Tumor deposits in thyroid carcinomas.

Tumor deposits (TDs) are defined as discontinuous neoplastic masses within the lymphatic drainage pathway of the primary tumor. The poor prognostic implication of these masses have been demonstrated in various cancers. The aim of this study is to investigate the incidence of TDs in our thyroid carcinoma cases, which has not been studied so far to the best of our knowledge, and to determine the prognostic value of their existence. In this retrospective cohort study, 194 thyroid carcinoma cases with cervical lymph node sampling and/or dissection were reevaluated for TDs. The case series consisted of 176 thyroid papillary carcinoma (TPC) and 18 thyroid medullary carcinoma (TMC) patients. TDs were detected in 54 (27.8%) patients. TMC cases (55.6%) had significantly more TDs compared to TPCs (25.0%; P = .006). TDs were more common in women (P = .045), and in multifocal tumors (P = .017). In addition, cases with TDs had larger tumor size (P = .002), more lymphatic invasion (P = .009), extrathyroidal extension (P < .001), and distant metastasis (P < .001). The mean follow-up period of the patients was 120.1 months (range, 4-341 months). Locoregional recurrence detected in 17 patients (8.8%) was more common in TMC (33.3%) than TPC cases (6.3%; P = .002). Distant metastasis was identified in 27 patients (13.9%). Ten-year recurrence free survival (RFS) and overall survival (OS) for all patients were 89.0% and 92.4%, respectively. Mean estimated OS time for TD negative and TD positive cases were: 281.9 (±17.2), 325.6 (±6.2) and 217.6 (±27.4) months, respectively (P = .002). Sex (P = .001), tumor type (P = .002), pT classification of the tumor (P < .001), perineural invasion (P = .002) and TDs (P = .002) were significantly associated with OS. In TPC cases individually, extrathyroidal extension (P = .001) and TDs (P = .002) were significantly correlated with distant metastasis. In multivariate analysis, only tumor size was detected as an independent prognostic marker in TPC cases (P = .005). Our results demonstrate the existence of TDs in thyroid carcinoma cases, and indicate a more aggressive behavior pattern of TDs in these tumors.

Comparison of unilateral versus bilateral central neck dissection for clinically invasive papillary thyroid carcinoma.

BACKGROUND: The American Thyroid Association guidelines primarily recommend central neck dissection for papillary thyroid carcinoma with advanced primary tumors or clinically positive neck nodes. However, the appropriate extent of dissection remains unclear. We aimed to compare the rate of locoregional recurrence between unilateral and bilateral central neck dissection in invasive papillary thyroid carcinoma. METHODS: Among 330 consecutive patients who underwent total thyroidectomy with central neck dissection for advanced papillary thyroid carcinoma, 212 underwent unilateral central neck dissection (UCND group) while 118 underwent bilateral central neck dissection (BCND group). We performed 1:1 propensity score matching, resulting in 99 matched pairs. Surgical outcomes and safety were compared between the two groups. Additionally, the impact of surgery on locoregional recurrence was compared using survival analysis. RESULTS: During a follow-up of 47.8 ± 20.4 months, 29 (8.8%) patients experienced locoregional recurrence within the entire study cohort. Following propensity score matching, no significant difference in recurrence-free survival was observed between the two groups (log-rank p = 0.516). Multivariate analysis revealed that only T4 staging was an independent risk factor for locoregional recurrence (p = 0.006). The mean number of total and metastatic central lymph nodes retrieved were significantly greater in BCND group (14.1 vs. 9.3, p < 0.001 and 6.8 vs. 4.6, p = 0.005, respectively). There was no significant difference in postoperative stimulated thyroglobulin levels between the two groups (0.79 ng/mL vs. 1.44 ng/mL, p = 0.389). CONCLUSION: The present study demonstrates no prognostic benefit in conducting bilateral central neck dissection. Unilateral central neck dissection may be the preferred choice for clinically invasive papillary thyroid carcinoma.

Prognostic prediction of patients having classical papillary thyroid carcinoma with a 4 mRNA-based risk model.

