Childhood Papillary Thyroid Carcinoma: A Case Report

Background: Thyroid cancer is a rare disease yet the most common endocrine malignancy in pediatrics. Unlike adult patients, children with thyroid nodules typically don’t complain of pain, soreness, or difficulty swallowing. Additionally, using the recommended therapy for adults to treat paediatrics is not appropriate. There is an unmet need for updated unique guidelines for the management of papillary thyroid carcinoma (PTC) in paediatrics and adolescents. Case Report: A 12-year-old girl had an atypical presentation of metastatic PTC in lymph nodes. She was treated initially with hemi-thyroidectomy, followed by total thyroidectomy. A multidisciplinary team followed her up till successful results were found. Conclusion: Due to the difference in pathophysiology between thyroid tumors in children and adults, a unique approach to PTC management is to be implemented. Further trials are required for a better understanding of risk factors, the likelihood of recurrence, and the long-term side effects of the chosen management plan.

Papillary thyroid carcinoma with nodular fasciitis-like stroma-an unusual variant with distinctive histopathology:A case report

BACKGROUND Papillary thyroid carcinoma(PTC)is regarded as a fairly common endocrine malignancy,which can be divided into different multiple variants due to wide morphologic differences.The majority of PTC variants have been reported,but PTC with nodular fasciitis-like stroma(NFS)is a rare pathological variant and has been infrequently reported in the relevant literature.This condition involves abundant reactive stromal components rich in spindle cells,which may account for 60%-80%of the tumor along with a typical papillary carcinoma.CASE SUMMARY A 44-year-old man presented with a 4-mo history of a palpable mass over the anterior aspect of the left neck,the tumor demonstrated gradual enlargement but was painless during the 4 mo prior to discovery.Thyroid function test results were normal.Physical examination showed an enormous and firm nodular mass in the left lobe of the thyroid gland extending to the level of the hyoid bone.Ultrasonography of the neck revealed a well-defined heterogeneous lesion measuring around 5.0 cm×4.0 cm with a hypoechoic complex nodule,decreased vascularity and speckles of microcalcification.The patient underwent left thyroidectomy with central compartment lymph node dissection.Final histopathological examination confirmed the diagnosis of PTC with extensive fibromatosis-like stroma combined with typical PTC.The patient was asymptomatic at the 3-mo follow-up.CONCLUSION PTC-NFS is a rare pathological variant and its diagnosis and prognosis may be similar to typical papillary carcinoma.

Papillary Thyroid Carcinoma and Pregnancy: What Impact on Prognosis?

Introduction: The impact of pregnancy on the prognosis of papillary thyroid carcinoma (PTC) has been debated for several decades;however, no definitive conclusions have been reached. The main objective of this study is to demonstrate the short-term influence of pregnancy on the evolution and prognosis of PTC. Materials and Methods: A prospective descriptive and analytical study was conducted in the Endocrinology and Diabetology Department at the Hassan II University Hospital in Fez, including patients followed for papillary thyroid carcinoma presenting with a pregnancy during the year 2019 and 2020. The follow-up of these patients was continued until 1 year postpartum. We studied the clinical, paraclinical and therapeutic factors that could influence the prognosis of the disease. Results: We included 26 patients. Our study showed a significant correlation between recurrence and the presence of unfavorable histological signs (p = 0.02) as well as the initial Tg level (0.01). However, pregnancy was not an influencing factor (p = 0.41). Conclusion: Pregnancy does not seem to be a factor aggravating the prognosis of differentiated thyroid cancers.

