CircTIAM1 overexpression promotes the progression of papillary thyroid cancer by regulating the miR-338-3p/LASP1 axis

Background:Papillary thyroid cancer(PTC)is the most prevalent histological type of differentiated thyroid malignancy.Circular RNAs(circRNAs)have been implicated in the pathogenesis and progression of various cancers.circTIAM1(hsa_circ_0061406)is a novel circRNA with aberrant expression in PTC.However,its functional roles in PTC progression remain to be investigated.Methods:The expression levels of circTIAM1 in the PTC and the matched para-cancerous tissues were detected by quantitative real-time reverse-transcription PCR(qRT-PCR).The subcellular localization of circTIAM1 was examined by fluorescence in-situ hybridization(FISH).Kaplan-Meier plot was used to analyze the association of clinicopathological features with circTIAM1 expression.Bioinformatics databases were utilized to predict the target miRNAs of circTIAM1 and the downstream target mRNAs.RNA pulldown,RIP assay,and dual-luciferase reporter assay were used to confirm the interactions.Functional experiments,such as CCK-8,EDU staining,and apoptosis assays,as well as in vivo xenograft model were employed to explore the impacts of circTIAM1,miR-338-3p,and LIM/SH3 protein 1(LASP1)on the malignant phenotype of the PTC cells.Results:CircTIAM1 was highly expressed in PTC cells.Moreover,circTIAM1 silencing suppressed the proliferation and invasion of PTC cells in vitro and impaired tumorigenesis in vivo.Furthermore,miR-338-3p was verified as a miRNA target of circTIAM1.LASP1 was also identified as a downstream target of miR-338-3p.The anti-tumorigenic effect of miR-338-3p overexpression and the pro-tumorigenic effect of LASP1 was further explored by functional assays,which demonstrated that circTIAM1 modulated the PTC progression through targeting miR-338-3p/LASP1 axis.Conclusion:The overexpression of circTIAM1 is associated with the malignant progression of PTC.A high level of circTIAM1 promotes the malignancy of PTC cells via the miR-338-3p/LASP1 axis.

Predictive Value of BRAF^V600E Mutation for Lymph Node Metastasis in Papillary Thyroid Cancer:A Meta-analysis

BRAF^V600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC).But whether BRAF^V600E mutation is associated with lymph node metastasis (LNM)remains controversial. Different surgical strategies may bring a bias in demonsstrating the association between them.In order to delineate a risk stratification to guide a tailored initial approach to tumors that express BRAF^V600E mutation,we performed this meta-analysis by using the articles in which total or near-total thyroidectomy plus bilateral central lymph node dissection was routinely performed to avoid the bias from the surgical strategy.We searched the Medline,Embase and CNKI database for eligible studies from January 2003 to May 2018.Meta-analysis was performed using the STATA 12.0 software.Odds ratios (ORs)and 95% confidence intervals (CIs)were calculated under fixed-effects or random-effects models.Fifteen clinical studies were included with a total of 4909 PTC patients. Our meta-analysis results reported that BRAF^V600E mutation was associated with LNM (OR=1.34;95% CI:1.09-1.65;P=0.005),as well as central LNM (OR=1.59;95% CI: 1.35-1.88;P<0.00001).Moreover,in patients with papillary thyroid microcarcinoma, we also confirmed the predictive value of BRAF^V600E mutation for LNM (OR=3.49;95% CI:2.02-6.02;P<0.00001).This meta-analysis demonstrates that BRAF^V600E mutation is closely related to LNM in PTC patients.The results suggest that BRAF^V600E mutation can be considered as a risk factor for LNM in PTC.Moreover,combining BRAF^V600E mutation with other risk factors to determine the initial surgical treatment may bring benefits for PTC patients.