The dysregulation of protein-coding genes involved in various biological functions is closely associated with the progression of thyroid cancer. This study aimed to investigate the effects of dysregulated gene expressions on the prognosis of classical papillary thyroid carcinoma (cPTC). Using expression profiling datasets from the Cancer Genome Atlas (TCGA) database, we performed differential expression analysis to identify differentially expressed genes (DEGs). Cox regression and Kaplan-Meier analysis were used to identify DEGs, which were used to construct a risk model to predict the prognosis of cPTC patients. Functional enrichment analysis unveiled the potential significance of co-expressed protein-encoding genes in tumors. We identified 4 DEGs (SALL3, PPBP, MYH1, and SYNDIG1), which were used to construct a risk model to predict the prognosis of cPTC patients. These 4 genes were independent of clinical parameters and could be functional in cPTC carcinogenesis. Furthermore, PPBP exhibited a strong correlation with poorer overall survival (OS) in the advanced stage of the disease. This study suggests that the 4-gene signature could be an independent prognostic biomarker to improve prognosis prediction in cPTC patients older than 46.

Exploration of the prognostic value of methylation regulators related to m5C in papillary thyroid carcinoma.

The incidence of papillary thyroid carcinoma (PTC) has increased significantly in recent years, and for patients with metastatic and recurrent PTC, the options for treatment currently available are insufficient. To date, the exact molecular mechanism underlying PTC is still not fully understood. 5-Methylcytosine (m5C) RNA methylation is associated with the prognosis of a variety of tumors. However, the molecular mechanisms and biomarkers associated with m5C in the diagnosis, treatment, and prognosis of this disease have not been fully elucidated. Ten m5C regulators with significantly different expression levels were included in this study. Immune infiltration analysis revealed significant negative correlations between most of these regulators and regulatory T cells. TRDMT1, NSUN5, and NSUN6 had high weights and strong correlations in the protein-protein interaction network. Using gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis, 1489 differentially expressed genes were screened from The Cancer Genome Atlas messenger RNA matrix, indicating that these differentially expressed genes were significantly enriched in various pathways and functions related to cancers. Four m5C regulators, NSUN2, NSUN4, NSUN6, and DNMT3B, were screened as prognostic markers by least absolute shrinkage and selection operator regression analysis, and NSUN2 and NSUN6 were identified as risk factors for poor prognosis. We found that the prognostic prediction model constructed using the m5C regulators NSUN2, NSUN4, NSUN6, and DNMT3B showed good prognostic prediction ability and diagnostic ability. This model was applied to predict the survival probability of patients with PTC, the prediction ability of 5-year survival was the best. The multi-factor prognostic prediction model combined with the tumor node metastasis stage and risk score grouping showed better prognostic predictive power.

Analysis of lncRNA-miRNA-mRNA interactions identified a novel biomarker LINC00657 to improve prognosis prediction of papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Identification of novel biomarkers can potentially help explore the underlying molecular mechanisms of PTC. Long non-coding RNAs (lncRNAs) are involved in cancer development. However, understanding the role of lncRNA in PTC remains challenging. METHODS: Based on the competitive endogenous RNA (ceRNA) theory, we constructed a comprehensive PTC-related lncRNA-miRNA-mRNA network using data from The Cancer Genome Atlas. To evaluate the prognostic power, we performed survival analysis for patients with PTC with low and high lncRNA expression levels, and examined the relationship between lncRNA and immune-related functions. RESULTS: We identified a hub node, long intergenic non-coding RNA, LINC00657, as a novel prognostic biomarker in PTC. LINC00657 was differentially expressed between tumor and adjacent normal samples. Low LINC00657 expression levels was significantly associated with better survival outcome. Our functional analyses showed that LINC00657 was related with infiltration of CD8+ T cell and macrophage; immune check point molecules; and immune metagenes such as IgG, LCK, MHC_I/II and etc. These results suggest that LINC00657 is an immune-related biomarker with potential clinical applicability. Additionally, cancer-related signaling pathway and high frequency of gene BRAF mutation were found in PTC samples with high LINC00657 expression level, which were consistent with previous findings. CONCLUSION: LINC00657 is an immune-related biomarker that can potentially improve prognosis prediction in PTC. Our study provided new treatment target of PTC in clinical practice and offered the novel insights in elucidating the functional role of lncRNAs.

