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 calcifica-tion in thyroid nodules detected on ultrasonography and thyroid malignancy.Methods.We retro-spectively 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 dimen-sion/transverse dimension ratio), internal echogenicity (hypoechoic, isoechoic, hyperechoic, or invisi-ble), 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 thy-roid nodules with peripheral calcification were malignant, and 53 (81.5%) were benign. Patient demo-graphics (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 cri-terion for malignancy in thyroid nodules with peripheral calcification indicate that fine-needle aspira-tion or careful ultrasonographic follow-up may be warranted in these cases. Key words:calcification; thyroid carcinoma; thyroid nodule; ultrasonography.
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, 2007. Revised manuscript accepted for publication May 21, 2007.
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 134-701, Korea.
E-mail: [email protected]
Abbreviations
AP/T, anteroposterior dimension/transverse dimension; FNA, fine-needle aspiration
hyroid nodules are very common, found by palpa-tion in 4% to 7% of the asymptomatic populapalpa-tion,1 in 17% to 27% of cases on ultrasonography,2–4and in 50% of cases at autopsy.5Although most thyroid nodules are benign, approximately 4% to 14% of such nodules are malignant.1,6–8Thus, 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 irregu-lar margins, hypoechogenicity, the absence of a halo, a pre-dominantly 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 thy-roid ultrasonography, including microcalcification, coarse and dense calcification, and rimlike peripheral calcification.11–13 Among these, both microcalcification and coarse calcification within the nodule are known to be associated with an increased likelihood of malignan-cy.7–16To our knowledge, however, there are insufficient
© 2007 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 2007; 26:1349–1355 • 0278-4297/07/$3.50
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Article includes CME test
data to know whether peripheral calcification, as opposed to intranodular calcification, is associ-ated with malignancy.
The purpose of this study was to investigate the association between peripheral calcifica-tion detected on ultrasonography and thyroid malignancy.
Materials and Methods Patients
This was a retrospective study analyzing 66 patients who had thyroid nodules with peripher-al cperipher-alcification 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 allow-ing matchallow-ing of any subsequent characters (eg, “-cation,” “-cations,” or “-ed”). Peripheral calcifi-cation 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 intran-odular calcification.
Thirteen lesions in 10 patients were excluded for the following reasons: ultrasonographically guid-ed fine-neguid-edle aspiration (FNA) or surgery not performed (n = 8) and lesions with nondiagnostic FNA results (n = 5). This yielded a final study pop-ulation of 56 patients (48 women and 8 men; mean age ± SD, 53.5 ± 12.9 years; range, 28–82 years) with 65 thyroid nodules (a single thyroid nodule in 47 patients and 2 nodules in 9 patients). The final diagnosis was determined pathologi-cally 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 nod-ule, 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 present-ed for readers on a picture archiving and commu-nication 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 hypere-choic in comparison with the background thy-roid 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 analy-sis 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, curvi-linear, 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 characteris-tics of each thyroid nodule with the histopatho-logic findings (benign or malignant). Statistical analysis was performed with the Student t test and the χ2test. P< .05 was considered
statistical-ly significant. All statistical anastatistical-lyses were per-formed 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 malig-nant. The histologic type of all malignant thyroid tumors was papillary carcinoma.
Patient demographics and ultrasonographic features of the benign and malignant nodules are summarized in Table 1. There were no signif-icant 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 maxi-mum 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 nod-ules smaller than 10 mm in maximum dimen-sion, 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 preva-lence of malignancy ranged from 14.3% for type 2 calcification to 25% for type 1 calcification. Among nodules with rim-type peripheral calcifi-cation, 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 dif-ferences 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
Calcification within the thyroid gland is a com-mon finding on ultrasonography. It has been reported to be present in 14% to 55% of thyroid sonograms.11,15,17–19Prior 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 al20 correlated the types of thyroid calcification with pathologic results. They found 14 lesions with peripheral
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C B A
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 curvilin-ear calcification.
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 malig-nant, 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 sig-nificance (P= .68). On the basis of these results, we suggest that the type of peripheral calcifica-tion cannot be used as a reliable predictor for malignancy.
The halo sign, a complete or incomplete hypoe-choic rim surrounding peripheral calcification, was identified in 40% of the lesions in this series. The histologic correlate of this halo surrounding Table 1. Differences Between Benign and Malignant Thyroid Lesions
Parameter Benign (n = 53) Malignant (n = 12) P
Sex NS Male 6 (11.3) 2 (16.7) Female 47 (88.7) 10 (83.3) Age, y* 54.3 ± 12.7 50.4 ± 14.0 NS Maximum diameter, mm NS <10 mm 20 (37.7) 3 (25.0) 10–15 mm 18 (34.0) 6 (50.0) >15 mm 15 (28.3) 3 (25.0) AP/T ratio† NS ≤1 37 (90.2) 9 (81.8) >1 4 (9.8) 2 (18.2) Internal echogenicity NS 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 NS Absent 32 (60.4) 7 (58.3) Present 21 (39.6) 5 (41.7)
Type of peripheral calcifications NS
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 NS
Arc 28 (52.8) 5 (41.7)
Rim 25 (47.2) 7 (58.3)
NS 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.
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).
peripheral calcification is unclear, but it may cor-respond to a fibrous capsule, compressed normal thyroid tissue, or a viable tumor. A halo sign has been associated with a greater likelihood of benig-nity in previous studies.3,7,9In 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 lami-nated round calcium deposits in the epitheli-um.11,21 It is now well accepted that papillary thyroid carcinoma frequently forms
psammo-matous 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.11,21This type of calcification is thought to correspond to coarse calcification shown on ultrasonography, which occurs in both benign and malignant con-ditions.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 benignity23; 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 calcifi-cation in our series. Pathologic examination of these nodules showed extensive areas of dys-trophic calcification, which were associated or not associated with malignant cells.
Peripheral calcification in thyroid nodules often presents a diagnostic dilemma to radiolo-gists 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 attenua-tion of the ultrasonic beam. Furthermore, when ultrasonographically guided FNA is performed
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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.
Figure 3. Longitudinal sonogram of the right thyroid lobe from a 52-year-old man with an adenomatous goiter. A well-circum-scribed isoechoic mass (calipers) with rim-type smooth curvilin-ear calcification (type 2) is shown.
on such nodules, poor visualization of the lesion or needle may result in inadequate sampling. Of the 67 ultrasonographically guided FNAs per-formed on thyroid nodules with peripheral calci-fication in this series, however, 12 procedures yielded cytologic findings that were questionable or malignant, all of which were confirmed at sur-gical pathologic examination, whereas 50 proce-dures 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 pri-marily 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 pat-terns of calcification or may have only men-tioned 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, per-formed 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 periph-eral calcification. In addition, we did not find any distinct ultrasonographic feature that could dis-tinguish benign from malignant thyroid nodules. Further diagnostic evaluation with ultrasono-graphically guided FNA or ultrasonographic follow-up should therefore be considered when assessing any patient with a thyroid mass with peripheral calcification.
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