papillary thyroid microcarcinoma ( ptmc ) is defined as a papillary thyroid carcinoma that 's equal to or less than 1.0 cm at the greatest dimension according to the world health organization classification system for thyroid tumors ( 1 ) . the prevalence of ptmc in the general population with no thyroid disease is reportedly high at 3 - 36% , according to autopsy studies ( 2 - 4 ) . the majority of ptmcs are not palpable and show an asymptomatic course ( 5 ) . high - resolution thyroid ultrasonography and fineneedle aspiration cytology ( fnac ) under ultrasound guidance have recently enabled making an accurate diagnosis of ptmc , which may explain why the reported incidence of ptmc is increasing ( 6 ) . although ptmc generally has a favorable prognosis , the tumor may show locoregional recurrence and distant metastases ( 7 - 10 ) . for ptmc patients , the reported incidence of lymph node metastasis is as high as 40% , and these occur mainly in the central compartment of the neck ( 2 , 3 , 11 ) . however , the prognostic factors that can differentiate silent ptmc from potentially aggressive ptmc remain unclear . one of the major issues for the treatment of ptmc is whether central neck lymph node dissection ( cnd ) should be routinely performed during the initial operation . while cnd is not generally performed due to the excellent prognosis of ptmc , some reports have recommended performing routine cnd even in ptmc patients with no clinical nodal metastases ( 12 , 13 ) . the present study reviewed the surgery , pathology , laboratory and follow - up data of 101 patients who underwent surgery for ptmc . in order to determine the clinical necessity of performing cnd in ptmc patients , the patients were analyzed in terms of those who underwent cnd ( cnd ) and those who did not ( no cnd ) . the clinical data was reviewed on 106 ptmc patients who underwent total thyroidectomy between september 2001 and july 2005 . the pathology of all the patients were papillary carcinoma , as indicated by fine needle aspiration cytology that was guided by high - resolution ultrasonography , and the aspiration pathology was confirmed by the surgical pathology . preoperative evaluation included taking a clinical history and a physical examination , thyroid function tests and radiography of the thorax and ultrasonography . the ultrasonograpnic examinations were performed preoperatively by the same experienced radiologist ( j.h.l ) in order to evaluate lymph node metastasis . five patients who were preoperatively suspected of having cervical lymph node metastasis and who underwent therapeutic neck lymph node dissection were excluded from the study . thus , 101 patients with primary tumor sizes 1.0 cm and no preoperative evidence of nodal metastases were finally included in the study . for analysis , the patients were divided into 2 groups : the total thyroidectomy without cnd group ( the no cnd group , n=53 ) and the total thyroidectomy plus cnd group ( the cnd group , n=48 ) ( table 1 ) . the study cohort was not randomized and the decision to perform cnd was made by both the surgeon and the patient . this study was reviewed and approved by the institutional review board of the asan medical center and informed consent was waived . cnd was carried out in a conventional manner and microdissection methods were not used ( 14 ) . node clearance was performed cranially to both superior thyroid arteries and the pyramidal lobe , caudally to the innominate vein , laterally to the carotid sheaths and dorsally to the prevertebral fascia ( 5 ) . the central compartment was divided into 4 node sites : the pretracheal site , the ipsilateral site , the contralateral paratracheal site and the superior mediastinal site below the sternal notch . particular attention was given to identifying the parathyroid glands , and parathyroid autotransplantation was carried out as required , not on principle . the pathology was carefully reviewed with focusing on the primary tumor size and multifocality , extrathyroidal extension and lymph node metastases . hypocalcemia was defined as the need for exogenous calcium replacement in order to maintain a normal range of serum total calcium ( 8 - 10.4 mg / dl ) or to eliminate the clinical signs and symptoms of hypocalcemia . all the patients received radioactive iodine ablation therapy ( rai ) with 2.78 - 5.55 gbqi at 5 - 6 weeks after surgery . prior to rai , the serum thyroid - stimulating hormone ( tsh ) level was elevated to > 30 mu / l , and then the serum levels of stimulated tg ( ablation - tg ) and anti - tg antibody were measured . a whole body scan ( wbs ) using 148 mbqi was performed at 5 - 7 days and at 6 - 12 months after rai with a simultaneous measurement of the serum stimulated tg ( control - tg ) . the serum tg levels were measured using a solid phase two - site immunoradiometric assay kit ( elsa - htg , schering - cis bio international , gif / yvette , france ) as previously described ( 15 ) . the