Association of BRAF or TERT Promoter Mutations and Advanced Papillary Thyroid Carcinoma.

BACKGROUND/AIM: BRAF and TERT promoter mutations are associated with the poor prognosis of papillary thyroid carcinoma. This single-center retrospective study investigated the influence of these genes on advanced cases. PATIENTS AND METHODS: Advanced cases who underwent gene panel testing and cases who underwent complete resection were classified as groups A and C, respectively. The gene mutations were determined using gene panel testing or Sanger sequencing using tumor DNA. RESULTS: The study included 51 cases in group A and 44 cases in group C. In group A, all cases had unresectable lesions or distant metastasis; 82.4% of cases showed no accumulation of radioactive iodine in metastasis and 47.1% of cases were administered drug therapy. Meanwhile, all cases of group C did not have distant metastasis. The prevalence of TERT promoter mutations was significantly higher in group A compared to group C (70.6% vs. 18.2%, p<0.001). However, there was no significant difference in the prevalence of BRAF mutations between the two groups (86.3% vs. 90.9%). In Group C, disease-free survival was significantly shorter in patients harboring the TERT promoter mutations (p<0.001), despite no significant difference in that according to the BRAF mutation status. In addition, there was no significant difference in overall survival in group A according to the TERT promoter mutation status. CONCLUSION: Advanced papillary thyroid carcinoma was associated with the TERT promoter mutations, but not with BRAF mutation. Meanwhile, TERT promoter mutations did not affect overall survival among the advanced cases.

Natural History and Prognostic Model of Untreated Papillary Thyroid Cancer: A SEER Database Analysis.

PURPOSE: This investigation leveraged the SEER database to delve into the progression patterns of PTC when left untreated. Furthermore, it aimed to devise and authenticate a nomogram for prognosis prediction for such patients. METHODS: We extracted data from the SEER database, focusing on PTC-diagnosed individuals from 2004-2020. To discern disease progression intervals, median survival times across stages were gauged, and the disease progression time was estimated by subtracting the median survival time of a more severe stage from its preceding stage. Prognostic determinants in the training set were pinpointed using both univariate and multivariate Cox regression. Using these determinants, a prognostic nomogram was crafted. RESULTS: In untreated PTC patients, those in stages I and II had a favorable prognosis, with 10-year overall survival rates of 86.34% and 66.03%, respectively. Patients in stages III and IV had a relatively poorer prognosis. The median survival time of stage III, stage IVA, stage IVB and stage IVC patients was 108months, 43 months, 20 months and 8 months, respectively. The deduced progression intervals from stages III-IVC were 65, 23, and 12 months. In the training set, age, tumor stage, gender, and marital status were identified as independent risk factors influencing the prognosis of untreated PTC, and a nomogram was constructed using these variables. CONCLUSION: In the absence of treatment intervention, early-stage PTC progressed slowly with an overall favorable prognosis. However, in mid to advanced-stage PTC, as tumor stage increased, disease progression accelerated, and prognosis gradually worsened. Age, tumor stage, marital status, and gender were independent risk factors influencing the prognosis of untreated PTC, and the nomogram based on these factors demonstrated good prognostic capability.

PurposeThis investigation leveraged the SEER database to delve into the progression patterns of PTC when left untreated. Furthermore, it aimed to devise and authenticate a nomogram for prognosis prediction for such patients.MethodsWe extracted data from the SEER database, focusing on PTC-diagnosed individuals from 2004-2020. To discern disease progression intervals, median survival times across stages were gauged, and the disease progression time was estimated by subtracting the median survival time of a more severe stage from its preceding stage. Prognostic determinants in the training set were pinpointed using both univariate and multivariate Cox regression. Using these determinants, a prognostic nomogram was crafted.ResultsIn untreated PTC patients, those in stages I and II had a favorable prognosis, with ten-year overall survival rates of 86.34% and 66.03%, respectively. Patients in stages III and IV had a relatively poorer prognosis. The median survival time of stage III, stage IVA, stage IVB and stage IVC patients was 108months, 43 months, 20 months and 8 months, respectively. The deduced progression intervals from stages III-IVC were 65, 23, and 12 months. In the training set, age, tumor stage, gender, and marital status were identified as independent risk factors influencing the prognosis of untreated PTC, and a nomogram was constructed using these variables.ConclusionIn the absence of treatment intervention, early-stage PTC progressed slowly with an overall favorable prognosis. However, in mid to advanced-stage PTC, as tumor stage increased, disease progression accelerated, and prognosis gradually worsened. Age, tumor stage, marital status, and gender were independent risk factors influencing the prognosis of untreated PTC, and the nomogram based on these factors demonstrated good prognostic capability.

