Recurrent Papillary Thyroid Cancer Research Articles

Epithelial-to-mesenchymal transition of circulating tumor cells and CD133 expression on predicting prognosis of thyroid cancer patients.

The present study aimed to explore the epithelial-to-mesenchymal transition of circulating tumor cells (CTCs) and CD133 expression in determining the prognosis of patients with thyroid cancer. It enumerated different CTC subtypes and analyzed CD133 gene expression in patients with thyroid cancer to evaluate the relationship between CTC number and thyroid cancer prognosis. In total 394 patients with thyroid cancer were enrolled. Among these, 270 cases had papillary thyroid cancer (PTC), 60 had follicular thyroid cancer (FTC), 30 had medullary thyroid cancer (MTC), 15 had poorly differentiated thyroid cancer, 19 had anaplastic thyroid cancer and 10 had non-malignant thyroid nodules based on their histopathological characteristics. CTC cell counts were determined by CanPatrol CTC capture technique before treatment. The present study also performed reverse transcription-quantitative PCR for CD133 gene expression and evaluated the relationship between CD133 expression and clinical pathology. A total of 330 cases of enrolled patients were classified as differentiated thyroid cancer, which included PTC and FTC. Their prognosis was excellent. The positivity rate of CTCs at diagnosis was 95.5%. The data of the present study showed that early recurrence and metastasis rates in PTC and FTC patients with >6 CTCs and positive mesenchymal circulating tumor cells (MCTCs) were significantly higher than those in patients with <6 CTCs and MCTCs. It was also found that those patients with >6 CTCs and MCTCs had shorter overall survival. In addition, CD133 levels in patients with thyroid cancer were strongly associated with the differentiation grades of thyroid cancers. The detection of >6 CTCs and positive MCTCs in patients with differentiated thyroid cancer was an excellent biomarker for predicting the prognosis of patients. CD133 expression was also identified as a good biomarker for thyroid cancer differentiation.

Alternative biomarkers of thyroid cancer

Serum thyroglobulin is the main biomarker for postoperative monitoring of papillary thyroid cancer recurrence however, the high prevalence of the disease dictates the need to find a reliable indicator for laboratory diagnosis of the tumor process. The presence of antibodies to thyroglobulin affects the prognosis of the disease and determines the likelihood of relapse; however, it is impossible to influence the level of antibodies using currently available methods. More commonly, trends in anti-thyroglobulin levels at the time of disease detection and after radical treatment are considered, but there is disagreement on the interpretation of the results. Currently, various alternative biomarkers are being proposed and studied, the evaluation and comparison of which will be the subject of this literature review.

Nomograms based on sonographic and clinicopathological characteristics to predict lateral lymph node metastasis in classic papillary thyroid carcinoma.

Lateral lymph node metastasis (LLNM) has been considered a risk factor of recurrence in papillary thyroid cancer (PTC). Preoperative detecting LLNM accurately is difficult. Solitary lateral lymph node metastasis is a special type of LLNM. We aimed to develop nomograms for predicting LLNM and multiple lateral lymph node metastasis (MLLNM). We retrospectively retrieved 528 classic PTC patients that underwent surgery between March 2019 and May 2020. Sonographic and clinicopathological features were collected. Risk factors of LLNM and MLLNM were determined by univariate and multivariate analysis. Nomograms for predicting LLNM and MLLNM were developed. LLNM was independently associated with tumor size, the number of foci, location, margin, central lymph node metastasis, and lymph node ratio. Independent predictors of MLLNM were age, margin, and the number of metastatic lymph nodes in central compartment. By using above variables, we constructed nomograms for predicting LLNM and MLLNM, with area under curves of 0.864 and 0.748, respectively. Through these accurate and easy-to-use nomograms, we can detect the risk of residual LLNM postoperatively for classic PTC patients who did not receive lateral neck dissection and provide an individualized plan for postoperative management of classic PTC patients.

