The results of the present study showed that microcalcification is directly associated with increased risk of thyroid nodule malignancy, which is in agreement with the existing data in the literature [9, 10]. It was also found that the calculated sensitivity for the microcalcification was 26%. In contrast, the specificity was as high as 89.8%. The low sensitivity was not unexpected and could be explained by that the microcalcification is generally observed at a low rate on the thyroid nodule ultrasonography.
We also tried to find out whether accompanying microcalcification by coarse calcification affects the diagnostic accuracy of microcalcification alone. In this regard, our analyses did not indicate a significant association between fine-coarse calcification and nodule malignancy, contrary to microcalcification alone. This finding is similar to our previously published data . In other words, it seems that simultaneous presence of coarse calcification will probably decrease the diagnostic value of microcalcification for predicting malignancy. According to the literature, the association of malignancy with coarse calcification has remained debatable, especially in nodules lacking other malignant features [12, 13]. Our finding is notable in terms of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS). Based on ACR TI-RADS, when different calcification types are simultaneously observed on sonography, the score of each echogenic foci type should be summed to yield an overall calcification score , while our results do not support this approach. Altogether, more surveys need to be carried out to clearly determine the accuracy of simultaneous presence of coarse and microcalcification in predicting malignant thyroid nodules.
As results demonstrated, irregular and lobulated margins (but not regular margin) were identified as ultrasonographic features suggesting malignancy in the nodules with microcalcification. Recently, a study by Siebert et al.  concluded that jagged edges and lobulated margin could be considered as predictors of papillary thyroid carcinoma. Overall, the information on the association between different margin types and cancer risk in the nodules with microcalcification is limited and more studies are needed.
In this study, no diagnostic value was identified for the composition stratification of the nodules with microcalcification. According to the recent studies, a variable rate of thyroid cancer has been seen in both cystic and solid nodules (about 5–18%) [16, 17]. Some studies declared that the cancer risk in solid nodules is higher than in cystic nodules. Moreover, simultaneous presence of microcalcification and predominantly solid component is associated with an about 3-fold increase in malignancy risk , which was inconsistent with our results. However, further investigations are necessary to make this association clear.
Our results indicated no significant relation between the nodule size and risk of malignancy. There is a controversy whether thyroid cancer risk rises with increasing nodule size [18, 19]. It has also been mentioned that the impact of size on the nodule malignancy risk could be variable by histopathologic type of the thyroid cancers. For instance, some studies noted that larger nodules could be associated with higher risk of non-papillary thyroid carcinoma [20, 21]. In other words, larger nodule sizes can increase risk of malignancy in low- or intermediate-suspicion nodules, but not in high-suspicion nodules. However, more studies need to clarify this issue.
According to the present study, ultrasonographic hypoechogenicity could be potentially a predictor of malignancy in the nodules with microcalcification. Despite the conflicting findings, hypoechoic nodules have been reported to be at higher risk of malignancy compared with iso- or hyperechoic nodules in most of the studies . In addition, it has been revealed that marked and/or moderate hypoechogenicity have a higher malignancy risk than mild hypoechogenicity . In a recent meta-analysis by Remonti et al. , the sensitivity for hypoechogenicity was estimated to be 62.7% among unselected thyroid nodules.
In the present study, it was found that the thyroid nodules with >5 intranodular microcalcifications were at higher risk of malignancy compared with those with <5 microcalcifications. Theoretically, it might be assumed that multiple intranodular microcalcification is probably associated with higher risk of thyroid malignancy than single intranodular microcalcification. However, no sufficient evidence exists on this subject. In the study by Kobayashi et al. , the authors stated that multiple punctate echogenic foci (>5 microcalcification number) were observed in all diffuse sclerosing variant of papillary carcinoma, but not in any follicular carcinoma lesions. Also, multiple punctate echogenic foci has been reported to be found in both benign and malignant thyroid nodules . Thus, other sonographic features along with the cytopathological appearance should be assessed for a correct diagnosis of nodules with multiple punctate echogenic foci. Based on the present results, as a suggestion, the subcategory of “intranodular microcalcification number” could be added to the TI-RADS echogenic foci scoring, upon which the microcalcification number is directly correlated with echogenic foci score. Altogether, more surveys are needed to find out whether risk of malignancy increases with the number of intranodular microcalcification.
A limitation of our study was the lack of access to the results of repeat FNA in some patients with the atypia. Further, the pathological results of malignant thyroids of patients who underwent surgery were not collected. Therefore, we suggest designing new studies to compare the sonographic and FNA results with pathological findings. Moreover, multicenter studies with larger sample size are recommended to enable more generalizable results.
A strength of the present study is the prospective design versus the previous studies which were retrospective. Therefore, our results are potentially more comprehensive and precise compared with other studies due to various issues in data collection (e.g., more accurate data recording and less recall bias).