detection limit of thyroglobulin was 1.0 ng / ml . the anti - tg levels were measured using radioligand assays ( henning test anti - tg ; brahms diagnostica , berlin , germany ) . when the control - tg level was above 2 ng / ml , then neck ultrasonography with or without fine needle aspiration cytology was performed to localize the potentially malignant thyroid lesions . the t - test was used to analyze the mean differences of the pathologic findings and the other clinical parameters between the groups . fisher 's exact test or  test was used to investigate differences among the categorical data . a p - value of less than 0.05 was deemed to indicate a significant difference . the clinical data was reviewed on 106 ptmc patients who underwent total thyroidectomy between september 2001 and july 2005 . the pathology of all the patients were papillary carcinoma , as indicated by fine needle aspiration cytology that was guided by high - resolution ultrasonography , and the aspiration pathology was confirmed by the surgical pathology . preoperative evaluation included taking a clinical history and a physical examination , thyroid function tests and radiography of the thorax and ultrasonography . the ultrasonograpnic examinations were performed preoperatively by the same experienced radiologist ( j.h.l ) in order to evaluate lymph node metastasis . five patients who were preoperatively suspected of having cervical lymph node metastasis and who underwent therapeutic neck lymph node dissection were excluded from the study . thus , 101 patients with primary tumor sizes 1.0 cm and no preoperative evidence of nodal metastases were finally included in the study . for analysis , the patients were divided into 2 groups : the total thyroidectomy without cnd group ( the no cnd group , n=53 ) and the total thyroidectomy plus cnd group ( the cnd group , n=48 ) ( table 1 ) . the study cohort was not randomized and the decision to perform cnd was made by both the surgeon and the patient . this study was reviewed and approved by the institutional review board of the asan medical center and informed consent was waived . cnd was carried out in a conventional manner and microdissection methods were not used ( 14 ) . node clearance was performed cranially to both superior thyroid arteries and the pyramidal lobe , caudally to the innominate vein , laterally to the carotid sheaths and dorsally to the prevertebral fascia ( 5 ) . the central compartment was divided into 4 node sites : the pretracheal site , the ipsilateral site , the contralateral paratracheal site and the superior mediastinal site below the sternal notch . particular attention was given to identifying the parathyroid glands , and parathyroid autotransplantation was carried out as required , not on principle . the pathology was carefully reviewed with focusing on the primary tumor size and multifocality , extrathyroidal extension and lymph node metastases . hypocalcemia was defined as the need for exogenous calcium replacement in order to maintain a normal range of serum total calcium ( 8 - 10.4 mg / dl ) or to eliminate the clinical signs and symptoms of hypocalcemia . all the patients received radioactive iodine ablation therapy ( rai ) with 2.78 - 5.55 gbqi at 5 - 6 weeks after surgery . prior to rai , the serum thyroid - stimulating hormone ( tsh ) level was elevated to > 30 mu / l , and then the serum levels of stimulated tg ( ablation - tg ) and anti - tg antibody were measured . a whole body scan ( wbs ) using 148 mbqi was performed at 5 - 7 days and at 6 - 12 months after rai with a simultaneous measurement of the serum stimulated tg ( control - tg ) . the serum tg levels were measured using a solid phase two - site immunoradiometric assay kit ( elsa - htg , schering - cis bio international , gif / yvette , france ) as previously described ( 15 ) . the detection limit of thyroglobulin was 1.0 ng / ml . the anti - tg levels were measured using radioligand assays ( henning test anti - tg ; brahms diagnostica , berlin , germany ) . when the control - tg level was above 2 ng / ml , then neck ultrasonography with or without fine needle aspiration cytology was performed to localize the potentially malignant thyroid lesions . the t - test was used to analyze the mean differences of the pathologic findings and the other clinical parameters between the groups . fisher 's exact test or  test was used to investigate differences among the categorical data . a p - value of less than 0.05 was deemed to indicate a significant difference . the study cohort consisted of 17 men and 84 women , with a mean age of 49.8 years ( range : 23 to 76 years ) ( table 1 ) . the cnd and no cnd groups were similar in terms of gender and the age distribution . the mean follow - up time after surgery was 24.4 months ( range : 13 - 55 months ) . the overall incidence of hypocalcemia was 15 of 101 patients ( 14.9% ) , of whom only one patient had permanent hypocalcemia . other complications ( e.g. , bleeding , hematoma and seroma ) were not noted in either group ( data not shown ) . the presence of multifocality and an extrathyroidal extension of the primary tumors were the same for both groups . for the cnd group , 18 of 48 patients ( 37.5% ) had central nodal metastasis . the levels of ablation - tg and control - tg were compared between the no cnd patients and the cnd patients with or without central nodal metastases ( fig . 