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Purpose: This study compared the malignancy risk of intermediate suspicion thyroid nodules according to the presence of suspicious ultrasonographic (US) findings. Methods: From January 2014 to December 2014, 299 consecutive intermediate suspicion thyroid nodules in 281 patients (mean age, 50.6±12.5 years) with final diagnoses were included in this study. Two radiologists retrospectively reviewed the US findings and subcategorized the intermediate suspicion category into nodules without suspicious findings and nodules with suspicious findings, including punctate echogenic foci, nonparallel orientation, or irregular margins. The malignancy rates were compared between the two subcategory groups. Results: Of the 299 intermediate suspicion thyroid nodules, 230 (76.9%) were subcategorized as nodules without suspicious findings and 69 (23.1%) as nodules with suspicious findings. The total malignancy rate was 33.4% (100/299) and the malignancy rate of nodules with suspicious findings was significantly higher than that of nodules without suspicious findings (47.8% vs. 29.1%, P=0.004). In nodules with suspicious findings, the most common suspicious finding was punctate echogenic foci (48/82, 58.5%) followed by nonparallel orientation (22/82, 26.8%) and irregular margins (12/82, 14.6%). Thirteen nodules had two suspicious findings simultaneously. A linearly increasing trend in the malignancy rate was observed according to the number of suspicious US findings (P for trend=0.001). Conclusion: Intermediate suspicion thyroid nodules with suspicious findings showed a higher malignancy rate than those without suspicious findings. Further management guidelines for nodules with suspicious findings should differ from guidelines for nodules without suspicious findings, even in the same US category. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the ultrasound (US) features of malignancy in patients with Hürthle cell neoplasms (HCNs) of the thyroid gland. Methods: The present study included 139 HCNs that had undergone surgical excision at a single institution from 1996 to 2020 and had preoperative US images. The sonographic characteristics of HCNs were correlated with their pathological results. The US findings associated with malignancy were explored using logistic regression analysis, and the diagnostic performance and cutoff were assessed using receiver operating characteristic analysis. Results: The most common US findings of HCNs were a solid content (76.3%), oval to round shape (100%), hypoechogenicity (70.5%), a smooth margin (95.0%), the halo sign (90.6%), and no calcifications (93.5%). HCNs were commonly smaller in pathologic measurements than in US measurements (smaller, same, and greater than US measurements in 60.4%, 21.6%, and 18.0% of HCNs, respectively; P<0.001). On US, malignant nodules were significantly larger than benign nodules (3.4±1.6 cm vs. 2.2±1.2 cm, P<0.001). Multiple logistic regression showed that the US tumor size was an independent predictor of malignancy (P=0.001; odds ratio, 1.730 for a 1-cm increase [95% confidence interval, 1.258 to 2.375]). The best cutoff US tumor size for predicting malignancy was 3.35 cm (sensitivity, 53.1%; specificity, 87.9%). Conclusion: The US tumor size was found to be an independent predictor of malignancy in HCNs, and a US tumor size >3.35 cm might be used as a criterion to suggest malignancy. The size of HCNs often showed discrepancies between US and pathologic measurements. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of the tall cell variant of papillary thyroid carcinoma (TCVPTC), which has a poor prognosis, has increased as its definition has been modified. We sought to investigate whether TCVPTC is different from the classic type on ultrasonography (US). Methods: This study included 46 consecutive TCVPTC patients and 92 classic papillary thyroid carcinoma (PTC) patients who were confirmed surgically at the authors' institution. The US findings and pathologic reports of these patients were retrospectively reviewed. US features based on the Korean Thyroid Imaging Reporting and Data System, preoperative US suspicion for lymph node metastasis, and the presence of capsular location were evaluated. Results: Univariable and multivariable analyses identified that TCVPTC showed more frequent irregular tumor margin (odds ratio [OR], 6.62; 95% confidence interval [CI], 1.46 to 30.09; P=0.014) and capsular location (OR, 4.63; 95% CI, 1.49 to 14.41; P=0.008) than classic PTC. Capsular location was an independent predictor of TCVPTC for tumors less than or equal to 1.5 cm in size (OR, 4.23; 95% CI, 1.12 to 15.92; P=0.033). Irregular margin was an independent predictor of TCVPTC for tumors larger than 1.5 cm (OR, 10.46; 95% CI, 1.16 to 94.48; P=0.037). Extrathyroidal extension was not significantly different between the two groups. Conclusion: The two key features of TCVPTC on US are frequent capsular location for tumors less than or equal to 1.5 cm in size and the higher likelihood of an irregular margin for tumors larger than 1.5 cm. [ABSTRACT FROM AUTHOR]

