Prediction model for pheochromocytoma/paraganglioma using nCounter assay.

BACKGROUND: World Health Organization defined pheochromocytomas/paragangliomas (PPGL) as malignant tumors in 2017 because the existing classification system could not reflect locally aggressive behavior sufficiently. However, predicting the likelihood of metastasis remains a crucial part of the treatment strategy. METHODS: From one tertiary care hospital and one secondary hospital, 97 PPGL cases were selected. Medical records of PPGL cases with the presence of formalin-fixed and paraffin-embedded (FFPE) tissue of primary lesion were reviewed. For FFPE tissues, a nCounter assay was conducted to determine differently expressed genes between metastatic and non-metastatic PPGL groups. Performances of prediction models for the likelihood of metastasis were calculated. RESULTS: Of a total of 97 PPGL cases, 39, 20, and 38 were classified as benign, malignant, and validation, respectively. In the nCounter assay, CDK1, TYMS, and TOP2A genes showed significant differences in expression. Tumor size was positively correlated with CDK1 expression level. The Lasso regression model showed supreme performance of sensitivity 91.7% and specificity 95.5% when those significant factors were considered. CONCLUSION: Machine learning of multi-modal classifiers can be used to create a prediction model for metastasis of PPGL with high sensitivity and specificity using nCounter assay. Moreover, CDK1 inhibitors could be considered for developing drug treatment.

Association of Ultrasonography Features of Follicular Thyroid Carcinoma With Tumor Invasiveness and Prognosis Based on WHO Classification and TERT Promoter Mutation.

OBJECTIVE: To investigate the association of ultrasound (US) features of follicular thyroid carcinoma (FTC) with tumor invasiveness and prognosis based on the World Health Organization (WHO) classification and telomerase reverse transcriptase (TERT) promoter mutations. MATERIALS AND METHODS: This retrospective study included 54 surgically confirmed FTC patients with US images and TERT promoter mutations (41 females and 13 males; median age [interquartile range], 40 years [30-51 years]). The WHO classification consisted of minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTCs. Alternative classifications included Group 1 (MI-FTC and EA-FTC with wild type TERT), Group 2 (WI-FTC with wild type TERT), and Group 3 (EA-FTC and WI-FTC with mutant TERT). Each nodule was categorized according to the US patterns of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and American College of Radiology-TIRADS (ACR-TIRADS). The Jonckheere-Terpstra and Cochran-Armitage tests were used for statistical analysis. RESULTS: Among 54 patients, 29 (53.7%) had MI-FTC, 16 (29.6%) had EA-FTC, and nine (16.7%) had WI-FTC. In both the classifications, lobulation, irregular margins, and final assessment categories showed significant differences (all Ps ≤ 0.04). Furthermore, the incidences of lobulation, irregular margin, and high suspicion category tended to increase with increasing tumor invasiveness and worse prognosis (all Ps for trend ≤ 0.006). In the WHO groups, hypoechogenicity differed significantly among the groups (P = 0.01) and tended to increase in proportion as tumor invasiveness increased (P for trend = 0.02). In the alternative group, punctate echogenic foci were associated with prognosis (P = 0.03, P for trend = 0.03). CONCLUSION: Increasing tumor invasiveness and worsening prognosis in FTC based on the WHO classification and TERT promoter mutation results were positively correlated with US features that indicate malignant probability according to both K-TIRADS and ACR-TIRADS.

Mortality rate and causes of death in papillary thyroid microcarcinoma.

PURPOSE: Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis; however, some PTMCs exhibit poor outcomes. Cancer-specific death from PTMC has been rarely reported, so we aimed to evaluate mortality rates and causes of death in patients who died with PTMC. METHODS: We retrospectively reviewed 8969 PTMC patients treated at Samsung Medical Center from 1994 to 2017. Mortality rate and causes of death in PTMC patients were evaluated and compared with those of 7873 patients with papillary thyroid carcinoma (PTC) > 1 cm. In addition, we reviewed previous publications reporting cancer-specific deaths from PTMC. RESULTS: Among the 8969 PTMC patients, 107 (1.2%) patients died. Only two (0.02%) patients have died of PTMC, which was less than the cancer-specific deaths from PTC > 1 cm (0.71%). Among the deceased PTMC patients, 63 (58.9%) died of other malignancies, three (2.8%) died of cardiovascular diseases, and five (4.7%) died of other diseases. Compared with PTC > 1 cm, cancer-specific deaths was less (1.9% vs. 15.1%, P < 0.001), and deaths from other malignancies were higher in deceased PTMC patients (58.9% vs. 30.5%, P < 0.001). According to 18 studies, PTMC-specific mortality rates ranged from 0.05% to 14.3%, and 336 cancer-specific deaths (0.43%) occurred among 78,770 PTMC patients. CONCLUSION: The cancer-specific mortality rate of PTMC patients was extremely low (0.02%). More than half of deceased PTMC patients died of other malignancies, which was significantly more than those with PTC > 1 cm. These results support that active surveillance can be selected as a therapeutic option for PTMC.

Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes.

CONTEXT: Clinical implications of unilateral primary aldosteronism (PA) histopathology remain to be determined in various ethnic populations. OBJECTIVE: We examined the histopathology of unilateral PA using CYP11B2 immunostaining in relation to clinical phenotypes and postsurgical outcomes. METHODS: Patients consecutively operated for unilateral PA from 2010 to 2020 at three tertiary hospitals in South Korea were retrospectively enrolled. Adrenals with solitary aldosterone-producing adenomas and/or dominant aldosterone-producing nodules were classified as the classical and the others as the nonclassical groups. The classical group was subdivided into mixed or solitary group according to whether other aldosterone-producing lesions coexist or not. RESULTS: Of the 240 cases, 124 were solitary, 86 mixed, and 30 nonclassical. Baseline serum potassium concentration was lower in the solitary group than the mixed or nonclassical group. Plasma aldosterone concentration after saline loading was the highest in the solitary group (median 31.65 ng/dl), followed by the mixed group (median 25.40 ng/dl), and the lowest in the nonclassical group (median 14.20 ng/dl). Solitary and mixed groups showed higher lateralization indices and lower contralateral indices than the nonclassical group. The contralateral index was lower in the solitary group than the mixed group. At 6-12 months after adrenalectomy, fewer antihypertensive medications were required for the solitary and mixed groups than the nonclassical group. CONCLUSIONS: The solitary group, followed by the mixed group, was associated with more severe hyperaldosteronism and more suppressed aldosterone production from the contralateral side than the nonclassical group. Histopathologic phenotypes were related to the clinical manifestations and may suggest postoperative prognosis.

Age-associated mortality is partially mediated by TERT promoter mutation status in differentiated thyroid carcinoma.

BACKGROUND: Age at diagnosis (AAD) and telomerase reverse transcriptase (TERT) promoter mutations are prognostic factors in differentiated thyroid carcinoma (DTC), and the prevalence of the mutations increases with AAD. Considering this correlation, we investigated whether an interaction between AAD and the mutations is present and whether the mutation mediates the effect of AAD on the mortality rate in DTC. METHODS: The study included 393 patients with DTC who were followed-up after thyroidectomy at a single medical center in Korea from 1994 to 2004. Multivariable Cox regression was used to investigate the interaction of AAD and TERT promoter mutation. Mediation analysis was conducted using a regression-based causal mediation model. RESULTS: The age-associated mortality rate increased progressively in all DTC patients and wild-type TERT group (WT-TERT) with a linear trend (p < 0.001) contrary to mutant TERT group (M-TERT) (p = 0.301). Kaplan-Meier curves declined progressively with increasing AAD in the entire group, but the change was without significance in M-TERT. The effect of AAD on mortality was not significant (adjusted HR: 1.07, 95% CI 0.38-3.05) in M-TERT. An interaction between AAD and TERT promoter mutation (p = 0.005) was found in a multivariable Cox regression. TERT promoter mutations mediated the effect of AAD on the mortality rate by 36% in DTC in a mediation analysis. CONCLUSIONS: Considering the mediation of TERT promoter mutation on the effect of AAD on mortality, inclusion of TERT promoter mutation in a stage classification to achieve further individualized prediction in DTC is necessary.

Preoperative identification of low-risk medullary thyroid carcinoma: potential application to reduce total thyroidectomy.

