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Background: The tall cell variant papillary thyroid carcinoma (TCV‐PTC) shows aggressive behaviour. Thus far, the diagnosis of TCV‐PTC can only be confirmed using the postoperative specimen. This study aims to evaluate whether fine‐needle aspiration (FNA) or core needle biopsy (CNB) could diagnose TCV‐PTC preoperatively. Methods: This is a retrospective cohort study. We included adult patients diagnosed with TCV‐PTC or PTC with tall cell features (TCF) at final surgical pathology between January 2015 and December 2018. Preoperative histology was reviewed for six cytomorphologic features suggesting TCV‐PTC in FNA or the percentage of tall cells in the CNB specimen. The postoperative pathology was also reviewed to confirm the percentage of tall cells. Results: A total of 119 patients were included in this study; 35 (29%) patients with PTC with TCF served as controls. The most frequent cytomorphological feature in FNA samples of TCV‐PTC was tall columnar cells, including single tombstone‐like cells (70%). Among 43 TCV‐PTC evaluated by FNA, 3 FNA (7%) revealed the absence of any of the six cytomorphologic features suggesting TCV‐PTC. When we defined 30% of tall cells in CNB specimens as a cutoff suggesting TCV‐PTC, only 16 (41%) TCV‐PTCs could be preoperatively detected, and 3 (7%) TCV‐PTCs did not have any tall cells. The proportion of tall cells was not associated with the postoperative percentage of tall cells. Conclusion: Both cytomorphologic features in FNA and the percentage of tall cells in CNB present limitations for use as accurate preoperative diagnostic tools of TCV‐PTC. [ABSTRACT FROM AUTHOR]

Background: Some papillary thyroid microcarcinomas (PTMCs) may progress with tumor enlargement or development of new lymph node (LN) metastasis during active surveillance (AS). This study evaluated the relevant predictors of disease progression, especially new cervical LN metastasis. Methods: This was a long-term follow-up study conducted using a previous multicenter cohort of AS in Korea. After excluding 54 (14.2%) patients with a short follow-up duration, 326 PTMC patients were evaluated for tumor kinetics, including changes in tumor volume (TV) and TV doubling time (TVDT). Results: During a median follow-up duration of 4.9 years, 17 (5.2%, 95% confidence intervals [CI] 2.7–7.6%) patients showed a maximal diameter increase of ≥3 mm after a median of 4.0 years follow-up, while 9 (2.8%, CI 1.0–4.5%) developed new LN metastasis after a median of 2.2 years follow-up. New cervical LN metastasis occurred exclusively of a maximal diameter increase of ≥3 mm. The prevalence of new development of LN metastasis was higher in patients with TVDT <5 years (7.4%) than in those with TV ≥50% (3.2%). Furthermore, only TVDT <5 years was significantly associated with LN metastasis (p = 0.002). In univariate and multivariate analyses, TVDT <5 years was an independent risk factor for disease progression with respect to new development of LN metastasis (hazard ratio [HR] = 6.51, CI 1.73–24.50; p = 0.002) and tumor enlargement (HR = 20.89, CI 5.78–75.48; p < 0.001). Finally, 86 (22.6%) patients underwent delayed surgery, and the most common reason was patient anxiety. Conclusions: TVDT <5 years is a predictor of disease progression during AS in terms of new LN metastasis development as well as tumor enlargement. Determination of TVDT in the early phase of AS could help in predicting disease progression, tailoring follow-up intensity of AS and in determining if early surgical intervention is needed. [ABSTRACT FROM AUTHOR]

Background: Although several studies have examined the value of thyroid nodule size as a malignancy predictor, the results are conflicting. Purpose: To investigate the relationship between nodule size and malignancy risk and to evaluate the impact of nodule size on the false-negative rate of fine needle aspiration or core needle biopsy according to the histological type of thyroid cancer. Material and Methods: From January 2013 to December 2013, 3970 thyroid nodules that underwent ultrasound-guided fine needle aspiration or core needle biopsy were retrospectively reviewed. We assessed the relationship between nodule size and malignancy risk according to histological type of thyroid cancer. In addition, we compared the false-negative rate by thyroid nodule size category. Results: Of 3970 thyroid nodules, 1170 nodules were malignant. For papillary thyroid carcinoma, nodule size was inversely related to malignancy risk, whereas in nodules of follicular carcinoma and follicular variant papillary thyroid carcinoma, nodule size was positively related to malignancy risk (P < 0.001). The false-negative rate tended to increase as nodule size increased (P = 0.002) for all nodules and the overall false-negative rate was 2.3%. Conclusion: Overall, nodule size does not correlate with risk of malignancy, but the relationship between nodule size and malignancy risk depends on the histological type of thyroid cancer. [ABSTRACT FROM AUTHOR]

