papillary thyroid carcinoma ( ptc ) is the most common form of thyroid gland carcinoma which accounts for 1% of all human malignant tumors . it was reported that the prognosis of ptc is excellent with a 10-year survival exceeding 90% . however , approximately 2050% of ptc patients were found to have central lymph node metastases ( clnms ) [ 2 , 3 ] . there is still a recurrence rate of 825% after primary surgical treatment , and many scholars hold the opinions that routine central lymph node dissection ( clnd ) may decrease the rate of recurrence . this retrospective study was approved by department of breast - thyroid - vascular surgery at shanghai general hospital of nanjing medical university . from january 2013 to february 2015 , a total of 543 ptc patients who underwent radical operation of thyroid were enrolled in this study . total thyroidectomy and ipsilateral clnd might be performed for unilateral ptc patients who met one or more of the following conditions according to the nccn guidelines : radiation history , known distance metastases , extrathyroidal extension , and tumor size > 4  cm in diameter . other unilateral ptc patients underwent unilateral and contralateral partial resection of thyroid gland or hemithyroidectomy with ipsilateral clnd . its upper bound was to the thyroid cartilage , and its lower bound was to thymus , and both sides were to the inner side of the central bilateral carotid sheath , including lymph nodes prior to cricothyroid membrane , lymph nodes surrounding thyroid , and paratracheal and prelaryngeal lymph node . intraoperative frozen section ( fs ) is a popular method for doctors to determine surgical extent in surgery . it was reported that the accuracy rates for fs in thyroid surgery was 97.8% . and preoperative ultrasonography , preoperative thyroid function tests , and postoperative pathologic examination were performed in all patients . based on the nccn guidelines for ptc , all of the 543 patients with clinically lymph node that was negative according to the preoperative physical examination and ultrasound underwent the surgical treatment . 79 patients underwent unilateral and contralateral partial resection of thyroid gland with bilateral / unilateral clnd . six patients performed secondary surgical intervention because they were diagnosed as having benign lesions according to intraoperative fs , but the postoperative pathological diagnosis of the first surgery was ptc . in this study , the preoperative fine needle aspiration was carried out on 337 patients , and 322 cases were diagnosed with ptc . from a total of 543 patients , 537 cases were diagnosed with ptc by the intraoperative fs , and 6 cases were diagnosed postoperatively after the histopathological examination of thyroid gland . lt4 was given to all the patients as an alternative treatment besides the inhibition of tsh therapy . chi - square test or fisher 's exact test was used to analyze the significance of differences of the categorical variables and logistic regression was performed to analyze the multiplicity . all the data were processed using statistic package for social science ( spss 22.0 ) and p < 0.05 was considered as a statistically significant difference . 410 ( 75.5% ) females and 133 ( 24.5% ) males were included in this study . the average age of all the patients was 47 years , ranging from 16 to 78 years . the mean size of the tumors was 0.95  0.73  cm ( ranging from 0.1  cm to 5  cm ) . 132 ( 24.3% ) patients had bilateral lesions , 180 ( 33.1% ) cases had multifocal lesions , 517 ( 95.2% ) cases had tumor 0.25  cm in size , and 36 ( 6.6% ) cases had ptc with extrathyroidal extension . 190 ( 35.0% ) cases had ptc with hashimoto 's thyroiditis ( ht ) and 78 ( 14.4% ) cases had abnormal thyroid function . we analyzed these factors including the gender , age , bilaterality , multifocality , tumor size , extrathyroidal extension , ht , and abnormal thyroid function to find the risk factors for ptc patients with clnms . in the univariate analysis , male gender ( p = 0.012 ) , age < 45 years ( p < 0.001 ) , bilateral lesions ( p = 0.042 ) , tumor size 0.25  cm ( p = 0.003 ) , and external invasion ( p = 0.003 ) were significantly associated with clnms . multifocal lesions , ht , and abnormal thyroid function were not significant for clnms ( table 1 ) . the multivariate analysis ( table 2 ) showed that the male gender ( p < 0.001 , or : 1.984 ) , age < 45 years ( p < 0.001 , or : 1.934 ) , bilateral lesions ( p = 0.006 , or : 1.585 ) , tumor size 0.25  cm ( p = 0.001 , or : 7.579 ) , and external invasion ( p = 0.002 , or : 2.370 ) were independent risk factors for clnms in ptc patients . we grouped all the ptc patients into five groups based on the size of tumors : < 0.25  cm , 0.25 and < 0.5  cm , 0.5 and < 0.75  cm , 0.75 and < 1  cm , 1  cm . and the rate of clnms increased as the tumor size increased . there were significant differences for these groups ( p < 0.001 ) ( table 3 ) . among the 543 cn0 table 4 showed that no clnms were found in all 7 males and 21 patients with unilateral lesion in cn0 ptc patients with tumor size < 0.25  cm . the percentages of patients with clnms whose conditions met only zero , one , two , three , four , or all of the five risk factors were 0 ( 0/6 ) , 22.5% ( 39/173 ) , 43.7% ( 104/238 ) , 46.3% ( 50/108 ) , 77.8% ( 14/18 ) , and 0 . among the 6 patients without these five risk factors , 0% ( 0/6 ) papillary thyroid carcinoma which is considered to have relatively good prognosis still has at least 10% risk of recurrence in long - term follow - up [ 79 ] . a large study found that the mortality of ptc patients with clnms was much higher than that of patients without clnms . pellegriti et al .   