Survival Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases: A SEER Population-Based Study.

Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occurs in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010-2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and the following: patient age (p < 0.001), tumor size (p < 0.01), and site of distant metastasis (p < 0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; p < 0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; p < 0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (≤57 years vs. ≥58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (≤4 cm vs. >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size for determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population.

Patterns in the Reporting of Aggressive Histologic Subtypes in Papillary Thyroid Cancer.

INTRODUCTION: The tall cell, columnar, and diffuse sclerosing subtypes are aggressive histologic subtypes of papillary thyroid cancer (PTC) with increasing incidence, yet there is a wide variation in reporting. We aimed to identify and compare factors associated with the reporting of these aggressive subtypes (aPTC) to classic PTC (cPTC) and secondarily identify differences in outcomes. METHODS: The National Cancer Database was utilized to identify cPTC and aPTC from 2004 to 2017. Patient and facility demographics and clinicopathologic variables were analyzed. Independent predictors of aPTC reporting were identified and a survival analysis was performed. RESULTS: The majority of aPTC (67%) were reported by academic facilities. Compared to academic facilities, all other facility types were 1.4-2.0 times less likely to report aPTC (P < 0.05). Regional variation in reporting was noted, with more cases reported in the Middle Atlantic, despite there being more total facilities in the South Atlantic and East North Central regions. Compared to the Middle Atlantic, all other regions were 1.4-5 times less likely to report aPTC (P < 0.001). Patient characteristics including race and income were not associated with aPTC reporting. Compared to cPTC, aPTC had higher rates of aggressive features and worse 5-y overall survival (90.5% versus 94.5%, log rank P < 0.001). CONCLUSIONS: Aggressive subtypes of PTC are associated with worse outcomes. Academic and other facilities in the Middle Atlantic were more likely to report aPTC. This suggests the need for further evaluation of environmental or geographic factors versus a need for increased awareness and more accurate diagnosis of these subtypes.

Tumour size predicts risk of recurrence in tall cell subtype papillary thyroid carcinoma.

BACKGROUND: The tall cell subtype of papillary thyroid cancer (TCPTC) is the most common aggressive subtype and often treated aggressively. This approach may not be necessary in smaller tumours without adverse histological characteristics. METHODS: 97 patients with TCPTC defined as a height-to-width ratio of ≥3:1 and at least 30% tall cells were compared against 390 classical papillary thyroid carcinoma (CPTC) based on tumour size with recurrence free survival (RFS) as the primary outcome. RESULTS: TCPTC are more likely to present with adverse histological characteristics. In smaller tumours (<2 â€‹cm), only central lymph node metastasis (HR7.16 p â€‹= â€‹0.03) and multifocality (HR10.11 p â€‹= â€‹0.026) increased recurrence risk. In larger tumours, TCPTC histology (HR3.78 p â€‹= â€‹0.002), lymphovascular invasion (HR3.02 p â€‹= â€‹0.014) and central lymph node metastasis (HR3.24 p â€‹< â€‹0.001) significantly increased recurrence risk. CONCLUSION: TCPTC tumours <2 â€‹cm without central lymph node metastasis and multifocality are similar in risk of recurrence to classical PTC and could be managed with lobectomy.

A prediction model based on random survival forest analysis of the overall survival of elderly female papillary thyroid carcinoma patients: a SEER-based study.

