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.

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.

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.

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.

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.

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.

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.

Microwave ablation of solitary T1N0M0 papillary thyroid carcinoma:A case report

BACKGROUND The gold standard treatment for papillary thyroid carcinoma is total thyroidectomy and indications for microwave thermal ablation for primary thyroid cancers have not yet been clearly established However,some patients refuse surgery and others have no indication for it,for example patients under palliative care as in this case,or cannot undergo surgery,based on their comorbidities.These indications are described in the most recent Korean,North American and European guidelines.Laser ablation,radiofrequency ablation,and microwave ablation are similarly safe and effective,so the choice should be based on the specific competences and resources of the pertaining centers.These indications are Percutaneous minimally-invasive techniques;they can be useful to stop disease progression and as an alternative to surgery in patients with contraindication or who refuse surgery.We present a case of a thyroid papillary carcinoma with 17 mm effectively treated with microwave thermal ablation and without recurrence after one year of follow up.CASE SUMMARY The authors present a case of a 71-years-old patient with a left lobe papillary thyroid carcinoma with 13 mm×17 mm×13 mm,with no indication for thyroid surgery given the context of another cancer in palliative treatment.Microwave thermoablation was performed on December 2021.Four months later he repeated computed tomography(CT)scan,which showed that the tumor had disappeared.Six months after ablation he underwent a positron emission tomography/CT-fluorodeoxyglucose scan,which didn’t show any evidence of hypermetabolic tumor lesions.CONCLUSION This case shows microwave thermoablation can be a safe and effective alternative to surgery in patients with no conditions to undergo surgery or when they refuse it.By treating the tumor,with this minimally invasive technique,we are stopping its growth and avoiding disease progression.

Unusual Scalp Process Revealing a Thyroid Cancer: “Illustrative Case”

Background: Thyroid cancers commonly display slow evolution with local and or regional extension. The classic presentation is a painless nodule of the thyroid region in a euthyroid patient. Sometimes, the nodule is discovered only on ultrasonography. Cervical lymph node is often seen in papillary thyroid cancer due to their propensity to invade lymph node. This means that follicular thyroid cancers are more insidious. Observation: We report a painless slow-growing lesion of the scalp revealing a skull metastasis of thyroid cancer. Despite catastrophic intraoperative bleeding, a total removal was achieved. Lessons: Thus, in addition to local and regional control in the management of thyroid cancers, distant metastasis should be surgically removed to provide the best chance to prolong the patient’s survival. Moreover, neurosurgeon must be prepared to deal with massive bleeding in skull metastasis of thyroid cancer.

Sclerosing Mucoepidermoid Cancer: A Unique Entity

Sclerosing mucoepidermoid thyroid cancer (SMECE) is a rare entity with less than 100 cases reported in the literature. Previously considered to have an indolent course, however, recent evidence has reported an aggressive nature ranging from local invasion to distant metastasis. We present a 66-year-old Caucasian female with SMECE who initially presented neck compressive symptoms. A thyroid ultrasound (US) revealed a solid hypoechoic mass replacing the left thyroid lobe. Fine needle aspiration cytology (FNAC) of the nodule resulted in suspicion of Papillary Thyroid Cancer, Bethesda category 5. The patient underwent total thyroidectomy and surgical pathology showed SMECE. Post-therapy whole-body scan following treatment with 150 mCi I-131 showed no residual or metastatic disease. SMECE is more common in females, between the third to eighth decade of life. Preoperative diagnosis may not be accurate given variable cytopathologic features. Differential diagnoses include primary squamous cell carcinoma of the thyroid, squamous differentiation of other thyroid malignancies, anaplastic thyroid cancer and nodular sclerosing variety of Hodgkin’s lymphoma. Due to its rarity, treatment of SMECE has ranged from thyroid surgery without or with radioactive iodine therapy, to surgery and external beam radiation and even chemotherapy.

Pregnancy outcomes in papillary thyroid cancer survivors:A retrospective cohort study

