Objective To determine the association of macrocalcification and rim calcification with malignancy and to stratify the malignancy risk of thyroid nodules with macrocalcification and rim calcification based on ultrasound (US) patterns. Materials and Methods The study included a total of 3603 consecutive nodules (≥ 1 cm) with final diagnoses. The associations of macrocalcification and rim calcification with malignancy and malignancy risk of the nodules were assessed overall and in subgroups based on the US patterns of the nodules. The malignancy risk of the thyroid nodules was categorized as high (> 50%), intermediate (upper-intermediate: > 30%, ≤ 50%; lower-intermediate: > 10%, ≤ 30%), and low (≤ 10%). Results Macrocalcification was independently associated with malignancy in all nodules and solid hypoechoic (SH) nodules ( p < 0.001). Rim calcification was not associated with malignancy in all nodules ( p = 0.802); however, it was independently associated with malignancy in partially cystic or isoechoic and hyperechoic (PCIH) nodules ( p = 0.010). The malignancy risks of nodules with macrocalcification were classified as upper-intermediate and high in SH nodules, and as low and lower-intermediate in PCIH nodules based on suspicious US features. The malignancy risks of nodules with rim calcification were stratified as low and lower-intermediate based on suspicious US features. Conclusion Macrocalcification increased the malignancy risk in all and SH nodules with or without suspicious US features, with low to high malignancy risks depending on the US patterns. Rim calcification increased the malignancy risk in PCIH nodules, with low and lower-intermediate malignancy risks based on suspicious US features. However, the role of rim calcification in risk stratification of thyroid nodules remains uncertain.

Objective: To determine the malignancy risk of isolated macrocalcifications (a calcified nodule with complete posterior acoustic shadowing) detected on ultrasonography (US) and to evaluate the postoperative American Thyroid Association (ATA) risk stratification of malignant tumors manifesting as isolated macrocalcifications. Materials and Methods: A total of 3852 thyroid nodules (≥ 1 cm) of 3061 consecutive patients who had undergone biopsy between January 2011 and June 2018 were included in this study. We assessed the prevalence, malignancy rate, and size distribution of isolated macrocalcifications and evaluated the histopathologic features and postoperative ATA risk stratification of malignant tumors manifesting as isolated macrocalcifications. Results: Isolated macrocalcifications were found in 38 (1.2%) of the 3061 patients. Final diagnosis was established in 30 (78.9%) nodules; seven malignant tumors were diagnosed as papillary thyroid carcinomas (PTCs). The malignancy rate of the isolated macrocalcifications was 23.3% in the 30 nodules with final diagnoses and 18.4% in all nodules. Among the six surgically-treated malignant tumors, five (83.3%) had an extrathyroidal extension (ETE) (minor ETE 1, gross ETE 4), and two (33.3%) had macroscopic lymph node metastasis. Four (66.7%) malignant tumors were categorized as high-risk tumors, one as an intermediate-risk tumor, and one as a low-risk tumor using the ATA risk stratification. Histopathologically, out of the six malignant tumors, ossifications were noted in four (66.7%) and predominant calcifications in two (33.3%). Conclusion: The US pattern of isolated macrocalcifications (≥ 1 cm) showed an intermediate malignancy risk (at least 18.4%). All malignant tumors were PTCs, and most showed an aggressive behavior and a high or intermediate postoperative ATA risk.

Raf-1 kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, suppresses metastasis in a number of cancer types, including colorectal carcinoma (CRC); thus, RKIP downregulation significantly contributes to CRC invasiveness and metastatic potential. However, our previous study demonstrated that RKIP-positive tumors in CRC patients are predictive of hepatic colorectal metastases (HCMs). Based on the previous finding that the ERK pathway can be activated independently of RKIP, we hypothesized that RKIP-expressing HCMs may express significant levels of phosphorylated ERK (pERK). Thus, the present study evaluated the expression of RKIP and pERK in 68 HCM tissue samples using immunohistochemistry. RKIP expression was positive in 22 (32.4%) of the 68 samples, seven (31.8%) of which exhibited nuclear pERK immunoreactivity exclusively at the invasive tumor front. Furthermore, pERK expression at the invasive front was significantly associated with recurrent HCM following hepatic resection, and pERK expression observed at the invasive front of RKIP-expressing HCMs indicated that the activation of the ERK pathway may also be involved in the invasive process of these tumors, despite the presence of RKIP. A strong association between pERK expression and the presence of recurrent HCM may indicate that the ERK pathway is important in the metastatic recurrence of RKIP-positive HCM.