Risk prediction and clinical model building for lymph node metastasis in papillary thyroid microcarcinoma

Analysis of risk factors for lymph node meta-stasis in papillary thyroid microcarcinoma

Objective To analyze the risk factors for cervical lymph node metastasis in patients with papillary thyroid microcarcinoma (PTMC). Methods The clinical data of 289 patients with PTMC from January 2013 to December 2014 were analyzed retrospectively. All patients underwent thyroidectomy and thyroid isthmectomy/total thyroidectomy plus central (and lateral) cervical lymph node dissection. Results In 289 patients, postoperative pathology confirmed that the central lymph node metastasis was in 118 cases (40.8%); 64 of them performed central and lateral cervical lymph node dissection, and the rate of lateral cervical lymph node metastasis was 42.2% (27/64). The smooth curve fitting chart showed that the risk of central cervical lymph node metastasis was significantly increased when the tumor diameter >6 mm. Univariate analysis result showed that central cervical lymph node metastasis was associated with gender, number of primary lesions, unilateral and bilateral tumor, capsule invasion, tumor diameter and Hashimoto thyroiditis (P 6 mm was the independent risk factor for central cervical lymph node metastasis (OR= 2.036, 95% CI 1.160-3.573, P= 0.013). Univariate analysis result showed that lateral cervical lymph node dissection was associated with central cervical lymph node dissection (P < 0.05); multivariate Logistic regression analysis result showed that central cervical lymph node dissection was the independent risk factor for lateral cervical lymph node dissection in patients with PTMC (OR= 9.630, 95% CI 1.150-80.628, P= 0.037). Conclusions PTMC patients with central or lateral cervical lymph node metastasis is very common, and central lymph node metastasis risk increases significantly when tumor diameter > 6 mm; the risk of lateral cervical lymph node metastasis also significantly increases in patients with central cervical lymph node metastasis. Key words: Thyroid neoplasms; Carcinoma, papillary; Neoplasm metastasis; Risk factors; Retrospective studies

Patterns and Predictive Factors of Lateral Lymph Node Metastasis in Papillary Thyroid Microcarcinoma

Objective: The clinicopathologic features of central area and lateral neck lymph nodes metastasis were retrospectively analyzed in order to better understand the characteristics of cervical lymph node metastasis, and provide an objective reasonable choice basis of surgical treatment cervical lymph node for the surgeons. Methods: All patients from January 2008 to July 2010 in our hospital were collected, 329 cases of resection of thyroid cancer and central lymph node dissection treatment of PTC were analyzed (Including 115 cases of lateral neck lymph nodes dissection at the same time). We then analyzed the correlation between the clinicopathological features of central lymph nodes and lateral lymph node metastasis. Results: The average age of 329 cases of patients was 43 years, male 66 cases, female 263 cases, tumor diameter average 1.11cm, the average number of tumors 1.76, 97 cases of bilateral, 232 cases of unilateral, 44.07% of central lymph node metastasis in 329, 57.39% of lateral lymph node metastasis in 115 cases of lateral neck lymph nodes dissection, 35.11% of central lymph node metastasis in 262 cases of patients with a clinincal negative result of central lymph nodes preoperative examination, 28.81% of lateral lymph node metastasis in 59 cases of patients with a negative result of lateral lymph nodes preoperative examination. (1) Papillary thyroid carcinoma those who were in the groups of male, >45 years old, associated with extrathyroidal invasion, the diameter >1cm, absence of other thyroid diseases, absence of nodular goiter had a higher rate of central lymph node metastasis (P=0.028, 0.003, 0.001, 0.000, 0.000, 0.001, espectively). And the group that Ultrasonography examination showed a positive result of central lymph nodes had a higher rate of central lymph node metastasis than the group that Ultrasonography showed a negative result (P=0.000). (2) Papillary thyroid carcinoma those who were in the groups of male, >45 years old, unilateral tumor had a higher rate of lateral lymph node metastasis (P=0.040, 0.008, 0.021, 0.000). And the group of central lymph node metastasis positive had a higher rate of lateral lymph node metastasis than the group of central lymph node metastasis negative (P=0.000). (3) Those clinically examination negative central lymph nodes metastasis papillary thyroid carcinoma who were in the groups of the diameter > 1cm, absence of other thyroid diseases, absence of nodular goiter had a higher rate of central lymph node metastasis(P=0.018, 0.001, 0.004). (4) Those cases with a negative result of lateral cervical lymph nodes examination whom in the group of central lymph node metastasis had a higher rate of lateral lymph node metastasis than the group of absence of central lymph node metastasis(P=0.027). Conclusions: There were certain associations between the central lymph nodes metastasis, lateral lymph node metastasis and clinicopathological features in thyroid papillary carcinoma patients. This is of important significance for clinical treatment choice.