The Prognostic Implication of the BRAF V600E Mutation in Papillary Thyroid Cancer in a Chinese Population.

Background The BRAF V600E mutation is an important genetic event in papillary thyroid cancer (PTC). This study aimed to provide additional information regarding the association of the BRAF V600E mutation with PTC prognosis. Methods A retrospective single-center study based on a Chinese population was performed to analyze the association of the BRAF V600E mutation with several clinicopathological features. Kaplan–Meier survival curves and Cox proportional hazards regression analysis were applied to implement the survival analysis. Results The BRAF V600E mutation was present in 1102 (87.7%) of the 1257 patients and was significantly associated with older age, conventional subtype, multifocality, advanced TNM stage, and a reduced prevalence of Hashimoto's thyroiditis. The Kaplan–Meier survival curves demonstrated that the difference between the BRAF V600E-positive and BRAF V600E-negative groups was significant with a log-rank P-value of 0.048. The Cox proportional hazards regression analysis adjusted HR was 3.731 (95% CI, 1.457 to 9.554). We further demonstrated that larger tumor size (>1 cm), extrathyroidal extension (ETE), and lateral lymph node metastasis (LNM) were associated with a higher probability of PTC recurrence in patients harboring the BRAF V600E mutation. Conclusions The BRAF V600E mutation remains an independent risk factor for PTC recurrence and may be useful for clinical decisions when it combines with some pathological factors.

Lymph Node Metastases Identified at the Post-Ablation 131I SPECT/CT Scan Is a Prognostic Factor of Intermediate-Risk Papillary Thyroid Cancer.

The intermediate-risk category of papillary thyroid cancer (PTC) comprises heterogeneous patients within a wide range of stages and varied care management. Understanding the risk features of recurrence observed after the initial therapy should be emphasized. We aimed to evaluate the prognostic significance of radioactive iodine-avid lymph nodes observed during the initial treatment of patients with PTC that were considered to be at intermediate risk. Data on patients with intermediate-risk PTC treated from 2012 to 2018 were retrospectively reviewed. Post-therapeutic SPECT/CT (Rx SPECT/CT) was evaluated in the enrolled patients. The clinical, pathologic, and incidence of radioiodine-avid (RAI-avid) lymph node metastasis (mLN) on Rx SPECT/CT were reviewed, and risk factors related to recurrent disease were analyzed. After a median follow-up of 37.26 (30.90, 46.33) months, structural persistent/recurrent disease was detected in 9.81% (36/367) of patients with intermediate-risk tumors. The incidence of recurrence was higher in patients who demonstrated RAI-avid mLN after the initial therapy than in those who did not (p < 0.001). In a multivariate Cox proportional hazard regression analysis, RAI-avid mLN appeared to be a robust risk factor for recurrent disease after the initial therapy (HR: 8.967, 95% CI: 3.433–23.421, p = 0.000). RAI-avid mLN is a significant risk factor for recurrent intermediate-risk PTC after the initial treatment.

Serum Linkage-Specific Sialylation Changes Are Potential Biomarkers for Monitoring and Predicting the Recurrence of Papillary Thyroid Cancer Following Thyroidectomy.

BackgroundAlthough papillary thyroid cancer (PTC) could remain indolent, the recurrence rates after thyroidectomy are approximately 20%. There are currently no accurate serum biomarkers that can monitor and predict recurrence of PTC after thyroidectomy. This study aimed to explore novel serum biomarkers that are relevant to the monitoring and prediction of recurrence in PTC using N-glycomics.MethodsA high-throughput quantitative strategy based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to obtain serum protein N-glycomes of well-differentiated PTC, postoperative surveillance (PS), postoperative recurrence (PR), and matched healthy controls (HC) including linkage-specific sialylation information.ResultsSerum N-glycan traits were found to differ among PTC, PS, PR, and HC. The differentially expressed N-glycan traits consisting of sixteen directly detected glycan traits and seven derived glycan traits indicated the response to surgical resection therapy and the potential for monitoring the PTC. Two glycan traits representing the levels of linkage-specific sialylation (H4N3F1L1 and H4N6F1E1) which were down-regulated in PS and up-regulated in PR showed high potential as biomarkers for predicting the recurrence after thyroidectomy.ConclusionsTo the best of our knowledge, this study provides comprehensive evaluations of the serum N-glycomic changes in patients with PS or PR for the first time. Several candidate serum N-glycan biomarkers including the linkage-specific sialylation have been determined, some of which have potential in the prediction of recurrence in PTC, and others of which can help to explore and monitor the response to initial surgical resection therapy. The findings enhanced the comprehension of PTC.

