BRAF^(V600E) Mutation and Its Association with Clinicopathological Features of Papillary Thyroid Microcarcinoma: A Meta-Analysis

Summary： Recent studies have demonstrated that the BRAFv600E mutation is associated with aggres- sive clinicopathological features of papillary thyroid carcinoma （PTC）. However, the BRAF mutation as a prognostic biomarker in papillary thyroid microcarcinoma （PTMC） is unclear. A systematic search of the electronic databases, including Medline, Scopus, CNKI and the Cochrane Library was performed up to July 1, 2014. Outcomes of interest included age, gender, concomitant hashimoto thyroiditis or nodular goiter, tumor size, pathological stage, tall cell variant of PTMC （TCVPTMC）, multifocality, extrathyroidal extension （ETE） and lymph node metastasis （LNM）. A total of 19 studies published from 2008 to 2014 comprising 2253 patients fulfilled the inclusion criteria and were in- cluded in the meta-analysis, and 1143 （50.7%） of these patients were BRAF mutation positive. BRAF mutation was associated with larger tumor size （OR： 1.64; 95% CI： 1.16-2.32）, multifocality （OR： 1.58; 95% CI： 1.25-2.00）, ETE （OR： 2.59; 95% CI： 2.03-3.29）, LNM （OR： 1.73; 95% CI： 1.14-2.62）, advanced stage （OR： 2.03; 95% CI： 1.14-3.64） and TCVPTMC （OR： 5.07; 95% CI： 1.49-17.27; P=0.009）. Additionally, the BRAF mutation was found to be not associated with age, gender, con- comitant hashimoto thyroiditis or nodular goiter （P〉0.05 for all）. This meta-analysis revealed that in patients with PTMC, BRAF mutation is associated with tumor size, multifocality, ETE, LNM, ad- vanced stage and TCVPTMC, and it may be used as a predictive factor for prognosis of PTMC.

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.

2016 Chinese expert consensus and guidelines for the diagnosis and treatment of papillary thyroid microcarcinoma

The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues in PTMC management have received researchers'attention.To further improve the clinical management of PTMC in China,

Thermal ablation for papillary thyroid microcarcinoma: Some clarity amid controversies

The increasing incidence of papillary thyroid microcarcinoma(PTMC)has become a global challenge.Because of its indolent nature,active surveillance(AS)has been proposed as a treatment option in selected PTMC patients to prevent surgery-related complications.However,only a few patients with PTMC receive the AS approach because of the serious psychological burden following the“cancer”diagnosis and the uncertainty of the timing for metastatic dissemination.Ultrasound(US)-guided thermal ablation can bridge the gap in the treatment options of PTMC patients who wish for a minimally invasive management approach.However,it has acquired only marginal attention from the thyroid guideline societies because of concerns regarding incomplete elimination.The recently published guidelines from the European Thyroid Association-Cardiovascular and Interventional Radiological Society of Europe and the American Head Neck Society Endocrine Section-initiated global consensus provide the most definitive evidence and essential foundational experience to address the long-term controversy over USguided thermal ablation for low-risk PTMC patient management and facilitate the responsible global dissemination of minimally invasive strategies.

Pathological characteristics of posterior echo attenuation of papillary thyroid microcarcinoma and cystic degeneration of cervical lymph node metastasis

Objective: The aim of our study was to evaluate the pathological features of posterior echo attenuation of papillary thyroid microcarcinoma (PTMC) and cystic degeneration of cervical lymph node metastasis. Methods: We retrospectively evaluated the ultrasound results from 36 cases of PTMC with 20 nodules of cystic degeneration of cervical lymph node metastasis and correlated the results with the histopathologic findings. Results: The preliminary study indicated certain correlation between histopathologic findings and ultrasound results of posterior echo attenuation of papillary thyroid microcarcinoma and cystic degeneration of cervical lymph node metastasis. Conclusion: Posterior echo attenuation detected by ultrasound was associated with fibrous structures in PTMC nodules, while cystic degeneration and papillary changes of cervical lymph node metastasis in PTMC showed liquefactive necrosis, degenerative changes and enlarged follicular of nodular structures.

Hepatopulmonary metastases from papillary thyroid microcarcinoma:A case report

BACKGROUND Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of PTC cases.However,concurrent pulmonary and hepatic metastases of PTMC are rarely seen.Here,we present a patient with coexisting liver and lung metastases from PTMC.CASE SUMMARY We describe a 26-year-old woman with PTMC with multiple concurrent metastases.After 3 d of unexplained fever,she was admitted to our hospital.Her thyroid functional tests were abnormal.Her positron emission tomography(PET)/magnetic resonance imaging(MRI)examination showed increased fluorodeoxyglucose(FDG)metabolism and space-occupying lesions in the left lobe of the thyroid.Additionally,PET/MRI images revealed multiple nodules in the lung and liver with increased FDG metabolism.Chest computer tomography(CT)showed multiple pulmonary metastases.Abdominal ultrasound and liver MRI showed multiple space-occupying lesions in the liver.The patient underwent total thyroidectomy and central lymph node dissection.Postoperative pathological analysis showed a papillary microcarcinoma multiplex in the left lobe of the thyroid.A diagnosis of hepatopulmonary metastases from papillary thyroid microcarcinoma was made.The patient was given iodine-131 treatment one year after the surgery.She recovered well after the operation,and the incision healed well.After discharge,she was treated with oral levothyroxine sodium tablets,and symptomatic and supportive treatments were also given to promote radioactive excretion and prevent bone marrow suppression by iodine-131 treatment.CONCLUSION Since patients with thyroid cancer concurrent with hepatopulmonary metastases have rarely been reported,our case will highlight the clinical and pathological profiles of these patients.