1 ) . three no cnd patients were excluded from the tg analyses due to positive anti - tg antibody results ( > 100 u / ml ) . of the remaining 50 no cnd patients , 12 ( 24.0% ) had ablation - tg levels > 5 ng / ml , 11 ( 22.0% ) had levels from 2 - 5 ng / ml , and 27 ( 54.0% ) had levels < 2 ng / ml ( fig . the 48 cnd patients were analyzed as those with ( n=18 ) or without ( n=30 ) pathologic central nodal metastases . while the proportion of patients with a serum stimulated ablation - tg level > 5 ng / ml appeared to be higher in the node - positive compared to the node - negative group ( 4/18 vs. 1/30 , respectively ) , this difference did not reach statistical significance ( p=0.058 ) . the same analysis with using an ablation - tg threshold level of < 2 ng / ml showed the proportion of such patients was similar in both the node - positive and node - negative groups ( 12/18 vs. 24/30 , respectively , p=0.325 ) . on the analyses of the control - tg levels , 4 no cnd patients and 3 cnd patients were excluded due to positive anti - tg levels ( > 100 u / ml ) . the proportion of patients with serum stimulated control - tg levels > 2 ng / ml did not significantly differ between the no cnd or the node - positive cnd patients and the node - negative cnd patients ( 5/49 or 2/18 vs. 1/27 , respectively , p>0.1 ) ( fig . 3 ) . three patients experienced recurrence during follow - up ( 2 no cnd patients and 1 node - positive cnd patient ) , as confirmed by ultrasonography - guided fineneedle aspiration cytology . the ablation - tg levels and control - tg levels of all the patients with recurrences were as high as > 8.0 ng / ml . the overall incidence of hypocalcemia was 15 of 101 patients ( 14.9% ) , of whom only one patient had permanent hypocalcemia . other complications ( e.g. , bleeding , hematoma and seroma ) were not noted in either group ( data not shown ) . the presence of multifocality and an extrathyroidal extension of the primary tumors were the same for both groups . for the cnd group , 18 of 48 patients ( 37.5% ) had central nodal metastasis . the levels of ablation - tg and control - tg were compared between the no cnd patients and the cnd patients with or without central nodal metastases ( fig . 1 ) . three no cnd patients were excluded from the tg analyses due to positive anti - tg antibody results ( > 100 u / ml ) . of the remaining 50 no cnd patients , 12 ( 24.0% ) had ablation - tg levels > 5 ng / ml , 11 ( 22.0% ) had levels from 2 - 5 ng / ml , and 27 ( 54.0% ) had levels < 2 ng / ml ( fig . the 48 cnd patients were analyzed as those with ( n=18 ) or without ( n=30 ) pathologic central nodal metastases . while the proportion of patients with a serum stimulated ablation - tg level > 5 ng / ml appeared to be higher in the node - positive compared to the node - negative group ( 4/18 vs. 1/30 , respectively ) , this difference did not reach statistical significance ( p=0.058 ) . the same analysis with using an ablation - tg threshold level of < 2 ng / ml showed the proportion of such patients was similar in both the node - positive and node - negative groups ( 12/18 vs. 24/30 , respectively , p=0.325 ) . on the analyses of the control - tg levels , 4 no cnd patients and 3 cnd patients were excluded due to positive anti - tg levels ( > 100 u / ml ) . the proportion of patients with serum stimulated control - tg levels > 2 ng / ml did not significantly differ between the no cnd or the node - positive cnd patients and the node - negative cnd patients ( 5/49 or 2/18 vs. 1/27 , respectively , p>0.1 ) ( fig . 3 ) . three patients experienced recurrence during follow - up ( 2 no cnd patients and 1 node - positive cnd patient ) , as confirmed by ultrasonography - guided fineneedle aspiration cytology . the ablation - tg levels and control - tg levels of all the patients with recurrences were as high as > 8.0 ng / ml . the present study found that cnd was not associated with any increase in postoperative complications . the incidence of hypocalcemic was the same for both cnd and no cnd groups , suggesting that exploration of the central neck compartment did not lead to increased damage to the parathyroid glands during cnd . these findings are in disagreement with those of others researchers who reported that while cnd was not associated with an increased risk of postoperative vocal fold paralysis , it was linked to a higher rate of transient and permanent hypoparathyroidism ( 16 , 17 ) . however , the current study shows that cnd can be safely performed by an experienced surgeon