Peripheral Calcification in Thyroid Nodules

Transcription

1 CME Article Peripheral Calcification in Thyroid Nodules Ultrasonographic Features and Prediction of Malignancy Dae Young Yoon, MD, PhD, Joon Won Lee, MD, Suk Ki Chang, MD, Chul Soon Choi, MD, PhD, Eun Joo Yun, MD, PhD, Young Lan Seo, MD, PhD, Keon Ha Kim, MD, Hee Sung Hwang, MD Objective. The purpose of this study was to investigate the association between peripheral calcification in thyroid nodules detected on ultrasonography and thyroid malignancy. Methods. We retrospectively analyzed the ultrasonographic features of 65 pathologically proven thyroid lesions showing peripheral calcification for their correlation with histopathologic results. The following ultrasonographic parameters were assessed for each nodule: size (maximal dimension), shape (anteroposterior dimension/transverse dimension ratio), internal echogenicity (hypoechoic, isoechoic, hyperechoic, or invisible), halo sign (present or absent), type of calcification (stippled, curvilinear/smooth margin, or curvilinear/irregular margin), and extent of calcification (arc or rim). Results. Twelve (18.5%) of 65 thyroid nodules with peripheral calcification were malignant, and 53 (81.5%) were benign. Patient demographics (age and sex) and ultrasonographic features of the nodules (size, shape, internal echogenicity, halo sign, and type and extent of calcification) did not show any significant differences between benign and malignant groups. Conclusions. The relatively high prevalence of malignancy and no reliable criterion for malignancy in thyroid nodules with peripheral calcification indicate that fine-needle aspiration or careful ultrasonographic follow-up may be warranted in these cases. Key words: calcification; thyroid carcinoma; thyroid nodule; ultrasonography. Abbreviations AP/T, anteroposterior dimension/transverse dimension; FNA, fine-needle aspiration Received April 25, 2007, from the Department of Radiology, Kangdong Seong-Sim Hospital, Hallym University College of Medicine, Seoul, Korea (D.Y.Y., J.W.L., S.K.C., C.S.C., E.J.Y., Y.L.S.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea (K.H.K.); and Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea (H.S.H.). Revision requested May 15, Revised manuscript accepted for publication May 21, Address correspondence to Dae Young Yoon, MD, PhD, Department of Radiology, Kangdong Seong-Sim Hospital, Hallym University College of Medicine, 445 Gil-dong, Kangdong-gu, Seoul , Korea. CME Article includes CME test Thyroid nodules are very common, found by palpation in 4% to 7% of the asymptomatic population, 1 in 17% to 27% of cases on ultrasonography, 2 4 and in 50% of cases at autopsy. 5 Although most thyroid nodules are benign, approximately 4% to 14% of such nodules are malignant. 1,6 8 Thus, it is important to identify which nodules are more likely to be malignant. Several ultrasonographic characteristics that have been studied as potential predictors of thyroid malignancy include irregular margins, hypoechogenicity, the absence of a halo, a predominantly solid composition, intranodular vascularity, and the presence of calcification. 2,7,9,10 Calcification is a common finding on thyroid imaging, and various patterns of calcification may be seen on thyroid ultrasonography, including microcalcification, coarse and dense calcification, and rimlike peripheral calcification Among these, both microcalcification and coarse calcification within the nodule are known to be associated with an increased likelihood of malignancy To our knowledge, however, there are insufficient 2007 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2007; 26: /07/$3.50