Relationship between Expression of Vascular Endothelial Growth Factor and Cervical Lymph Node Metastasis in Papillary Thyroid Cancer: A Meta-analysis

The aim of the present study was to examine the relationship between the protein expression of vascular endothelial growth factor（VEGF） and lymph node metastasis（LNM） in papillary thyroid cancer（PTC）. VEGF-related articles that had been published until August 2016 were searched from the Pub Med, EMBASE, and MEDLINE to identify the risk factors of LNM in PTC. Rev Man 5.3 software was used for the meta-analysis. Finally, 9 articles met the inclusion criteria and were included in our meta-analysis. LNM was found to be present in 176 of 318 patients（57.8%） with high VEGF expression and in 71 of 159 patients（47.0%） with low VEGF expression. The overall OR was 2.81（95% confidence interval, 1.49–5.29）. LNM occurred more frequently in patients with high VEGF expression than in those with low VEGF expression（P=0.001）. Heterogeneity was markedly decreased in the subgroup analyses of LNM in terms of the patients＇ country of origin and the detection methods. Our meta-analysis concluded that the VEGF protein expression is associated with LNM in PTC.

Ultrasound features of extranodal extension in the metastatic cervical lymph nodes of papillary thyroid cancer:a case-control study

Objective：Extranodal extension in cervical lymph nodes is an important risk factor for the progression and prognosis of papillary thyroid cancer.The purpose of this study was to identify the common and characteristic preoperative ultrasonography features that are associated with the pathologic extranodal extension of metastatic papillary thyroid carcinoma.Methods：We retrospectively assessed and compared clinicopathologic and ultrasound features between 60 papillary thyroid cancer patients with extranodal extension and 120 control patients with papillary thyroid cancer without extranodal extension.Results：With respect to the pathological N stage and clinicopathologic features,N1b stage papillary thyroid carcinomas were more frequently found in patients who were extranodal extension-positive,in comparison with those who were extranodal extension-negative（78.3%vs.63.3%,P=0.043）.Extranodal extension was detected most frequently in level VI cervical lymph nodes（48.7%）.In our univariate analysis of patients with papillary thyroid carcinoma,cervical lymph nodes with extranodal extension showed higher incidences of node matting,microcalcification,cystic area,aspect ratio＆lt;2,and larger diameter than those without extranodal extension（all P〈0.05）.Our multivariate analysis demonstrated that node matting and cystic area were independent risk factors for the presence of extranodal extension[odds ratio（OR）：4.751,95%confidence interval（CI）：1.212~18.626,P=0.025;OR：2.707,95%CI：1.127~6.502,P=0.026].Conclusions：Common ultrasound features may indicate the presence of extranodal extension in patients with metastatic cervical lymph nodes of papillary thyroid carcinoma.

Papillary thyroid cancer and inflammatory bowel disease:Is there a relationship?