Objective To analyze the clinical features of lymph node metastasis in papillary thyroid microcarcinoma(PTMC). Methods 198 patients with PTMC who have underwent total thyroidectomy and at least one 131I treatment were divided into two groups according to the occurrence of lymph node metastasis. The clinical features of lymph node metastasis in PTMC were retrospective analyzed, and independent risk factors of the central and lateral lymph node metastasis in PTMC patients were further analyzed. Results Clinical features of PTMC patients with cervical lymph node metastasis: (1)Most of them were<45 years old(63.4% vs 44.9%, P=0.012); (2)More patients with cancer in bilateral lobes and extrathyroidal extension in lymph node metastasis groups(56.7% vs 42.0%, P=0.043; 63.6% vs 36.4%, P=0.034); (3)The average tumor size of the patients of lymph node metastasis was larger than that of the patients without lymph node metastasis[(0.71±0.25 vs 0.64±0.24)cm, P=0.047]; (4)Preoperative thyroglobulin antibody(TgAb)level of PTMC patients with cervical lymph node metastasis was higher than the control group[(65.27±139.179 vs 36.36±95.647)IU/L, P=0.03]; (5)After the 131I treatments and by 1-6 years of follow-up, it is found no statistically significant difference in cure rate between patients with cervical lymph node metastasis after total thyroidectomy and its control group. But the frequency of 131I treatment required in patients with cervical lymph node metastasis was higher than that of the control group(1.77±0.77 vs 1.49±0.74, P=0.006). Univariate analysis revealed that central lymph node metastasis was correlated with age, tumor size and other factors. There were more patients with cancer in bilateral lobes and extrathyroidal extension in lymph node metastasis group. And lateral lymph node metastasis was correlated with Hashimoto′s thyroiditis. Multivariate analysis showed that age, tumor size, involvement of bilateral glandular lobes and extrathyroidal extension were independent risk factors for central lymph node metastasis. Conclusion The risk factors of lymph node metastasis should be fully evaluated to carry out individualized treatment for the first operation of PTMC patients. (Chin J Endocrinol Metab, 2016, 32: 900-905) Key words: Papillary thyroid microcarcinoma; Lymph node metastasis; Clinical feature; Risk factors

Cervical lymph node metastases are quite common in papillary thyroid cancer (PTC) and they usually spread in a contiguous fashion. However, "skip metastasis," defined as lateral lymph node metastasis without central lymph node metastasis, also occurs in patients with PTC. There is little information regarding skip metastasis in papillary thyroid microcarcinoma (PTMC). The goal of this study was to determine the prevalence and associated clinical and imaging features of skip metastasis in PTMC. We performed a retrospective study of 245 patients with PTMC who underwent either thyroidectomy and central lymph node dissection or thyroidectomy, central lymph node dissection, and lateral lymph node dissection if preoperative ultrasonography or computed tomography suggested lateral node metastasis. Clinicopathologic results were reviewed, and the patterns of cervical lymph node metastasis were analyzed. Cervical lymph node metastases were present in 26.5% of cases. The frequency of lymph node metastases was 21.8% in the group that only had thyroidectomy and central lymph node dissection and 51.3% in the group that had thyroidectomy, central lymph node dissection, and lateral lymph node dissection. Younger age, larger tumor size, multiplicity, bilaterality, encapsulation, extrathyroid extension, and lymphatic invasion were associated with metastasis to nodes in the central or lateral compartment. Lateral lymph node dissection was performed in 15.9% of patients. Skip metastasis was observed in 7.7% of the cases in which combined central and lateral node dissection was performed. No features of the primary thyroid tumor could be associated with the development of skip metastasis. Skip metastases occur in a minority of patients with PTMC. We recommend, therefore, that preoperative studies in patients suspected of having PTMC focus not only on nodes in the central compartment but also lateral cervical nodes since the information obtained would guide the extent of surgery.