Objective: Evidence for American Thyroid Association (ATA) risk stratification stems largely from studies involving patients undergoing total thyroidectomy. We aimed to assess the risk of recurrence according to the present ATA risk stratification system in patients who underwent lobectomy. Design: Retrospective cohort study. Patients: Patients who underwent thyroid lobectomy for 1‐4 cm‐sized papillary thyroid carcinoma (n = 571). Measurements: Disease‐free survival (DFS) was compared according to the ATA risk stratification, and specific lymph node (LN) characteristics were evaluated to modify the ATA criteria with a higher predictability for recurrence. Results: Based on the ATA risk stratification, 439 patients (61.1%) were classified into intermediate‐ or high‐risk group, and consideration for completion thyroidectomy is suggested by ATA guidelines for these patients. However, no significant differences were found in DFS among the low‐, intermediate‐ and high‐risk groups (P =.9). In contrast, when patients were stratified according solely to the LN criteria from the ATA risk stratification, only 127 patients (22.2%) had intermediate risk (intermediate‐N1a) and exhibited significantly poorer DFS than those with N0 disease (P =.035). Modifying the intermediate‐N1a criteria by adding the extranodal extension (ENE) status and omitting the clinical nodal disease enabled the subclassification of 19 patients (3%) with a high risk for recurrence. Conclusions: The present study suggests that risk stratification based solely on LN metastases is more reasonable for predicting structural persistence/recurrence following lobectomy than that based on the overall ATA criteria. Considering the ENE status can assist in selecting patients with a high risk of recurrence to minimize further treatments. [ABSTRACT FROM AUTHOR]

Objective: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine therapy (RAIT) affects clinical outcomes in papillary thyroid carcinoma (PTC). Therefore, we evaluated the impact of timing of the first post‐thyroidectomy RAIT in intermediate‐to‐high‐risk PTC. Design and Patients: This retrospective propensity score‐matched cohort study included 720 PTC patients who received RAIT for <90 or 90‐180 days (early and delayed groups, n = 360 each) after thyroidectomy. Responses to therapy, disease‐free survival (DFS) and overall survival (OS) were compared between the two groups. Results: After matching, the baseline characteristics of the 360 patients in each group were similarly adjusted. Within the first 2 years after initial therapy, the number of patients classified into excellent, indeterminate, biochemical incomplete and structural incomplete response categories were 221 (61%), 74 (21%), 39 (11%) and 26 (7%) in the early group, and 204 (57%), 73 (20%), 59 (16%) and 24 (7%) in the delayed group, respectively. There was no significant difference in response to therapy between the two groups (P = 0.183). During the median follow‐up of 8.6 years, there was no significant difference in DFS (P = 0.060) and OS (P = 0.400) curves between the two groups. Delayed RAIT was not significantly associated with worse DFS (HR = 1.3, 95% CI 0.9‐1.8, P = 0.061) or OS (HR = 1.5, 95% CI 0.6‐3.4, P = 0.388). Conclusions: Delaying the first RAIT until 180 days after total thyroidectomy had no impact on restaging, recurrence and mortality in intermediate‐to‐high‐risk PTC. [ABSTRACT FROM AUTHOR]

