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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.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.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.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.

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.

OBJECTIVE We aimed to evaluate differences in serum thyroid-stimulating hormone (TSH) levels according to smoking status and urine iodine concentration (UIC) in a healthy Korean population using data from the Sixth Korean National Health and Nutrition Examination Survey (KNHANES VI). STUDY DESIGN Sixth Korean National Health and Nutrition Examination Survey (2013-2015) is a nationwide, cross-sectional survey of the Korean population. PATIENTS Research subjects were selected by two-stage stratified cluster sampling of the population and housing census data. A total of 5639 subjects aged >18 years, who were not pregnant, and had undergone thyroid function testing during the survey period, were included. MEASUREMENT The level of serum TSH according to smoking status, iodine intake and presence of TPOAb were evaluated. RESULTS In the reference population, mean serum TSH level in current smokers (1.87 mIU/L, 95% CI, 0.52-5.37 mIU/L) was significantly lower than that in nonsmokers (2.33 mIU/L, 95% CI, 0.79-6.69 mIU/L, P

OBJECTIVE Distinguishing malignancy from benign thyroid nodule has always been challenging, especially in follicular lesions. Thyroid nodules with small size and indeterminate cytology do not lead to immediate surgery. We tried to evaluate whether tumour size and tumour growth rate can distinguish follicular thyroid carcinoma (FTC) from follicular adenoma (FA). DESIGN AND PATIENTS This retrospective study included patients with pathologically proven FTCs (n = 50) and FAs (n = 110) who underwent preoperative serial neck ultrasonography (US) at least 3 times: it comprises 30% of all follicular tumours (32% FAs and 25% FTCs). The growth rates of follicular tumours on serial US were measured using at least 3 consecutive examinations during a median follow-up of 4.1 years (range, 0.7-13.3 years) by experienced radiologists. RESULTS The FA and FTC groups showed no significant difference in clinicopathological characteristics, including age, proportion of large nodules (>4 cm) and preoperative cytology. The maximum diameter of thyroid nodule was gradually increased in both groups with statistical significance (P

SummaryObjective Previous studies did not focus on the differences in the extent of cervical lymph node (LN) dissection according to coexistent Hashimoto's thyroiditis (HT) in patients with papillary thyroid carcinoma (PTC) and its clinical impact. We aimed to determine whether extensive cervical LN dissection is responsible for favourable clinical outcomes in PTC patients with HT and whether the coexistence of HT itself has an independent protective effect regardless of LN status. Design Retrospective cohort study. Patients 1369 patients with PTC who underwent total thyroidectomy with central compartment neck dissection. Measurements Metastatic LN ratio, defined as number of metastatic LNs divided by number of removed LNs, was used to evaluate the extent of LN dissection as well as the status of LN metastasis. Disease-free survival and dynamic risk stratification were compared for clinical outcomes. Results Presence of HT did not lower the risk of cervical LN metastasis (61.6% in patients with HT vs 65.1% in patients without HT, P = .292). Patients with HT had significantly larger numbers of removed LNs than patients without HT (11 vs 8, respectively, P

SummaryObjectives Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis with an indolent disease course. However, some PTMCs have an aggressive course with lateral cervical lymph node (LCLN) metastasis or distant metastasis. This study aimed to evaluate the pre-operative features of PTMC associated with LCLN metastasis. Design and Patients This retrospective cohort study with a nested, matched case–control design included 199 PTMC patients with LCLN metastasis at initial surgery (N1b group) and 196 PTMC patients without any LN metastasis or persistent disease (N0 NED group) as controls; primary tumour sizes were matched. Results Compared with the N0 NED group, the N1b group was younger (

SummaryObjective Age >45 years is included as a variable in the tumor, node, metastases (TNM) staging of differentiated thyroid cancer (DTC), but a higher cut-off value has been suggested to be more clinically relevant and prevent over-staging. We evaluated the optimal age cut-off to predict disease-specific survival (DSS) in patients with DTC. Design and Patients This cohort study included 6333 patients with DTC who underwent thyroid surgery at two tertiary referral centres between 1996 and 2005. The optimal age cut-off value between 45 and 65 years for prediction of DSS was assessed. The proportion of variation explained (PVE) and Harrell's c-index was calculated to compare the predictability of each model. Results The median age of patients was 46·0 years (IQR 37·8–54·6), and 5498 (87%) were female. Median follow-up period was 10·0 years, and 10-year DSS rate was 98%. Using TNM staging with 45 years as the cut-off (TNM45), 10-year DSS rates of stage I–IV were 99·4%, 96·1%, 97·7% and 85·9%, respectively (PVE = 3·0%, Harrell's c-index = 0·693); and using 55 years as the cut-off (TNM55), 99·4%, 92·2%, 95·3% and 79·7%, respectively (PVE = 4·3%, Harrell's c-index = 0·776). On receiver operating characteristic curve analysis, the optimal age cut-off for prediction of DSS was 55·4 years (area under the curve = 0·837, P < 0·001). About 20% of patients were down-staged to stage I using TNM55 compared to that using TNM45. Conclusions The cut-off age of 55 years was more appropriate for TNM staging to achieve better predictability for DSS in patients with DTC. This change would prevent over-staging in low-risk patients and prevent over-aggressive treatment.