and this procedure does not increase the risk of surgical morbidity . in the current study , occult metastasis to the central neck compartment was found in 37.5% of the cnd patients with no clinical nodal metastasis , which is consistent with the other recent reports ( 5 , 18 ) . the pathologic finding of ptmc having a high proclivity for regional metastases seems to justify performing routine cnd in these patients . a recent study of 600 ptmc patients who underwent cnd found there was no significant difference for disease - free survival between the patients who were positive ( 43% ) or negative ( 57% ) for central nodal metastasis ( 18 ) . another study asserted that nodal recurrence did not differ between the prophylactic dissection group and the no - dissection group , prophylactic cnd for ptmc is not beneficial to the patients with no palpable lymphadenopathy . a major issue of ptmc treatment is the prognostic value of microscopic lymph node involvement . measurement of the serum tsh - stimulated tg levels is an important method for detecting the presence of residual or recurrent malignant thyroid tissue during follow - up . the meaning of the tg levels at rai is still debatable because the thyroid remnants and untreated occult metastasis contribute to tg synthesis and therefore , the increased tg levels . however , a prior report suggested that the ablation - tg levels were well correlated with the control - tg levels , and that levels > 2.0 ng / ml were highly associated with persistent or recurrent disease in the low - risk patients with well - differentiated thyroid carcinoma ( 15 ) . therefore , we used both the ablation - tg and control - tg levels for predicting recurrences . the ablation - tg levels appeared to be higher in the controls or the cnd patients with nodal metastases than that in the cnd patients without nodal metastases . in addition to the pathologic information on nodal metastases in ptmc patients , this may also suggest a role for cnd in planning rai after surgery . recent studies have investigated whether the control - tg values can predict recurrent and persistent disease ( 19 , 20 ) . the current study found that control - tg levels did not differ among the 3 groups , and that the recurrence rate was very low . moreover , no recurrence was found in any of the cnd patients without occult nodal metastasis , suggesting that this group has a good prognosis and there is no need for high - dose rai . thus , cnd may have a role in determining the plan for postoperative rai and also the patient 's prognosis . the present study data allowed us to investigate whether rai was sufficient to remove occult metastasis . for the control patients , 44.0% had a stimulated tg level above 2 ng / ml prior to rai , while only 10.2% were above 2 ng / ml at 6 - 12 months after rai . this result suggests that rai may be an effective method for ablating the remnant thyroid tissue or disease . however , the potential benefits of rai on lowering the disease recurrence rate and the mortality rate of ptmc patients remains as a controversial issue ( 9 , 21 - 23 ) , and no randomized , controlled clinical trials have yet been performed on a large number of patients . furthermore , rai has side effects , including radiation sialadenitis in up to 40% of patients , with the incidence linked to the dose of radioiodine ( 24 ) . the recent data suggests that low - risk patients with ptmc do not benefit from rai ( 23 ) . thus , cnd may help discriminate between the patients with and without ptmc - associated metastatic neck diseases and so this can abrogate the necessity of high - dose rai for the low - risk patients . the present study may have been limited by its retrospective non - randomized design . the decision to perform a cnd however , the general demographic and pathologic data were comparable between the control and cnd groups . the study also included more than 100 ptmc patients with a clinical n0 neck , which is a large number of patients and it is more than sufficient for making between - group comparisons . a relatively short follow - up period may also have been a limitation , and it may have affected the findings regarding recurrence or survival . the present data showed that the serum tsh - stimulated tg levels were predictive of recurrence , and now a larger study with a longer follow - up period is warranted to confirm our results . the present study found that occult metastasis to the central compartment is a common event in ptmc patients . a cnd provides pathologic information on nodal metastases , which may assist the postoperative rai planning . it appears that the stimulated tg levels at rai and follow - up may help predict recurrence , and while this observation did not reach statistical significance in this study , we believe it may reach significance in a larger study . however , our present findings indicate that these questions may be answered by a longer follow - up of these patients .