 36 to 74 years (mean age, 55.4 years) FNA FNA was performed in all thyroid nodules 1 2 cm in diameter except entirely cystic nodules in our institution. US was performed with a high-frequency (7 13 MHz) linear transducer (GE Logic 9, GE Healthcare systems, Milwaukee, WI; and Philips IU 22, Philips Medical Systems, Bothell, WA) in order to localize the nodule for sampling. The nodules were measured in 3 dimensions. FNA was performed with a 23- to 25-gauge needle on a 10-mL syringe. US guidance was used to confirm the correct placement of the needle in the nodules. One to 3 passes were made per nodule. For partially cystic nodules, sampling was directed to their solid portion. Specimens were smeared on a slide, immediately fixed in 95% ethanol and stained using the Papanicolaou method. The radiologists determined the adequacy of the specimen and the number of passes. The 2 pathologists with 7 and 6 years of experience at the thyroid division, respectively, interpreted cytology. Fig. 1. A typical malignant thyroid nodule in a 50-year-old female patient. Ultrasonography shows a 12-mm, markedly hypoechoic nodule with irregular, taller-than-wide shape and spiculated margin in the right lobe. Intranodular microcalcification (arrow) is seen. The nodule has 5 US characteristics significant for a malignant nodule. It was confirmed as papillary carcinoma after total thyroidectomy. nodules reported by previous studies [9 16]; marked hypoechogenecity, hypoechogenecity, isoechogenecity, hyperechogenecity, microcalcification, coarse calcification, rim calcification, spiculated margin, taller-than-wide shape, irregular shape, hypoechoic rim and honeycomb appearance. Hypoechogenecity was defined as decreased echogenecity of a nodule compared with normal thyroid parenchyma while marked hypoechogenecity was defined as decreased echogenecity compared with the strap muscle (Fig. 1) [7]. A nodule with a taller-than-wide shape was defined as being greater in the anteroposterior direction than in the transverse direction (Fig. 1) [7]. Honeycomb appearance was defined as having multiple small cystic spaces with thin echogenic walls (Fig. 2) [8]. The area of posterior shadowing was avoided when analyzing the echogenecity of nodules having calcifications. The maximum diameters of the nodules and thickness of hypoechoic rim were measured with an electronic caliber Imaging analysis Three radiologists with 8, 7 and 7 years of experience in thyroid imaging, respectively, reviewed the US images and discussed the subject until they came to a consensus. All US features were reviewed on 21-in. monitors at a Picture Archiving and Communication System (PACS) workstation. All 123 nodules were analyzed to determine whether there were the characteristic US features for malignant or benign Fig. 2. A benign thyroid nodule with honeycomb appearance in a 56-year-old male patient. Longitudinal ultrasonography shows an 11-mm, hypoechoic, honeycombappearing nodule. Multiple small anechoic cystic spaces are seen within the nodule. The cytology report after FNA revealed that it was a benign lesion.