Predictive value of metastatic lateral lymph node ratio for recurrence in pathologically lateral lymph node-positive papillary thyroid cancer patients with palpable lymph nodes.

This study aimed to identify the predictive value of the extent of metastatic lymph nodes in the central and lateral neck compartment for recurrence in papillary thyroid cancer (PTC) patients with pathologically lateral lymph node metastasis (pN1b). This study enrolled 252 patients with pN1b from PTC. During a mean follow-up of 17.6 years, 55 (21.8%) patients experienced recurrence. Patients with palpable lymph nodes were more likely to have a recurrence than those with nonpalpable lymph nodes (30.1% vs. 17.8%, relative risk 1.7, 95%CI: 1.1-2.7). For patients with palpable metastatic lymph nodes, lymph node ratio of lateral lymph nodes ≥0.5 (aHR=2.906, 95%CI: 1.29-6.54) and age ≥55 years (aHR=2.508, 95%CI: 1.12-5.63) were independent prognostic factors. For those without palpable nodes, age ≥55 years (aHR=2.224, 95%CI: 1.08-4.60) and tumor size >4cm (aHR=2.168, 95%CI: 1.01-4.66) were independently predictive of worse RFS. Palpable lymph nodes were approximately twice as likely to recur as nonpalpable nodes. Metastatic lateral lymph node ratio predicts recurrence in pN1b PTC patients with palpable lymph nodes, but not those without ones.

Iodine Maps from Dual-Energy CT to Predict Extrathyroidal Extension and Recurrence in Papillary Thyroid Cancer Based on a Radiomics Approach.

Accurate prediction of extrathyroidal extension and subsequent recurrence is crucial in papillary thyroid cancer clinical management. Our aim was to conduct iodine map-based radiomics to predict extrathyroidal extension and to explore its prognostic value for recurrence-free survival in papillary thyroid cancer. A total of 452 patients with papillary thyroid cancer were retrospectively recruited between June 2017 and June 2020. Radiomics features were extracted from noncontrast images, dual-phase mixed images, and iodine maps, respectively. Random forest and least absolute shrinkage and selection operator (LASSO) were applied to build 6 radiomics scores (noncontrast radiomics score_random forest; noncontrast rad-score_LASSO; mixed rad-score_random forest; mixed rad-score_LASSO; iodine radiomics score_random forest; iodine radiomics score_LASSO) respectively. Logistic regression was used to construct 6 radiomics models incorporating 6 radiomics scores with clinical risk factors and to compare them with the clinical model. A radiomics model that achieved the highest performance was presented as a nomogram and assessed by discrimination, calibration, clinical usefulness, and prognosis evaluation. Iodine radiomics scores performed significantly better than mixed radiomics scores. Both of them outperformed noncontrast radiomics scores. Iodine map-based radiomics models significantly surpassed the clinical model. A radiomics nomogram incorporating size, capsule contact, and iodine radiomics score_random forest was built with the highest performance (training set, area under the curve = 0.78; validation set, area under the curve = 0.84). Stratified analysis confirmed the nomogram stability, especially in group negative for CT-reported extrathyroidal extension (area under the curve = 0.69). Nomogram-predicted extrathyroidal extension risk was an independent predictor of recurrence-free survival. A high risk for extrathyroidal extension portended significantly lower recurrence-free survival than low risk (P < .001). Iodine map-based radiomics might be a supporting tool for predicting extrathyroidal extension and subsequent recurrence risk in patients with papillary thyroid cancer, thus facilitating clinical decision-making.

TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer.

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among the triggering receptors expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease-free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not in macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

Association of BRAF V600E Mutation with Tumor Recurrence in a Small Sample of Filipino Patients with Papillary Thyroid Cancer in a Single Center.

Epidemiological studies have shown that Filipinos have a higher prevalence of welldifferentiated thyroid cancer and a higher rate of recurrence. The BRAF V600E mutation has been proposed as a potential prognostic marker in aggressive papillary thyroid cancers. In this study, we determined whether this mutation is a risk factor for tumor recurrence in papillary thyroid cancer among Filipinos. We conducted an age and sex-matched case-control study of patients with papillary thyroid cancer; we had two groups - with and without tumor recurrence - of 14 patients each, with at least a 5-year follow-up. We extracted the DNA samples from the patients' (paraffin-embedded) tumor biopsy tissue blocks from thyroidectomy specimens, then detected the BRAF V600E mutation using polymerase chain reaction. The McNemar's test for difference of proportions in paired data was used to determine the association of BRAF V600E mutation with recurrence. The BRAF V600E mutation was found in 57.14% of all cases. We found a prevalence of 64.29% among those with recurrence and 50.00% among those without recurrence, with no significant difference between the two groups (p = 0.688). Our study showed the BRAF V600E mutation was not associated with recurrence. We encountered several limitations: we had limited data regarding molecular methodologies in the Philippine setting, we had a small sample size, and therefore we could not study other parameters (e.g., tumor characteristics, lymph node metastasis, stage of disease). We hope that this paves the way for future studies and collaborations to establish the role of BRAF V600E in Filipinos with papillary thyroid tumor recurrence.

Is eNAMPT/visfatin a potential serum marker of papillary thyroid cancer?

Purpose:The role of nicotinamide phosphoribosyltransferase (NAMPT)/visfatin in a more aggressive course of many malignancies has been proven. Previous studies have noticed the importance of visfatin in thyroid neoplastic tissue, but the diagnostic and prognostic value of its serum concentration has not been investigated so far. Our study aimed to consider whether extracellular NAMPT (eNAMPT) could be a potential serum marker in recurrent papillary thyroid cancer (PTC).Methods:It was a prospective observational study with consecutive enrolment. We recruited 100 patients with PTC after thyroidectomy with postoperative 131I ablation and 100 healthy controls. Also, 50 randomly selected patients underwent laboratory assessment (including eNAMPT serum concentration by ELISA Assay Kit, TSH, free thyroid hormones, TSH-stimulated thyroglobulin Tg, antibodies – TgAbs, TPOAb) and body composition analysis twice: at admission and 6 months after being on suppressive levothyroxine doses. TSH-stimulated Tg of 1 ng/ml was defined as the cutoff value for predicting disease status as complete remission (n = 55) and recurrent or persistent structural disease (n = 45).Results:The visfatin serum concentrations in patients diagnosed with PTC and in healthy subjects were not statistically significantly different (p = 0.9425). The eNAMPT levels were also similar in disease-free patients and the ones with tumour relapse. Besides, ROC curve analysis did not detect eNAMPT as a biomarker of PTC.Conclusion:We have not found visfatin as a potential serum marker of papillary thyroid cancer. Also, eNAMPT has no prognostic value in assessing the risk of disease recurrence or metastasis in PTC management.

An ultrasound model for predicting recurrence of papillary thyroid carcinoma after complete endoscopic resection.