2 Peripheral Calcification in Thyroid Nodules data to know whether peripheral calcification, as opposed to intranodular calcification, is associated with malignancy. The purpose of this study was to investigate the association between peripheral calcification detected on ultrasonography and thyroid malignancy. Materials and Methods Patients This was a retrospective study analyzing 66 patients who had thyroid nodules with peripheral calcification on ultrasonography. Cases were selected from a radiology report database over a 3-year period (August 2003 August 2006) at our institution. This subset of reports was then searched for peripheral calcifi*, ring calcifi*, and rim calcifi*, where * was a wildcard allowing matching of any subsequent characters (eg, -cation, -cations, or -ed ). Peripheral calcification was defined as bright echoes observed on the surface of a thyroid nodule with or without the ability to interpret the tumor by its acoustic shadows. In contrast, any hyperechoic structure inside a thyroid nodule was considered intranodular calcification. Thirteen lesions in 10 patients were excluded for the following reasons: ultrasonographically guided fine-needle aspiration (FNA) or surgery not performed (n = 8) and lesions with nondiagnostic FNA results (n = 5). This yielded a final study population of 56 patients (48 women and 8 men; mean age ± SD, 53.5 ± 12.9 years; range, years) with 65 thyroid nodules (a single thyroid nodule in 47 patients and 2 nodules in 9 patients). The final diagnosis was determined pathologically by FNA (n = 44), thyroidectomy (n = 3), or both (n = 18). Ultrasonographically guided FNA was performed by 2 experienced radiologists (D.Y.Y. and S.K.C) with a 23-gauge needle according to a previously described technique. 17 Five or more passes were made through the nodule, and specimens were withdrawn by capillary action. Thirty cases with benign FNA results had ultrasonographic follow-up (>6 months; mean period, 12.2 ± 4.2 months; range, 6 30 months). During the follow-up period, none of these patients had any changes in nodule volume or imaging features. The entire study protocol was approved by our Institutional Review Board. Because the patients data were evaluated retrospectively and anonymously, no written informed consent was necessary. Ultrasonographic Examinations and Image Interpretation Ultrasonographic examination of the thyroid gland was performed with an HDI 5000 system (Philips Medical Systems, Bothell, WA) or an Acuson Sequoia 512 system (Siemens Medical Solutions, Mountain View, CA) equipped with a commercially available 8- to 15-MHz linear array transducer. All sonograms were interpreted by 2 experienced radiologists (D.Y.Y. and S.K.C.), who were unaware of the histopathologic diagnosis. Final decisions regarding the findings were reached by consensus. The images were presented for readers on a picture archiving and communication system workstation (Infinitt Technology, Seoul, Korea), in an anonymous random fashion. The following ultrasonographic parameters were assessed for each nodule: size (maximal dimension), shape (anteroposterior dimension/ transverse dimension [AP/T] ratio), internal echogenicity (hypoechoic, isoechoic, or hyperechoic in comparison with the background thyroid tissue or invisible because of posterior attenuation of the ultrasonic beam), halo sign (present or absent), and type and extent of peripheral calcification. Thirteen nodules were excluded from the analysis for shape; in each case, the AP/T ratio could not be assessed because of extensive attenuation of the ultrasonic beam. The types of calcification were classified into 3 categories as follows: type 1, stippled (fine or coarse nonlinear particles); type 2, curvilinear, smooth margin; and type 3, curvilinear, irregular margin (Figure 1). The lesions were also categorized as arc or rim depending on whether the calcification was limited to part of the lesion border or involved the entire lesion border. Statistical Analysis We compared the ultrasonographic characteristics of each thyroid nodule with the histopathologic findings (benign or malignant). Statistical analysis was performed with the Student t test and the χ 2 test. P <.05 was considered statistical J Ultrasound Med 2007; 26:

3 Yoon et al ly significant. All statistical analyses were performed with commercially available software (SPSS version 10.0 for Windows; SPSS Inc, Chicago, IL). Results Of the 65 thyroid lesions included in the study, 53 (81.5%) were benign, and 12 (18.5%) were malignant. The histologic type of all malignant thyroid tumors was papillary carcinoma. Figure 1. Diagrammatic representation of the types of thyroid peripheral calcification. A, Type 1: stippled calcification. B, Type 2: smooth curvilinear calcification. C, Type 3: irregular curvilinear calcification. A B Patient demographics and ultrasonographic features of the benign and malignant nodules are summarized in Table 1. There were no significant differences in age (P =.37) and sex (P =.98) between the patients with malignant and benign thyroid tumors. The mean sizes ± SD as determined by maximum dimension were 13 ± 8 mm (range, 3 37 mm) for benign nodules and 14.4 ± 6.8 mm (range, 5 28 mm) for malignant nodules. The maximum dimension did not show statistically significant differences between the benign and malignant nodules (P =.56) when thyroid nodules smaller than 10 mm in maximum dimension, 10 to 15 mm, and larger than 15 mm were compared. Furthermore, we wanted to evaluate whether the risk of malignancy was altered by the type and extent of calcification described. The prevalence of malignancy ranged from 14.3% for type 2 calcification to 25% for type 1 calcification. Among nodules with rim-type peripheral calcification, 7 (21.9%) of 32 had thyroid cancer, whereas 5 (15.2%) of 33 nodules with arc-type peripheral calcification had thyroid cancer. No significant associations were found between the type (P =.68) and extent (P =.70) of calcification and histologic differentiation (Figures 2 6). In addition, we did not find any significant differences between malignant and benign thyroid nodules for lesion shape (P =.81), internal echogenicity (P =.50), and the presence of the halo sign (P =.84). Discussion C Calcification within the thyroid gland is a common finding on ultrasonography. It has been reported to be present in 14% to 55% of thyroid sonograms. 11,15,17 19 Prior studies also revealed a strong association between ultrasonographically detected thyroid calcification and malignancy; those studies reported malignancy rates of 29% to 59%. 12,16,18 20 To our knowledge, however, only 1 article in the literature described the association between peripheral calcification within a thyroid nodule and thyroid malignancy. Taki et al 20 correlated the types of thyroid calcification with pathologic results. They found 14 lesions with peripheral J Ultrasound Med 2007; 26:

4 Peripheral Calcification in Thyroid Nodules Table 1. Differences Between Benign and Malignant Thyroid Lesions Parameter Benign (n = 53) Malignant (n = 12) P Sex Male 6 (11.3) 2 (16.7) Female 47 (88.7) 10 (83.3) Age, y* 54.3 ± ± 14.0 Maximum diameter, mm <10 mm 20 (37.7) 3 (25.0) mm 18 (34.0) 6 (50.0) >15 mm 15 (28.3) 3 (25.0) AP/T ratio 1 37 (90.2) 9 (81.8) >1 4 (9.8) 2 (18.2) Internal echogenicity Hypoechoic 19 (35.8) 6 (50.5) Isoechoic 13 (24.5) 4 (33.3) Hyperechoic 2 (3.8) 0 (0) Invisible 19 (35.8) 2 (16.7) Halo sign Absent 32 (60.4) 7 (58.3) Present 21 (39.6) 5 (41.7) Type of peripheral calcifications Type 1 (stippled) 12 (22.6) 4 (33.3) Type 2 (curvilinear, smooth margin) 24 (45.3) 4 (33.3) Type 3 (curvilinear, irregular margin) 17 (32.1) 4 (33.3) Extent of peripheral calcifications Arc 28 (52.8) 5 (41.7) Rim 25 (47.2) 7 (58.3) indicates not significant (P >.05). Data in parentheses are percentages. *Data are mean ± SD. Thirteen nodules (12 benign and 1 malignant) were excluded from the analysis because of marked acoustic shadowing. calcification in 151 surgically resected thyroid nodules, and 43% (6 of 14) of those lesions proved to be malignant. We evaluated a relatively large series of histopathologically proven cases of thyroid nodules with peripheral calcification. In our study, 11 (18.5%) of 65 nodules with this type of calcification were associated with cancer, and this prevalence was lower than that previously reported by Taki et al (43%). 20 We observed 3 types of peripheral calcification: the most frequent type was curvilinear with a smooth margin (type 2, 43.1%), followed by curvilinear with an irregular margin (type 3, 32.3%), and stippled calcification (type 1, 24.6%). Four (25%) of the 16 type 1 lesions were malignant, whereas 4 (19%) of the 21 type 3 lesions and 4 (14.3%) of the 28 type 2 lesions were malignant. However, this trend did not reach statistical significance (P =.68). On the basis of these results, we suggest that the type of peripheral calcification cannot be used as a reliable predictor for malignancy. The halo sign, a complete or incomplete hypoechoic rim surrounding peripheral calcification, was identified in 40% of the lesions in this series. The histologic correlate of this halo surrounding Figure 2. Longitudinal sonogram of the left thyroid lobe from a 58-year-old woman with an adenomatous goiter. A hypoechoic mass (arrows) with peripheral stippled calcification (type 1; arrowheads) surrounded by a hypoechoic halo is shown. Also shown is another thyroid mass (calipers) J Ultrasound Med 2007; 26:

5 Yoon et al Figure 3. Longitudinal sonogram of the right thyroid lobe from a 52-year-old man with an adenomatous goiter. A well-circumscribed isoechoic mass (calipers) with rim-type smooth curvilinear calcification (type 2) is shown. peripheral calcification is unclear, but it may correspond to a fibrous capsule, compressed normal thyroid tissue, or a viable tumor. A halo sign has been associated with a greater likelihood of benignity in previous studies. 3,7,9 In this study, however, a slightly greater proportion of malignant nodules had this characteristic than did benign nodules (41.7% versus 39.6%, respectively). Histologically, thyroid calcification is divided into psammomatous and dystrophic types. 11 Psammomatous calcification consists of laminated round calcium deposits in the epithelium. 11,21 It is now well accepted that papillary thyroid carcinoma frequently forms psammomatous calcification, which can be detected as microcalcification on ultrasonography. 11,14,22 By contrast, dystrophic calcification consists of nonlaminated amorphous deposits in fibrous tissue septa rather than the epithelium. 11,21 This type of calcification is thought to correspond to coarse calcification shown on ultrasonography, which occurs in both benign and malignant conditions. 12 Peripheral calcification is one of the patterns of dystrophic calcification located around the nodule. It was generally thought to be more frequently associated with benignity 23 ; however, cases of papillary thyroid carcinoma associated with this type of calcification have been reported. 20,24 Pathologic correlation was available for all nodules with peripheral calcification in our series. Pathologic examination of these nodules showed extensive areas of dystrophic calcification, which were associated or not associated with malignant cells. Peripheral calcification in thyroid nodules often presents a diagnostic dilemma to radiologists because of its acoustic shadowing and no visualization of the internal architecture. In our series, the AP/T ratio and internal echogenicity could not be assessed in 16 (20%) and 21 (32.3%) of the 65 thyroid nodules, respectively; in each case, the only presenting feature was isolated posterior shadowing due to complete attenuation of the ultrasonic beam. Furthermore, when ultrasonographically guided FNA is performed Figure 4. Transverse sonogram of the left thyroid lobe from a 63-year-old man with papillary carcinoma. A hypoechoic mass (calipers) with rim-type smooth curvilinear calcification (type 2) is shown. Figure 5. Transverse sonogram of the right thyroid lobe from a 48-year-old woman with nodular hyperplasia. A hypoechoic mass (arrows) with arc-type irregular curvilinear calcification (type 3) surrounded by an irregular hypoechoic halo is shown. J Ultrasound Med 2007; 26:

6 Peripheral Calcification in Thyroid Nodules Figure 6. Longitudinal sonogram of the left thyroid lobe from a 58-year-old man with papillary carcinoma. A hypoechoic mass (calipers) with arc-type irregular curvilinear calcification (type 3) surrounded by thin hypoechoic halo (arrows) is shown. The internal architecture of the mass is not visible because of a marked posterior acoustic shadow. on such nodules, poor visualization of the lesion or needle may result in inadequate sampling. Of the 67 ultrasonographically guided FNAs performed on thyroid nodules with peripheral calcification in this series, however, 12 procedures yielded cytologic findings that were questionable or malignant, all of which were confirmed at surgical pathologic examination, whereas 50 procedures yielded benign cytologic findings, and 5 were nondiagnostic. The rate of nondiagnostic specimens (7.5% [5/67]) in our study was highly comparable with those of previous reports, which revealed nondiagnostic results in 6% to 16% of cases. 25,26 Our study had several limitations based primarily on its retrospective design. First, there was a possibility of a selection bias because of the criteria used to select our study population. A source of this bias was the dependence on the original ultrasonography report to detect peripheral calcification of the thyroid gland; the radiologist reporting on the ultrasonographic examination may have described specific patterns of calcification or may have only mentioned the presence or absence of calcification. Therefore, we did not attempt to determine the prevalence of peripheral calcification on thyroid ultrasonography in our series. Second, our results were limited by the fact that most benign conditions were diagnosed on the basis of FNAs. Follow-up ultrasonographic evaluation, performed after at least 6 months on patients with benign cytologic findings, showed no major changes in all cases. However, the follow-up period in our study was short for thyroid cancer (1 year on average). In conclusion, we found an 18.5% prevalence of malignancy among thyroid nodules with peripheral calcification. In addition, we did not find any distinct ultrasonographic feature that could distinguish benign from malignant thyroid nodules. Further diagnostic evaluation with ultrasonographically guided FNA or ultrasonographic follow-up should therefore be considered when assessing any patient with a thyroid mass with peripheral calcification. References 1. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993; 328: Frates MC, Benson CB, Doubilet PM, Cibas ES, Marqusee E. Can color Doppler sonography aid in the prediction of malignancy of thyroid nodules? J Ultrasound Med 2003; 22: Ezzat S, Sarti DA, Cain DR, Braunstein GD. Thyroid incidentalomas: prevalence by palpation and ultrasonography. Arch Intern Med 1994; 154: Brander AE, Viikinkoski VP, Nickels JI, Kivisaari LM. Importance of thyroid abnormalities detected at US screening: a 5-year follow-up. Radiology 2000; 215: Mortenson J, Woolner L, Bennett W. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955; 15: Cochand-Priollet B, Guillausseau PJ, Chagnon S, et al. The diagnostic value of fine-needle aspiration biopsy under ultrasonography in nonfunctional thyroid nodules: a prospective study comparing cytologic and histologic findings. Am J Med 1994; 97: Papini E, Guglielmi R, Bianchini A, et al. Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color Doppler features. J Clin Endocrinol Metab 2002; 87: Marqusee E, Benson C, Frates M, et al. Usefulness of ultrasonography in the management of nodular thyroid disease. Ann Intern Med 2000; 133: J Ultrasound Med 2007; 26:

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