Clinical and Sonographic Assessment of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma

The purpose of this study was to assess the differences in clinical and sonographic features of papillary thyroid carcinoma（PTC） between cervical lymph node metastatic（CLNM） and nonmetastatic groups.Clinical data of PTC patients（414 patients with 624 malignant nodules） who underwent a preoperative ultrasonography and surgery between June 2010 and March 2015 at Renmin Hospital of Wuhan University were retrospectively analyzed.Clinical factors,preoperative ultrasound features and the final pathological findings were obtained.The differences in the sonographic features of PTC between the CLNM group and the non-CLNM group were analyzed.There were 187 CLNM and 227 non-CLNM patients.The median age at the diagnosis of this cohort was 45.4 years old（ranging from 18 to 77 years）.Ultrasonographic parameters that were significantly associated with CLNM [OR=2.569（1.502,4.393）,P〈0.001）] were as follows：the mulifocality of the nodules,size over 2 cm,the presence of microcalcifications,the distance ratio（DR） pattern showing the contact of the nodules with the thyroid capsule,and the extracapsular spread of the nodules.No significant differences in age,gender,thyroid stimulating hormone（TSH） levels and other ultrasonography parameters were found between the CLNM and the non-CLNM groups.Therefore,our results suggest that a larger size,microcalcifications,mulifocality,and the DR pattern showing the contact of the nodules with the thyroid capsule and extracapsular spread are significantly more indicative of CLNM in PTC.

Active surveillance in low risk papillary thyroid carcinoma

In recent decades,while the incidence of thyroid cancer has increased exponentially around the world,mortality has remained stable.The vast majority of this increase is attributable to the identification of intrathyroidal papillary microcarcinomas,which exhibit slow growth rates with indolent courses.A diagnosis of thyroid cancer based upon the presence of these small tumors could be considered as an overdiagnosis,as the majority of these tumors would not likely result in death if left untreated.Although surgical resection was the classical standard therapy for papillary microcarcinomas,active surveillance(AS)has emerged over the last three decades as an alternative approach that is aimed to recognize a minority group of patients who will clinically progress and would likely benefit from rescue surgery.Despite the encouraging results of AS,its implementation in clinical practice is strongly influenced by psychosocial factors.The aim of this review is to describe the epidemiology,clinical evolution,prognostic factors,and mortality of papillary thyroid microcarcinomas.We also summarize the AS strategy according to published evidence,characterize the criteria for selecting patients for AS according to risk factors and environmental characteristics,as well as analyze the current limitations for AS implementation.

Skull metastasis revealing a papillary thyroid carcinoma

Although thyroid carcinoma is a relatively common form of malignancy,metastatic spread to the skull is rare.Here,we report a case of papillary thyroid carcinoma with frontal and parietal metastasis.A 61-year-old Chinese woman presented with a one year history of a growing mass on the center of the frontal and parietal bone,initially thought to be meningioma.Biopsy of the skull base mass after intracalvarium excision,indicated a tumor of thyroid origin.One month later the patient underwent a total thyroidectomy.Pathological examination confirmed a diagnosis of papillary thyroid carcinoma with frontal and parietal bone metastasis.Based on this experience,the key to successful management of the skull metastasis of thyroid carcinoma is prompt diagnosis and appropriate treatment.Skull metastasis should be considered at the outset of the clinical course of papillary thyroid cancer.To facilitate this,patients should be meticulously investigated by a multidisciplinary team to improve quality of life.

Needle tract seeding of papillary thyroid carcinoma after fine-needle capillary biopsy:A case report

BACKGROUND Fine-needle biopsy is an accurate and cost-efficient tool for the assessment of thyroid nodules.It includes two primary methods:Fine-needle capillary biopsy(FNCB)and fine-needle aspiration biopsy.Needle tract seeding(NTS)is a rare complication of thyroid fine-needle biopsy mainly caused by fine-needle aspiration biopsy rather than FNCB.Here,we present an extremely rare case of a papillary thyroid carcinoma(PTC)patient with FNCB-derived NTS.CASE SUMMARY We report a 32-year-old woman with PTC who showed subcutaneous NTS 1 year after FNCB and thyroidectomy.NTS was diagnosed based on clinical manifestations,biochemistry indices,and imaging(computed tomography and ultrasound).Pathological identification of PTC metastases consistent with the puncture path is the gold standard for diagnosis.Surgical resection was the main method used to treat the disease.After surgery,thyroid function tests and ultrasound scans were performed every 3-6 mo.To date,no evidence of tumor recurrence has been observed.CONCLUSION FNCB is a safe procedure as NTS is rare,and can be easily removed surgically with no recurrence.Accordingly,NTS should not limit the usefulness of FNCB.

