cN0 Papillary Thyroid Microcarcinoma Research Articles

Management of cN0 papillary thyroid microcarcinoma patients according to risk-scoring model for central lymph node metastasis and predictors of recurrence.

The role of routine prophylactic central neck dissection (pCND) in clinically lymph node-negative (cN0) papillary thyroid microcarcinoma (PTMC) patients remains controversial. This retrospective study aimed to identify the clinical and pathologic factors of central lymph node metastasis (CLNM) and recurrence in PTMC patients. A total of 371 cN0 PTMC patients from two hospitals were retrospectively analyzed. All patients underwent thyroidectomy plus pCND between January 2010 and January 2018. Clinicopathological features were collected, univariate and multivariate analyses were performed to determine the risk factors of CLNM. A scoring model was constructed on the basis of the results of independent risk factors of CLNM. The Cox proportional hazards model was used to analyze the risk factors of recurrence. CLNM occurred in 123 (33.2%) patients. Multivariate analysis showed male, tumor size > 0.75cm, multifocality, extrathyroidal extension (ETE) and tumor in the middle/lower pole were independent risk predictors of CLNM (P < 0.05). A seven-point risk-scoring model was established to predict the stratified CLNM in cN0 PTMC patients. Multivariate Cox regression model showed ETE, vascular invasion and CLNM were independent risk predictors of recurrence (P < 0.05). Our study suggested that routine pCND should be performed for cN0 PTMC patients with score ≥ 3 according to the risk-scoring model. Moreover, patients with risk factors of recurrence should consider more complete treatment and more frequent follow-up.

Select Group of Patients Might Benefit From Prophylactic Central Lymph Node Dissection in Clinically Node Negative Papillary Thyroid Microcarcinoma

Objective The aim of this study was to identify predictive factors for pathologic central lymph node metastasis (CLNM) in patients with clinically negative CLNM (cN0) papillary thyroid microcarcinoma (PTMC) to suggest a specific group of cN0 PTMC patients who benefit from prophylactic central lymph node dissection (CLND). Background PTMC have excellent prognosis, however, 8% have recurrent disease. Recurrence is associated with regional lymph node metastasis. It has been reported that pathologic CLNM is found in 30 to 65% of cN0 PTMC patients. However, prophylactic CLND for cN0 PTMC remains controversial. Methods We reviewed the records of papillary thyroid carcinoma patients with a tumor size on preoperative ultrasonography (US) of ≤10 mm and negative CLNM on preoperative physical examination, US, and positron emission tomography/computed tomography (PET/CT), who underwent total thyroidectomy or thyroid lobectomy with prophylactic CLND between April 2010 and February 2013. In total, 163 patients were included. We evaluated the relationship between preoperatively assessable factors including age, gender, body mass index, preoperative metformin use, primary tumor size through preoperative US, the maximum standardized uptake value (SUVmax) of the primary tumor through preoperative PET/CT, and the bilaterality of the primary tumor and pathologic CLNM. Results A SUVmax of the primary tumor of &amp;gt;3 was an independent preoperatively assessable factor predictive of pathologic CLNM in cN0 PTMC patients. Conclusions Prophylactic CLND might be considered in cN0 PTMC patients with a SUVmax of the primary tumor of &amp;gt; 3 to reduce the risks of residual CLNM and recurrence.

Prognostic Value of Hyperechoic Echo Halo in cN0 Papillary Thyroid Microcarcinoma and Its Correlation with Age and Gender.