Currently the surgical approach for papillary thyroid microcarcinoma (PTMC), particularly the range of lymph node dissection, remains controversial. The present study aims to evaluate the risk factors for central and lateral lymph node metastasis (CLNM and LLNM) for appropriate clinical decision of neck lymph node dissection in PTMC. A total of 66 cases of PTMC that underwent unilateral or bilateral lobectomy plus prophylactic cervical lymph node dissection were collected for clinicopathological evaluation, including age, gender, tumor size, subtypes, extrathyroidal invasion, multifocality, calcifications, loss of cellular polarity/cohesiveness (LOP/C) in the invasive front, CLNM and LLNM, and retrospectively analysis. Univariate analysis revealed that LOP/C was significantly associated with CLNM (P=0.001) and LLNM (P<0.0001). The male gender was a risk factor of CLNM (P=0.04), while the age <45 years, tumor size >0.5 cm and multifocality were high-risk factors of LLNM (P=0.022, 0.044 and 0.005, respectively). Multivariable analysis revealed that LOP/C was significantly associated with CLNM [P=0.007, odds ratio (OR)=7.765, 95% confidence interval (CI)=1.773–33.996] and LLNM [P=0.029, OR=5.717, 95% CI=1.190–27.470]. Both multivariable analysis and χ2 test revealed that CLNM was another important high-risk factor of LLNM (P=0.021, OR=5.444, 95% CI=1.290–22.969, χ2=17.867, P<0.001). The present study revealed that prophylactic central lymph node dissection is essential for PTMC surgery and that prophylactic lateral lymph node dissection is recommend for patients with LOP/C and CLNM, which can be performed by intraoperative frozen section pathological examination. This must be considered discreetly in the case of patients with age <45 years, tumor size >0.5 cm and multifocal lesions.

The elevation for lateral lymph node metastasis (LLNM) plays an important role in therapeutic decision-making for thyroid carcinoma. A reliable forecasting model for LLNM in patients with papillary thyroid micro-carcinoma (PTMC) is needed, using clinicopathological characteristics. A total of 576 PTMC patients with suspicious lateral cervical lymph node (II, III, IV or V region) metastasis and known clinicopathological variables were randomly collected at Shenzhen Second People's Hospital. Cervical lymph node status of every patient was assessed by ultrasonography (US). The patients in this cohort study underwent thyroidectomy and lateral neck lymph node dissection. Univariate analysis and logistic regression analysis were performed to screen out the predictive variables associated with LLNM, and a nomogram was constructed by integrating clinicopathological features collected in our study. The overall LLNM rate was 23.0% (133/576). After statistical analysis, central lymph node metastasis (CLNM), prelaryngeal lymph node metastasis (PLNM), bilateral lesions, tumor location in thyroid (upper or lower), and gross extrathyroidal extension (ETE) were found to be independent predictive factors for LLNM (P < 0.01). The nomogram built to predict LLNM in PTMC patients passed the calibration step and the area under the receiver operating characteristic curve was 0.967, which showed that the nomogram we used had a good predictive effect. The nomogram constructed in this study has a good predictive value for LLNM, which will help thyroid surgeons to make a more accurate surgical plan for patients with PTMC. A strict preoperative evaluation and total thyroidectomy and lateral neck dissection may be indicated when patients with PTMC have a high score.

Risk factors for skip metastasis and lateral lymph node metastasis of papillary thyroid cancer

ABSTRACTObjective The aim of this study was to investigate the incidence and risk factors for lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC).Subjects and methods 356 patients diagnosed with PTC who underwent total thyroidectomy and central lymph node dissection and lateral lymph node dissection between January 2005 and December 2011 were enrolled. The relation between LLNM and clinicopathological features such as gender, age, tumor size, tumor spread, psammoma bodies, tumor multifocality, extrathyroidal extension (ETE), unilateral or bilateral disease, tumor primary location and central lymph node metastases (CLNM) was analyzed.Results The rate of LLNM was 75.0%. In the univariate analysis, it was significantly associated with age, tumor size, tumor spread, extrathyroidal extension, primary tumor location and central lymph node metastasis (p < 0.05). In contrast, in the multivariate analysis, it was significantly associated with primary tumor location, central lymph node metastasis (p < 0.05) and tumor size > 1.5 cm with p = 0.05 but was unrelated to the other factors.Conclusion Patients with PTC, with the primary tumor located in the upper part of the lobe and positive central compartment lymph node metastasis with a tumor size > 1.5 cm diameter are more likely to have LLNM. Therefore, more meticulous evaluations including the lateral lymph nodes should be performed before surgery.