Relationship between subgroups of central and lateral lymph nodemetastasis in clinically node-negative papillary thyroid carcinoma

BACKGROUND Lymph node metastasis(LNM) of papillary thyroid carcinoma(PTC) has a certain regularity and occurs first to the central lymph node and then to the lateral lymph node. The pathway of PTC LNM can guide surgical prophylactic lymph node dissection(LND) for clinical surgeons.AIM To investigate the relationship between subgroups of central LNM and lateral LNM in unilateral clinically node-negative PTC(cN0-PTC).METHODS Data were collected for 1089 PTC patients who underwent surgical treatment at the Department of Endocrine and Breast Surgery of the First Hospital of Chongqing Medical University from January 2016 to December 2017. A total of 388 unilateral cN0-PTC patients met the inclusion criteria and were enrolled in this study. The clinical and pathological data for these 388 patients who underwent total thyroidectomy + central LND + lateral LND were retrospectively analyzed. The relationship between the central LNM and lateral LNM subgroups was investigated.RESULTS The coincidence rate of cN0-PTC was only 30.0%.Optimal scaling regression analysis showed that sex(57.1% vs 42.9%, P = 0.026), primary tumor size(68.8% vs 31.2%, P = 0.008), tumor location(59.7% vs 40.3%, P = 0.007), extrathyroid extension(ETE)(50.6% vs 49.9%, P = 0.046), and prelaryngeal LNM(57.1% vs 42.9%, P = 0.004) were significantly associated with ipsilateral level-II LNM. Their importance levels were 0.122, 0.213, 0.172, 0.110, and 0.227, respectively. Primary tumor size(74.6% vs 30.2%, P = 0.016), pretracheal LNM(67.5% vs 32.5%, P < 0.001), and paratracheal LNM(71.4% vs 28.6%, P < 0.001) were significantly associated with ipsilateral level-Ⅲ LNM. Their importance levels were 0.120, 0.408, and 0.351, respectively. Primary tumor size(72.1% vs 27.9%, P = 0.003), ETE(70.4% vs 29.6%, P = 0.016), pretracheal LNM(68.3% vs 31.7%, P=0.001), and paratracheal LNM(80.8% vs 19.2%, P < 0.001) were significantly associated with ipsilateral level-IV LNM. Their importance levels were 0.164, 0.146, 0.216, and 0.472, respectively.CONCLUSION The LNM pathway of thyroid cancer has a certain regularity. For unilateral cN0-PTC patients with a tumor diameter > 2 cm and pretracheal or ipsilateral paratracheal LNM, LND at ipsilateral level Ⅲ and level IV must be considered. When there is a tumor in the upper third of the thyroid with prelaryngeal LNM, LND at level II, level Ⅲ and level IV must be considered.

Papillary thyroid carcinoma occurring with undifferentiated pleomorphic sarcoma: A case report

BACKGROUND Papillary thyroid cancer(PTC)is the most common malignant tumor of the thyroid.However,the coexistence of PTC and sarcoma in one patient is rare.In this article,we report the case of a patient who presented with both PTC and undifferentiated pleomorphic sarcoma(UPS),which has not been previously reported in the online Medline database(PubMed).CASE SUMMARY A 71-year-old man was admitted to our hospital for a mass on the right side of his neck for one month,which rapidly enlarged within 2 wk with distending pain.The patient was diagnosed with a thyroid malignancy by fine-needle aspiration and underwent total thyroidectomy and bilateral central lymph node dissection.Histology and immunohistochemistry revealed features of both PTC and UPS.The thyroid cancer 8 gene detection kit results showed BRAF and telomerase reverse transcriptase mutations.The disease progressed rapidly,and the patient died four months after surgery from extensive lung metastasis.CONCLUSION Our report highlights the patient’s pathological characteristics and related genetic mutations.Due to the rapid development and poor prognosis of cooccurring PTC and sarcoma,it is important for clinical physicians and pathologists to raise awareness of this type of tumor.