Purpose. To investigate the pathology and prognostic value of hyperechoic echo halo in cN0 papillary thyroid microcarcinoma (PTMC) and the relationship between age, gender, and the formation of abnormal hyperechoic echo halo and cervical lymph node metastasis. Data of 97 patients who underwent surgical treatment for the first time for single PTMC between April 2016 and March 2017 were analyzed retrospectively. The boundary status of the PTMC was determined preoperatively. Grayscale values of the nodular center, hyperechoic echo halo, and normal thyroid tissue were acquired with Adobe Photoshop CS6 software. The histopathology of the boundary and status of the cervical lymph node metastasis were analyzed. Formation of abnormal hyperechoic halo and cervical lymph node metastasis in relation to age and gender were explored. The abnormal hyperechoic halo mainly represents cancer cell infiltration with reactive hyperplasia of inflammatory cells and fibrous tissue. In the hyperechoic halo group, the grayscale values for the nodular center, hyperechoic echo halo, and normal thyroid tissue were 1552.6 ± 578.6, 5792.0 ± 747.6, and 3582.7 ± 759.0, respectively (P < 0.05). The cervical lymph node metastasis rate was significantly lower in patients with hyperechoic halo (15.0%) than in those without (41.6%; P < 0.05) and significantly higher in those aged <45 years (53.3%) than in those aged ≥45 years (28.4%; P < 0.05). There were no significant correlations between gender and cervical lymph node metastasis or between age, gender, and hyperechoic halo formation (P > 0.05). cN0 PTMC patients with abnormal hyperechoic halo and age >45 years have a significantly reduced risk of cervical lymph node metastasis and relatively good prognosis.

Predicting the factors associated with central lymph node metastasis in clinical node-negative (cN0) papillary thyroid microcarcinoma.

The aim of the present study was to investigate the risk factors associated with central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC). A total of 553 patients with PTMC confirmed by histological examination, who underwent thyroidectomy and central neck dissection (CND), were enrolled. The clinicopathological and ultrasonographic features from the patients were analyzed retrospectively. PTMC patient age, Hashimoto thyroiditis (HT), tumor location, extrathyroidal extension (ETE), microcalcification and higher E values were correlated with the incidence of CLNM. Multivariate logistic regression analysis showed that age, HT, tumor location, ETE and Emax were related to the extent of CLNM. Chi-squared automatic interaction detection (CHAID) classification tree model showed that patients with tumor in upper/lower third combined ETE had a high risk of CLNM. Furthermore, cN0 PTMC patients with age ≤ 45years and ETE had more extensive CLNM. Our observations could be helpful for the assessment of prognostic factors of PTMC patients with CLNM.

Randomized trial of prophylactic ipsilateral central lymph node dissection in patients with clinically node negative papillary thyroid microcarcinoma.

This study aimed to evaluate the role of prophylactic ipsilateral central neck dissection (pCND) in patients with clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC). In this randomized control trial, a total of 164 consecutive patients were enrolled. By double-blinded randomization protocol, patients were allocated into hemithyroidectomy with pCND (n = 82) or without pCND (n = 82). With intention-to-treat analysis, post-surgical pathological and clinical course, surgery-related complications, causes and clinical course of protocol-violated cases and 5-year recurrence-free survival were compared. Operation time, hospital stay, and post-surgical complication were not significantly different between the two groups. In the pCND (+) group, occult lymph node metastasis rate was 50.0%, and lymph node ratio (metastatic/harvested lymph nodes) was 45.2%. Ten patients in the pCND (+) group had converted to undergo onsite or staged completion total thyroidectomy due to the presence of metastatic central lymph nodes and/or positive resection margin. Until last follow-up (mean 73.4 months), one regional recurrence developed in the pCND (-) group, and three regional recurrences occurred in the pCND (+) group. Five-year recurrence-free survival was similar between the two groups. Although ipsilateral pCND could clear occult lymph node metastasis in the central compartment, it failed to provide any oncological benefit for cN0 PTMC patients.

Risk factors for high-volume lymph node metastases in cN0 papillary thyroid microcarcinoma.