OBJECTIVE The follicular variant of papillary thyroid carcinoma (FVPTC) has multiple histological subtypes. Clinical outcomes of FVPTC are variable depending on the subtypes. This study evaluated the association of pre-operative ultrasonographic (US) findings and clinico-pathological features of FVPTC. PATIENTS This retrospective study enrolled patients with FVPTC (n = 70), size-matched classical variant of papillary thyroid carcinoma (CPTC, n = 328), follicular carcinoma (n = 85) and follicular adenoma (FA, n = 120). We defined the histological subtypes of FVPTC as infiltrative (I-FVPTC; n = 19) or encapsulated (E-FVPTC; n = 51) according to the presence of a fibrous capsule. Pre-operative US was reviewed using a US scoring system and classified into low US score (n = 42) and high US score (n = 28). RESULTS The median US score for FVPTC was lower than CPTC (2 vs 7, P < 0·001), but higher than FA (2 vs 0, P < 0·001). The median US score for I-FVPTC was significantly higher than E-FVPTC (4 vs 2, P = 0·009). I-FVPTC was more likely to be diagnosed as a malignancy or suspicious for malignancy on cytology than E-FVPTC (P = 0·002). The cumulative risks of cervical lymph node (LN) or distant metastasis according to tumour size were significantly higher in I-FVPTC than E-FVPTC (all P < 0·001). The cumulative risks for cervical LN metastasis or capsular invasion according to tumour size were significantly higher in FVPTC with high US score than FVPTC with low US score (P = 0·005, P < 0·001, respectively). CONCLUSIONS Pre-operative US findings of thyroid nodules were associated with not only histological subtypes, but also the clinical behaviour in FVPTC.

SummaryObjective Serum calcitonin (CT) level is used to detect medullary thyroid carcinoma (MTC), but the cut-off level is unclear. We aimed at identifying the optimal cut-off value of basal serum CT levels for detecting MTC. Design and patients We retrospectively enrolled patients with hypercalcitoninemia (≥2·9 pmol/l) who had undergone thyroid ultrasonography (US) and subsequent work-up between 2001 and 2013 at Asan Medical Center. We divided patients into four groups: proven MTC (group 1, n = 93), pathologically proven non-MTC after surgery (group 2, n = 57), benign single nodule by cytology (group 3, n = 68) and patients without nodules on US (group 4, n = 24). Measurement Basal serum CT levels were evaluated. Results The median CT level of group 1 (119·5 pmol/l) was significantly higher than those of other groups (4·0, 3·8 and 3·8 pmol/l, P

Summary Objective The effect of coexistent chronic lymphocytic thyroiditis (CLT) on prognosis in papillary thyroid carcinoma (PTC) patients remains controversial. We evaluated the influence of coexistent CLT on prognostic outcome and the association of coexistent CLT with clinicopathological parameters. Design A retrospective study with a median follow-up of 70 months. Patients and measurements Patients with PTC who underwent total thyroidectomy followed by 131I remnant ablation between 1995 and 2003 at Asan Medical Center, Seoul, Korea were enrolled. CLT was diagnosed histopathologically. Results Among 1441 patients, 214 (14·9%) had coexistent CLT. A greater female preponderance was noted in the patients with CLT compared with those without CLT (P

SummaryObjective A larger primary tumour size, greater numbers of cervical lymph node (LN) metastasis are associated with a higher risk of distant metastases in papillary thyroid carcinoma (PTC). However, the impact of the location of cervical LN metastasis on distant metastasis is controversial. The aim of this study was to evaluate the risk of distant metastases according to the tumour size and LN status in PTC patients, with special consideration of the LN metastasis pattern. Patients This retrospective cohort study reviewed 1700 classical PTC patients who underwent initial thyroid surgery at Asan Medical Center between 2000 and 2004. Results The cumulative risk of distant metastases was increased with the increase in tumour size and was significantly different according to the location of involved LNs by the tumour node metastasis (TNM) staging. The cumulative risk in pN1b group showed the steepest increasing pattern with the increase in tumour size compared with pN1a and pN0/Nx group. When we analysed the cumulative risk of distant metastases according to the number of involved LNs, patients with more than 20 involved LNs also had the steepest increase in the risk of distant metastases with the increase in tumour size. However, only the location of involved LNs, not the number of involved LNs, was associated with distant metastases in multivariate analysis. Conclusions We confirm that the location of involved LNs categories based on the TNM staging system is more useful than the number of involved LNs categories for estimating the risk of distant metastasis in PTC. Differentiating N1a disease from N1b disease is important for the follow-up and management of patients with PTC.