Synchronous parathyroid adenoma, papillary thyroid carcinoma and thyroid adenoma in pregnancy: A case report

BACKGROUND There is a common pathologic relationship between parathyroid adenoma and thyroid cancer,but this relationship is infrequent in pregnant patients with primary hyperparathyroidism(PHPT).CASE SUMMARY A 27-year-old gravida 1 woman was transferred to our hospital at 16 wk of pregnancy.She was diagnosed with parathyroidoma,papillary carcinoma of the thyroid and thyroid adenoma and was managed surgically.Both the mother and the newborn were stable after a right inferior parathyroidectomy and total thyroidectomy.The healthy infant was delivered at the 40th week of pregnancy.The mother had no evidence of recurrence over three years of follow-up.CONCLUSION Awareness of concomitant PHPT and thyroid diseases may help in managing patients with a history of hypercalcemia.

Residual tumor and central lymph node metastasis after thermal ablation of papillary thyroid carcinoma: A case report and review of literature

BACKGROUND Debate exists regarding the use of thermal ablation(TA)to treat papillary thyroid carcinoma(PTC).Some studies have recommended TA as a new,ef
cient and safe technology for PTC.In this article,we report one case of a residual tumor and central lymph node metastasis(CLNM)after TA for PTC.CASE SUMMARY A 63-year-old female underwent bilateral ultrasound(US)-guided radiofrequency ablation for PTC.Three months later,she was diagnosed as thyroid cancer with suspected CLNM by US and contrast-enhanced computed tomography.The subsequent fine-needle aspiration(FNA)biopsies were negative.Due to her strong personal preference,she underwent total thyroidectomy and central lymph node dissection.Local tissue adhesion and a difficult dissection were noted during the operation.The pathology of the frozen sections during the operation was still negative.The final pathology results of paraffin-embedded sections revealed residual tumor cells at the edge of the PTC and CLNM.CONCLUSION TA may lead to a residual tumor in patients with PTC.Follow-up using US and FNA biopsy may not be adequate to evaluate the residual tumor.TA should be carefully considered in PTC treatment.

Right time to detect urine iodine during papillary thyroid carcinoma diagnosis and treatment:A case report

BACKGROUND This is the first documentation of a spontaneous and nonspecific chemical reaction of an iodinated contrast media with ammonium persulfate used in As3+-Ce4+catalytic spectrophotometry for urine iodine concentration(UIC)detection.CASE SUMMARY We herein report an incidental case who had a dual source computed tomography examination for papillary thyroid carcinoma diagnosis.Serial spot urine specimens were collected during her hospitalization and were measured by As3+-Ce4+catalytic spectrophotometry on a Beckman Coulter AU5800.The reacted solutions were“brownish”,and the results showed extremely high iodine concentrations despite serial dilutions.The patient claimed no dietary habit of iodized salt or iodine-containing medical history,which strongly pointed to iodinated contrast media(ICM)via intravenous injection.Even with 0.01%ICM,its interruption is still profound on the desired urine iodine reaction with ammonium persulfate,leading to inaccurate UIC and possibly inappropriate treatment.CONCLUSION The following laboratory suggestions should be considered:(1)As3+-Ce4+catalytic spectrophotometry is only suitable for UIC measurement after confirmed ICM renal clearance;(2)A mass spectrometry-based method can be applied as an alternative during the ICM clearance period;and(3)The UIC baseline can be confirmed after ICM injection by consecutive detection for at least 2 mo.