Current guidelines recommend total thyroidectomy with central lymph node dissection (CND) for patients with medullary thyroid carcinoma (MTC). This study aimed to identify low-risk MTC patients who may be candidates for lobectomy. We retrospectively reviewed MTC patients who underwent primary surgery at a tertiary referral center from 1998 to 2019. Eighty-five MTC patients were enrolled, excluding patients with primary tumor size > 2.0 cm. Among them, one (1.2%) patient had bilateral tumors. During a median follow-up of 84 months, 12 of the 85 patients experienced structural recurrence. 13 patients had occult lymph node metastasis, and structural recurrence occurred in 2 patients. Factors that significantly affected disease-free survival were clinical N stage (cN0 vs. cN1, log-rank P < 0.001), pathological N stage (pN0 vs. pN1, P < 0.001), and preoperative calcitonin levels (≤ 250 vs. > 250 pg/mL, P = 0.017). After categorizing patients into four groups, patients with preoperative calcitonin levels > 250 pg/mL and cN1 or pN1 had a significantly worse prognosis. Patients with a primary tumor size of 2 cm or less, cN0, and preoperative calcitonin of 250 pg/mL or less can be classified as low-risk MTC patients. We used preoperative clinical information to identify low-risk MTC patients. Lobectomy with prophylactic CND may be a potential therapeutic approach.

Role of computed tomography in predicting adrenal adenomas with cortisol hypersecretion.

OBJECTIVES: To investigate performance of adrenal CT-derived multivariate prediction models in differentiating adenomas with cortisol hypersecretion from the other subtypes. METHODS: This retrospective study included 127 patients who underwent adrenal CT and had a surgically proven adrenal adenoma. Adenoma subtypes were defined according to biochemical test results: Group A, overt cortisol hypersecretion; Group B, mild cortisol hypersecretion; Group C, aldosterone hypersecretion; and Group D, non-function. Two independent readers analyzed size, attenuation, and washout properties of adenomas, and performed quantitative and qualitative analyses for assessing contralateral adrenal atrophy. Actual and internally validated areas under the curves (AUCs) of adrenal CT-derived multivariate prediction models for differentiating adenomas with cortisol hypersecretion from the other subtypes were assessed. RESULTS: In differentiating Group A from the other groups, the actual and internally validated AUCs of the prediction model were 0.856 (95% confidence interval [CI]: 0.786, 0.926) and 0.847 (95% CI: 0.695, 0.999) for Reader 1, respectively, and 0.901 (95% CI: 0.845, 0.956) and 0.897 (95% CI: 0.783, 1.000) for Reader 2, respectively. In differentiating Group B from groups C and D, the actual and internally validated AUCs of the prediction model were 0.777 (95% CI: 0.687, 0.866) and 0.760 (95% CI: 0.552, 0.969) for Reader 1, respectively, and 0.783 (95% CI: 0.690, 0.875) and 0.765 (95% CI: 0.553, 0.977) for Reader 2, respectively. CONCLUSION: Adrenal CT may be useful in differentiating adenomas with cortisol hypersecretion from the other subtypes. ADVANCES IN KNOWLEDGE: Adrenal CT may benefit in adrenal adenoma subtyping.

NTRK Fusion in a Cohort of BRAF p. V600E Wild-Type Papillary Thyroid Carcinomas.

Owing to the availability of a potent tropomyosin receptor kinase (TRK) inhibitor, it is necessary to develop an effective strategy to identify an enriched population of NTRK fusions in papillary thyroid carcinoma (PTC) in routine diagnostic practice. The reported prevalence of NTRK fusion in a large cohort of PTC is ∼3%. We performed an analysis to refine the characteristic histologic features of PTCs harboring NTRK fusions and further validate the diagnostic utility of pan-TRK immunohistochemistry as a screening tool. In this study, 450 PTCs known to harbor no BRAF p. V600E mutations were screened by pan-TRK immunohistochemistry, and the cases with TRK expression were confirmed by RNA-based next-generation sequencing assay. Eleven NTRK fusion cases were detected (2.4%), and all PTCs were classical subtypes. NTRK1 and NTRK3 were involved in the fusion with 9 different partner genes. Most cases showed similar characteristic histologic findings. Nodular permeative border, multinodular growth with a predominantly follicular pattern, extensive lymphatic invasion, and prominent internodular and intratumoral fibrosis were the characteristic histologic features of NTRK-rearranged PTCs. The ill-defined margins in the ultrasonography findings, which could not be clearly distinguished from the adjacent nontumorous thyroid tissue, were nodular permeative margins in histologic findings. Therefore, preoperative ultrasonographic findings in nodule margins were consistent with the final histologic findings. NTRK1/3 fusion in PTCs showed an overall sensitivity of 100% (95% CI, 71.51%-100%) and specificity of 100% (95% CI, 71.51%-100%) in the 22 cases examined, as confirmed with next-generation sequencing. Our study provides an integrative report of the preoperative ultrasonographic, histologic, immunohistochemical, and molecular features of NTRK-rearranged PTCs. Based on these findings, we propose an algorithmic approach for the stepwise assessment of NTRK fusions in PTCs.