Lymph node metastasis (LNM) often occurs in clinical lymph node negative (cN0) papillary thyroid microcarcinoma (PTMC). The risk factors for LNM, especially for high-volume LNM, were investigated in this study. The medical records of 1,974 consecutive PTMC patients admitted to the Peking Union Medical College Hospital (PUMCH) from 2013 to 2015 were reviewed. Their clinicopathological features were collected. Univariate and multivariate analyses were performed to identify the risk factors for LNM/high-volume LNM. Of all the patients, cervical lymph node metastases were detected in 690 patients (34.95%), and high-volume LNM was detected in 75 patients (3.80%). The results of univariate analysis revealed that sex, age, chronic thyroiditis, multifocality, and tumor diameter were significantly correlated with LNM (P<0.05) and that sex, age, multifocality, and tumor diameter were significantly correlated with high-volume LNM (P<0.05). Multivariate logistic regression analysis demonstrated that male sex [odds ratio (OR) =1.657, P<0.001], multifocality (OR =1.601, P<0.001), and tumor diameter >0.5 cm (OR =1.770, P<0.001) were independent risk factors for LNM; age of 40-59 years old (OR =0.427, P<0.001), age ≥60 years old (OR =0.291, P<0.001), and chronic thyroiditis (OR =0.562, P<0.001) were independent protective factors for LNM. For high-volume LNM, male sex (OR =2.250, P=0.002), tumor diameter >0.5 cm (OR =3.664, P=0.013) and multifocality (OR =2.034, P=0.004) were independent risk factors, whereas age ≥40 years old (OR =0.240, P<0.001) was an independent protective factor. Lymph node metastases are common in cN0 PTMC, whereas high-volume LNM is rare. Active surveillance may be reasonable for patients with tumor diameter ≤0.5 cm, age ≥40 years old, female sex and isolated lesions.

A multivariable model of BRAFV600E and ultrasonographic features for predicting the risk of central lymph node metastasis in cN0 papillary thyroid microcarcinoma.

Background: Prophylactic central lymph node dissection (CLND) in papillary thyroid microcarcinoma (PTMC) patients without clinical evidence of central lymph node metastasis (CLNM) remains controversial. The purpose of our study is to identify preoperative predictive factors for finding CLNM in Chinese PTMC patients, which may allow tailored CLND.Methods: We retrospectively reviewed 182 consecutive Chinese PMTC patients with negative central lymph nodes who underwent total thyroidectomy plus central neck dissection from October 2015 to December 2017. Chi-squared and multivariate analysis were performed to evaluate the association of CLNM with ultrasonographic and clinicopathologic characteristics. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the utility of markers in predicting CLNM.Results: The CLNM was found in 39.0% (71 of 182) of cN0 PTMC patients. In multivariate analysis, tumor size>7 mm (OR: 3.636, 95% CI: 1.671–7.914), marked hypoechogenicity (OR: 2.686, 95% CI: 1.080–6.678), multifocality (OR: 4.184, 95% CI: 1.707–10.258) and BRAFV600E mutation (OR: 5.339, 95% CI: 2.529–11.272) were independent predictors of CLNM. In ROC analysis integrating these predictors, the sensitivity was 63.4% and specificity was 80.2%, and the area under the ROC (AUC) was 0.755.Conclusion: In conclusion, we found tumor size>7 mm, marked hypoechogenicity, multifocality, and BRAFV600E mutation were risk factors for CLNM. In term of these preoperative risk factors for CLNM, prophylactic CLND should be cautiously performed in cN0 PTMC patients.

Clinical analysis of risk factors for lateral cervical lymph node metastasis in stage cN0 papillary thyroid carcinoma and preventive dissection