3 J.Y. Kim et al. / European Journal of Radiology 82 (2013) Fig. 3. A malignant thyroid nodule with hypoechogenecity in a 58-year-old female patient. Transverse US shows a 16.5-mm, hypoechoic nodule (arrow). No other US features suggestive of malignancy is seen. It was confirmed as papillary carcinoma after total thyroidectomy Statistical analysis The maximal diameter of nodules and the thickness of hypoechoic rims were compared by means of Student s T-test. Univariate analysis for individual US characteristics between the benign and malignant groups was performed using the Chi-square test and the Fisher s exact test. Specificity and sensitivity of each of the US characteristics and 3 US criteria for FNA indication were analyzed. Odds ratio was calculated. Receiver operating characteristic (ROC) was used to determine optical cut-off for the combined numbers of US characteristics significant for malignancy per nodule. Statistical analyses were performed using SPSS software package (version 19.0, SPSS Inc, Chicago, IL) and Medcalc for Windows (Medcalc, MedCalc Software version ; Mariakerke, Belgium). For all tests, P < 0.05 was considered statistically significant. 3. Results 3.1. Univariate analysis There was no significant difference in age and sex between the malignant and benign groups. The maximum diameters were not significantly different between malignant (13.5 ± 2.3 mm [mean ± SD]) (P > 0.05) and benign (13.2 ± 2.4 mm) groups. Table 1 shows the results of the univariate analysis of the US characteristics observed in malignant and benign nodules 1 2 cm in diameter. Microcalcification, taller-than-wide shape, marked hypoechogenecity, hypoechogenecity, coarse calcification, irregular shape and spiculated margin were significant characteristics for the malignant nodules (Figs. 1, 3 and 4). Microcalcification showed the highest odds ratio (55.2) for malignancy, followed by taller-than-wide shape (26.8), coarse calcification (19.5), marked hypoechogenecity (16.0), spiculated margin (13.2), irregular shape (13.2) and hypoechogenecity (2.9). Isoechogenecity, hypoechoic rim and honeycomb appearance were significant characteristics for the benign nodules (Figs. 2 and 5). Rim calcification (Fig. 6), hyperechogenecity and thickness of hypoechoic rim were statistically insignificant (P > 0.05). Table 2 summarizes the sensitivity, specificity, a positive predictive value (PPV) and a negative predictive value (NPV) of each of the significant US characteristics. Microcalcification showed a high specificity of 85.8% and PPV of 92.1%. Isoechogenecity showed NPV Fig. 4. Malignant thyroid nodule with coarse calcifications in a 53-year-old male patient. Transverse ultrasonography shows a 13.1-mm, hypoechoic nodule with intranodular coarse calcification (arrows). It was confirmed as papillary carcinoma after total thyroidectomy. of 85%. Taller-than-wide shape, marked hypoechogenecity, coarse calcification, irregular shape and spiculated margin showed a high specificity and a low sensitivity. Honeycomb appearance showed a specificity of 100% and an NPV of 100% but a low sensitivity and PPV US criteria for FNA indication The mean number of US characteristics significant for malignancy per nodule was 2.1 ± 1.0 in the malignant group and 0.4 ± 0.7 in the benign group. The optimal cut-off of combined number of malignant US features per nodule was 2 or more, which showed low sensitivity, 78.5% and high specificity, 95.83%. When this cut-off value was regarded as positive FNA indication (PFI-A) to perform biopsy, 13 of 51 malignant nodules are misdiagnosed as benign and excluded from biopsy. If the cut-off value of combined number of malignant US features per nodule was regulated as 1 or more to increase the sensitivity of PFI-A, the sensitivity became much higher, 98.0% and specificity became much lower, 70.8%. When this cut-off value was regarded as positive FNA indication Fig. 5. A typical benign thyroid nodule with isoechogenecity and partial hypoechoic rim in a 57-year-old female patient. Longitudinal ultrasonography shows an 18.5-mm, isoechoic nodule with partial hypoechoic rim. These US characteristics were consistent with benign nodule. The cytology report after FNA was negative for malignant cells. The nodule showed no interval changes in size and shape at 17-month US follow-up.