Thyroid pathology, a clue to PTEN hamartoma tumor syndrome.

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline inactivating mutations in the PTEN tumor suppressor gene. As a type of PHTS, Cowden syndrome is associated with abnormalities of the thyroid, breast, uterus, and gastrointestinal tract. A 52-year-old-woman visited the outpatient clinic of our endocrinology clinic with multiple thyroid nodules and Hashimoto's thyroiditis. Computed tomography imaging revealed a multinodular mass measuring up to 3.5 cm in the left thyroid lobe, causing laryngotracheal airway displacement. The total thyroidectomy specimen revealed multiple follicular adenomas and adenomatous nodules with lymphocytic thyroiditis and lipomatous metaplasia in the background. The patient was suspected of PTHS based on her thyroid pathology, family history, and numerous hamartomatous lesions of the breast, uterus, and skin. Her diagnosis was confirmed through molecular testing. This case demonstrates that pathologists must be well acquainted with thyroid pathology in PHTS.

Comparison of clinicopathological characteristics and survival between symptomatic and asymptomatic anaplastic thyroid carcinoma.

Although anaplastic thyroid carcinoma (ATC) is a fatal form of thyroid cancer with an overall survival of only a few months, there are some factors associated with longer survival. However, it remains unknown whether asymptomatic ATC differs from symptomatic ATC in terms of characteristics and overall prognosis. Therefore, we aimed to examine the clinicopathological characteristics and prognosis of asymptomatic ATC compared with those of symptomatic ATC. We retrospectively reviewed the medical records of 113 patients with ATC who were registered at our institution between November 1994 and July 2020. A total of 86 patients (59 women and 27 men; mean age, 66.9 ± 11.1 years) were enrolled for analysis. The clinicopathological characteristics of the ATC cohort were evaluated, and prognostic factors associated with disease-specific mortality were assessed. Of the 86 patients with ATC, 78 were symptomatic and eight were asymptomatic. Compared with the symptomatic group, the asymptomatic group had a younger age at diagnosis (59.3 ± 10.3 vs. 67.7 ± 11.0 years, p = 0.045), smaller tumor size (2.8 ± 1.2 vs. 5.8 ± 2.0 cm, p < 0.001), and longer survival period (37.5 ± 46.4, 9.5 ± 16.8 months, p < 0.001). However, the ATC component (%) of the tumor, sex, ultrasonographic risk category, and distant metastasis at diagnosis did not differ significantly between the two groups. In the multivariate Cox regression analysis, asymptomatic ATC (HR: 0.33, 95% CI 0.11-0.99, p = 0.045) and absence of distant metastasis (hazard ratio (HR): 0.56, 95% Confidence interval (CI) 0.35-0.88, p = 0.012) were associated with longer survival. Patients with asymptomatic ATC have a smaller tumor size, a longer survival period, and a younger age than those with symptomatic ATC. Being asymptomatic and having no distant metastasis were associated with longer survival in patients with ATC in a clinical setting.

Selection Criteria for Completion Thyroidectomy in Follicular Thyroid Carcinoma Using Primary Tumor Size and TERT Promoter Mutational Status.