Advances in BRAF gene mutations in papillary thyroid carcinoma

Thyroid cancer is the most common endocrine system tumor.Ultrasound guided fine needle puncture(FNA)can identify benign and malignant thyroid nodules.However,due to the limitation of cytological detection,some thyroid nodules are difficult to distinguish benign and malignant.BRAF gene mutation is a common human oncogenic mutation and the highest mutation frequency in papillary thyroid carcinoma.The combination of FNA and BRAF gene detection can significantly improve the diagnostic rate of benign and malignant thyroid nodules and make up for the deficiency of single diagnosis of cytology.Moreover,while the incidence of thyroid cancer is growing rapidly worldwide,its mortality remains stable.The problem of overdiagnosis and overtreatment of thyroid cancer is becoming more and more obvious.However,due to the limitations of current studies on BRAF genes,its prognostic value for papillary thyroid carcinoma remains controversial.Therefore,in order to reduce the adverse effects of overdiagnosis and treatment,the relationship between gene and tumor biological behavior needs further study in the future.

SURGICAL TREATMENT OF PAPILLARY THYROID CARCINOMA──REPORT OF 437 CASES

Four hundred and thirty-seven patients with papillary thyroid carcinoma were treated from April 1963 to December 1989. The main treatment was surgery which was divided into 4 types: lobectomy combined with neck dissection (RND or MND); total thyroidectomy; isthmusectomy plus lobectomy; lobectomy combined with RND and then followed by contralateral MND. The 10-year survival rates of these four groups were 88.6%, 89.5% to % and 80%, respectively. The overall 5, 10 and 15-year survival rates were 92.7%, 87.9%,79.4%. Lymph node metastasis was present in 80%. The authors believe that functional neck dissection is indicated if the number of lymph node is limited and the size is small.

Risk factors for lymph node metastasis of cN0 papillary thyroid carcinoma

Objective To investigate the risk factors for cervical lymph node metastasis of clinically lymph node-negative(cN0)papillary thyroid carcinoma(PTC).Methods Patients and Methods:The clinicopathologic data of patients with cN0 PTC who underwent at least one lobectomy plus central lymph node dissection at Xuzhou Central Hospital from January 2018 to December 2020 were retrospectively collected and the risk factors of lymph node metastasis analyzed.Univariate and multivariate analyses were performed to detect the risk factors for cervical lymph node metastasis.Results A total of 312 patients with cN0 PTC were enrolled in this study.The postoperative pathology results showed that 134 patients(42.9%)had central lymph node metastasis,of whom 24(17.9%)had lateral lymph node metastasis(LLNM).The univariate analysis results showed that male gender,age<45 years,tumor diameter≥10 mm,bilateral cancer,capsule invasion,and multiple foci were associated with cervical lymph node metastasis of cN0 PTC(P<0.05).Further logistic regression analysis results showed that these factors,except age,were independent risk factors for cervical lymph node metastasis of cN0 PTC(P<0.05).The results also showed that the risk of LLNM increased with an increase in the number of positive central lymph nodes in patients with cN0 PTC(P<0.05).Conclusion Cervical lymph node metastasis of cN0 PTC is related to many factors,and a high number of positive central lymph nodes indicates a high risk of LLNM.Patients with risk factors should undergo preventive central lymph node dissection at the first surgery,and in patients with a high number of positive central lymph nodes,lateral lymph node dissection should be discreetly performed.