IntroductionPapillary thyroid cancer (PTC) is one of the most common malignancies involving the endocrine system.AimTo explore the clinical value of ultrasound-based radiomics for predicting the recurrence of PTC after complete endoscopic resection.Material and methodsThe general data of 361 PTC patients were collected. They were randomly assigned to the modeling group (n = 253) and the validation group (n = 108) according to the ratio of 7 : 3. In the modeling group, the PyRadiomics package was applied to extract radiomic features from preoperative ultrasound images, and least absolute shrinkage and selection operator (LASSO) was used to screen and to construct a radiomics score (Rad-score). Independent prognostic predictors were identified using the Cox proportional hazards model, and a nomogram prediction model was constructed by R software.ResultsUsing the LASSO regression model, 7 radiomic features were screened and then the Rad-score was calculated. Based on the Rad-score, modeling and validation groups were divided into low-, medium- and high-risk groups, and the 10-year recurrence-free survival rates were 94.7% vs. 95.9%, 83.6% vs. 80.0%, and 50.0% vs. 66.6%, respectively (p < 0.001). Multivariate analysis revealed that age, lymph node metastasis and Rad-score were independent predictors for recurrence-free survival (p < 0.05).ConclusionsThe ultrasound-based radiomics score can effectively predict the postoperative recurrence-free survival in patients with PTC. The nomogram prediction model is superior to the AJCC staging system in terms of predictive accuracy and consistency.

Evaluation of recurrence risk in patients with papillary thyroid cancer through tumor-node-metastasis staging: A single-center observational study in Taiwan

BackgroundMany patients with papillary thyroid cancer (PTC) demonstrate satisfactory outcomes. However, 8%–28% of patients with PTC show tumor recurrence, which may affect prognosis. Therefore, identifying factors associated with tumor recurrence in patients with PTC may be helpful to refine therapeutic strategies. MethodsTo identify factors associated with PTC recurrence, we retrospectively reviewed demographic features (sex and age), operation method, image character, serum thyroglobulin (Tg), accumulated radioactive iodine (I-131) therapeutic dose, I-131 uptake, and metastases at diagnosis in 829 patients with PTC. Patients were grouped into early (stage I and II; n = 698) and advanced (stage III and IV; n = 131) tumor-node-metastasis (TNM) stages. Recurrence rate, mortality rate, risk factors of recurrence, recurrent free survival and overall survival curve were compared between two groups. ResultsPatients in the early stage demonstrated a lower recurrence rate (7.2%) than did those in the advanced stage (28.2%, p < 0.05). The mortality rate of patients with recurrence in the advanced stage was higher than that of those in the early stage (51.4% vs. 12.0%). The major impact factors on tumor recurrence in early TNM stage were distant metastasis and lymph node metastasis, while in advanced TNM stage were distant metastasis, male gender, total thyroidectomy with limited lymph node dissection, and a high serum Tg level. ConclusionsStrategies to monitor tumor recurrence might be refined according to the TNM stages of PTC patients.

Recurrence of Papillary Thyroid Cancer: A Systematic Appraisal of Risk Factors.

ContextThyroid cancer recurrence is associated with increased mortality and adverse outcomes. Recurrence risk is currently predicted using clinical tools, often restaging patients after treatment. Detailed understanding of recurrence risk at disease onset could lead to personalized and improved patient care.ObjectiveWe aimed to perform a comprehensive bioinformatic and experimental analysis of 3 levels of genetic change (mRNA, microRNA, and somatic mutation) apparent in recurrent tumors and construct a new combinatorial prognostic risk model.MethodsWe analyzed The Cancer Genome Atlas data (TCGA) to identify differentially expressed genes (mRNA/microRNA) in 46 recurrent vs 455 nonrecurrent thyroid tumors. Two exonic mutational pipelines were used to identify somatic mutations. Functional gene analysis was performed in cell-based assays in multiple thyroid cell lines. The prognostic value of genes was evaluated with TCGA datasets.ResultsWe identified 128 new potential biomarkers associated with recurrence, including 40 mRNAs, 39 miRNAs, and 59 genetic variants. Among differentially expressed genes, modulation of FN1, ITGα3, and MET had a significant impact on thyroid cancer cell migration. Similarly, ablation of miR-486 and miR-1179 significantly increased migration of TPC-1 and SW1736 cells. We further utilized genes with a validated functional role and identified a 5-gene risk score classifier as an independent predictor of thyroid cancer recurrence.ConclusionOur newly proposed risk model based on combinatorial mRNA and microRNA expression has potential clinical utility as a prognostic indicator of recurrence. These findings should facilitate earlier prediction of recurrence with implications for improving patient outcome by tailoring treatment to disease risk and increasing posttreatment surveillance.

