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ORIGINAL RESEARCH

Sonographic Features of Medullary Thyroid Carcinomas According to Tumor Size Comparison With Papillary Thyroid Carcinomas Liguang Zhou, MD, Bo Chen, MD, Miaoqing Zhao, MD, Huawei Zhang, MD, Bo Liang, MD Objectives—The aim of this study was to evaluate the differences in sonographic features of medullary thyroid carcinomas according to nodule size and compared with findings for papillary thyroid carcinomas. Methods—This study included 38 medullary thyroid carcinoma nodules and 91 papillary thyroid carcinoma nodules, which were confirmed by pathologic examination between May 2008 and September 2013. Nodules were divided into those that were greater than 10 mm (large nodules) and 10 mm or less (small nodules). The differences in sonographic features (composition, echogenicity, margin, calcifications, and shape) between groups were analyzed with a χ2 test.

Received June 5, 2014, from the Departments of Ultrasound (L.Z., H.Z., B.L.) and Pathology (M.Z.), Provincial Hospital Affiliated With Shandong University, Jinan, China; and Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China (B.C.). Revision requested July 24, 2014. Revised manuscript accepted for publication September 19, 2014. This study was supported by the National Natural Science Foundation of China (grant 81102019), the Foundation of Shandong Provincial Science and Technology Development Program (grant 2012G002182), and the Shandong Province Young and Middle-Aged Scientists Research Awards Fund (grant 2012BSBl4065). Liguang Zhou and Bo Chen are co–first authors. Address correspondence to Bo Liang, MD, Department of Ultrasound, Provincial Hospital Affiliated With Shandong University, 250021 Jinan, China. E-mail: [email protected] doi:10.7863/ultra.34.6.1003

Results—Large medullary thyroid carcinomas more frequently showed an ovoid-toround shape and a smooth margin; small medullary thyroid carcinomas more frequently showed a taller-than-wide shape and a spiculated margin; the differences were statistically significant between the groups (P < .05). Compared with papillary thyroid carcinomas, large medullary thyroid carcinomas tended to have an ovoid-to-round shape, a smooth margin, and macrocalcifications and were more frequently diagnosed as indeterminate nodules (P < .05); however, there were no significant differences in the internal composition, calcifications, echogenicity, margin, and shape between small medullary thyroid carcinomas and small papillary thyroid carcinomas (P > .05). Conclusions—Our data indicate that the sonographic features of medullary thyroid carcinomas are associated with tumor size; furthermore, the sonographic features of medullary thyroid carcinomas are similar to those of small papillary thyroid carcinomas but greatly different from those of large papillary thyroid carcinomas. Large medullary thyroid carcinomas are more commonly diagnosed as indeterminate nodules by sonography than large papillary thyroid carcinomas, and fine-needle aspiration biopsy or serum calcitonin measurement may be helpful. Key Words—head and neck ultrasound; medullary thyroid carcinoma; papillary thyroid carcinoma; sonography; thyroid gland

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edullary thyroid carcinoma is a malignant tumor originating from parafollicular C cells of the thyroid, which secrete calcitonin and other neuroendocrine peptides.1 Approximately 75% are sporadic, and 25% are inherited.2 This tumor accounts for 3% to 4% of all thyroid malignant tumors.3 It has a more aggressive behavior than the well-differentiated thyroid carcinoma, and 10-year mortality rates for patients with medullary thyroid car-

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cinomas vary from 13.5% to 38%.4–6 Therefore, early and precise preoperative diagnosis is fundamental to improve survival rates for patients with this tumor. Sonography is a useful tool for detecting and diagnosing thyroid diseases, especially thyroid nodules. Numerous studies have reported the sonographic appearance of papillary thyroid carcinomas, such as the presence of a solid or predominantly solid composition, hypoechogenicity, microcalcifications, an irregular or spiculated margin, and a taller-than-wide shape.7–10 However, at present, the sonographic features of medullary thyroid carcinomas remain open, and few studies have analyzed sonographic features associated with this cancer type,11–14 which is attributed to its lower prevalence and diversified sonographic features. We speculate that diversified sonographic features might be related to the differential growth stages of the tumor. In this study, we focused on evaluating the sonographic features of medullary thyroid carcinomas according to nodule size and compared them with the sonographic features of papillary thyroid carcinomas to further define the sonographic features of medullary thyroid carcinomas and determine which features are different from those of papillary thyroid carcinomas.