Effects of BRAF^(V600E) Mutation on Na^+/I^- Symporter Expression in Papillary Thyroid Carcinoma

Radioiodine ablation（RIA） therapy is one of the most important treatments for papillary thyroid carcinoma（PTC）, but some patients who received 131 I have radioiodine-refractory disease caused by the decreased expression of the Na^＋/I^- symporter（NIS）. BRAF^V600E mutation is one possible risk factor that can disturb the NIS expression, but the roles are unclear in clinical practice. This research discussed the association of BRAF^V600E mutation and NIS expression in PTC tissue and the clinical implications in RIA therapy. 134 PTC samples were collected between June 2013 and June 2014 from Tongji Hospital affiliated to Tongji Medical College, and their clinical characteristics were analyzed. RT-PCR was used to detect the BRAF^V600E mutation from formalin-fixed paraffin-embedded samples, and immunohistochemistry was applied to detect the NIS expression. IPP software was used to calculate the relative expression quantity of NIS. We found that there was no significant correlation between the absorbance（A） values of NIS and clinicopathologic features in these cases, even thyroid stimulating hormone. BRAF^V600E mutation showed inhibitory effect on the NIS expression without statistically significant difference in all PTC cases（β=–0.0195, P=0.085）, but in the subgroup without hashimoto＇s thyroiditis（HT）, BRAF^V600E mutation could significantly inhibit the NIS expression（β=–0.0257, P=0.046）. The results indicate that BRAF^V600E mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.

Diagnostic Value of Serum TSH,Ultrasound,and Enhanced CT in Papillary Thyroid Carcinoma with Lymph Node Metastasis

Objective:To explore the diagnostic value of serum TSH,ultrasound,and enhanced CT in papillary thyroid carcinoma with lymph node metastasis.Methods:168 patients who underwent thyroidectomy in Shaanxi Provincial People’s Hospital from January 2020 to December 2021 were selected as the research subjects.Based on the pathological nature(benign or malignant),they were divided into two groups,with 86 patients in the control group and 82 patients in the study group.Based on whether the pathology was accompanied with lymph node metastasis,the PTC group was divided into a lymph node metastasis group and a non-lymph node metastasis group,with 51 and 31 patients in the respective groups.Retrospective analysis was conducted to observe and analyze the pathological results of the thyroid nodules’thyroid ultrasound results,neck enhanced CT results,and thyroid function test serology results.Results:Compared with the PTC group,there were significant differences in TR classification,ultrasonic lymph nodes,and enhanced CT lymph nodes,but no significant differences in the course of disease,nodule distribution,and the number of nodules between the benign nodule group and PTC group;in the comparison of lymph node metastasis using ultrasound and enhanced CT,the number of patients with ultrasound lymph nodes without abnormal metastasis in the non-metastasis group was 28,while that of the metastasis group was 21;the number of patients with abnormal metastasis in the non-metastasis group was 3,while that of the metastasis group was 30.The number of patients with a single node without metastasis and metastasis was 14 and 8,respectively,whereas the number of patients with multiple nodes without metastasis and metastasis was 17 and 43,respectively.There were statistically significant differences in the number of ultrasound lymph nodes and nodules,but no statistically significant differences in TR classification,enhanced CT lymph nodes,nodules distribution,and disease course.Conclusion:Serum TSH can be used to identify the nature(benign and malignant)of thyroid nodules,and enhanced CT is better than ultrasound when evaluating complex lesions.It can be used as a supplement to ultrasound based on clinical context.

Effect of Hashimoto’s Thyroiditis on Efficacy of 131I Ablation Therapy in Intermediate- and High-Risk of Thyroid Papillary Carcinoma

Objective: The purpose of this study was to investigate the effect of Hashimoto’s thyroiditis on efficacy of 131I ablation in intermediate- and high-risk of thyroid papillary carcinoma patients. The findings will help to develop a personalized treatment plan for patients with thyroid papillary carcinoma complicated with Hashimoto’s thyroiditis. Material and Methods: From January 2016 to December 2020, patients who were diagnosed with intermediate- and high-risk PTC with lymph node metastasis were analyzed retrospectively, excluding patients with incomplete clinical data, distant metastasis, positive TGAb, TSH Results: A total of 525 patients (166 males and 359 females) were included in the study, including 368 patients in ER group (70.1%) and 157 patients in NER group (29.9%). Eleven factors including combining Hashimoto’s thyroiditis, pre-ablative Tg levels, sex, tumor diameter, extraglandular invasion, multifocal, bilateral lesions, central lymph node metastasis, lateral lymph node metastasis, lymph node metastasis rate, thyroglobulin were statistically different between ER group and NER group with significance at P Conclusion: Hashimoto’s thyroiditis, Ps-Tg level and lateral lymph node metastasis are potential predictors for short-term efficacy of 131I treatment in intermediate- and high-risk thyroid papillary carcinoma. Hashimoto’s thyroiditis, high Ps-Tg level and increased number of lateral lymph node metastasis reduce the efficacy of 131I therapy in patients with intermediate and high risk thyroid papillary carcinoma.