Objective:The purpose of this study was to evaluate the pregnancy outcomes among papillary thyroid cancer survivors.Methods:65 cases singleton gravidas of papillary thyroid cancer survivors treated in the Department of Obstetrics,Peking University People's Hospital between January 2011 and January 2020 were selected retrospectively as the study group,and 130 cases of singleton pregnancy during the same time were randomly selected as the control group.The differences in general conditions,maternal and fetal complications between the two groups were analyzed.Risk factors of maternal complications and fetal malformation in patients with papillary thyroid cancer survivors were analyzed.Data was analyzed with t-test,χ^(2)test and logistic regression for statistical differences.Results:Totally 65 cases of papillary thyroid cancer with 70 pregnancies were analyzed,which including 65 cases achieved live birth,5 cases underwent induced labor because of fetal malformation.The study group showed higher incidence in gestational diabetes(20%vs 10%),cesarean section(39.1%vs 24.6%),postpartum hemorrhage(350
193 ml vs 290
181 ml)and fetal malformation(5.7%vs 1.5%),and lower live birth rate(91.4%vs 99.2%)(P<0.05).Multivariate analysis by logistic regression found that the patient's age,thyroid function,operation mode and postoperative I-131 treatment were not the risk factors which may affect the pregnancy outcomes or fetal malformation.Conclusion:Elevated maternal and fetal complications were observed among pregnancies in papillary thyroid cancer survivors.Management of these survivors may require a careful gestation monitoring,and further investigation is needed.

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.

A Metabolic-associated Nomogram Predicts Recurrence Survival of Thyroid Cancer

Objective:Various studies have suggested that metabolic genes play a significant role in papillary thyroid cancer(PTC).The current study aimed to identify a metabolic signature related biomarker to predict the prognosis of patients with PTC.Methods:We conducted a comprehensive analysis on the data obtained from the Cancer Genome Atlas(TCGA)database.The correlation between survival result and metabolic genes was evaluated based on the univariate Cox analyses,least absolute shrinkage and selection operator(LASSO)and multivariate Cox analyses.The performance of a 7-gene signature was assessed according to Kaplan-Meier and receiver operating characteristic(ROC)analysis.Multivariate Cox regression analysis was adopted to unearth clinical factors related to the recurrence free survival(RFS)of patients with PTC.Finally,a prognostic nomogram was developed based on risk score,cancer status and cancer width to improve the prediction for RFS of PTC patients.Results:Seven metabolic genes were used to establish the prognostic model.The ROC curve and C-index exhibited high value in training,testing and the whole TCGA datasets.The established nomogram,incorporating the 7-metabolic gene signature and clinical factors,was able to predict the RFS with high effectiveness.The 7-metabolic gene signature-based nomogram had a good performance to predict the RFS of patients with PTC.Conclusion:Our study identified a 7-metabolic gene signature and established a prognostic nomogram,which were useful in predicting the RPS of PTC.

Current Understanding of Papillary Thyroid Carcinoma

The term thyroid neoplasm incorporates tumors that originate from follicular cells and those that arise from parafollicular cells (C cells). Differentiated thyroid cancer, which originates from follicular cells, includes papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), oncocytic cell carcinoma (Hürthle), poorly differentiated carcinoma, and anaplastic thyroid carcinoma (ATC). PTC tends to have an indolent clinical course with low morbidity and mortality. However, this entity has a broad range of biological and clinical behavior that can result in disease recurrence and death, depending on patient and tumor characteristics and the initial treatment approach. PTC is the most common form of well-differentiated thyroid cancer (WDTC) and based on the most recent statistics, accounts for approximately 89.4% of all thyroid malignancies. PTC appears as an irregular solid or cystic nodule in normal thyroid parenchyma. PTC has the propensity for lymphatic invasion, but it is less likely to have hematogenous spread. Around 11% of patients with PTC present with distant metastases outside the neck and mediastinum. This manuscript with review the current understanding of the epidemiology, pathology, molecular characteristics, prognostic factors, and dynamic risk stratification of PTC centered on an evidence-based and personalized approach.

Pattern of Thyroid Cancer at King Abdulaziz University Hospital, Jeddah: A 10-Year Retrospective Study

Background and objective: Thyroid cancer is the most common endocrine malignancy. This report aims to describe the pattern of thyroid cancer presentations at King Abdulaziz University Hospital, Jeddah. Methods: This was a retrospect chart review of all thyroid cancer cases diagnosed between 2001 and 2010 at King Abdulaziz University Hospital, Jeddah. We documented patients’ demographic and clinical data, including age at diagnosis, tumor type and size, extrathyroidal extension, and metastasis. Results: A total of 114 thyroid cancer cases were diagnosed from 2001 through 2010. Females comprise the majority of cases (female to male ratio of 4:1). The mean ages of patients diagnosed with different thyroid cancers were: papillary thyroid cancer, 39.6 years;follicular thyroid cancer, 43.2 years;medullary thyroid cancer, 55.8 years;and anaplastic thyroid cancer, 46.0 years. Papillary thyroid cancer was diagnosed in 88 cases (77%), follicular thyroid cancer in 19 cases (17%), medullary thyroid cancer in 5 cases (4%), and anaplastic thyroid cancer in 2 cases (2%). Conclusion: Thyroid cancers are more common among females. The disease is diagnosed at a relatively young age among our patients (40 years). Papillary thyroid cancer is the most common type of thyroid cancer.