We previously reported that high thyroid-stimulating hormone (TSH) levels are associated with papillary thyroid microcarcinoma (PTMC) progression during active surveillance. However, validation with multicenter, long-term data, and identification of appropriate age or TSH levels are needed. This multicenter retrospective study enrolled PTMC patients under active surveillance with TSH measurements and ultrasonography. The primary outcome was PTMC progression (volume increase ≥50%, size increase ≥3 mm, or new lymph node (LN) metastasis). PTMC progression according to time-weighted average of TSH (TW-TSH) groups was compared using survival analyses in overall patients and each age subgroups (<40, 40-49, 50-59, and ≥60 years). The identification of TW-TSH cutoff point for PTMC progression and trend analysis of PTMC pro gression rate according to LT4 treatment were also performed. During 1061 person-years of follow-up, 93 of 234 patients (39.7%) showed PTMC progression (90, 17, and 5 patients for volume increase ≥50%, size increase ≥3 mm, and new LN metastasis, respectively). The highest TW-TSH group was the risk factor most strongly associated with PTMC pr ogression (hazard ratio 2.13 (1.24-3.65); P = 0.006), but the impact was significant only in patients aged <4 0 or 40-49 years (hazard ratio 30.79 (2.90-326.49; P = 0.004), 2.55 (1.00-6.47; P = 0.049)). For patients aged <50 years, TW-TSH cutoff for PTMC progression was 1.74 mU/L, and PTMC progression rates successively increased in the order of effective, no, and ineffective LT4 treatment group (P for trend = 0.034). In young PTMC patients (<50 years), sustained lownormal TSH levels during active surveillance might be helpful to prevent progression. [ABSTRACT FROM AUTHOR]

Purpose: This study compared the diagnostic performance of the modified Korean Thyroid Imaging Reporting and Data System (K-TIRADS) for thyroid malignancy with three international guidelines. Methods: From June to September 2015, 5,708 thyroid nodules (≥ 1.0 cm) in 5,081 consecutive patients who underwent thyroid ultrasound (US) at 26 institutions were evaluated. The US features of the thyroid nodules were retrospectively reviewed and classified according to all four guidelines. In the modified K-TIRADS, the biopsy size threshold was changed to 2.0 cm for K-TIRADS 3 and 1.0 or 1.5 cm for K-TIRADS 4 (K-TIRADS1.0cm and K-TIRADS1.5cm, respectively). We compared the diagnostic performance and unnecessary fine-needle aspiration biopsy (FNAB) rates for thyroid malignancy between the modified K-TIRADS and three international guidelines. Results: Of the 5,708 thyroid nodules, 4,597 (80.5%) were benign and 1,111 (19.5%) were malignant. The overall sensitivity was highest for the modified K-TIRADS1.0cm (91.0%), followed by the European (EU)-TIRADS (84.6%), American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME) (80.5%), American College of Radiology (ACR)-TIRADS (76.1%), and modified K-TIRADS1.5cm (76.1%). For large nodules (>2.0 cm), the sensitivity increased to 98.0% in both the modified K-TIRADS1.0cm and K-TIRADS1.5cm. For small nodules (≤ 2.0 cm), the unnecessary FNAB rate was lowest with the modified K-TIRADS1.5cm (17.6%), followed by the ACR-TIRADS (18.6%), AACE/ACE/AME (19.3%), EU-TIRADS (28.1%), and modified K-TIRADS1.0cm (31.2%). Conclusion: The modified K-TIRADS1.5cm can reduce the unnecessary FNAB rate for small nodules (1.0-2.0 cm), while maintaining high sensitivity for detecting malignancies >2.0 cm. [ABSTRACT FROM AUTHOR]