BRAFV600E mutation is not a positive predictor for distant metastasis in sporadic papillary thyroid carcinoma

Background BRAFV600E mutation is correlated with local aggressive clinicopathological features in papillary thyroid carcinoma; yet the relationship between this genetic variation and distant papillary thyroid carcinoma metastasis was unclear.This study aimed to investigate whether BRAFV600E is predictive for distant metastasis in the Chinese population.Methods One hundred and seven patients with papillary thyroid carcinoma were enrolled in this study,including 43 patients with distant metastasis and 64 patients without.Quantitative real-time polymerase chain reaction was used to detect BRAFV600E mutation,while immunohistochemistry was performed to detect vascular endothelial growth factor （VEGF） expression.The associations between distant metastasis and BRAFV600E mutation,and VEGF expression as well as local clinicopathological factors were determined.Results A total of 28.6％ of the patients in the distant metastasis group harbored BRAFV600E mutation,which was significantly lower than in the without distant metastasis group （68.8％,P ＜0.001）.BRAFV600E mutation was negatively correlated with positive VEGF expression （P=0.001）.Furthermore,52.2％ of the patients with distant metastasis exhibited VEGF expression,compared with 25.0％ of those without.Higher levels of VEGF expression were also observed in the distant metastasis group.Tumor size,extra-thyroid invasion,and BRAFV600E mutation were independent predictors for distant metastasis according to multivariate analysis （odds ratios were 2.8,12.4,and 0.3; 95％ CI 1.483-5.334,and 2.950-52.407,0.100-0.890; P=0.002,0.001,and 0.030,respectively）.BRAFV600E mutation was negatively correlated with distant metastasis in adult subgroup analysis （P=0.005） but was not an independent parameter.Conclusions BRAFV600E mutation is predictive for distant metastasis in papillary thyroid carcinoma but not positively.VEGF may be involved in the pathogenesis of distant metastasis.

A three-microRNA panel in serum as novel biomarker for papillary thyroid carcinoma diagnosis

Background:Accumulating evidence has revealed that circulating microRNAs(miRNAs)can serve as non-invasive biomarkers for cancer diagnosis.This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma(PTC).Methods:The experiment was carried out between 2015 and 2017.In the screening stage,the Exiqon miRNA quantitative real-time polymerase chain reaction(qPCR)panel was applied to select candidate miRNAs.In the following training,testing,and external validation stages,the serum samples of 100 patients and 96 healthy controls(HCs)were analyzed to compare the expression levels of the identified miRNAs.The areas under the receiver operating characteristic curves(AUCs)were calculated to assess the diagnostic value of the identified signature.Results:Three miRNAs(miR-25-3p,miR-296-5p,and miR-92a-3p)in serum were consistently up-regulated in PTC patients compared with HCs.A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection.The AUCs of the panel were 0.727,0.771,and 0.862 for the training,testing,and external validation stage,respectively.Meanwhile,the panel showed stable capability in differentiating PTC patients from patients with benign goiters,with an AUC as high as 0.969.For further exploration,the three identified miRNAs were analyzed in tissue samples(23 PTC vs.23 HCs)and serum-derived exosomes samples(24 PTC vs.24 HCs),and the altered expression in the tumor also indicated their close relationship with PTC disease.Conclusion:We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.