The US findings of the MTCs and PTCs are summarized in the Table 1. For the MTCs, a solid internal content (19 of 21, 90.5%), ovoid to round shape (12 of 21, 57.1%), marked hypoechogenicity (11 of 21, 52.4%), microcalcifications or macrocalcifications (11 of 21, 52.4%) and a spiculated or ill-defined margin (17 of 21, 80.9%) were the prevailing findings seen on US. For 21 MTCs, 17 (81%) were categorized as suspicious malignant nodules, and four (19%) were categorized as indeterminate nodules (Figs. 1, 2). None of the lesions were categorized as probably benign nodules. For the PTCs, the prevailing findings as seen on US were a solid internal content (110 of 114, 96.5%), taller than wide shape (48 of 114, 48%), irregular border (48 of 114, 42.1%), marked hypoechogenicity (65 of 114, 57.0%) and microcalcifications or macrocalcifications (74 of 114, 64.9%). For 114 PTCs, 107 (94%) were categorized as suspicious malignant nodules and seven (6%) were categorized as indeterminate nodules (Fig. 3). The mean size (19 ± 13.9 mm vs. 11 ± 7.5 mm) and ovoid to round shape (57.1% vs. 25.4%) were statistically different between the MTCs and PTCs. However, the internal content, margin, echogenicity and calcifications were not statistically significantly different between the two types of nodules. Most of the MTC and PTC nodules were classified as suspicious malignant; however, the frequency of an indeterminate nodule was higher for the MTCs than for the PTCs.

Eighty to ninety percent of MTCs have been considered as sporadic and the rest have been classified as hereditary (1). The familial form of the tumor usually occurs as a component of type IIa MEN (Sipple syndrome), which is characterized by the combination of an MTC, adrenal pheochromocytoma and hyperplasia of the parathyroid glands. MEN type IIb is a highly unusual form of the MEN II syndrome and consists of elements of type IIa and additional features of marfanoid habitus, mucosal neuromas and intestinal ganglioneuromatosis. In the present study, 16 patients were categorized as having the sporadic form and two patients were categorized as having MEN type IIa.

Fine needle aspiration (FNA) of thyroid nodules has become one of the most useful, safe and accurate methods used to diagnose thyroid pathology. US findings are important to evaluate and prioritize nodules during FNA. US findings have been reported to be of great help to distinguish malignant from benign nodules (6-11, 13). The US findings that have been reported for malignant thyroid nodules have included completely solid or predominantly solid nodules, hypoechogenicity as compared with the strap muscles, an irregular margin, intranodular microcalcifications, a taller than wide orientation and increased intranodular vascularity. Moon et al. (6) reported in a multicenter retrospective study the US findings of benign and malignant thyroid nodules (6). The Thyroid Study Group of the KSNHNR organized this study, which was performed on patients from nine university hospitals and large general hospitals in the Republic of Korea. The findings suggested malignancy in nodules with a taller than wide shape, spiculated margin, marked hypoechogenicity, and intranodular calcifications (including microcalcifications or macrocalcifications). The findings of the study demonstrated a high sensitivity (93.8%) and a high negative predictive value (95.9%). In most cases, the malignant nodules that were included in the Moon et al. (6) study and similar studies were PTCs, and most of the PTCs correlated with the US findings of malignant thyroid nodules (10-13). However, studies on the US findings of MTC are not common (14, 15). Gorman et al. (14) reported on the high-resolution US findings of MTC in 1987. All of the tumors (six lesions in six patients) appeared hypoechoic and were relatively well defined. Bright echogenic foci were reported in five patients (83.3%), and this finding was supported by the histological finding of focal deposits of calcium surrounded by amyloid. In 2002, Saller et al. (15) reported the US findings of 19 MTC cases. All of the cases showed hypoechogenicity. The present study evaluated 21 MTC cases, a higher number than in previous studies. Most MTC nodules (95.3%) were markedly hypoechoic (52%) or hypoechoic (42.9%), and our findings are similar to the findings of the above two studies (14, 15). In the current study, intranodular calcifications were observed in 52% of the MTC patients. As compared to the results of the Gorman et al. (83.3%) and Saller et al. (95%) studies, we found a low calcification rate.

Studies comparing the US findings of MTC with PTC have not been previously conducted and we compared and analyzed the US findings of 21 MTC cases and 114 PTC cases. The mean size of MTC nodules was larger than that of PTC nodules (19 ± 13.9 mm vs. 11 ± 7.5 mm, p < 0.05). In a comparison of the US findings, 57% of MTCs and 25% of PTCs exhibited an ovoid to round shape, which was significantly higher for the MTC nodules (p < 0.05). However, internal content, margin, echogenicity and frequency of calcifications were not significantly different between MTCs and PTCs. Most MTC (80.9%) and PTC (93.9%) nodules were classified as suspicious malignant nodules. However, in a comparison of MTCs with PTCs, suspicious malignant nodules were found less frequently and indeterminate nodules were found more frequently in MTC than in PTC. This finding can be attributed to a significantly higher frequency of ovoid to round shape in MTC, which is not a suspicious malignant feature. Both MTCs and PTCs have been associated with calcifications more than other thyroid malignancies. The association of an MTC with amyloid deposition pathologically distinguishes this type of tumor from other thyroid malignancies (16). Amyloid deposits may be associated with reactive fibrosis and calcified deposits that give rise to characteristically dense, irregular foci throughout the tumor mass. This observation is in contrast with the faint homogeneous calcifications seen in other thyroid tumors (1). Dense and irregular calcifications are known as a characteristic finding of MTC; these macrocalcifications were seen in five MTC nodules (23.8%) and in 21 PTC nodules (18.4%). Saller et al. (15) defined calcifications longer than 2 mm as macrocalcifications, and reported the presence of macrocalcifications in 53% of MTC patients in their study; this frequency was higher than in our study. Chan et al. (11) found that among 55 PTC cases, 11% were associated with macrocalcifications; this frequency was similar to the frequency seen in the present study. The presence of microcalcifications is a known characteristic finding of PTC and microcalcifications have been reported in 29-59% of all thyroid carcinomas (17). In our study, microcalcifications were found in 29% of MTCs and 47% of PTCs. According to the findings in the study by Chan et al. (11), 42% of PTCs were associated with microcalcifications, a finding that is similar to our results. Saller et al. (15) reported that microcalcifications less than 2 mm in length were seen in 42% of MTCs.

Serum calcitonin levels rise in MTC patients as MTCs are derived from parafollicular C-cells that produce calcitonin (2). However, not all MTCs secrete calcitonin and in particular, more advanced tumors may dedifferentiate with a subsequent decrease in calcitonin production (3). In the present study, the basal calcitonin level was elevated in 14 patients and was within the normal range in one patient. The patient with a normal calcitonin level had a huge, 7 cm thyroid mass with an extensive necrotic lymph node metastasis and perithyroidal soft tissue invasion. The pathological result was a poorly differentiated pattern of MTC.

In conclusion, the common US features of MTC are a solid internal content, an ovoid to round shape, marked hypoechogenicity and calcifications. Most MTCs showed US findings of suspicious malignant nodules, as reported by the Thyroid Study Group of the KSNHNR. The US findings were not greatly different between MTCs and PTCs, except that the ovoid to round shape was more abundant in MTCs.