OBJECTIVE: Papillary thyroid carcinoma (PTC) is a common malignancy whose incidence is three times greater in females than in males. The prognosis of ageing patients is poor. This research was designed to construct models to predict the overall survival of elderly female patients with PTC. METHODS: We developed prediction models based on the random survival forest (RSF) algorithm and traditional Cox regression. The data of 4539 patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Twelve variables were analysed to establish the models. The C-index and the Brier score were selected to evaluate the discriminatory ability of the models. Time-dependent receiver operating characteristic (ROC) curves were also drawn to evaluate the accuracy of the models. The clinical benefits of the two models were compared on the basis of the DCA curve. In addition, the Shapley Additive Explanations (SHAP) plot was used to visualize the contribution of the variables in the RSF model. RESULTS: The C-index of the RSF model was 0.811, which was greater than that of the Cox model (0.781). According to the Brier score and the area under the ROC curve (AUC), the RSF model performed better than the Cox model. On the basis of the DCA curve, the RSF model demonstrated fair clinical benefit. The SHAP plot showed that age was the most important variable contributing to the outcome of PTC in elderly female patients. CONCLUSIONS: The RSF model we developed performed better than the Cox model and might be valuable for clinical practice.

Young and resilient: Unraveling papillary thyroid cancer outcomes in males under 40.

BACKGROUND: While males present with more adverse clinicopathologic features in papillary thyroid carcinoma (PTC), younger age has previously been shown to be a favorable prognostic factor. We examined the combined effect of male sex and young age on PTC outcomes. METHODS: We conducted a retrospective analysis of a prospectively maintained database of thyroid cancer surgery patients (2000-2020) at a single quaternary care institution. We included papillary thyroid carcinoma cases and excluded those with prior cancer-related thyroid surgery. We examined demographics, cancer stage, surgical outcomes, and complications by age and sex, analyzing groups below and above the age of 40 years. RESULTS: A total of 680 patients with PTC were included. Females constituted 68% (age ≥40 years: 44% and <40 years: 24%) and males 32% (≥40 years: 24% and <40 years: 8%). A significant difference (p < 0.001) of N1 disease distribution was found between the groups. N1a metastasis was greater in patients younger than 40 regardless of sex ((M < 40 (15%), F < 40 (15%), M ≥ 40 (12%), and F ≥ 40 (9%)). While, M < 40 had greater N1b metastasis (36%) than all other groups (M ≥ 40 (28%), F < 40 (22%), and F ≥ 40 (10%)). There was no significant difference in the distribution of T stages between groups. Groups showed no differences in 30-day outcomes, recurrence at 1 year, reoperation, mortality, nerve injury, or hypocalcemia. CONCLUSIONS: Young males with PTC face increased occurrence of nodal metastasis yet experience similar recurrence rates as their female and older counterparts. Subgroup analysis underscores the predictive role of sex and age in advanced PTC cases.

Racial implications of time to surgery in disparities in thyroid cancer survival.

INTRODUCTION: The influence of time to surgery on racial/ethnic disparities in papillary thyroid carcinoma (PTC) survival remains unstudied. MATERIALS AND METHODS: The National Cancer Database (2004-2017) was queried for patients with localized PTC. Survival data was compared by time to surgery, patient demographics, and multivariable Cox regression was performed. RESULTS: Of 126,708 patients included, 5% were Black, 10% Hispanic. Of all patients, 85% had no comorbidities. Non-Hispanic White (NHW) patients had a shorter median time to surgery than Black and Hispanic patients (36 vs. 43 vs. 42 days, respectively p â€‹< â€‹0.001). In multivariable analysis, longer time to surgery (>90 days vs â€‹< â€‹30 days) and Black race vs NHW, were associated with worse survival (HR: 1.56, (95%CI, 1.43-1.70), p â€‹< â€‹0.001 and HR: 1.21, (1.08-1.36), p â€‹= â€‹0.001), respectively. CONCLUSION: Delaying surgery for thyroid cancer is associated with worse survival. However, independent of time to surgery and other confounders, there remains a disparity as black patients have poorer outcomes.

Low expression of TFF3 in papillary thyroid carcinoma may correlate with poor prognosis but high immune cell infiltration.