The article titled "Re: Subdivision of intermediate suspicion, the 2021 K-TIRADS, and category III, indeterminate cytology, the 2017 TBSRTC, 2nd edition, in thyroidology: let bygones be bygones?" discusses a letter to the editor from Sengul and Sengul regarding a recent paper on the subcategorization of intermediate suspicion thyroid nodules based on suspicious ultrasonographic findings. The authors appreciate the interest and insightful comments from Sengul and Sengul, particularly regarding the echogenicity of the included nodules. The study population was limited to thyroid nodules in the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) category 4, which excluded certain types of nodules. The authors agree with the importance of subdividing the intermediate or indeterminate category and express gratitude for the contribution to the discussion. [Extracted from the article]

Purpose: This study was conducted to evaluate the diagnostic performance of machine learning in differentiating follicular adenoma from carcinoma using preoperative ultrasonography (US). Methods: In this retrospective study, preoperative US images of 348 nodules from 340 patients were collected from two tertiary referral hospitals. Two experienced radiologists independently reviewed each image and categorized the nodules according to the 2015 American Thyroid Association guideline. Categorization of a nodule as highly suspicious was considered a positive diagnosis for malignancy. The nodules were manually segmented, and 96 radiomic features were extracted from each region of interest. Ten significant features were selected and used as final input variables in our in-house developed classifier models based on an artificial neural network (ANN) and support vector machine (SVM). The diagnostic performance of radiologists and both classifier models was calculated and compared. Results: In total, 252 nodules from 245 patients were confirmed as follicular adenoma and 96 nodules from 95 patients were diagnosed as follicular carcinoma. As measures of diagnostic performance, the average sensitivity, specificity, and accuracy of the two experienced radiologists in discriminating follicular adenoma from carcinoma on preoperative US images were 24.0%, 84.0%, and 64.8%, respectively. The sensitivity, specificity, and accuracy of the ANN and SVMbased models were 32.3%, 90.1%, and 74.1% and 41.7%, 79.4%, and 69.0%, respectively. The kappa value of the two radiologists was 0.076, corresponding to slight agreement. Conclusion: Machine learning-based classifier models may aid in discriminating follicular adenoma from carcinoma using preoperative US. [ABSTRACT FROM AUTHOR]

Background: Follicular variant of papillary thyroid carcinoma (FVPTC) is traditionally divided into infiltrative and encapsulated types. Adding to this classification, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a reclassification of a subset of cases (encapsulated tumors without lymphovascular or capsular invasion). The purpose of this study was to assess the role of ultrasound (US) in predicting tumor invasiveness in FVPTC. Methods: From January 2014 to May 2016, preoperative US examinations were performed on 151 patients with 152 FVPTCs who underwent surgery. Based on a pathologic analysis, the FVPTCs were categorized into three groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I-FVPTC). Each nodule was categorized based on the US pattern according to the Korean Thyroid Imaging Reporting and Data System (KTIRADS) and the American Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness and the K-TIRADS or ATA category was investigated using Spearman's rank correlation coefficient. Results: Among the 152 FVPTCs, there were 48 (31.6%) NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) IFVPTCs. US characteristics of the FVPTCs differed significantly according to tumor invasiveness (p ≤ 0.030). Tumor invasiveness showed a significant positive correlation with K-TIRADS (tumors of all sizes: r = 0.591, p < 0.001; tumors ≥1.0 cm: r = 0.427, p < 0.001) and ATA categories (tumors of all sizes: r = 0.532, p < 0.001; tumors ≥1.0 cm: r = 0.466, p < 0.001). According to both K-TIRADS and ATA guidelines for all-sized tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and 51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases were confirmed in two (4.2%) NIFTP cases, three (5.0%) iEFVPTC cases, and eight (18.2%) I-FVPTC cases (p = 0.001). The results of the BRAF mutation analysis were not significantly different between the groups ( p = 0.507). Conclusions: Increasing tumor invasiveness from NIFTP to iE-FVPTC to I-FVPTC is positively correlated with the level of suspicion on US using both K-TIRADS and ATA guidelines. [ABSTRACT FROM AUTHOR]