Background: Tumor volume (TV) of papillary thyroid carcinoma (PTC) increases exponentially during active surveillance, and the growth rate differs for each patient. TV doubling time (TVDT) is considered a strong dynamic marker for the prediction of the growth rate and progression of the tumor. Methods: This cohort study analyzed 273 PTC patients who underwent active surveillance for more than one year rather than immediate thyroid surgery. TVDT was calculated in each patient, and patients were divided into two groups: rapid-growing (TVDT <5 years) and stable (TVDT ≥5 years). Clinical and initial ultrasonography (US) features between the two groups were compared. Results: The median patient age was 51.1 years (interquartile range [IQR] 42.2–61.0 years), and 76% of the patients were women. The initial TV of PTC was 62.1 mm3 (IQR 28.1–122.8 mm3). During a median of 42 months (IQR 29–61 months) of active surveillance, 10.3% of the patients had a TVDT of less than two years, 5.1% had a TVDT between two and three years, 6.2% had a TVDT between three and four years, 6.6% had a TVDT between four and five years, and 71.8% had a TVDT of five years or more. Patients in the rapid-growing group (77 patients; 28.2%) were significantly younger (p = 0.004) than those in the stable group (196 patients; 71.8%). Being younger than 50 years of age was significantly associated with rapid tumor growth of PTC (odds ratio = 2.31 [confidence interval 1.30–4.31], p = 0.004) in multivariate analysis. In ultrasound findings, macrocalcification was independently associated with rapid tumor growing of PTCs (odds ratio = 4.98 [confidence interval 2.19–11.69], p < 0.001). Conclusions: TVDT is a good indicator for presenting the growing velocity of PTCs during active surveillance. Younger age and macrocalcification in the initial US were associated with rapid-growing PTCs. Determination of TVDT during the early phase of active surveillance may be helpful for the prediction of rapidly progressing PTCs and deciding whether to adopt an early surgical approach. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of ultrasound (US)-guided radiofrequency ablation (RFA) according to the types of thyroid carcinoma, particularly in patients with a high-surgical risk. Materials and methods: Eight patients with nine tumours of pathologically proven papillary and anaplastic carcinoma were treated by US-guided RFA. Patients with primary thyroid carcinoma were divided into three groups; group (1) Anaplastic carcinoma, group (2) papillary macrocarcinoma, and group (3) papillary microcarcinoma. We evaluated changes in clinical symptoms, tumour volume and local tumour recurrence/metastasis after RFA. Patients were followed up at 1, 6 and 12 months and annually thereafter. Results: Among nine tumours, one anaplastic carcinoma was treated three times and the other anaplastic carcinoma and one papillary macrocarcinoma were treated twice. Group 3 were treated once. The initial mean tumour volume was 107.9 ± 78.6 (with neck bulging), 126.9 (with neck bulging) and 0.16 ± 0.08 mL (without cosmetic or symptomatic problems) in groups 1-3, respectively. Group 1 showed no improvement in clinical symptoms or neck bulging after RFA, whereas group 2 demonstrated a decreased tumour volume measuring 0.7 mL with improved neck bulging. In group 3, mean volume decreased measuring 0.07 ± 0.12 mL. No local tumour recurrence or metastatic lesion was detected during the mean follow-up of 19.3 months in papillary carcinomas. No major complications were encountered. Conclusions: In patients with primary thyroid carcinoma, RFA achieved excellent local tumour control for papillary macro- and microcarcinoma; however, its clinical effect on anaplastic carcinoma was questionable. [ABSTRACT FROM AUTHOR]

Background: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor previously known as noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). The absence of BRAFV600E mutations has been considered characteristic of NIFTPs. However, a recent study from Korea found that 28.6% of NIFTPs harbored a BRAF mutation. This study evaluated BRAF and RAS mutations in NIFTPs and invasive subtype of EFVPTCs. Methods: This study enrolled 32 patients with NIFTP and 48 with invasive EFVPTC. BRAF, NRAS, HRAS, and KRAS mutations were evaluated by direct sequencing using DNA from fresh-frozen tissues and formalin-fixed, paraffin-embedded tissue samples. Results: The primary tumor size of NIFTP was smaller than that of invasive EFVPTC (median 2.8 cm vs. 3.2 cm; p = 0.03). Cervical lymph node metastases were found in only four (8%) patients with invasive EFVPTC. There was no BRAF mutation in NIFTPs, whereas invasive EFVPTCs had three (6%) BRAFV600E mutations and one (2%) BRAFK601E mutation. RAS mutations were detected in 15 (47%) NIFTPs and 22 (46%) invasive EFVPTCs. NRAS mutations in codon 61 were the most common mutations in NIFTPs (34%) and invasive EFVPTCs (27%). There was no significant difference in the frequency of RAS mutations between the two groups. Conclusions: There was no BRAF mutation in any of the NIFTPs. RAS mutations, particularly mutations in codon 61 of NRAS, were the most common mutations in both NIFTPs and invasive EFVPTCs. The presence of a RAS mutation is not helpful for preoperative differentiation between NIFTPs and invasive EFVPTCs. [ABSTRACT FROM AUTHOR]