AIM:To formally study age of diagnosis of papillary thyroid cancer(PTC) in inflammatory bowel disease(IBD) patients and evaluate the prevalence of PTC in IBD patients compared to a control population.pothesis that patients with IBD are more likely to be diagnosed with PTC than a control population.A retrospective cohort analysis was performed using the University of Pennsylvania Health System's electronic database.Outpatients from 1998-2009 were included in the search,and patients in the cohort were selected based on ICD-9 codes.Inclusion criteria included the diagnosis of Crohn's disease(CD) or ulcerative colitis(UC) and the concurrent diagnosis of thyroid cancer in comparison to a control population.Using these methods 912 patients with CD and 1774 with UC were compared to 1638 diverticulitis and 19 447 asthma controls.Statistics were performed using corrected chisquare analysis.The primary outcome for this study was the diagnosis of PTC.Approval to conduct this study was obtained by the Institutional Review Board at the University of Pennsylvania.RESULTS:The mean age was 47.5 years(range:18-102 years) and 66% patients were female.An analysis of variance model was used to compare the age of PTC diagnosis between the CD,UC,asthma and diverticulitis groups,and a statistically significant difference in age at PTC diagnosis was noted across all groups(F = 6.35,df = 3,P = 0.0006).The age of PTC diagnosis in CD patients was statistically significantly lower than UC,asthma,and diverticulitis patients(average PTC diagnosis age for CD 25,UC 49,asthma 45,diverticulitis 63).After covarying for sex and age in 2009,the difference in age at PTC diagnosis remained statistically significant(F = 4.13,df = 3,P = 0.0089).A total of 86 patients were diagnosed with PTC.Nine patients(0.5%) with UC were diagnosed with PTC.Patients with UC were not shown to be more likely to develop PTC [odds ratio(OR):1.544,95%CI 0.767-3.108] compared to asthma controls.Four patients(0.4%) with CD were diagnosed with PTC.Patients with CD were not shown to be more likely to develop PTC(OR:1.334,95%CI 0.485-3.672) compared to a control population with asthma.Nine patients(0.5%) with a history of diverticulitis were diagnosed with PTC.Patients with diverticulitis were not shown to be more likely to develop PTC(OR:1.673,95%CI 0.831-3.368) compared to asthma controls.Patients with CD or UC were not less likely to develop PTC compared to those with diverticulitis(CD OR:0.80,95%CI 0.25-2.60;UC OR:0.92,95%CI 0.37-2.33).None of the patients used immunosuppressant medications prior to the diagnosis of PTC(azathioprine,6-mercaptopurine,and methotrexate).CONCLUSION:There is a significant difference in age of diagnosis of PTC in patients with CD compared to patients with UC and the control populations studied.

Strong Correlation of Abnormal Serum and Urinary Iodine Levels with Papillary Thyroid Cancer:A Case-control Study

Thyroid cancer is the most common malignancy of the endocrine system,and its incidence is increasing worldwide.In China,its incidence has increased from 1.78/104 in 1988 to 10.58/104 in2013.Thyroid cancers are mainly classified into papillary thyroid cancer(PTC),follicular thyroid cancer(FTC),medullary thyroid cancer(MTC).

Identification of a four-miRNA signature predicts the prognosis of papillary thyroid cancer

BACKGROUND In recently diagnosed patients with thyroid cancer,papillary thyroid cancer(PTC),as the most common histological subtype,accounts for 90%of all cases.Although PTC is known as a relatively adolescent malignant disease,there still is a high possibility of recurrence in PTC patients with a poor prognosis.Therefore,new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment.Accumulating evidence demonstrates that microRNAs(miRNAs)have broad application prospects as diagnostic biomarkers in cancer.AIM To explore novel markers consisting of miRNA-associated signatures for PTC prognostication.METHODS We obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas.The patients were randomly assigned to either a training or testing cohort.RESULTS We discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues,which contained 172 up-regulated and 65 downregulated miRNAs.The evaluation of differently expressed miRNAs was conducted using our risk score model.We then successfully generated a fourmiRNA potential prognostic signature[risk score=(-0.001×hsa-miR-181a-2-3p)+(0.003×hsa-miR-138-5p)+(-0.018×hsa-miR-424-3p)+(0.284×hsa-miR-612)],which reliably distinguished patients from high and low risk with a significant difference in the overall survival(P<0.01)and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts,respectively.Additionally,there was a trend indicated that high-risk patients had shorter relapse-free survival,although statistical significance was not reached(P=0.082)in our sequencing cohort.CONCLUSION Our results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC.Accordingly,we would recommend more radical therapy and closer follow-ups for highrisk groups.