Ultrasonography (US) is routinely used to evaluate thyroid nodules. The US features of papillary thyroid carcinoma (PTC), the most common thyroid malignancy, include hypoechogenicity, spiculated/microlobulated margins, microcalcifications, and a nonparallel orientation. However, many PTC variants have been identified, some of which differ from the classic type of PTC in terms of biological behavior and clinical outcomes. This review describes the US features and clinical implications of the variants of PTC. With the introduction of active surveillance replacing immediate biopsy or surgical treatment of indolent, small PTCs, an understanding of the US characteristics of PTC variants will facilitate the individualized management of patients with PTC. [ABSTRACT FROM AUTHOR]

PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142). In addition, we analyzed the relationships between PD-L1 expression and clinicopathologic factors, including TERT promoter, BRAF status and disease progression. Tumoral PD-L1 was expressed in 6.1% of papillary thyroid carcinomas, 7.6% of follicular thyroid carcinomas and 22.2% of anaplastic thyroid carcinomas. The distribution of PD-L1 positivity was different according to cancer histology types (P < 0.001). All PD-L1-positive cases of follicular thyroid carcinoma and anaplastic thyroid carcinoma showed strong intensity. The proportions of positivity in PD-L1 positive anaplastic thyroid carcinomas were more than 80%. PD-L1 in immune cells was positive in 28.5% of papillary thyroid carcinoma, 9.1% of follicular thyroid carcinomas and 11.1% of anaplastic thyroid carcinomas. There was no significant association between clinicopathologic variables, disease progression, oncogenic mutation and PD-L1 expression. PD-L1 was highly expressed in a subset of patients with advanced thyroid cancer, such as follicular and anaplastic thyroid carcinoma. Identification of PD-L1 expression may have direct therapeutic relevance to patients with refractory thyroid cancer. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to investigate the level of agreement between tumor sizes measured on ultrasonography (US) and in pathological specimens of papillary thyroid carcinomas (PTCs) and to identify the US characteristics contributing to discrepancies in these measurements. Methods: We retrospectively reviewed the US findings and pathological reports of 490 tumors in 431 patients who underwent surgery for PTC. Agreement was defined as a difference of <20% between the US and pathological tumor size measurements. Tumors were divided by size into groups of 0.5-1 cm, 1-2 cm, 2-3 cm, and ≥3 cm. We compared tumors in which the US and pathological tumor size measurements agreed and those in which they disagreed with regard to the following parameters: taller-than-wide shape, infiltrative margin, echogenicity, microcalcifications, cystic changes in tumors, and the US diagnosis. Results: The rate of agreement between US and the pathological tumor size measurements was 64.1% (314/490). Statistical analysis indicated that the US and pathological measurements significantly differed in tumors <1.0 cm in size (P=0.033), with US significantly overestimating the tumor size by 0.2 cm in such tumors (P<0.001). Cystic changes were significantly more frequent in the tumors where US and pathological tumor size measurements disagreed (P<0.001). Conclusion: Thyroid US may overestimate the size of PTCs, particularly for tumors <1.0 cm in size. This information may be helpful in guiding decision making regarding surgical extent. [ABSTRACT FROM AUTHOR]