BACKGROUND: A stepwise surgical approach with hemithyroidectomy and completion thyroidectomy was used to achieve definite characterization of follicular thyroid carcinoma (FTC). Choosing appropriate candidates for completion thyroidectomy has been controversial. OBJECTIVE: The aim of this study was to clarify the selection criteria for completion thyroidectomy using telomerase reverse transcriptase (TERT) promoter mutation. METHODS: A total of 87 FTC patients who had information about TERT promoter mutation from August 1995 to November 2020 were investigated. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each of the World Health Organization (WHO) 2017 classifications were calculated. RESULTS: Of the 87 patients, 8 (9.2%) had initial distant metastasis and 15 (17.2%) had persistent disease or developed structural recurrence. The threshold diameter for initial distant metastasis, disease recurrence, and cancer-specific death was 2 cm in minimally invasive FTC (MI-FTC) with mutant TERT (M-TERT) and in encapsulated angioinvasive FTC (EA-FTC) with M-TERT, while that in MI-FTC with wild-type TERT (WT-TERT) and EA-FTC with WT-TERT was 4 cm. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each WHO 2017 classification was significantly different only in patients with WT-TERT (p = 0.001, p = 0.019, and p = 0.005, respectively). CONCLUSIONS: The data suggest 2 cm as a critical threshold diameter for performance of completion thyroidectomy in MI-FTC with M-TERT and EA-FTC with M-TERT. TERT promoter mutational status can help select candidates for completion thyroidectomy.

Optimal value of lymph node ratio and metastatic lymph node size to predict risk of recurrence in pediatric thyroid cancer with lateral neck metastasis.

BACKGROUND: No specific guideline exists for risk stratification based on lymph node (LN) status in pediatric thyroid cancer. The purpose of our study is to identify optimal values of lymph node ratio (LNR) and largest metastatic LN size for predicting recurrent/persistent disease, especially in children with lateral neck metastasis (N1b). METHODS: We conducted a retrospective study from January 1997 to June 2018 at Samsung Medical Center. A total of 50 papillary thyroid carcinoma (PTC) patients who underwent total thyroidectomy + both central neck dissection (CND) + modified radical neck dissection (MRND) (unilateral or bilateral) was enrolled. RESULTS: The median follow-up duration was 60.8 months (range, 6.2-247 months). The mean age was 14.6 years, and the mean tumor size was 2.9 cm. Mean size of the largest metastatic LN was 1.5 cm. Mean value of central LNR was 0.6, and mean value of lateral LNR was 0.3. Largest metastatic LN size [HR = 2.0 (95% CI 1.0-4.0), p = 0.040] and lateral LNR [HR = 43.6 (95% CI 2.2-871.0), p = 0.014] were significant prognostic factors for recurrence. The optimal combination of lateral LNR and largest metastatic LN size to predict recurrence were 0.3 and 2.5 cm, respectively, with the largest AUC (AUC at 60 months = 77.4) and significant p-value (p = 0.009 and p = 0.021) (Table 3). Kaplan-Meier curves showed significant differences in recurrence-free survival (RFS) rates among four groups (Fig. 2A,2B). CONCLUSIONS: In pediatric PTC patients with N1b, lateral LNR and largest metastatic LN size are significant predictors for recurrence. Children with lateral LNR > 0.3 or any metastatic lymph node > 2.5 cm in the largest dimension have higher risk for recurrence. Children are classified as extensive N1b if lateral LNR > 0.3 or pathologic N1 with largest LN size > 2.5 cm, and vice versa.

Papillary and medullary thyroid carcinomas coexisting in the same lobe, first suspected based on fine-needle aspiration cytology: a case report.

Because different types of thyroid malignancies have distinct embryological origins, coexisting tumors are rarely observed. We describe a coexisting papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) first suspected by fine-needle aspiration cytology (FNAC). A 57-year-old female presented with an irregular mass in the right thyroid lobe. The cytopathologic findings of fine-needle aspiration showed two components: a papillary-like arrangement consisting of cells with pale enlarged nuclei indicative of PTC and loose clusters comprised of oval cells with granular chromatin indicative of MTC. The diagnosis of a coexisting PTC and MTC was initially confirmed by calcitonin immunocytochemistry and later after total thyroidectomy. Although some surgical case reports of PTC and MTC coexisting in either the same or different lobes have been documented, a case suspected by FNAC before the surgery has rarely been reported. Because appropriate treatment and prognosis of PTC and MTC are different, cytopathologists should be aware of this rare entity.

Ultrasonographic characteristics of Hürthle cell neoplasms: prediction of malignancy.

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.

Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients.