Background: The follicular variant of papillary thyroid cancer (FVPTC), especially the encapsulated non-invasive subtype, is a controversial entity. Recent study suggested using ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)’ for these indolent carcinomas. We evaluated the impact of reclassification from non-invasive encapsulated FVPTCs (EFVPTCs) to NIFTPs in the diagnosis of thyroid nodules with architectural atypia. Methods: We reviewed 1301 thyroid nodules with architectural atypia in core needle biopsy (CNB) specimens obtained from March 2012 to February 2013. Nodules were classified into atypia of undetermined significance with architectural atypia (AUS-A, 984, 76%) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, 317, 24%). Among them, diagnostic surgery was performed in 384 nodules (30%). Results: In total, 160 nodules (42%) presented final malignant diagnoses including 39 non-invasive encapsulated FVPTCs (10%). The malignancy rate was estimated to be 7–35% in AUS-A nodules and 28–49% in FN/SFN nodules. After reclassification, the malignancy rate was much decreased and estimated to be 5–24% in AUS-A nodules, and 23–39% in FN/SFN nodules. Thyroid nodules with final malignant diagnoses were significantly more likely to have a FN/SFN CNB diagnosis, malignant US features and concomitant nuclear atypia in CNB specimens. However, these factors could not differentiate NIFTPs from other malignancies. Conclusions: After reclassification of non-invasive EFVPTCs to NIFTPs, the malignancy rate of thyroid nodules with architectural atypia in CNB specimens was decreased. However, there were no preoperative factors differentiating other malignancies from NIFTPs. The presence of malignant US features or concomitant nuclear atypia might help clinicians deciding diagnostic surgery but, these features also might indicate NIFTPs. [ABSTRACT FROM AUTHOR]

Background: The recent increase in the incidence of thyroid cancer has been mainly attributed to papillary thyroid microcarcinomas (PTMCs), and many studies have suggested conservative strategies for the diagnosis and treatment of PTMC. However, PTMCs may be associated with distant metastasis. This study aimed to evaluate the clinicopathological features and identify the risk factors for distant metastasis in patients with PTMCs. Methods: The medical records of 8808 patients who were diagnosed with PTMC from 1999 to 2012 were reviewed, and 12 (0.1%) patients with distant metastasis were identified. Forty-one PTMC patients who initially had lateral cervical lymph node (LN) metastasis and were cured with no evidence of a distant metastasis were also selected as a control group. Results: Of the 12 patients with distant metastasis, nine had synchronous metastasis and three had metachronous metastasis. All 12 patients had primary tumors >0.5 cm and cervical LN metastasis at initial surgery. Ten patients had clinically apparent lateral cervical LN metastases, while two patients had only microscopic involvement of a central LN. Four patients died of thyroid carcinoma. Disease-specific mortality was associated with old age, large metastatic LNs with extranodal extension, and aggressive pathologic subtype of metastatic LNs. When the clinicopathological features of the patients with distant metastasis were compared with the control patients, the presence of extranodal extension and change to an aggressive pathologic subtype of metastatic LNs were significantly associated with distant metastasis and persistent structural distant PTMC metastasis. Conclusions: Most patients with PTMC demonstrate excellent clinical outcomes, and distant metastases rarely occur. However, distant metastasis of PTMC can be fatal. Performing a meticulous pathologic examination of metastatic LNs to identify the presence of extranodal extension and the pathologic subtype of metastatic LNs helps to assess the risk of a distant metastasis in patients with PTMC. [ABSTRACT FROM AUTHOR]