Background: Bethesda System category III (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) creates a dilemma because of heterogeneity. The aim of this study was to assess whether ultrasonography (US) contributes to differentiating AUS from FLUS and may suggest characteristics of malignancy within category III. Methods: From April 2011 to April 2012, 433 thyroid nodules that had been interpreted as nuclear atypia (AUS group; n = 322) or microfollicular architecture (FLUS group; n = 111) were included in the retrospective study. Final diagnoses were acquired in 327 nodules after surgery and clinico-radiological follow-up. The AUS group and FLUS group were compared in terms of US features (composition, echogenicity, margin, shape, and calcifications), US diagnosis (probably benign, malignant), malignancy rate, and final malignant histology. Results: In univariate and multivariate analysis, the AUS group more frequently had non-circumscribed margins, taller-than-wide shape, and an US diagnosis suggestive for malignancy than the FLUS group did. The risk of malignancy was significantly higher in the AUS group than it was in the FLUS group (51.0% vs.8.1%; p < 0.001). There was a significant difference in the presence of a BRAF mutation between the AUS group and the FLUS group (47.6% vs. 4.2%; p < 0.001). Of the patients with malignancy, papillary thyroid carcinoma was found more frequently in the AUS group than in the FLUS group (97.7% vs. 66.7%; p = 0.004). The incidence of follicular thyroid carcinoma was significantly higher in the FLUS group than it was in the AUS group (33.3% vs.1.6%; p = 0.004). Conclusion: Bethesda System category III subcategorization into AUS and FLUS can be supported by US features. In Bethesda III nodules, US features may further help in predicting a malignant histology. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare ultrasonographic features in patients with lymphocytic thyroiditis (LT) and papillary thyroid carcinoma (PTC) having suspicious thyroid nodule(s) in a background of heterogeneous parenchyma and to determine the clinical and radiological predictors of malignancy. Methods: We reviewed the cases of 100 patients who underwent ultrasonography between April 2011 and October 2012, and showed suspicious thyroid nodule(s) in a background of heterogeneous parenchyma. Eight patients who did not undergo ultrasonography-guided fineneedle aspiration cytology (FNAC) and 34 cases of follow-up ultrasonography after initial FNAC were excluded. We compared the benign and malignant nodules in terms of their clinical and radiological factors. Results: For the 58 nodules including 31 LTs (53.4%) and 27 PTCs (46.6%), the mean tumor sizes of the two groups were 0.96 cm for LT and 0.97 cm for PTC. A univariate analysis revealed that PTCs were more frequent in patients younger than 45 years and having microcalcifications than was LT. An independent predictor of PTC after adjustment was an age of <45 years. Conclusion: LT mimics malignancy in a background of heterogeneous parenchyma on ultrasonography. A young age of <45 years is the most important predictor of malignancy in this condition. [ABSTRACT FROM AUTHOR]

Background:Hyalinizing trabecular tumors of the thyroid (HTT) is a rare entity. Most behave as benign neoplasms, but their cytological features are challenging and can be similar to those of papillary thyroid carcinoma (PTC). The aim of this study was to compare the ultrasonography (US) readings of HTT with the cytology and frozen section readings.Methods:We retrospectively analyzed the US and cytology features in 10 patients (mean age, 47.5 years, range 26–81; M:F, 1:9) seen between March 2006 and November 2009 who had a histopathological diagnosis of HTT. The US findings were categorized according to the size, shape, margin, echogenicity, echotexture, presence of hypoechoic halo, and microcalcifications. Preoperative fine-needle aspiration cytology, frozen section results, and surgical treatment were reviewed. US features of HTT were compared with those of other tumors including follicular adenomas, follicular variant of PTCs, and conventional PTC.Results:Out of the 10 patients in our series, 7 underwent total thyroidectomy, and 3 had lobectomy. The sizes of the HTTs ranged from 0.6 to 4.2 cm (mean, 1.77 cm). The most common US features were solid texture (10/10), oval to round shape (10/10), a well-defined aspect (10/10), hypoechoic character (8/10), heterogeneous character (7/10), the presence of a hypoechoic halo (8/10), and no microcalcifications (10/10). The US diagnosis was indeterminate in all but one case and that was read as a benign lesion. As far as the shape and margin US features were concerned, HTT was considered to be most similar to follicular adenomas and follicular variant of PTC, but not to classical PTC. The cytology reading was PTC in 6 of 10 cases, suspicious for PTC in 2, and a HTT versus PTC in 2. The histological diagnosis of frozen sections, when performed, was PTC in three, HTT in three, medullary thyroid carcinoma in two, and deferred in one.Conclusion:HTT often appears similar to follicular neoplasm on US, but it can be misjudged on cytology as PTC, even in frozen sections. HTT should be included in the list of discordant US—cytology readings of thyroid tumors. This rare tumor might be suspected more often preoperatively by careful attention to cytology in the context of the US reading. [ABSTRACT FROM AUTHOR]