A Possible Role for Serum Thyroglobulin to Predict Structural Recurrence of Papillary Thyroid Cancer After Thyroid Lobectomy

A Possible Role for Serum Thyroglobulin to Predict Structural Recurrence of Papillary Thyroid Cancer After Thyroid Lobectomy

Lymph node yield in the initial central neck dissection (CND) associated with the risk of recurrence in papillary thyroid cancer: A reoperative CND cohort study

BackgroundTo evaluate the relationship between lymph node yield (LNY) from the initial central neck dissection (CND) and the risk of recurrence in patients undergoing reoperative CND for papillary thyroid cancer (PTC). MethodWe reviewed clinical data from all patients with pathologically proven PTC who underwent central neck and/or lateral neck dissection reoperations at Nanfang Hospital between 2012 and 2020. Patient demographics, tumor characteristics, clinical data and follow-up information were obtained. In the initial CND, the total number of lymph nodes removed (LNY), total positive nodes removed, and the percentage of positive lymph nodes to the number of lymph nodes removed (PLN%) were determined. ResultsA total of 162 patients were included in the study, with a median follow-up of 44 months. 62 had central neck disease recurrence. The optimal LNY and PLN% cut-off values for recurrence were 11 and 65%, respectively. Group 2 (LNY ≥ 11, PLN% < 65%) showed a significantly higher RFS rate than group 1 (LNY < 11 and PLN% < 65%; P < 0.001), group 3 (LNY < 11, PLN% ≥ 65%; P < 0.001), and group 4 (LNY ≥ 11, PLN% ≥ 65%; P = 0.038). Furthermore, group 4 had a higher RFS rate than group 1 (P = 0.008) and group 3 (P = 0.001). Multivariate analysis revealed that LNY < 11 in the central neck was an independent risk factor for recurrence/persistence in the initial surgery (P < 0.001). ConclusionHigher LNY in central and neck dissections is associated with lower papillary thyroid cancer recurrence rates, which was confirmed by a reoperative CND procedure. To minimize the risk of recurrence and the need for secondary therapy, surgeons should perform compartment-oriented CNDs when indicated.

Metabolic and functional imaging employment in the differentiation of brown tumors from bone metastases in a case of primary papillary thyroid cancer and parathyroid adenoma: case report