Objective To discuss the clinical characteristics for lateral cervical lymph node metastasis in stage cN0 papillary thyroid microcarcinoma and significance and feasibility of preventive dissection, and provide reference for clinical treatment. Methods Reviewd the clinical data of 191 patients with stage cN0 papillary thyroid microcarcinoma patients from Jul. 2011 to Dec. 2016 underwent surgery in the Department of General Surgery of Lianyungang Oriental Hospital. Assessed the need for preventive cervical lymph node dissection.Chi-square test and logistic regression were used to analyze the relationship between cervical lymph node metastasis and gender, age, tumor number, tumor size, capsule infiltration, single and bilateral tumors, Hashimoto′s disease, and central lymph node metastasis. Results The positive rate of cervical lymph node metastasis in papillary thyroid microcarcinoma was 27.9% (50/191). Univariate analysis showed that the metastasis of the cervical lymph nodes was associated with infiltration of the capsule, Hashimoto disease, and CLN metastasis (all P<0.05). Multivariate logistic regression analysis showed that the capsule infiltration (OR=7.563, P=0.000), Hashimoto′s disease (OR=4.635, P=0.003), and central lymph node metastasis (OR=3.075, P<0.001) were able to be independent risk factors for cervical lymph node metastasis. When the positive number of lymph node metastasis in the central region was ≥ 2, the positive rate of cervical lymph nodes was significantly increased (P<0.001). Eleven patients (5.8%) had temporary recurrent laryngeal nerve palsy, 29 patients (15.1%) had transient hypoparathyroidism, and no patients with permanent recurrent laryngeal nerve palsy and hypoparathyroidism. Conclusions The removal of the cervical lymph nodes helps to accurately classify the tumor and assess the risk.It is important to choose the postoperative treatment follow-up plan for patients.For patients with capsule infiltration, Hashimoto′s disease, and central lymph node metastasis, cervical lymph node dissection should be routinely performed. Key words: Surgical procedures, operative; Parathyroid glands; Neck dissection; Papillary thyroid microcarcinoma; Prophylactic lateral cervical lymph node dissection

Predictors for central lymph node metastases in CN0 papillary thyroid microcarcinoma (mPTC): A retrospective analysis of 1304 cases

Presence of lymph node metastases increases the risk of recurrence, but prophylactic central neck node dissection for patients with micropapillary thyroid cancer (mPTC) is controversial. We aim to find the clinical predictors of central lymph node metastases (CLNM) in patients with cN0 mPTC. We retrospectively reviewed the clinicopathological and molecular genetic characteristics of 1304 patients with cN0 mPTC operated at the First Hospital of Jilin University between January 1, 2013 and May 31, 2016, all underwent thyroid lobectomy or total thyroidectomy with unilateral or bilateral prophylactic central neck dissection. Univariate and multivariate analysis were used to identify the predictors of CLNM. 30.7% of cN0 mPTC patients had CLNM. Univariate analysis found CLNM to be associated with younger age (≤45), male gender, larger tumor (>0.5cm), multifocality, bilaterality, capsular invasion, lymphovascular invasion and extrathyroidal infiltration, but not associated with BRAF mutation, tumor location, preoperative TSH and anti-thyroglobulin antibody level. Multivariate logistic regression showed age ≤45 years (p<0.001, OR=2.05), male gender (p<0.001, OR=1.94), tumor size >0.5cm (p<0.001, OR=1.87), bilaterality (p=0.003, OR=1.86) and capsular invasion (p=0.013, OR=1.49) to be independent predictors for CLNM in cN0 mPTC patients. Prophylactic central neck dissection has higher yield for cN0 mPTC patients with age ≤45 years, male gender, tumor size>0.5cm, bilaterality and capsular invasion. BRAF mutation is not a predictor for CLNM in cN0 mPTC patients.

Clinical analysis of risk factors for central compartment lymph node metastasis in stage cNO papillary thyroid microcarcinoma and preventive dissection