4 324 J.Y. Kim et al. / European Journal of Radiology 82 (2013) Table 1 Univariate analysis of US characteristics of thyroid nodules sized at 1 2 cm. Malignant (n = 51) Benign (n = 72) Total (n = 123) P value Odds ratio Microcalcification a 36 (70.6%) 3 (4.2%) 39 (31.7%) < ( ) Taller-than-wide shape a 14 (27.5%) 1 (1.4%) 15 (12.2%) < ( ) Coarse calcification a 11 (21.6%) 1 (1.4%) 12 (9.8%) < ( ) Marked hypoechogenecity a 16 (31.4%) 2 (2.8%) 18 (14.6%) < ( ) Spiculated margin a 8 (15.7%) 1 (1.4%) 9 (7.3%) ( ) Irregular shape a 8 (15.7%) 1 (1.4%) 9 (7.3%) ( ) Hypoechogenecity a 26 (50%) 19 (26.8%) 45 (36.6%) ( ) Isoechogenecity b 9 (17.6%) 48 (66.7%) 57 (46.3%) < ( ) Honeycomb appearance b 0 11 (15.3%) 11 (8.9%) Hypoechoic rim b 4 (7.8%) 22 (30.6%) 26 (21.1%) ( ) Thickness of hypoechoic rim c 0.75 ± ± Rim calcification c 5 (9.8%) 2 (2.8%) 7 (5.7%) ( ) Hyperechogenecity c 0 3 (4.2%) 3 (2.4%) Numbers in parenthesis are 95% CI. a Diagnostic variables for malignant thyroid nodules. b Diagnostic variables for benign thyroid nodules. c Diagnostic variables were statistically insignificant. Table 2 Diagnostic efficacy for each of the significant US characteristics of thyroid nodules 1 2 cm. US characteristics Sensitivity (%) Specificity (%) PPV (%) NPV (%) Microcalcification a 70.6 ( ) 95.8 ( ) Taller-than-wide shape a 27.5 ( ) 98.6 ( ) Coarse calcification a 21.6 ( ) 98.6 ( ) Marked hypoechogenecity a 31.4 ( ) 97.2 ( ) Spiculated margin a 15.4 ( ) 98.6 ( ) Irregular shape a 15.7 ( ) 98.6 ( ) Hypoechogenecity a 50.9 ( ) 73.6 ( ) Isoechogenecity b 82.5 ( ) ( ) Honeycomb appearance b 15.3 ( ) ( ) Hypoechoic rim b 30.6 ( ) 92.2 ( ) Numbers in parenthesis are 95% CI. a Diagnostic variables for malignant thyroid nodules. b Diagnostic variables for benign thyroid nodules. (PFI-B) to perform biopsy, 51 of 72 true benign nodules and 1 of 51 true malignant nodules would be excluded from biopsy. 3 benign nodules which showed honeycombing appearance were misdiagnosed as malignant nodule because the nodules were hypoechoic. To improve the specificity of PFI-B, honeycomb appearance was added as one of US criteria for FNA indication, regarding its specificity of 100%. Then, US criteria for negative FNA indication (NFI) to dismiss biopsy was defined as follows: (1) A nodule has honeycomb appearance, or (2) A nodule has none of US characteristics significant for malignancy. If NFI was applied, 54 of 72 (75%) true benign nodules and 1 of 51 (1.9%) true malignant nodules (Fig. 7) would be excluded from biopsy (Fig. 8). The sensitivity and specificity of NFI were 98.0% and 75.0%, respectively. NFI showed the highest odds ratio (150.0) among 3 US criteria. Table 3 summarizes diagnostic efficacy of 3 US criteria for FNA indication. 4. Discussion The present study was attempted to determine whether US characteristics of nonpalpable thyroid nodules 1 2 cm in diameter could be used to select nodules for biopsy and to limit the frequency of the FNA procedure. Microcalcification, taller-than-wide shape, marked hypoechogenecity, hypoechogenecity, coarse calcification, irregular shape and spiculated margin were significant characteristics of malignant nodules in this study. The result is generally similar to that of a previous study which analyzed a large amount of data from multiple institutions [9]. However, US feature of irregular shape was not significant in previous study, which is inconsistent with the present result. Our previous study reported that hypoechogenecity is insignificant for malignant nodules [10]. However, the finding was proved to be significant for malignancy in the present study. In our institution, FNA is performed on nodules measuring 1 cm or smaller only if it has US features suspicious for malignancy. However, all the nodules larger than 1 cm are indicated for FNA if they are not entirely cystic. In the our previous study, hypoechoic nodules <1 cm which did not showed calcification, taller-thanwide shape or spiculated margin were not included in the study population. This difference of FNA indication according to the size of nodules caused selection bias in the previous study [10]. Thus, it is conceivable that the result of this study from homogenous population is more reliable. Coarse calcification is known as a feature of benign nodules, especially with long disease duration [11,12]. However, recent studies reported that coarse calcification Table 3 Diagnostic efficacy of suggested US Criteria for FNA indication of thyroid nodules 1 2 cm. US criteria Sensitivity (%) Specificity (%) PPV (%) NPV (%) P value Odds ratio PFI-A < ( ) PFI-B < ( ) NFI < ( ) Numbers in parenthesis are 95% CI. PPV: positive predictive value. NPV: negative predictive value.