BackgroundBrown tumors are benign osteoclastic bone lesions encountered in patients with hyperparathyroidism. These tumors may demonstrate aggressive, destructive features in the skeleton and imitate metastatic bone lesions, particularly in patients with known primary neoplasm. In this case report of recurrent papillary thyroid cancer and ectopic parathyroid adenoma, we shed light on the importance of combining different nuclear medicine imaging modalities to differentiate brown tumors from metastatic bone lesions.Case presentationWe present a 39-year-old woman with a known history of papillary thyroid carcinoma classic type stage pT1N1b post-total thyroidectomy and radioactive iodine (I-131) therapy (RAI) presented with upper limb weakness and pain. An expansile lytic lesion involving the 6th cervical vertebra was seen in cervical spine MRI, which was suspicious for metastatic deposit. Therapeutic and diagnostic I-131 whole-body scans were negative for any I-13-avid lesions. Laboratory results revealed high calcium, parathyroid hormone, and alkaline phosphatase. A Technetium-99m-sestamibi (Tc-99m MIBI) scan was done with the standard protocol of spot views to the neck and upper chest area to localize any suspicious parathyroid adenoma. The scan demonstrated right supraclavicular and mediastinal Tc-99m MIBI-avid lesions suspicious for being ectopic parathyroid adenomas. Whole-body fluorine-18-2-fluoro-2-deoxy-d-glucose (18F-FDG), positron emission tomography/computed tomography (PET/CT) (18F-FDG PET/CT) was performed for further evaluation. It demonstrated multiple focal lytic skeletal lesions of abnormal increased FDG uptake as well as right supraclavicular FDG-avid lymph nodes. However, the superior mediastinal lesion was non-FDG-avid, suggesting the existence of two different entities: ectopic parathyroid adenoma with multiple brown tumors and metastatic right supraclavicular lymph nodes. The patient underwent right neck dissection and superior mediastinal mass excision. An intra-operative fresh serum parathyroid sample was sent, which dropped down to 100ng/ml from 863.7ng/ml. Later, histopathological results revealed that the right supraclavicular lymph nodes were metastatic papillary thyroid carcinoma. At the same time, the superior mediastinal mass proved to be parathyroid adenoma by histopathology, confirming the 18F-FDG PET/CT findings.ConclusionsIn the case of papillary thyroid carcinoma, metastatic lymph nodes with hyperparathyroidism, and evidence of lytic bone lesions, careful interpretation of the different metabolic and functional imaging modalities are needed to exclude the concurrent parathyroid adenoma and facilitate the differentiation of brown tumors from bone metastases, leading to appropriate surgical and medical treatment plans.

S2491 Diagnosis of Papillary Thyroid Carcinoma by Transesophageal Endoscopic Ultrasound-Guided Fine-Needle Biopsy (EUS-FNB)

Introduction: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) can be used as a diagnostic modality with tissue sampling of both intra- and extra-luminal lesions. EUS allows for a less invasive, real-time image-guided biopsy of adjacent extraluminal structures. We present EUS-guided FNB evaluation in a patient with suspected recurrent thyroid cancer and a suspicious portocaval lymph node (PCNL). Case Description/Methods: A 36-year-old male with recurrent papillary thyroid cancer that had been previously treated with total thyroidectomy and modified radical neck dissection and iodine ablation presents with intermittent dysphagia to solid foods and a pressure sensation in his mid-neck. He reported poor compliance with follow-up appointments, surveillance imaging, and post-treatment TSH-suppressive T4 therapy. CT neck showed non-specific bilateral nodular changes in the thyroidectomy bed which were thought to reflect postsurgical changes versus recurrent neoplasm. A whole-body PET/CT showed no substantial FDG uptake in the neck but rather increased uptake in a PCNL concerning for intra-abdominal metastases. Surface ultrasound-guided FNA (USG-FNA) of the left neck mass was non-diagnostic. As the lymph node was inaccessible by percutaneous biopsy, and previous USG-FNA of thyroid bed was non-diagnostic, a EUS guided biopsy of both, the left neck mass and PCNL was pursued. The EUS revealed a 12mm x 8mm mass in the thyroid resection bed. EUS-guided thyroid biopsy was performed from the level of the upper esophageal sphincter, with 5 passes of a 25 gauge SharkCoreTM needle (C-25-05 Medtronic, Dublin, Ireland). Two enlarged ( >1cm) hypoechoic PCNL with well-defined borders were identified with EUS. Using a 22 gauge SharkCoreTM needle biopsy, FNB x 3 was performed on the PCNL. The pathology from the left thyroid mass revealed papillary thyroid carcinoma, and the histopathology from the PCNL was a benign lymphoid sample. The patient did well on follow-up and had no periprocedural adverse events. By demonstrating recurrent cancer, without PCNL involvement. This allowed the patient to undergo local surgical resection. Discussion: The evaluation and management of suspicious lesions in the superior mediastinum have evolved since the inception of EUS. We demonstrate that EUS can be used in the evaluation of recurrent thyroid cancer when USG-FNA is not diagnostic. An additional advantage of EUS is the ability to sample suspicious lymph nodes adjacent to the GI tract at the same time.Figure 1.: EUS guided fine needle biopsy of the enlarged lymph node in the porta hepatis region (a) revealed a benign lymphoid sample (c). A 1.2 x 0.8 cm lesion found in the left thyroid bed on EUS (b) with EUS-FNB showing malignant cells diagnostic of papillary thyroid carcinoma (d).