BACKGRUOUND: Telomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients. METHODS: We prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma. RESULTS: Of 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; P<0.001), larger primary tumor size (OR, 2.02; P<0.001), and aggressive histological type (OR, 7.78 in follicular thyroid carcinoma; OR, 10.33 in poorly differentiated thyroid carcinoma; OR, 45.92 in anaplastic thyroid carcinoma; P<0.001). Advanced T stage, advanced N stage, and distant metastasis at diagnosis were highly prevalent in mutated thyroid cancers. However, initial distant metastasis was not present in patients with TERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences. CONCLUSION: This study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

Is total thyroidectomy with bilateral central neck dissection the only surgery for papillary thyroid carcinoma patients with clinically involved central nodes?

BACKGROUND: In clinical practice, we often observed that patients who underwent total thyroidectomy due to clinically involved nodal disease (cN1a) actually had less extensive CLNM on final pathology. This study investigates whether total thyroidectomy and therapeutic bilateral CND are necessary for all PTC patients with cN1a. METHODS: This study retrospectively reviewed 899 PTC patients who underwent total thyroidectomy with bilateral CND from January 2012 to June 2017. The patients were divided into two groups according to pre-operative central lymph node (CLN) status: cN0, no suspicious CLNM; cN1a, suspicious CLNM. We compared the clinicopathological features of these two groups. RESULTS: There was no significant difference in recurrence between cN0 and cN1a groups after a mean follow-up time of 59.1 months. Unilateral cN1a was related to the largest central LN size ≥ 2 mm (OR = 3.67, p < 0.001) and number of CLNM > 5(OR = 2.24, p = 0.006). On the other hand, unilateral cN1a was not associated with an increased risk of contralateral lobe involvement (OR = 1.35, p = 0.364) and contralateral CLNM (OR = 1.31, p = 0.359). Among 106 unilateral cN1a patients, 33 (31.1%) were found to be pN0 or had ≤ 5 metastatic CLNs with the largest node smaller than 2 mm. CONCLUSIONS: Most cN1a patients were in an intermediate risk group for recurrence and required total thyroidectomy. However, lobectomy with CND should have performed in approximately 30% of the cN1a patients. Pre-operative clinical examination, meticulous radiologic evaluation, and intra-operative frozen sections to check the nodal status are prerequisites for this approach.

What is the difference between the tall cell variant and the classic type of papillary thyroid carcinoma on ultrasonography?

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.

Effect of TSH levels during active surveillance of PTMC according to age.

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 progression 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 progression (hazard ratio 2.13 (1.24-3.65); P = 0.006), but the impact was significant only in patients aged <40 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 low-normal TSH levels during active surveillance might be helpful to prevent progression.

Core needle biopsy and ultrasonography are superior to fine needle aspiration in the management of follicular variant papillary thyroid carcinomas.

PURPOSE: Follicular variant papillary thyroid carcinoma (FVPTC) is a problematic entity. FVPTCs are often misdiagnosed by the standard fine needle aspiration (FNA); in addition, FVPTCs represent a mixed group of tumors with two biologically distinct subtypes: The indolent encapsulated FVPTC and the aggressive infiltrative FVPTC. Recent changes in guidelines suggests that FVPTC management may be improved if subtypes can be determined preoperatively. Preoperative assays, FNA, core needle biopsy (CNB), and ultrasonography (US) were compared for their ability to identify and subtype FVPTCs to determine the most appropriate test to manage FVPTCs. METHODS: The preoperative assays and clinicopathologic variables of 255 resected FVPTCs cases at Samsung Medical Center between 2012 and 2016 were retrospectively evaluated. RESULTS: CNB had the overall best ability to manage FVPTCs with the highest rate of diagnosis indicating surgery, lowest rate of inconclusive results, high sensitivity (88.9%), specificity (87.7%), negative predictive value (97.0%), diagnostic odds ratio (DOR; 56.9), and excellent predictive ability (AUC 0.906) for differentiating FVPTC subtypes. US had a moderate DOR (12.8), good predictive ability (AUC 0.802), high sensitivity (75.0%) and specificity (81.0%). CNB and US both had significantly higher accuracy for discriminating FVPTC subtypes than FNA (AUC 0.908 and 0.877 > 0.671; p < 0.05). The excellent performance of CNB could be attributed to distinct histologic differences between FVPTC subtypes. CONCLUSION: CNB and US had superior performance to FNA in the identification and subtyping of FVPTC. In institutions with skilled and experienced operators, CNB is the preferred method for evaluating possible FVPTC lesions.