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 .
 objectivesit remains unclear as to whether routine central neck dissection ( cnd ) is necessary when performing surgery to treat patients with papillary thyroid microcarcinoma ( ptmc ) . to determine the necessity for routine cnd in ptmc patients 
 , we reviewed the clinicopathologic and laboratory data of the patients of ptmc.methodsbetween september 2001 and july 2005 , 101 patients with ptmc and clinical n0 disease were retrospectively reviewed . 
 the study cohort was devided into groups : the total thyroidectomy plus cnd group ( the cnd group , n=48 ) and the total thyroidectomy without cnd group ( the no cnd group , n=53 ) . 
 the serum stimulated thyroglobulin ( tg ) levels were measured after surgery and prior to radioactive iodine ablation therapy ( rai ) and at 6 - 12 months after rai . 
 pathology , the tg levels and recurrence data were compared between the 2 groups.resultscentral nodal metastases were found in 18 of the 48 cnd patients ( 37.5% ) . 
 the incidence of tg levels > 5 ng / ml at rai was higher in the no cnd patients and in the 18 node - positive cnd patients compared with the 30 node - negative cnd patients ( 22 - 24% vs. 3% , respectively , p=0.020 - 0.058 ) . 
 the difference when performing a similar comparison using a > 2 ng / ml tg threshold level showed no significance ( 10 - 11% vs. 4% , respectively , p>0.1 ) . 
 two of the no cnd patients and one node - positive cnd patient had recurrences in the thyroid bed or lateral neck during a mean follow - up of 24 months.conclusionthe data showed that occult metastasis to the central neck is common in ptmc patients . 
 a cnd provides pathologic information about the nodal metastases , and it potentially provides guidance for planning the postoperative rai . 
 however , the long - term benefit of cnd on recurrence and survival remains somewhat questionable . 
INTRODUCTION
MATERIALS AND METHODS
Patient population and study design
Central node dissection
Observation of the pathology and complications
Measurement of serum thyroglobulin and the follow-up
Statistical analysis
RESULTS
Complications and the pathologic findings
Serum thyroglobulin levels and recurrence
DISCUSSION
CONCLUSION