Background: Lateral cervical lymph node (LCLN) metastasis, or pathologic N1b disease, is an important risk factor in papillary thyroid carcinoma (PTC). However, many patients have favorable prognosis even with pathologic N1b patients in clinical practice. The study aims to identify high- and intermediate-risk groups based on initial pathologic characteristics in these patients. Patients: This study included 518 classical PTC patients confirmed as pathologic N1b at initial surgery between 2001 and 2010. All patients underwent a single fixed activity (5.6 GBq) of radioactive I-131 remnant ablation. Results: Patients with a primary tumor larger than 4 cm, gross extrathyroidal extension, metastatic LN larger than 3 cm, or greater than 10 metastatic LCLN were classified as high-risk group. These comprehensive pathologic criteria were retrieved from cox proportional hazard models. Twenty two percent of patients (n = 113) were classified as high-risk and 78% (n = 405) as intermediate-risk group. Successful ablation was identified in only 32% of the patients in the high-risk group and 61% in the intermediate-risk group (p < 0.001). The difference between the two risk groups was independent to gender. There was a significant difference in disease-free survival between the high- and intermediate- risk N1b groups during 5.1 years of median follow-up (84% vs. 59%, p < 0.001). Distant metastasis was more prevalent in the high-risk group (20%) than in the intermediate-risk group (4%, p < 0.001). Conclusions: The prognosis of PTC patients with LCLN metastasis varies depending on initial pathologic characteristics. We proposed the comprehensive pathologic criteria for sub-classification of N1b into high- and intermediate-risk groups and this sub-classification may permit personalized management of N1b PTC patients. [ABSTRACT FROM AUTHOR]

Objectives: Persistence of thyroglobulin antibody (TgAb) in patients with papillary thyroid carcinoma (PTC) years after total thyroidectomy (TT) followed by ablation occurs even without any evidence of structural disease. Few studies have studied the natural course of TgAb positivity and factors that may influence this course. The present study evaluated the time trends of TgAb in ablated PTC patients and aimed to identify the predictive factors for the rate of negative conversion of TgAb.Materials and Methods: Overall, 1279 patients who underwent TT and subsequent ablation for PTC, with available data on thyroid peroxidase Ab (TPOAb) and TgAb prior to surgery (preop-) and ablation (abl-) were enrolled. Patients with initial distant metastasis or recurrence during follow-up were excluded.Results and Conclusion: Preop-TgAb was positive in 24.9% of patients (n = 319), whereas abl-TgAb positivity decreased to 12.8% (n = 164). In 164 patients positive for abl-TgAb, TgAb in patients with higher abl-TgAb levels decreased more gradually than those observed in patients with lower abl-TgAb levels (p < 0.001). Furthermore, in patients within the same range of abl-TgAb levels, patients positive for abl-TPOAb had a higher rate of negative conversion of TgAb compared with negative patients for abl-TPOAb (log rank p < 0.001). TPOAb significantly increased the rate of negative conversion in multivariate analysis adjusted for abl-TgAb (odds ratio 1.59, 95% confidence interval 1.11-2.28, p = 0.011). This study clearly showed that abl-TgAb titers and abl-TPOAb status can predict the rate of negative conversion. These findings can guide the optimal timing for additional examination in patients positive for TgAb during follow-up. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to evaluate the diagnostic accuracies of ultrasound (US) and 18-F-FDG positron emission tomography (PET) or PET/computed tomography (CT) for detecting recurrent papillary thyroid carcinoma (PTC) after total thyroidectomy. Our study enrolled 76 postoperative patients who underwent both neck US and PET because of the suspicion of recurrence. The results of US and PET were correlated with the histopathology, the radioactive iodine whole body scan (WBS) or the clinical follow-up results. Among them, 53 patients had recurrent disease (local recurrence, 42; distant metastasis, 3; elevated Tg level, 8) and 23 showed no evidence of disease. From the analysis, US showed higher diagnostic accuracy, sensitivity and specificity compared with those of PET (71.1%, 71.7% and 69.6% vs. 55.3%, 56.6%, and 52.2%). PET added diagnostic information in a limited number of patients with negative results on neck US (3 with neck recurrence and 2 with distant metastasis). (E-mail: jeonghlee@hanmir.com) [ABSTRACT FROM AUTHOR]