Efficacy of anlotinib combined with radioiodine to treat scalp metastasis of papillary thyroid cancer:A case report and review of literature

BACKGROUND Papillary thyroid cancer(PTC)is one of the well-differentiated thyroid tumors.Cutaneous metastasis from differentiated thyroid cancers occurs in<1%of primary thyroid carcinomas but produces the worst survival prognosis.The multi-targeting tyrosine kinase inhibitor anlotinib has been approved to treat refractory advanced non-small-cell lung cancer as well as advanced soft-tissue and clear cell sarcomas in China.CASE SUMMARY In a patient with scalp metastasis caused by PTC,thyroid and skull metastasis tumor sizes were significantly reduced after a trial of neoadjuvant anlotinib therapy for 3 cycles.Anlotinib maintenance medication after thyroidectomy further reduced the metastatic skull tumor size thereby preventing the requirement for craniotomy.CONCLUSION The outcome of the present trial confirmed the potential of anlotinib therapy to treat scalp metastasis induced by PTC and point the way for the treatment of similar diseases in the future.

Low-Risk Papillary Thyroid Carcinoma Recurring as a Single Brain Metastasis: A Case Report and Literature Review

Background: Brain metastases from papillary thyroid carcinoma are infrequent occurring in 0.15% to 1.3% of patients, and they are generally accompanied by synchronous metastases in other sites and in isolation are even less frequent;the information about their management is limited and it has been based mainly on retrospective studies, experiences, case reports, and management guidelines of brain metastasis of other cancers. Aim: We report this case with the objective of describing how unpredictable the behavior of thyroid cancer can be despite being classified as low risk of recurrence. Case Presentation: A female patient with a diagnosis of papillary thyroid carcinoma classified as low risk who after more than a year of surveillance and without alterations in laboratory and imaging studies, developed a single brain metastasis susceptible to treatment with radioactive iodine (RAI) therapy. Conclusion: This case emphasizes the importance of a close follow-up of patients and not to minimize any symptom, no matter how simple it may seem, since cancer has no rules in its evolution.

Intratumoral Bacteria Dysbiosis Is Associated with Human Papillary Thyroid Cancer and Correlated with Oncogenic Signaling Pathways

Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.

Papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis and breast cancer: A case report

BACKGROUND The recognized pattern of cervical lymph node metastasis(CLNM)of papillary thyroid carcinoma involves a stepwise route.Contralateral lymph node skip metastasis is very rare.In addition,the patient in our case report also suffered from a breast carcinoma accompanied by left supraclavicular lymphadenopathy,which made it difficult to distinguish the origin of the CLNM.Based on this case,we recommended that more detailed physical and imaging examinations are needed for patients with uncommon cervical lymphatic metastasis of primary cancer.CASE SUMMARY A 53-year-old women was admitted to the hospital for a neck mass in the left cervical region that had existed for 2 mo.The neck mass was suspected to be an enlarged lateral LN originating from papillary thyroid microcarcinoma of the contralateral thyroid lobe,according to ultrasound and ultrasound-guided fine needle aspiration biopsy.The patient underwent total thyroidectomy and radical cervical LN dissection.Postoperative pathology confirmed the diagnosis of papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis.Unfortunately,a breast cancer was discovered 4 mo later,which was accompanied by ipsilateral supraclavicular LN metastasis.She accepted neoadjuvant chemotherapy and subsequent left modified radical mastectomy for treatment.The patient is currently receiving postoperative radiotherapy,and no local recurrence was observed in the 6-mo follow-up after surgery.CONCLUSIONWe present a rare case of papillary thyroid microcarcinoma with contralateral lymphatic skipmetastasis and breast cancer with supraclavicular lymphatic metastasis.

Late recurrence of papillary thyroid cancer from needle tract implantation after core needle biopsy: A case report

BACKGROUND Papillary thyroid cancer(PTC)has good prognosis so that the local recurrence or distant metastasis can occur later on the lifetime follow up.In this study,we report recurrence of PTC in subcutaneous area combined with lymph node metastasis.A suspicion of needle tract implantation after core needle biopsy was found.CASE SUMMARY A 66-year-old female patients who underwent right thyroid lobectomy for PTC complained of palpable nodule on anterior neck area.The location of the palpable nodule was not associated with her postoperative scar.After excision of the skin tumor,it was diagnosed as recurrence of PTC.Furthermore,results of subsequent imaging showed lymph node metastasis on her right cervical area.According to the previous medical records,the patient received core needle biopsy through the neck of the patient midline and hematoma was noted after the procedure.The time interval from the first diagnosis to local recurrence or metastasis to the skin and lymph nodes was ten years.As treatment,the patient underwent lymph node dissection in the right and completion thyroidectomy for radioisotope treatment.CONCLUSION Needle tract implantation can occur after core needle biopsy.Further studies are needed to compare core-needle biopsy and fine-needle aspiration.