Materials and Methods Patients This retrospective study was approved by the Institutional Review Board, and the need for informed consent was waived. From May 2008 to September 2013, a total of 124 consecutive patients received preoperative sonographic examinations and subsequently underwent thyroidectomy for nodular thyroid disease at the Provincial Hospital Affiliated With Shandong University. Among them, 37 patients (38 nodules) had a diagnosis of medullary thyroid carcinoma confirmed by pathologic examination (22 female and 15 male; age range, 20–70 years; mean age ± SD, 47.9 ± 12.4 years), and 87 patients (91 nodules) had a diagnosis of papillary thyroid carcinoma confirmed by pathologic examination (51 female and 36 male; age range, 27–76 years; mean age, 50.4 ± 14.3 years). Sonographic and Cytologic Examinations All sonographic examinations were performed with a LOGIQ E9 ultrasound system (GE Healthcare, Milwaukee, WI) a 750 XG ultrasound system (Toshiba Medical Systems Co, Ltd, Tokyo, Japan) equipped with a 10–15-MHz linear array transducer. Examinations were conducted and recorded by 2 skilled sonographers, and findings were prospectively described according to the following param-

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eters: size, composition, echogenicity, margin, calcifications, and shape. To match each nodule found at pathologic examination to the corresponding nodule on sonography, we took into account its location; all nodules were included in the study when it was possible to correlate exactly the locations of the nodules on sonography with the pathologic examination. With respect to the size of the nodules, the largest diameter measured by sonography was selected and was expressed as the mean ± standard deviation, and the nodules were divided into 2 groups: nodules of greater than 10 mm (large nodules) and nodules of 10 mm or less (small nodules). Sonographic features were classified by composition (solid, >50% solid, or .05). The sonographic features of large medullary thyroid carcinomas are presented in Table 1 and Figure 1, A–C. Large medullary thyroid carcinomas were solid (96.8%), were markedly hypoechoic (35.5%) or hypoechoic (61.3%), had an ovoid-to-round shape (61.3%), had microcalcifications (22.6%) or macrocalcifications (38.7%), and had a smooth margin (58.1%). Compared with large papillary thyroid carcinomas (Figure 2A), large medullary thyroid carcinomas tended to have an ovoid-toround shape, a smooth margin, and macrocalcifications (P < .05); the internal composition and echogenicity were equal to those of large papillary thyroid carcinomas (P > .05). Of the 31 large medullary thyroid carcinomas, 20 (64.5%) nodules were classified as suspiciously malignant; 11 (35.5%) were classified as indeterminate, and none was classified as probably benign on sonography. Suspiciously malignant nodules were found less frequently, and indeterminate nodules were found more frequently in large medullary thyroid carcinomas than large papillary thyroid carcinomas (P < .05). As shown in Table 2 and Figure1D, the predominant sonographic features of small medullary thyroid carcinomas were a solid composition (100%), marked hypoechogenicity (57.1%) or hypoechogenicity (42.9%), a spiculated margin (85.7%), microcalcifications (14.7%), and a taller-than-wide shape (57.1%). There were no significant differences compared with small papillary thyroid carcinomas (Figure 2B; P > .05). For the 7 small medullary thyroid carcinomas, 5 nodules (71.4%) were classified as suspiciously malignant; 2 (27.8%) were classified as indeterminate; and none was classified as probably benign. There was no statistical difference for the diagnosis of nodules between small medullary and small papillary thyroid carcinomas (P >0.05). A comparison between small and large medullary thyroid carcinomas is summarized in Table 3. There were no significant differences in the internal composition, microcalcifications, and echogenicity between the groups (P > .05). However, small nodules showed a taller-than-wide shape and a spiculated margin more frequently, whereas large J Ultrasound Med 2015; 34:1003–1009

nodules were more associated with an ovoid-to-round shape and a smooth margin (P < .05). Of the 37 patients with medullary thyroid carcinomas, 23 (62.2%) underwent preoperative fine-needle aspiration. On the basis of cytologic results, 10 nodules were true positive (43.5%), and 13 were false negative (56.5%).