5 J.Y. Kim et al. / European Journal of Radiology 82 (2013) Fig. 7. A malignant thyroid nodule with US characteristics suggestive of benign nodule in a 46-year-old female patient. Longitudinal US shows a 15-mm, isoechoic, nodule with hypoechoic rim (arrow). The US characteristics are consistent with benign nodules. It was confirmed as papillary carcinoma after total thyroidectomy. Fig. 6. Rim calcification. (a) A malignant nodule in a 54-year-old female patient. Ultrasonography shows a 15-mm nodule with arc calcification (arrow) and posterior shadowing in the left lobe. The nodule shows isoechogenecity except for the hypoechoic portion caused by posterior shadowing. It has a taller-than-wide shape, one of the malignant US characteristics. It was reported after FNA to be a suspected papillary carcinoma and was confirmed as a malignant nodule after total thyroidectomy in an outside hospital. (b) A benign nodule in a 47-year-old female patient. Ultrasonography shows a 10.3-mm, thyroid nodule with rim calcification (curved arrows) in the right lobe. Half of the nodule is veiled by posterior shadowing (straight arrow), and the remaining part is nearly isoechoic. Adenomatous goiter was reported after FNA. The nodule showed no interval changes in size and shape at 12-month US follow-up. is significantly more common in malignant nodules [9,10], which is in accord with that of our present study. Isoechogenecity, hypoechoic rim and honeycomb appearances were significant characteristics for benign nodules. The results correspond well with those of earlier reports which have demonstrated that most hyperplasic or adenomatous nodules are isoechoic compared with normal thyroid tissue. Honeycomb appearance is very specific for benign nodules, but it is less frequently seen [13]. Our study also showed only about 15% of benign nodules had honeycomb appearance. Hypoechoic rim is caused by the compression of normal thyroid tissue or capsule, highly suggestive of benign nodule [14]. Earlier study showed similar result to our study in that absence of hypoechoic rim is associated with the risk of malignancy [15]. Hyperechogenecity is known as specific findings for benign nodule [11]. In our study, all the hyperechogenic nodules also were benign. As for rim calcification, there are insufficient data for determining whether it is associated with malignancy [5]. In a study of 65 thyroid nodules, rim calcification is significantly more frequent in benign nodules (81.5%) than malignant nodules (18.5%) [16]. However, in this study, rim calcification was observed in both malignant and benign nodules without any significant difference. 5 of 7 nodules with rim calcifications were malignant and had at least 1 malignant US characteristics. Therefore all of them were correctly categorized as malignant nodule by US criteria of NFI. When analyzing US characteristics of other 2 benign nodules with rim calcifications, one showed malignant US characteristics and the other showed typical benign US characteristics. Rim calcification itself did not influence on the diagnosis of malignant nodules. Therefore, it is suggested that nodules with rim calcification be diagnosed based on the US characteristics of solid portion avoiding posterior shadowing. From this study, NFI reduced the number of FNA cases significantly, 75% in benign nodules, even though 2% of malignant nodule (1 case) was misdiagnosed. Regarding markedly increasing numbers of detection of nonpalpable thyroid nodules by ultrasonography and low mortality of thyroid carcinoma [17], diagnostic efficacy of NFI may be acceptable. PFI-A may be inappropriate as guideline for FNA because of its low sensitivity. PFI-B is more appropriate as guideline for FNA than PFI-A because of its high sensitivity. However, NFI showed the best diagnostic performance. The specificity was higher with same sensitivity compared with those of PFI-B. The improvement of specificity was resulted from including honeycombing appearance as one of US criteria for NFI. Honeycombing appearance proved to