kept the option that the development of distant metastases was associated with the presence of lymph node metastases at presentation . more and more scholars recommend that clnd is necessary for ptc patients because of the greater rate of clnms . wang et al .   reported that 44.1% cn0 ptc patients were found to have clnms . considered that clnms were associated with local recurrence and distant metastasis but did not impair survival . therefore , it is essential to investigate the indications for cn0 ptc patients . obviously , male gender , age < 45 years old , bilaterality , tumor size 0.25  cm , and external invasion were independent risk factors for cn0 ptc patients . several studies demonstrated that male ptc patients have higher significant risk of clnms [ 15 , 16 ] . however , jiang et al .   found that the gender had no association with clnms . in our study , the proportion of the male gender with clnms was significantly higher than that of female gender ( 47.4% versus 35.1% , p < 0.001 , or : 1.984 ) . age is often used to judge the stage of the differentiated thyroid carcinoma . we found that younger ptc patients ( < 45 years old ) were at higher risk of occurring clnms ( 46.6% versus 23.9% , p < 0.001 , or : 1.934 ) . analyzed 916 cn0 ptc patients and had similar finding that the rate of clnms was considerably higher in the cases of younger patients ( p < 0.001 ; or : 2.357 ) . jiang et al .   believed that age 35 years was a good prognostic factor for ptc patients with clnms . in agreement with pellegriti et al .   and vasileiadis et al . , we found that bilateral lesions made a meaningful difference with a higher percentage to develop clnms from the unilaterality ( 45.5% versus 35.7% , p = 0.006 , or : 1.585 ) . chang et al .   and zhang et al .   have demonstrated that larger tumor size ( > 0.5  cm , > 0.6  cm ) was associated with clnms . in our study , ptc patients with tumor size 0.25  cm were more prone to develop clnms ( 39.7% versus 7.7% , p = 0.001 , or : 7.579 ) . many studies have demonstrated that external invasion is a risk factor of clnms for ptc patients [ 4 , 13 , 15 , 18 ] . our study showed that nearly 61.1% percent of ptc patients with external invasion was found to have clnms and the multivariate analysis indicated that external invasion was an independent risk factor for clnms ( 61.1% versus 36.5% , p = 0.002 , or : 2.370 ) . with the development of ultrasound , palpation , fine needle aspiration ( fna ) , and intraoperative frozen section , increasing small malignant thyroid nodules were checked out . before the dispute regarding [ 20 , 21 ] the operation for ptc patients with tumor size 1  cm , studies shall need to advance . in this study , the rate of tumor size with clnms increased , obviously , with the increase of tumor size in a certain range ( < 0.25  cm : 7.6% , 0.25 and < 0.5  cm : 22.7% , 0.5 and < 0.75  cm : 30.1% , 0.75 and < 1  cm : 45.5% , 1  cm : 53.4% ) . 7.6% of ptc patients with tumor size < 0.25  cm were confirmed to have metastases in central lymph node , while about 39.7% of ptc patients whose tumor size was 0.25  cm were confirmed to have clnms . the incidence of clnms in ptc patients with tumor size 0.25 and < 0.5  cm was 22.7% . and the incidence of clnms in ptc patients with tumor size < 0.5  cm was reported to be 20.626.2% [ 13 , 15 , 17 ] . therefore , we think that clnd should be performed in ptc patients with tumor size 0.25  cm . in this study , similar studies in cn0 ptc patients reported that the incidence of clnms was 35.043.6% [ 15 , 16 , 22 ] . the clinic risk factors for ptc patients with clnms were analyzed above , and we also evaluated the incidence of clnms with every conceivable combination to further analyze the indication of clnd . eliminating tumor size 0.25  cm , no clnms were found in male patients and patients with unilateral lesion . in the present studies , clnd is necessary to be performed in the ptc patients because clnms are associated with a higher risk of recurrence [ 23 , 24 ] . hence , clnd should be performed in the patients with risk factors , and we recommend that , in cn0 ptc patients with tumor size < 0.25  cm , male patients and patients with unilateral lesion should be considered safe . in this study , some limitations should be considered . secondly , all patients are required to have long - term follow - up to analyze the significance of clnd for cn0 ptc patients . in summary , the incidence of ptc patients with clnms is 38.1% in our study . male gender , age < 45 years , bilaterality , tumor size 0.25  cm , and external extension were considered as independent risk factors for ptc patients . on this account , we think precautionary clnd should be considered for cn0 ptc patients with risk factors . and we believe that , in cn0 ptc patients with tumor size < 0.25  cm , male patients and patients with unilateral lesion could avoid clnd .