Discussion The advent of high-resolution sonography and its widespread use have improved detection of thyroid nodules, with a consequent increase in diagnosis of small tumors.17,18 In this study, we divided nodules into small (≤10 mm) and large (>10 mm) groups. The differences in the sonographic features of medullary thyroid carcinomas between small and large nodules were investigated. To date, only 1 report19 about the sonographic features of medullary thyroid carcinomas according to tumor size has been published, which concluded that medullary thyroid carcinomas smaller than 10 mm tend to have a spiculated margin, and those larger than 10 mm tend to have a smooth margin. Our study yielded similar results, and the differences in shape and Table 1. Sonographic Features of Medullary and Papillary Thyroid Carcinomas With a Nodule Size of Greater Than 10 mm

Sonographic Feature Diagnosis, n (%) Probably benign Indeterminate Suspiciously malignant Composition, n (%) Solid >50% solid .99

0 1 (3.2) 19 (61.3) 11 (35.5)

0 9 (13.2) 38 (55.9) 21 (30.9)

.241 .614 .650

19 (61.3) 4 (12.9) 8 (25.8)

14 (20.6) 35 (51.5) 19 (27.9)

.99 >.99 >.99

1 (14.3) 0

3 (13.0) 1 (4.3)

>.99 >.99

P

NA indicates not applicable.

Figure 2. Different sonographic features of papillary thyroid carcinomas. A, Transverse sonogram of papillary thyroid carcinoma in a 48-year-old woman showing a solid composition, hypoechogenicity, a spiculated margin, microcalcifications, and a taller-than-wide shape. B, Longitudinal sonogram of papillary thyroid carcinoma (arrow) in a 34-year-old woman (nodule size, 8.3 mm) showing a solid composition, marked hypoechogenicity, a spiculated margin, microcalcifications, and a taller-than-wide shape.

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Macrocalcifications, although not as specific as microcalcifications, were also associated with malignancy.25,26 Our results showed that the incidence of microcalcifications or macrocalcifications had no significant difference between papillary and medullary thyroid carcinomas with nodule sizes of 10 mm or less. Both microcalcifications and macrocalcifications are commonly seen in medullary thyroid carcinomas larger than 10 mm; although microcalcifications are more frequently seen in large papillary thyroid carcinomas, macrocalcifications are more frequently seen in large medullary thyroid carcinomas. This finding can be attributed to the different calcification mechanisms: medullary thyroid carcinoma calcifications are caused by amyloid deposits,27 and papillary thyroid carcinoma calcifications are caused by psammoma bodies.16 This study had limitations. First, the evaluation of cases was retrospective, and there was an unavoidable selection bias, which could have resulted in an artifact cased by a clinical practice pattern of more aggressive tissue sampling for nodules with suspicious features. A prospective analysis may provide more information and reduce the selection bias.

Table 3. Sonographic Features of Small and Large Medullary Thyroid Carcinomas Sonographic Feature Diagnosis, n (%) Probably benign Indeterminate Suspiciously malignant Composition, n (%) Solid >50% solid .99 >.99

7 (100) 0 0

30 (96.8) 1 (3.2) 0

>.99 >.99 NA

0 0 3 (42.9) 4 (57.1)

0 1 (3.2) 19 (61.3) 11 (35.5)

NA >.99 .425 .401

0 5 (71.4) 2 (28.6)

19 (61.3) 4 (12.9) 8 (25.8)

.008 .004 >.99

0 6 (85.7) 1 (14.3)

18 (58.0) 7 (22.6) 6 (19.4)

.009 .004 >.99

1 (14.3) 0

7 (22.6) 12 (38.7)

>.99 .074

P

Second, because of the low frequency of medullary thyroid carcinomas, fewer cases were included and were further divided into small and large lesions. In conclusion, our data indicate that the sonographic features of medullary thyroid carcinoma associated with tumor size more frequently include a taller-than-wide shape and a spiculated margin in small nodules and an ovoid-to-round shape and a smooth margin in nodules larger than 10 mm; furthermore, our findings also suggest that sonographic features for discrimination of medullary thyroid carcinoma from papillary thyroid carcinoma are an ovoid-to-round shape, a smooth margin, and the presence of macrocalcifications in large nodules. Large medullary thyroid carcinomas are more frequently diagnosed as indeterminate nodules by sonography than large papillary thyroid carcinomas.

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Sonographic features of medullary thyroid carcinomas according to tumor size: comparison with papillary thyroid carcinomas.

The aim of this study was to evaluate the differences in sonographic features of medullary thyroid carcinomas according to nodule size and compared wi...
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