be 100% specific for benign nodule in our study, which was almost similar to the result of a previous study [9]. In a study which analyzed the US pattern of thyroid nodules, it is suggested that a nodule with honeycomb appearance does not require biopsy [8]. Therefore, honeycombing appearance is thought be an excellent US criterion to avoid biopsy. In this study, malignant US characteristics and honeycombing appearance were used to select nodules to be aspirated, which proved to be effective to reduce the frequency of biopsy while reserving the diagnostic performance. One malignant nodule which was misdiagnosed showed typical benign US characteristics, isoechogenecity and hypoechoic rim, without any features suggesting malignancy. However, it is noticeable that the hypoechoic rim had inhomogenous thickness. If the irregularity and thickness of hypoechoic rims were analyzed in the significant number of nodules, it may be helpful to differentiate between malignant and benign nodules. In our study, the hypoechoic rims of malignant nodules were thicker than those of benign nodules. However, number of malignant nodules having hypoechoic rim was too small to be

6 326 J.Y. Kim et al. / European Journal of Radiology 82 (2013) Fig. 8. Graph shows the decreased number of FNA when NFI is applied to exclude nodules from biopsy. 54 of 72 (75%) true benign nodules and 1 of 51 (1.9%) true malignant nodules would be excluded from biopsy. statistically significant. Hyperechogenecity show 100% sensitivity and NPV for benign nodule in a previous study [18]. In our study, number of hyperechoic nodules was too small to be statistically significant although all the nodules were benign. Nevertheless, hyperechogenecity may be a potential excellent US criterion to dismiss biopsy for reducing the number of FNA. Follicular and medullary carcinomas are not uncommonly isoechogenic [5,9] and could be diagnosed as benign nodule when our suggested US criteria applied. Hence, the diagnostic accuracy of the US criteria may be a little decreased if patients with these two types of carcinoma are included in the study group. Thyroid scintigraphy is also an excellent tool in filtering benign nodule since hyperfunctioning ( hot ) nodules are almost never represent malignant nodules. However, role of scintigraphy is limited as the first-step evaluation of thyroid nodules in the countries with iodine-rich diets where thyroid US and hormone study correctly diagnose autonomous nodules [19]. Most of thyroid carcinomas are papillary type (75 80%) which grow very slowly and commonly are asymptomatic [5,9]. Remaining includes follicular (10 20%), medullary (3 50%) and anaplastic (1 2%) types [9]. In our study, all the carcinomas were papillary type. It can be implicit the difference of this histologic spectrum in this study may be affected by the selection of asymptomatic population from screening program. There are doubts about the benefit of diagnosing low risk malignancy such as small papillary carcinomas [5,6]. However, it was reported that the cumulative risk of extracapsular invasion and lymph node metastasis associated with increasing size of the nodules is more obvious in the papillary type than in the follicular type [10,20]. The risk of distant metastasis increases once the primary tumor size becomes 2 cm. Investigation has suggested that early diagnosis of thyroid carcinoma can reduce the risk of recurrence and mortality [20]. The results of our study are subject to 2 limitations. First, this study has a retrospective design. Second, the radiologists analyzed PACS images, but not real-time US. In conclusion, for the nonpalpable thyroid nodules 1 2 cm in diameter, US characteristics are useful for differentiating between malignant and benign nodules. Malignant US characteristics and honeycombing appearance have significant value in selecting nodules for biopsy and reducing the frequency of the FNA procedure. References [1] Hegedüs L. Clinical practice. The thyroid nodule. 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