e17583 Background: Papillary thyroid microcarcinoma (PTMC) accounts for nearly half of all cases of thyroid papillary cancer. Although PTMC has a good prognosis, lymph node metastasis, especially central lymph node metastasis (CLNM), is the leading cause of local recurrence. The value of central lymph node dissection in PTMC remains controversial. Few studies have focused on the relationship between CLNM and multifocality in PTMC. This retrospective study of a large cohort of patients with PTMC aimed to identify assess the predictive value of multifocality for identifying patients at high risk of CLNM who may benefit from central lymph node dissection. Methods: Patients with PTMC who underwent total or hemi-thyroidectomy with effective unilateral or bilateral central lymph node dissection at Zhejiang Caner Hospital between January 2007 and December 2015 were enrolled ( n = 3543). Number and laterality of PTMC foci, extrathyroidal extension (ETE), tumor size, age, sex, positive/total number of central lymph nodes and other clinicopathological factors were recorded. The chi-square test was used for univariate analysis; logistic regression, for multivariate analysis. Results: Multifocality, age, sex, tumor size, ETE and nodular goiter were significantly associated with central lymph node metastasis (CLNM) in univariate analysis. Multifocality was an independent predictive factor for CLNM in multivariate analysis. Compared to unifocal disease, the odds ratio (OR) for CLNM was 1.447 for patients with ¡Ý 2 tumor foci ( P &lt; 0.001) and 2.978 for patients with ¡Ý 3 tumor foci ( P &lt; 0.001). Conclusions: Multifocality with ¡Ý 3 tumor foci was an independent predictive factor for CLNM in PTMC. Multifocality should be assessed when selecting patients for prophylactic central neck lymph node dissection, and we recommend patients with multifocality should undergo more radical treatment.

Objective: To investigate the correlation between cervical lymph node skip metastasis with ultrasonographic characteristics of papillary thyroid micro- carcinoma (PTMC). Methods: We reviewed ultrasonographic features of 385 primary PTMC and cervical lymph node metastasis, confirmed by pathology in Tianjin Medical University Cancer Institute and Hospital, to evaluate the efficacy of ultrasonography in the diagnosis of cervical lymph node metastasis of PTMC patients. The relationship between ultrasonographic features of primary lesions and skip metastasis of cervical lymph nodes was analyzed by χ(2) test and multiple factor Cox regression. Results: Among the 385 cases of PTMC patients with cervical lymph node metastasis, 231 cases were central lymph node metastasis alone, 31 cases were lateral cervical lymph node metastasis alone, 123 cases were both central and lateral cervical lymph node metastasis. Among the 354 cases without skip metastasis of cervical lymph nodes, 48 cases were level Ⅱ, 92 cases were level Ⅲ, 83 cases were level Ⅳ, 9 cases were level Ⅴ, 354 cases were level Ⅵ. Among the 31 cases with skipping metastasis of cervical lymph nodes, 12 cases were level Ⅱ, 14 cases were level Ⅲ, 14 cases were level Ⅳ, 1 case was level Ⅴ. The sensitivity and specificity of preoperative ultrasonography in the diagnosis of central cervical lymph node metastasis were 46.3% and 66.7%, respectively, and those of lateral cervical lymph node were 91.0% and 87.8%, respectively. Univariate analysis showed that the abutment/perimeter, diameter and location of PTMC were significantly associated with skip metastasis (P<0.05), multivariate analysis showed that abutment/perimeter and location of PTMC were significantly associated with skip metastasis (P<0.05). Conclusions: The sensitivity and specificity of preoperative ultrasound diagnosis for lateral cervical lymph node metastasis of PTMC is higher than that of central metastasis. PTMC with abutment/perimeter ≥1/4 and upper portion location are prone to skip metastasis.

To investigate the impact of lateral lymph node metastasis in papillary thyroid microcarcinoma (PTMC). 5241 PTMC patients with follow-up information were enrolled in the current study. These patients underwent primary surgery in our situation from January 1997 to December 2016. Additionally, a validation cohort consisting of 274 PTMC patients who underwent primary surgery between January 2020 and December 2021 was also included. Univariable and multivariate logistic analyses were conducted to identify the association between clinicopathologic features and lateral lymph node metastasis (LLNM). Kaplan-Meier survival curve analysis was used to calculate the disease-free survival (DFS) rate. The fitting curve was generated to identify the quantitative relationship between central lymph node metastases (CLNM) and LLNM. Of 5241 PTMC patients, cervical lymph node metastasis was detected in 1494 (28.5%) cases, including 1364 (26.0%) with CLNM only and 130 (2.5%) with LLNM. With a median follow-up time of 60 months (interquartile range [IQR], 44-81), recurrence was detected in 114 patients (2.2%). Multivariate Cox regression analyses showed that LNM was the only independent risk factor for recurrence, with HR values of 3.03 in CLNM and 11.14 in LLNM, respectively. Tumor diameter >0.5 cm (hazard ratio [HR]:1.80), multifocality (HR:2.59), bilaterality (HR:2.13), extrathyroidal invasion (HR:2.13), and CLNM (HR:5.11) were independent risk factors for LLNM. The prevalence of LLNM escalated significantly with increasing number of lymph node involvement in CLNM when stratified by the number of metastatic lymph nodes and trend was observed similarly in the validation cohort. The fitting curve showed that the incidence of LLNM could be as high as 20.7% when the number of CLNM ≥ 5. By analyzing a large database with follow-up information, our study provides evidence that LLNM is significantly correlated with tumor recurrence in patients with PTMC. Tumor size (>0.5 cm), multifocality, bilaterality, extrathyroidal extension (ETE) and CLNM are independent risk factors for LLNM.