Objective To discuss the clinical characteristics for central compartment lymph node metastasis in stage cNO papillary thyroid microcarcinoma and significance and feasibility of preventive dissection, aimed to provide reference for clinical treatment. Methods Reviewed the clinical data of 277 patients with stage cN0 papillary thyroid microcarcinoma from Jul. 2011 to Dec. 2015 underwent surgery in the Department of General Surgery of Lianyungang East Hospital. Evaluated the necessity of prophylactic central lymph node dissection. Adopted chi square test and Logistic regression to analyze its relationship with patients′ gender, age, tumor number, tumor size, enveloped infiltration, single and bilateral tumor. All 277 patients underwent primary radical resection with ipsilateral central lymph node dissection. The specimen of resection was analyzed by routine pathology. Results The positive rate of thyroid papillary microcarcinoma lymph node metastasis was 36.8% (102/277). The elements of male patients (P=0.023), age 0.5 cm (P=0.019) had high positive rate. The multivariable analysis showed that male patients (OR=2.63, P 0.5 cm (OR=2.13, P=0.009) were independent risk factors for CLN metastasis.Forty-three (15.5%) cases had transient parathyroid function. No Permanent recurrent nerve paralysis and hyperparathyroidism occurred in this group. Conclusions Prophylactic central lymph node dissection is helpful for accurate staging of tumor classification and risk assessment, has important significance, on the follow-up of patients after treatment of choice. For male patients, age 0.5 cm, enveloped infiltration, the central compartment lymph node dissection may be necessary. Key words: Papillary thyroid carcinoma; Prophylactic lymph node cleaning; Lymphatic metastasis; Chi-square distribution; Neck dissection

The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis.

Although there have been many studies identifying clinical and pathologic factors that may predict central lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) patients without clinically cervical lymph node metastasis (cN0), the results were inconsistent. And whether prophylactic central lymph node dissection (pCLND) should be performed in cN0 PTMC remains controversial. The EMBASE, PubMed, MEDLINE and the Cochrane Library were searched until Oct 2015 to identify relevant studies. Primary outcomes were clinical and pathologic factors for CLNM. Secondary outcomes included CLNM rate, surgical complications of hypocalcaemia and recurrent laryngeal nerve(RLN) injury and neck recurrences. Statistical analysis was performed using Stata 12.0. Fourteen eligible studies enrolling 4573 patients were included in this meta-analysis. The overall incidence of CLNM was 33% (95% CI 29-37). An elevated risk of CLNM was significantly associated with male gender (OR 2.33, 95% CI 1.71-3.17), age<45years (OR 1.27, 95% CI 1.08-1.48), tumor size>5mm (OR 2.16, 95% CI 1.87-2.50), multifocality (OR 1.73, 95% CI 1.45-2.05), extrathyroidal extension (OR 1.99, 95% CI 1.66-2.37) and lymphovascular invasion (OR 3.87, 95% CI 1.64-9.10), but not with thyroid bilaterality (OR 1.41, 95% CI 0.89-2.22) and chronic lymphocytic thyroiditis (OR 0.98, 95% CI 0.66-1.47). The pooled frequency of permanent hypocalcaemia, permanent RLN injury and neck recurrences was 1.1, 0.5 and 2.8%, respectively. cN0 PTMC patients have a considerable CLNM rate and have a low pooled incident of surgical complications and neck recurrences with pCLND. Six unfavorable clinical and pathologic factors, which were significantly associated with CLNM, were identified. These findings may help guide the application of pCLND or subsequent treatment in cN0 PTMC.

Prediction of central lymph node metastasis in 392 patients with cervical lymph node-negative papillary thyroid carcinoma in Eastern China.

Central lymph node metastasis (CLNM) is common in papillary thyroid microcarcinoma (PTMC). The aim of the present study was to investigate the risk factors associated with CLNM in clinical lateral cervical lymph node-negative (cN0) PTMC in Eastern China. A total of 392 patients with confirmed PTMC by histological examination who underwent thyroidectomy and central neck lymph node dissection (CND) between May 2011 and October 2012 at the First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China) were enrolled. The clinicopathological and ultrasonographic data from the patients were analyzed retrospectively. A scoring system was developed on the basis of independent predictive factors for CLNM. Male gender, age <45 years, maximum tumor diameter >5 mm, lower lobe location, multifocal carcinoma with total tumor diameter >10 mm and extracapsular spread were independent predictive factors for CLNM according to logistic regression analysis. The clinicopathological score was statistically significant, with an index point ≥2 indicating CLNM with 86.2% sensitivity and 70.4% specificity. The findings of the present study indicate that CND may be recommended to be routinely performed when the clinicopathological index point ≥2.