Mechanism of SCD1 in promoting proliferation,migration and invasion of human papillary thyroid cancer cells

Objective:To investigate the effects of SCD1 on the proliferation,migration and invasion of human papillary thyroid cancer cell line TPC1.Methods:The expression of SCD1 in human thyroid follicular epithelial normal cells Nthy-ori 3-1 and thyroid papillary carcer cell lines TPC1,BCPAP and K1 was detected by Western blot.The negative control and SCD1 siRNA were transfected respectively into human thyroid papillary carcer cell line TPC1,then the expressions of SCD1 mRNA and protein in each group were tested by real-time fluorescence quantitative PCR(qRT-PCR)and Western blot.The effects of interfering SCD1 on the proliferation,migration and invasion of TPC1 cells were detected by CCK-8 method and Transwell chamber assay respectively.Meanwhile,the expression levels of epithelial-mesenchymal transition(EMT)related proteins(N-cadherin,Snail,vimentin and E-cadherin)were detected by qRT-PCR and Western blot.Results:The expression level of SCD1 in TPC1 was significantly higher than that in Nthy-ori 3-1,BCPAP and K1(P<0.05).Compared with the blank control group(Control)and the control interference group(si-NC),the expression of SCD1 mRNA and protein in the interference SCD1 group(si-SCD1)was significantly decreased(P<0.05).The proliferation,migration and invasion of TPC1 cells were significantly inhibited after interfering with SCD1(P<0.05).It was also found that interfering SCD1 could increase the expression of E-cadherin protein while the expression of vimentin,Snail and N-cadherin protein were inhibited significantly(P<0.05).Conclusion:Interfering SCD1 was able to inhibit the proliferation,migration and invasion of thyroid papillary cancer cell TPC1 with the potential mechanism by inhibition of the EMT procedure.

Correlation of the BRAFV600E and RAS mutations with clinicopathological characteristics of papillary thyroid cancer using TCGA database analysis

Objective:To investigate the occurrence of BRAFV600E and RAS mutations in thyroid papillary carcinoma (PTC) and to study their correlation with clinicopathological features of PTC. Methods Relevant information of PTC was downloaded and organized from The Cancer Genome Atlas (TCGA) via cBioPortal, then the gene mutation and clinical information of 402 PTC samples were analyzed. The correlation of BRAFV600E and RAS mutations with clinicopathological features and prognosis of PTC were subjected to univariate analysis. Secondly, we use Binary Logistic multivariate analysis to analyze the factors screened above. Results BRAFV600E mutation rate is 48.5% (195/402) and RAS mutation rate is 10.2% (41/402) in 402 cases of PTC. Univariate analysis showed that BRAFV600E mutation has nothing to do with age and sex of the patient. There is a significant correlation among BRAFV600E mutation and lymph node metastasis, extrathyroidal invasion, staging, recurrence, progression and pathological subtypes in PTC. There is no significant correlation among RAS and age, sex, staging, recurrence, progression. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC. Multivariate logistic regression analysis indicated that there is a significant correlation among BRAFV600E mutation and extrathyroidal invasion, pathological subtypes in PTC. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC.ConclusionThe mutation rate of BRAFV600E was significantly higher than that of RAS in PTC. Mutations in BRAFV600E and RAS can be used as predictors of prognosis in PTC.