The recent American Thyroid Association management guidelines suggest cervical ultrasonography (US) surveillance in patients with differentiated thyroid cancer (DTC). This study was conducted to identify predictive factors that can determine whether subsequent fine needle aspiration guided by ultrasound (US-FNA) is indicated in patients with lesions detected by US after surgery for DTC. Retrospective analysis at a university-based tertiary hospital. We reviewed 207 cases of postoperative US-FNA in 180 patients diagnosed with DTC. We examined the relationship between US-FNA histology and clinical factors, imaging abnormalities found by US and with other modalities and pathological staging. US-FNA recurrence was positive in 56 (27%) cases and negative in 151 (73%) cases. The mean lesion size for FNA was 0·83 cm (range 0·2-2·9 cm). Univariate analysis indicated that tumour recurrence on US-FNA is associated with elevated stimulated thyroglobulin (sTg) levels, with the initial size of the primary tumour, with abnormal US findings, including the ipsilateral site, level III or IV location and extrathyroidal extension, and with other imaging abnormalities. However, multivariate analysis revealed an independent association between recurrence on FNA and suspicious US findings (OR 9·410; 95% CI 3·322-26·654; P < 0·001) and elevated serum sTg (OR 5·001; 95% CI 1·067-23·485; P = 0·041). Findings on US that were discriminating for recurrent nodules at the thyroidectomy site were abnormalities that were not oval shape or which had an irregular margin. Calcifications or cystic change showed a low sensitivity of 14%. US-FNA for diagnosis of recurrence after surgery for DTC may be limited to patients with elevated sTg or with lesions that have specific suspicious US findings. [ABSTRACT FROM AUTHOR]

Diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is a rare variant of papillary thyroid carcinoma, for which the imaging and cytologic features have not been reported. The aim of this study is to gain better insight into the characteristic imaging and cytologic features of DSPC and to suggest treatment guidelines. We retrospectively analyzed the ultrasonographic and computed tomographic (CT) features in eight patients diagnosed with pathologically proven DSPC between 1996 and 2006. Of these eight patients, five patients underwent preoperative ultrasonography (US)–guided fine-needle aspiration (FNA). All the patients were women, who presented at a relatively young age (mean age: 31.9 years) with large tumors (mean diameter: 5.9 cm) and cervical lymph node metastases. The US features (7/8) of DSPC were heterogeneous echotexture (7/7), solid composition (7/7), ill-defined margins (4/7), scattered microcalcifications having snowstorm appearance (7/7), and various echogenicities. CT findings (6/8) revealed numerous microcalcifications and multiple enlarged nodes in all the patients. Cytological examination showed lymphocytes intermingled with nests of tumor cells, psammoma bodies, and squamous differentiation with typical nuclear features of papillary carcinoma in all. Through the combination of typical imaging findings and careful cytological examination, DSPC can be diagnosed preoperatively, allowing for the aggressive surgical treatment required in treating this disease. [ABSTRACT FROM AUTHOR]