Risk Factors for Nodal Metastasis in cN0 Papillary Thyroid Microcarcinoma.

Despite the majority of papillary thyroid microcarcinoma (PTMC) patients having an excellent prognosis, cervical lymph node metastases are common. The purpose of this study was to investigate the incidence and the predictive risk factors for occult central compartment lymph node metastasis (CLNM) in PTMC patients. 178 patients with clinically node-negative (cN0) PTMC undergoing prophylactic central compartment neck dissection in our hospital from January 2008 to Jun 2010 were enrolled. The relationship between CLNM and the clinical and pathological factors such as gender, age, tumor size, tumor number, tumor location, extracapsular spread (ECS), and coexistance of chronic lymphocytic thyroiditis was analyzed. Occult CLNM was observed in 41% (73/178) of PTMC patients. Multivariate analysis showed that male gender, tumor size (≥6mm) and ECS were independent variables predictive of CLNM in PTMC patients. Male gender, tumor size (≥6mm) and ECS were risk factors of CLNM. We recommend a prophylactic central lymph node dissection (CLND) should be considered in PTMC patients with such risk factors.

The clinical prognosis of patients with cN0 papillary thyroid microcarcinoma by central neck dissection

BackgroundCentral lymph node metastasis of papillary thyroid microcarcinoma (PTMC) is common; however, prophylactic central lymph node dissection (CLND) is still controversial because of the possible increased morbidity. The purpose of this study is to determine the clinical outcome of patients with cN0 PTMC by central neck dissection.MethodsA retrospective cohort study was conducted on patients with PTMC without preoperative evidence of lymph node disease (cN0), and the outcomes were compared between patients undergoing total thyroidectomy (TT) alone (group A) and patients undergoing TT with CLND (group B).ResultsIn this study, 242 patients with cN0 PTMC were included. Group A had 108 patients and group B had 134 patients. During a follow-up of over 60 months, the long-term postoperative complications were equivalent between the two groups. In group B, the presence of involved central neck lymph nodes upstaged 16% of patients to stage III disease, which necessitated additional postoperative radioactive iodine treatment. More patients had recurrences in group A. The rate of reoperation in the central compartment was higher in group A than in group B (8.3% vs 2.2%, P < 0.01).ConclusionsProphylactic CLND does not increase long-term postoperative complications and reduces the risk of recurrence in the central compartment.

Expression of Sodium–Iodide Symporter and TSH Receptor in Subclinical Metastatic Lymph Nodes of Papillary Thyroid Microcarcinoma

The clinical significance of the subclinical lymph node (LN) metastasis in clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC) has been debated. We investigated the expression of sodium-iodide symporter (NIS) and thyroid-stimulating hormone receptor (TSHR) in the subclinical metastatic LNs of PTMC, which are crucial prerequisites for the response to radioactive iodine treatment. Among 149 consecutive patients who received total thyroidectomy in conjunction with prophylactic central neck dissection for cN0 PTMC from October 2005 to December 2007, 20 who had single PTMC and subclinical LN metastasis (cN0, pN1, single PTMC) were included. Immunohistochemical staining was performed with anti-human NIS antibody and anti-human TSHR antibody in 20 primary tumors and 52 metastatic LNs. NIS and TSHR expression was detected in 19 (95%) and 18 (90%) of 20 PTMCs, respectively. NIS and TSHR expression were also detected in 50 (96.2%) and 39 (75%) of 52 metastatic LNs, respectively. In 85% of patients, the presence of NIS expression in primary PTMCs was concordant with that in corresponding metastatic LNs. Intensities of NIS and TSHR expression were diverse. In 6 of 12 cases of multiple metastatic LNs, the metastatic LNs showed heterogeneous intensities of NIS expression. The presence of NIS and TSHR expression was observed with high frequency in both PTMCs and corresponding subclinical metastatic LNs. However, the intensity of NIS and TSHR expression was diverse. Multiple metastatic LNs from single primary tumor focus could have heterogeneous intensity of NIS expression.