We aimed to investigate the association between iodine intake and nodal metastasis stratified by central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) of papillary thyroid microcarcinoma (PTMC). Urinary iodine concentration (UIC) and clinicopathological characteristics were used to identify factors associated with CLNM and LLNM using logistic regression analysis. A sum of 3,858 PTMC patients were enrolled. The median UIC (MUI) of patients with CLNM or LLNM was not statistically different from those without nodal metastasis. Male patients had a higher MUI than females (183.4 μg/L vs. 173.6 μg/L). Female patients with extracapsular extension had a higher MUI than those without it (210.0 μg/L vs. 172.1 μg/L). Male patients with LLNM had a significantly lower MUI than those without LLNM (134.7 μg/L vs. 187.9 μg/L). Female patients with more than adequate iodine intake were more likely to present with CLNM and extrathyroidal extension than those with adequate iodine intake with an odds ratio (95% confidence interval) of 1.23 (1.01-1.51) and 1.59 (1.09-2.32) after adjustment. Iodine nutrition was not found to be associated with LLNM. In addition, patients with a younger age, larger tumors, extrathyroidal extension, and intrathyroidal spread were more likely to be CLNM, whereas nodular goiter presented with a protective factor; CLNM was the only factor associated with LLNM of PTMC in both genders. In conclusion, iodine nutrition has a much closer association with female than male patients, and high iodine intake may be associated with CLNM and extrathyroidal extension in female PTMC patients.

BackgroundThe treatment for papillary thyroid microcarcinoma (PTMC) is controversial. Central lymph node metastasis (CLNM) is one of the main predictors of recurrence and survival, accurate preoperative identification of CLNM is essential for surgical protocol establishment for PTMC. The objective of this study was to establish a nomogram to predict the possibility of CLNM in PTMC patients.MethodsA total of 3023 PTMC patients were randomly divided into two groups by a ratio of 7 to 3, the training group (n = 2116) and validation group (n = 907). The LASSO regression model and multivariate logistic regression analysis were performed to examine risk factors associated with CLNM. A nomogram for predicting CLNM was established and internally validated. Meanwhile, we follow-up the serum thyroid function FT3, FT4, TSH, Tg, TGAb and TPOAb in 789 PTMC patients for 4 years after surgery and compared the differences between the CLNM (+) and CLNM (-) groups, respectively.ResultsThe LASSO regression model and multivariate logistic regression analysis showed that younger age, lower BMI, being male, location in the lower pole, calcification, 1 ≥ diameter ≥ 0.5 cm, multifocality lesions, extra thyroidal extension (ETE), enlargement of central lymph node (ECLN), lateral lymph node metastasis (LLNM) and higher carcinoembryonic antigen were the ultimate risk factors for determining CLNM. A nomogram for predicting CLNM was constructed based on the influencing factors and internally validated. By establishing the prediction model, the AUC of CLNM in the training and validation groups were 0.73 (95% CI, 0.70-0.76) and 0.75 (95% CI, 0.71-0.79) respectively. Results of the DCA showed that the model is clinically useful when deciding on intervention in the most range of the threshold probability. A 4-year follow-up of thyroid function showed that FT3 and FT4 remained at stable levels after 3 months postoperative and were higher in the CLNM (+) group than in the CLNM (-) group. Hypothyroidism appeared predominantly within 3 months after surgery. The overall incidence of the CLNM (+) group and CLNM (-) groups were 16.46% and 12.04%, respectively.ConclusionThe nomogram model constructed in this study has a good predictive effect on CLNM in PTMC patients and provides a reasonable reference for clinical treatment.