Importance and Risk Prediction of ABO Blood Group and Rh Factor in Papillary Thyroid Cancer

Objective:There are limited data in the literature regarding the potential relationship between thyroid cancer and ABO blood types and Rh factor.The aim of our study was to investigate whether papillary thyroid cancer(PTC)is associated with blood type.Materials and Methods:The present study included patients who pre­sented to Dicle University Faculty of Medicine between June 2009 and December 2020 and were diagnosed with PTC as a result of postoperative(thyroidectomy)histopathological analysis.The control group consisted of individuals whose blood type was analyzed at a random blood center.Results:Of the 223 patients diagnosed with PTC,163(73.1%)were fe­males and 60(26.9%)were males.In the comparison of patients based on ABO blood types and Rh factor,A Rh positive blood type was found 31%less frequently in the PTC group compared with the control group,and thus it was associated with a lower risk of PTC(OR:0.69;95%Confidence In­terval:0.50-0.96,p=0.029).Conclusions:In our study,we found A Rh positive blood type to be signifi­cantly less frequent among patients with PTC.A Rh positive blood type can be considered as a protective factor indicating a reduced risk of PTC.

Value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in papillary thyroid carcinoma

BACKGROUND Cervical lymph node metastasis in papillary thyroid carcinoma(PTC) affects the treatment and prognosis of patients. Ultrasound is a common imaging method for detecting cervical lymph nodes in PTC patients; however, it is not accurate in determining lymph node metastasis.AIM To evaluate the value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in PTC.METHODS A total of 94 patients with PTC were recruited. According to pathological results,lymph nodes were divided into two groups: metastatic group(n = 50) and reactive group(n = 63). The routine ultrasound findings, contrast-enhanced ultrasound and elastography data were recorded and compared. Logistic regression was used to generate predictive probability distributions for the diagnosis of lymph node metastasis with different indicators. Receiver operating characteristic curve analysis was used to test the efficacy of contrast-enhanced ultrasound combined with elastography based on routine ultrasound in evaluating PTC cervical lymph node metastasis.RESULTS The ratio of long diameter/short diameter(L/S) ≤ 2, irregular marginal morphology, missing lymphatic portal, peripheral or mixed blood flow distribution, peak intensity(PI), non-uniform contrast distribution and elasticity score in the metastatic group were significantly higher than those in the reactive group(P < 0.05). L/S ratio, missing lymphatic portal, PI and elasticity score had a significant influence on the occurrence of PTC cervical lymph node metastasis(P< 0.05). Furthermore, the area under the curve(AUC) for lymph node metastasis diagnosed using the combination of PI ratio, elasticity score, missing lymphatic portal and LS was 0.936, which was significantly higher than the AUC for PI ratio alone. The difference was statistically significant(P < 0.05). The fitting equation for the combined diagnosis was logit(P) =-12.341 + 1.482 × L/S ratio + 3.529 ×missing lymphatic portal + 0.392 × PI + 3.288 × elasticity score.CONCLUSION Based on the gray-scale ultrasound, the combination of contrast-enhanced ultrasound and elastography can accurately assess PTC cervical lymph node metastasis.

Difference between papillary and follicular thyroid carcinoma outcomes:an experience from Egyptian institution