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.

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.

Epidemiological and histopathological characteristics of thyroid carcinoma in a Tunisian health care center

Background:Thyroid carcinoma(TC)accounts for almost 0.5%–1%of total malignancies.Its incidence is increasing rapidly worldwide.Several studies have drawn up the epidemiological profile of TC and its clinical and pathological features.However,to date,no similar studies have been conducted in Tunisia.Aims:To establish an epidemiological profile of TC in a Tunisian health care institute and to analyze its clinical and histopathological characteristics in our institute.Materials and Methods:We present a retrospective study reviewing the cases of TC diagnosed in our institution in a 4-year period.Results:We collected a sample of 192 cases of TC.It consisted of 31 males and 161 females(83.8%)with a sex-ratio M/F of 0.19.The mean age was 46.4 years.Papillary thyroid carcinoma was the most frequent histological subtype.The multifocality rate was 33.8%.The mean size of TC was 2.2±1.9 cm.60.9%of TC were staged pT1 and 20.3%had nodal involvement.Papillary thyroid microcarcinomas were noted in 37.5%of cases.Conclusion:Our results were consistent with those of the literature.A high proportion of pT1 and pN0 tumors were noted in our series,suggesting that TC's diagnosis and management was performed at an early stage of the disease in our institution.In addition,our study enabled us to notice the impact of the Coronavirus disease 19 crisis on the management of TC in our institution.Further studies are needed to establish the epidemiological profile of TC in Tunisia and to assess its clinical and pathological features.

Comparative Study between Robotic Total Thyroidectomy with Central Lymph Node Dissection via Bilateral Axillo-breast Approach and Conventional Open Procedure for Papillary Thyroid Microcarcinoma

Background： A large proportion of the patients with papillary thyroid microcarcinoma are young women. Therefore, minimally invasive endoscopic thyroidectomy with central neck dissection （CND） emerged and showed well-accepted results with improved cosmetic outcome, accelerated healing, and comforting the patients. This study aimed to evaluate the safety and effectiveness of robotic total thyroidectomy with CND via bilateral axillo-breast approach （BABA）, compared with conventional open procedure in papillary thyroid microcarcinoma. Methods： One-hundred patients with papillary thyroid microcarcinoma from March 2014 to January 2015 in Jinan Military General Hospital of People＇s Liberation Army （PLA） were randomly assigned to robotic group or conventional open approach group （17 = 50 in each group）. The total operative time, estimated intraoperative blood loss, numbers of lymph node removed, visual analog scale （VAS）, postoperative hospital stay time, complications, and numerical scoring system （NSS, used to assess cosmetic effect） were analyzed. Results： The robotic total thyroidectomy with CND via BABA was successfully performed in robotic group. There were no conversion from the robotic surgeries to open or endoscopic surgery. The subclinical central lymph node metastasis rate was 35%. The mean operative time of the robotic group was longer than that of the conventional open approach group （118.8± 16.5 min vs. 90.7± 10.3 min, P 〈 0.05）. The study showed significant differences between the two groups in terms of the VASs （2.1 ± 1.0 vs. 3.8 ±~ 1.2, P 〈 0.05） and NSS （8.9 ± 0.8 vs. 4.8 ± 1.7, P 〈 0.05）. The differences between the two groups in the estimated intraoperative blood loss, postoperative hospital stay time, numbers of lymph node removed, postoperative thyroglobulin levels, and complications were not statistically significant （all P 〉 0.05）. Neither iatrogenic implantation nor metastasis occurred in punctured porous channel or chest wall in both groups. Postoperative cosmetic results were very satisfactory in the robotic group. Conclusions： Robotic total thyroidectomy with CND via BABA is safe and effective for Chinese patients with papillary thyroid microcarcinoma who worry about the neck scars.

Minimally invasive video-assisted thyroidectomy for accidental papillary thyroid microcarcinoma： comparison with conventional open thyroidectomy with 5 years follow-up

Background Minimally invasive video-assisted thyroidectomy （MIVAT） has received increasing attention for malignant thyroid diseases. The aim of this study was to compare the outcomes of MIVAT with conventional open thyroidectomy （CT） for papillary thyroid microcarcinoma （PTMC）. Methods Thirty-one patients were treated with MIVAT and 37 with CT. Their pathological characteristics, surgical complications, 5-year postoperative thyroglobulin （TG） and ultrasonic results were followed up. Results All the patients took levothyroxine for suppressing thyroid stimulating hormone （TSH） after surgery, and were followed up with measurement of serum TG and neck ultrasonography at intervals of 6 or 12 months. There was no statistically significant difference between the CT and MIVAT groups for sex ratio, operation time, positive lymph nodes, complications and prognosis, but the MIVAT group had better cosmetic results. Conclusions MIVAT did not differ significantly from CT for PTMC after 5 years follow-up, but it did have better cosmetic results. MIVAT is a safe and valid surgical technique for selected cases.