Objectives The simultaneous occurrence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) in the same thyroid gland is documented. In this study, we evaluated the prevalence and characteristics of patients with concurrent MTC and PTC. Design Retrospective analysis of patients with MTC in a single centre and review of the literature. Patients and measurements Patients with MTC who underwent initial surgical treatment between 1996 and 2006 at Asan Medical Centre, Seoul, Korea were enrolled. We additionally reviewed the medical records of patients who initially underwent surgery for Graves' disease (GD) or follicular thyroid carcinoma (FTC) during the same period. The concurrent occurrence rate of PTC in MTC patients was compared with that in GD and FTC patients. Results Ten of 53 (19%) MTC patients displayed the concomitant PTC. In all 10 cases, the MTC and PTC components were separated by normal thyroid tissue, with the maximal diameters of PTC being less than 1.0 cm in the majority of patients. The rates of concurrent PTC in patients with MTC, GD and FTC were 19%, 15% and 19%, respectively, which were not significantly different. Conclusions Our results suggest that the occurrence of concurrent MTC/PTC is generally a simple reflection of incidental papillary microcarcinoma.

Summary Objectives To evaluate the clinical outcomes of persistent radioiodine uptake (RAIU) in the neck by diagnostic whole body scan (DxWBS) after initial therapy and the efficacy of the second ablation in patients with differentiated thyroid carcinoma (DTC). Design Patients with DTC who underwent bilateral surgery and high-dose remnant ablation between 2000 and 2004 were included. Patients with elevated serum stimulated thyroglobulin (sTg) or extensive lateral neck lymph node involvement at initial surgery underwent a second ablation, and patients with undetectable sTg or in very low-risk groups were observed. Results Among 572 patients, 25 had persistent RAIU in the neck at first DxWBS. After a median 65·7 months of follow-up, five of these patients (20%) had persistent disease, whereas another 20 patients had no abnormal findings by ultrasonography (US) or other imaging modalities. Seven of 20 patients underwent second ablation and 13 were observed. RAIU disappeared spontaneously in about half of the patients in the observation group. There were no significant between-group differences in change of RAIU at follow-up DxWBS (P = 0·62). Serum sTg decreased and eventually disappeared over a few years in both groups. Ablation failure was not an independent risk factor for recurrence (P = 0·169). Conclusions Neck US and serum sTg, but not DxWBS, were useful diagnostic tools during follow-up of patients with persistent uptake in the neck at DxWBS. A second ablation was not necessary when neck US showed no evidence of disease, especially in patients with very low sTg concentration.

The effect of coexistent chronic lymphocytic thyroiditis (CLT) on prognosis in papillary thyroid carcinoma (PTC) patients remains controversial. We evaluated the influence of coexistent CLT on prognostic outcome and the association of coexistent CLT with clinicopathological parameters.A retrospective study with a median follow-up of 70 months.Patients with PTC who underwent total thyroidectomy followed by (131)I remnant ablation between 1995 and 2003 at Asan Medical Center, Seoul, Korea were enrolled. CLT was diagnosed histopathologically.Among 1441 patients, 214 (14.9%) had coexistent CLT. A greater female preponderance was noted in the patients with CLT compared with those without CLT (P0.01). Mean tumour size in the patients with CLT was smaller than that in patients without CLT (2.0 +/- 1.2 vs. 2.2 +/- 1.4 cm; P = 0.02). One hundred and fifty-one (12.3%) patients without CLT had recurrence, whereas 14 (7.1%) patients with CLT had recurrence during the follow-up period (P = 0.016). In patients with cervical lymph node metastases, those with coexistent CLT showed a significantly lower recurrence rate than those without CLT (P = 0.012). However, this association was lost on multivariate analysis adjusting for other clinicopathological predictors for recurrence.In this study, CLT was commonly associated with PTC and was associated with smaller size of the primary tumour at presentation. CLT was also associated with a reduced risk of recurrence during follow-up, although this was not significant after adjustment for other prognostic factors.