Objective： Differentiated thyroid carcinomas （DTCs） are classified into papillary thyroid carcinoma （PTC） and follicular thyroid carcinoma （FTC）. DTCs are analyzed as a single group in clinical studies that investigated the prognostic factors and prognosis of these malignancies. However, the biological behaviors of these carcinomas significantly differ. In the present study, we aimed to detect differences in the outcomes between PTC and FTC in Mansoura University Hospital in Egypt. Methods： A total of SS8 patients with histologically proven thyroid carcinomas from January 2003 to December 2012 were retrospectively enrolled. The clinical and pathological data of patients were reviewed. Results： Large primary tumor size, lymph node involvement, extrathyroid extension, and distant metastasis were significant poor prognostic factors for overall survival （OS） in old PTC patients. Cox hazard analysis showed that the patient＇s age, extra thyroid extension, and distant metastasis were the only independent prognostic factors. In FTC patients, only the distant metastasis and degree of tumor invasion were significant poor prognostic factors in OS univariate analysis. However, these factors were nonsignificant in multivariate analysis. The 10-year OS rates were 97% and 89% for PTC and FTC, respectively （P=0.003）. The 10-year disease-free survival （DFS） rates were 77.2% in PTC vs. 65% in FTC （P=0.179）. Conclusion： The significant prognostic factors vary between the two types of DTCs. Therefore, PTC and FTC patients need to be analyzed and reported independently. PTC survival is widely and significantly affected by age, extrathyroid extension, and distant metastasis. By contrast, these factors were nonsignificant in FTC, which showed poorer survival than 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.

Role of prophylactic central neck lymph node dissection for papillary thyroid carcinoma in the era of de-escalation

Thyroid cancer is the most common endocrine malignancy.While there has been no appreciable increase in the observed mortality of well-differentiated thyroid cancer,there has been an overall rise in its incidence worldwide over the last few decades.Patients with papillary thyroid carcinoma(PTC)and clinical evidence of central(cN1)and/or lateral lymph node metastases require total thyroidectomy plus central and/or lateral neck dissection as the initial surgical treatment.Nodal status in PTC patients plays a crucial role in the prognostic evaluation of the recurrence risk.The 2015 guidelines of the American Thyroid Association(ATA)have more accurately determined the indications for therapeutic central and lateral lymph node dissection.However,prophylactic central neck lymph node dissection(pCND)in negative lymph node(cN0)PTC patients is controversial,as the 2009 ATA guidelines recommended that CND“should be considered”routinely in patients who underwent total thyroidectomy for PTC.Although the current guidelines show clear indications for therapeutic CND,the role of pCND in cN0 patients with PTC is still debated.In small solitary papillary carcinoma(T1,T2),pCND is not recommended unless there are high-risk prediction factors for recurrence and diffuse nodal spread(extrathyroid extension,mutation in the BRAF gene).pCND can be considered in cN0 disease with advanced primary tumors(T3 or T4)or clinical lateral neck disease(cN1b)or for staging and treatment planning purposes.The role of the preoperative evaluation is fundamental to minimizing the possible detrimental effect of overtreatment of the types of patients who are associated with low disease-related morbidity and mortality.On the other hand,it determines the choice of appropriate treatment and determines if close monitoring of patients at a higher risk is needed.Thus,pCND is currently recommended for T3 and T4 tumors but not for T1 and T2 tumors without high-risk prediction factors of recurrence.

In the Basis of Hashimoto’s Thyroiditis, to Form Papillary Thyroid Carcinoma, Metastasized and Then to De-Differentiate into Poorly Differentiated Squamous Cell Carcinoma

Thyroid squamous cell carcinoma is very rare. At present, it is limited to case reports. Since the thyroid follicular epithelium is the non-squamous epithelium, how primary squamous cell carcinoma (SCC) of the thyroid occurs is still a controversial issue. Hashimoto’s thyroiditis (HT) is considered to be an independent risk factor for thyroid cancer, under the basis of HT, how tumor cells evolve and develop to papillary thyroid carcinoma (PTC), and particularly to de-differentiate into SCC is elusive. We report a 72-year-old female patient who developed multiple subtypes of PTC on a basis of HT, and finally to de-differentiate into SCC within the local foci of lymph node metastasis. We found that there was a variety of sub-types of PTC in this patient in the background of HT. SCC was found within local lymph node metastasis. Pathomorphology, immunohistochemistry, and molecular pathology have confirmed that the SCC was derived from PTC, and then developed into poorly differentiated SCC and/or anaplastic carcinoma. We also conducted a comprehensive literature review.