Background: Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignancies and has a favorable prognosis. However, optimal treatments and prognostic markers have not been clearly identified. Methods: Gene expression data from primary PTC were downloaded from the Gene Expression Omnibus database and subjected to two analyses of differentially expressed genes (DEGs), followed by intersecting individual and integrated DEGs analyses as well as gene set enrichment analysis. Analysis of data from Sequence Read Archive and The Cancer Genome Atlas, immunohistochemistry and qRT-PCR of TFF3 were performed to validate the results. Finally, the relationship between gene expression and disease-free survival as well as immune cell infiltration were investigated. Results: Six critical DEGs and several tumor-enriched signaling pathways were identified. Immunohistochemistry and qRT-PCR validated the low expression of TFF3 in PTC. TFF3 and FCGBP are coexpressed in PTC, and patients with lower gene expression had worse disease-free survival but higher immune cell infiltration. Conclusion: TFF3 was significantly underexpressed and may function with FCGBP synergistically in PTC.

Lay abstract Thyroid cancers are some of the most common endocrine malignancies. However, the optimal treatments and prognostic markers have not been clearly identified. We identified six critical differentially expressed genes and several tumor-enriched signaling pathways in papillary thyroid carcinoma, and found that TFF3 was the most underexpressed gene, as validated by experiment. In addition, TFF3 and FCGBP worked synergistically and may mark prognosis and tumor immune cell infiltration, which may benefit patients with papillary thyroid carcinoma by providing early indication and prompting further basic investigation.

Overall survival is improved with total thyroidectomy and radiation for male patients and patients older than 55 with T2N0M0 Stage 1 classic papillary thyroid cancer.

BACKGROUND: We examine whether surgery extent and radiation administration affect overall survival for cT2N0M0 classic papillary thyroid cancer according to age and sex. METHODS: Patients with cT2N0M0 classic papillary thyroid cancer tumors in the National Cancer Data Base (2004-2016) were selected. Multivariable Cox regression analysis compared patients (combined male + female cohorts) having lobectomy to those having total thyroidectomy with or without radiation (primarily radioactive iodine) for ages: 18 to 45, 46 to 55, and >55 years. In addition, 1:1 propensity score matching and Kaplan-Meier curves with 10-year overall survival estimates, and log-rank test were stratified by age and sex. RESULTS: Lobectomy had equivalent overall survival to total thyroidectomy without and with radiation for patients (combined male + female cohorts) aged 18 to 45 and 46 to 55 years on multivariable analysis. On propensity score matching there was overall survival advantage for total thyroidectomy with radiation over both lobectomy and total thyroidectomy for men (ages 18-90+ combined) and overall survival advantage in patients (combined male + female cohort) aged >55 years having total thyroidectomy with radiation versus lobectomy. On propensity score matching there were no overall survival differences in women (ages 18-90+ combined) or patients (combined male + female cohort) aged 18 to 45 and 46 to 55 years having either lobectomy, total thyroidectomy, or total thyroidectomy with radiation. CONCLUSION: For cT2N0M0 classic papillary thyroid cancer, total thyroidectomy with radiation improves 10-year overall survival for patients (combined male + female cohort) aged >55 years and men (ages 18-90+ combined).

Expression of cancer stem cell markers in tall cell variant papillary thyroid cancer identifies a molecular profile predictive of recurrence in classic papillary thyroid cancer.

BACKGROUND: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. METHODS: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. RESULTS: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). CONCLUSION: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.

A prospective randomized controlled trial to assess the efficacy and safety of prophylactic central compartment lymph node dissection in papillary thyroid carcinoma.

BACKGROUND: The efficacy of prophylactic central compartment lymph node dissection for papillary thyroid carcinoma remains controversial. We performed a randomized controlled trial to evaluate the efficacy and safety of prophylactic central compartment lymph node dissection in patients with papillary thyroid carcinoma. METHODS: In this parallel-group randomized controlled trial, we assessed 101 patients aged 20 to 70 years with small/noninvasive papillary thyroid carcinoma and no clinical metastases or history of cervical surgery/radiation exposure. Randomization ran from April 2015 to November 2017. Data were collected between April 2015 and October 2020. Of the 101 enrolled patients, 50 underwent total thyroidectomy (TTx group) and 51 underwent total thyroidectomy as well as prophylactic central compartment lymph node dissection (TTx+pCND group). Surgical completeness, local recurrence, successful ablation, postoperative complication, and papillary thyroid carcinoma upstaging were compared between the 2 groups. RESULTS: No patient showed structural recurrence after 46.6 ± 9.1 months of follow-up. Both groups had similar rates of surgical completeness and successful ablation. There was no difference in the incidence of complications. More patients were upstaged to pN1a in the TTx+pCND group compared to those in the TTx group (P < .05). CONCLUSIONS: Prophylactic central compartment lymph node dissection detected more lymph node metastases but did not affect recurrence. The 2 groups showed similar outcomes with regard to surgical completeness, successful ablation, and complications. In conclusion, for small/noninvasive papillary thyroid carcinoma without clinical evidence of lymph node metastases, prophylactic central compartment lymph node dissection may not be required if total thyroidectomy is planned.