Prognostic possibilities of molecular genetic testing for assessing the risk of recurrence of papillary thyroid cancer in children

The assessment of aggressiveness and risk of death in papillary thyroid cancer in children is currently based on clinical criteria. To ensure a more accurate risk stratification, new criteria and various molecular genetic markers are constantly being sought. The article studied the dependence of the clinical and pathological manifestations of papillary thyroid cancer in children on the level of expression of various microRNAs and the presence of the BRAF mutation. It was found that the BRAF mutation was present in 20.4% of cases, while the dependence of the clinical behavior of cancer on the BRAF mutation was not established. Of the 14 microRNAs studied, statistical differences were obtained for oncogenic miR-146b, -221, -31, and oncosuppressive miR-144, which correlated with signs such as extrathyroid tumor growth, multi-focus, and metastasis to the neck lymph nodes.

Prevalence of Hashimoto Thyroiditis in Adults With Papillary Thyroid Cancer and Its Association With Cancer Recurrence and Outcomes

Hashimoto thyroiditis (HT) has been suggested to be associated with papillary thyroid cancer (PTC) development. However, its association with PTC progression remains unclear. To examine the association between HT and PTC presentation and outcomes. This retrospective cohort study included a review of patients aged 18 to 75 years who had pathologically confirmed PTC treated at a single center in China from January 1, 2001, to December 31, 2014. Data analysis was performed from November 1 to December 31, 2020. Coexistent HT was defined according to evaluation of postoperative paraffin sections. The primary outcome was the association of HT with PTC-related mortality, assessed using Cox proportional hazards regression models. The secondary outcome was the association of HT with aggressive characteristics and structural recurrence of PTC, assessed using logistic regression and Cox proportional hazards regression with and without adjustment for related factors. Of 9210 patients with PTC (mean [SD] age, 43.6 [12.0] years; 6872 [75%] women) included in the analysis, 1751 (19%) had HT. In the logistic regression model, HT was negatively associated with frequencies of primary tumor size of 4 cm or greater (adjusted odds ratio [aOR], 0.20; 95% CI, 0.12-0.33; P < .001), gross extrathyroidal extension (aOR, 0.44; 95% CI, 0.36-0.54; P < .001), extranodal extension (aOR, 0.66; 95% CI, 0.55-0.80; P < .001), and distant metastasis (aOR, 0.17; 95% CI, 0.04-0.71; P = .02). After a median follow-up of 85 months (range, 12-144 months), 131 PTC-related deaths were identified in the cohort; 2 patients who died had HT. Patients with HT had significantly superior outcomes compared with patients without HT in terms of unadjusted 10-year disease-specific survival (99.9% vs 96.6%; log-rank P < .001) and recurrence-free survival (92.0% vs 87.6%; log-rank P = .001). After adjusting for sex, age, primary tumor size, extrathyroidal extension, lymph node metastasis, distant metastasis, extent of surgery, and radioactive iodine ablation, HT was associated with decreased PTC-related mortality (hazard ratio [HR], 0.19; 95% CI, 0.05-0.76; P = .02). Stratified analysis showed that HT was associated with less frequent structural recurrence in patients with extrathyroidal extension (HR, 0.52; 95% CI, 0.38-0.71; P < .001; P = .002 for interaction) or after total thyroidectomy (HR, 0.50; 95% CI, 0.35-0.69; P < .001; P = .009 for interaction). In this cohort study, patients with coexistent HT had less aggressive characteristics at presentation and better outcomes of PTC than did patients without HT. The findings suggest that autoimmune thyroiditis has a protective role in association with thyroid cancer.