Molecular Diagnosis of Thyroid Nodules and Its Future Implications for the Management of Thyroid Cancer

Molecular testing in thyroid nodules and thyroid cancer is rapidly evolving;care must be used when incorporating molecular testing for thyroid nodules into clinical practice. A clear appreciation of the goals and restraints of molecular testing must be integrated into how physicians use and explain molecular testing to patients. Molecular tests can help rule in cancer for indeterminate thyroid nodules with very specific mutations for thyroid cancer, such as BRAF and RET/PTC, and can help reduce the rates of completion thyroidectomies in this era of de-escalation of the management of thyroid disease. The positive predictive value (PPV) of malignant cytology (Bethesda VI) is 98%;and even though molecular testing improves specificity and PPV, it falls short of this ideal for other mutations. We present a detailed evaluation of the current state of molecular testing and their clinical relevance in the setting of diagnostic utility and their impact on surgical decision-making. By recapitulating the clinical impact of these tests and some of the related drawbacks, we hope to provide adequate up to date information of the appropriate utilization of these tools in the management of indeterminate or suspicious thyroid nodules and highlight future directions on their utilization for the management of thyroid cancer.

Unusual locations for differentiated thyroid cancer nodal metastasis

Lymph node metastasis is common in differentiated thyroid cancer especially papillary thyroid cancer.Presence of lymph node metastasis does not have an impact on survival in younger patients.Therapeutic central and lateral neck dissection in the presence of clinically or radiologically evident lymph nodes has resulted in good overall survival.However,disease persistence in the lymph node/early recurrences may be seen in patients owing to lymph nodes that may be missed during the initial neck dissection.These observed locations are retropharyngeal and parapharyngeal nodal location,retro carotid location,sublingual,axillary,and intraparotid locations,supraclavicular and superficial to the sternothyroid muscle.We aim to highlight these locations with the goal to minimize persistence or early recurrence of disease at these locations.

Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma

The aims of the present study were to reveal the prevalence of the TERT C228 T mutation in pediatric papillary thyroid carcinoma(PPTC) and to further investigate the role of the TERT C228 T mutation in PPTC. We also tested another TERT mutation, TERT C250 T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC(41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228 T mutation analysis was performed. Chi-squared analysis,Fisher’s exact test, and a t-test were applied to test the significance of differences. The TERT C228 T mutation presented in 13(27.1%) of the 48 PPTC patients and 10(24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228 T mutation and those without in terms of modified radical neck dissection, multifocality,capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer(AJCC) tumor stage(P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage(P=0.009)and American Thyroid Association(ATA) PPTC stage(P=0.021) between patients with and without the TERT C228 T mutation.These findings indicate that the TERT C228 T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.

Estimating the risk of completion total thyroidectomy using real-world data to guide initial surgical decision-making for patients with clinical low-risk papillary thyroid carcinoma

Background:Continuing controversy exists in diferent guidelines’recommendations regarding whether total thyroidectomy(TT)or lobectomy is the optimal surgery for patients with low-risk papillary thyroid carcinoma(PTC).Diverse perceptions of the risk of completion TT after lobectomy are the main debate between guidelines and institutions.Methods:Patients who underwent thyroidectomy and prophylactic central lymph node dissection for≤4 cm PTC(January 2007 to December 2020)by high-volume surgeons were included.Patients with preoperatively known highrisk characteristics or suspicious bilateral multifocality were excluded.The pathological fndings were defned as the risk stratifcations of completion TT from low to high to evaluate which initial surgical procedure could allow more patients to meet the criteria of optimal surgical extent.Results:Of 4965 consecutive patients met lobectomy criteria as the initial operation.Aggressive histological subtypes were found in 2.5%of patients,T3b disease in 1.1%,T4 disease in 3.1%,LNs involved≤5 in 29.5%,LNs involved>5 in 3.1%,and incidental bilateral multifocality in 7.9%.According to our defned risk stratifcation system,TT and lobectomy would be considered the optimal initial procedure in 12.0%and 67.2%PTC patients with a tumor≤1 cm and 28.7%and 36.6%in the 1-4 cm groups in our real-world cohort,respectively.Conclusion:Lobectomy alone,as an initial procedure,could allow more low-risk PTC patients with a tumor either≤1 cm or 1-4 cm to achieve the optimal surgical extent.Moreover,surgeons should balance the high-risk characteristics and complication risks during surgery to re-evaluate surgical decision-making.