Radioactive iodine does not improve overall survival for patients with aggressive variants of papillary thyroid carcinoma less than 2 cm.

BACKGROUND: Tall cell and diffuse sclerosing variants of papillary thyroid cancer are associated with aggressive features. Radioactive iodine after total thyroidectomy is poorly studied. METHODS: Patients ≥18 years in the National Cancer Data Base from 2004 to 2016 with classic papillary thyroid cancer, tall cell, or diffuse sclerosing 1 mm to 40 mm were identified. Logistic regression identified factors associated with aggressive features. Overall survival was assessed using Kaplan-Meier method and log-rank tests, after propensity score matching for clinicopathological and treatment variables. RESULTS: A total of 155,940 classic papillary thyroid cancer patients, 4,011 tall cell, and 507 diffuse sclerosing were identified. Tall cell patients represented an increasing proportion of the study population during the analysis period, whereas diffuse sclerosing and classic papillary thyroid cancer patients showed a statistically significant decline. Extrathyroidal extension and nodal involvement were more prevalent among tall cell and diffuse sclerosing patients when compared to those diagnosed with classic papillary thyroid cancer (P < .01). Adjuvant radioactive iodine was less frequently used in patients with classic papillary thyroid cancer when compared to tall cell and diffuse sclerosing patients (42.6% vs 62.4%, 59.0%; P < .001, respectively). Aggressive variants receiving total thyroidectomy versus total thyroidectomy + radioactive iodine propensity score matched across clinicopathologic variables were analyzed. There was no difference in overall survival between the 2 treatment groups for tumors <2 cm (01-1.0 cm, 92.2% vs 84.8%; P = .98); (1.0-2.0 cm, 72.7% vs 88.1%; P = .82). However, overall survival was improved for total thyroidectomy + radioactive iodine propensity score matched patients with tumor sizes 21 to 40 mm versus total thyroidectomy (83.4% vs 70.0%, P = .004). CONCLUSION: For aggressive tumor variants ≤2 cm treated with total thyroidectomy, there is no overall survival advantage provided by the addition of adjuvant radioactive iodine.

Thyroid lobectomy as a cost-effective approach in low-risk papillary thyroid cancer versus active surveillance.

BACKGROUND: An ongoing debate exists over the optimal management of low-risk papillary thyroid cancer. The American Thyroid Association supports the concept of active surveillance to manage low-risk papillary thyroid cancer; however, the cost-effectiveness of active surveillance has not yet been established. We sought to perform a cost-effectiveness analysis comparing active surveillance versus surgical intervention for patients in the United States. METHODS: A Markov decision tree model was developed to compare active surveillance and thyroid lobectomy. Our reference case is a 40-year-old female who was diagnosed with unifocal (<15 mm), low-risk papillary thyroid cancer. Probabilistic outcomes, costs, and health utilities were determined using an extensive literature review. The willingness-to-pay threshold was set at $50,000/quality-adjusted life year gained. Sensitivity analyses were performed to account for uncertainty in the model's variables. RESULTS: Lobectomy provided a final effectiveness of 21.7/quality-adjusted life years, compared with 17.3/quality-adjusted life years for active surveillance. Furthermore, incremental cost effectiveness ratio for lobectomy versus active surveillance was $19,560/quality-adjusted life year (

Extranodal Extension Is an Independent Prognostic Factor in Papillary Thyroid Cancer: A Propensity Score Matching Analysis.

Purpose: To investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC). Methods: Seven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan-Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC. Results: Thirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS. Conclusions: Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.