of thyroid nodules examined by the use of an us - fnab at our institution from may 2007 to april 2008 , small thyroid nodules less than 5 mm in the maximum diameter were included in the study .
high - resolution ultrasonography ( us ) was performed with either an hdi 5000 ( phillips medical systems , bothell , wa ) or iu 22 unit ( phillips medical systems ) using a 12 - 15 mhz linear probe for guidance during the us - fnab procedure .
we obtained informed written consent from all patients before performing us - fnabs and our institutional review board approved this study .
malignant sonographic findings included microcalcifications , marked hypoechogenicity , an irregular margin and a taller - than - wide shape . the inclusion criteria for an us - fnab of small thyroid nodules less than 5 mm in the maximum diameter were the following .
the criteria included a thyroid nodule with a likelihood of malignancy as depicted on diagnostic us ( n = 149 ) , a small solid thyroid nodule in the contralateral lobe in a patient with a known thyroid malignancy ( n = 41 ) or the presence of a small solid nodule in patients at a high risk for having a thyroid malignancy ( n = 11 ) .
risk factors for a thyroid malignancy included cervical lymphadenopathy with a positive cytology for a thyroid malignancy ( n = 3 ) , prior head and neck irradiation ( n = 1 ) and a newly developed nodule in the opposite or remaining thyroid lobe after surgery for a known thyroid malignancy ( n = 7 ) .
a repeat us - fnab was performed after the first biopsy whenever the cytology result was ' inadequate ' or when the cytology result did not match the sonographic impression .
a primary malignancy was defined as the largest malignant nodule in the thyroid and a satellite malignancy was defined as a smaller - sized , intraglandular metastatic lesion in the ipsilateral or contralateral lobe .
an experienced radiologist ( seven years experience for performing an us - fnab of thyroid nodules ) performed an us - fnab with the use of a 23-gauge needle attached to a 10-ml plastic syringe .
when the needle tip reached the target nodule , the needle was observed as a small echogenic spot within the nodule on the us monitor ( fig .
after the needle tip was placed in the appropriate area of the target nodule , sampling was commenced using the ' mixed sampling technique . '
this technique is an individual sampling technique where the needle is moved up and down for a few seconds only by movement of the wrist of the operator and without initial aspiration under us guidance . in all cases ,
after a sample was obtained , the specimen was mounted immediately onto a glass slide .
we obtained four to six slides by performing two or three smears from each nodule .
the cytological diagnosis was classified as ' benign , ' ' suspicious for a malignancy , ' ' malignant , ' ' indeterminate ' or ' inadequate . ' ' benign ' included a normal thyroid , nodular hyperplasia , lymphocytic thyroiditis or other benign conditions . '
suspicious for a malignancy ' included specimens showing clusters of atypical follicular cells with some nuclear grooves . ' malignant ' included specimens showing clusters of abnormal follicular cells with discrete nuclear grooves , intranuclear pseudoinclusions or a papillary projection . '
indeterminate ' referred to specimens showing follicular cell proliferative lesions that were indeterminate for a differential diagnosis of nodular hyperplasia , follicular neoplasm or a follicular variant of a ptc . in this study ,
an adequate specimen was defined as having more than six clusters of follicular thyroid cells and showing the presence of an identifiable colloid in each preparation ( 5 ) ; conversely , a specimen with less than six clusters of follicular thyroid cells in each slide was considered as ' inadequate . ' for each primary small malignancy , capsular invasion with tumor invasion into the thyroid capsule , a perithyroidal lymph node metastasis with tumor invasion into lymph nodes in the central neck , multifocality with an intraglandular metastasis in the ipsilateral lobe and bilaterality with an intraglandular metastatic lesion in the contralateral lobe were examined .
of 201 small nodules in 180 patients , 118 small nodules in 110 patients were not removed surgically and these nodules were excluded from the determination of diagnostic indices . of 83 nodules in 75 patients , lesions with ' benign ' cytology were regarded as having a negative cytology classification for a malignancy and lesions with ' suspicious for a malignancy ' or ' malignant ' cytology were regarded as having as a positive cytology classification for a malignancy .
lesions with an ' indeterminate ' ( n = 7 ) and ' inadequate ' ( n = 14 ) cytology as determined after the first us - fnab were excluded in the determination of the sensitivity , specificity , predictive value , accuracy , false positive rate and false negative rate . ultimately , of 62 nodules in 58 patients , the sensitivity , specificity , positive predictive value , negative predictive value , accuracy , false positive rate and false negative rate for the first us - fnab were examined .
of thyroid nodules examined by the use of an us - fnab at our institution from may 2007 to april 2008 , small thyroid nodules less than 5 mm in the maximum diameter were included in the study .
high - resolution ultrasonography ( us ) was performed with either an hdi 5000 ( phillips medical systems , bothell , wa ) or iu 22 unit ( phillips medical systems ) using a 12 - 15 mhz linear probe for guidance during the us - fnab procedure .
we obtained informed written consent from all patients before performing us - fnabs and our institutional review board approved this study .
malignant sonographic findings included microcalcifications , marked hypoechogenicity , an irregular margin and a taller - than - wide shape . the inclusion criteria for an us - fnab of small thyroid nodules less than 5 mm in the maximum diameter were the following .
the criteria included a thyroid nodule with a likelihood of malignancy as depicted on diagnostic us ( n = 149 ) , a small solid thyroid nodule in the contralateral lobe in a patient with a known thyroid malignancy ( n = 41 ) or the presence of a small solid nodule in patients at a high risk for having a thyroid malignancy ( n = 11 ) .
risk factors for a thyroid malignancy included cervical lymphadenopathy with a positive cytology for a thyroid malignancy ( n = 3 ) , prior head and neck irradiation ( n = 1 ) and a newly developed nodule in the opposite or remaining thyroid lobe after surgery for a known thyroid malignancy ( n = 7 ) .
a repeat us - fnab was performed after the first biopsy whenever the cytology result was ' inadequate ' or when the cytology result did not match the sonographic impression .
a primary malignancy was defined as the largest malignant nodule in the thyroid and a satellite malignancy was defined as a smaller - sized , intraglandular metastatic lesion in the ipsilateral or contralateral lobe .
an experienced radiologist ( seven years experience for performing an us - fnab of thyroid nodules ) performed an us - fnab with the use of a 23-gauge needle attached to a 10-ml plastic syringe .
procedures were performed under us guidance using a perpendicular puncture and without local anesthesia . when the needle tip reached the target nodule ,
the needle was observed as a small echogenic spot within the nodule on the us monitor ( fig .
after the needle tip was placed in the appropriate area of the target nodule , sampling was commenced using the ' mixed sampling technique . '
this technique is an individual sampling technique where the needle is moved up and down for a few seconds only by movement of the wrist of the operator and without initial aspiration under us guidance . in all cases ,
after a sample was obtained , the specimen was mounted immediately onto a glass slide .
we obtained four to six slides by performing two or three smears from each nodule .
the cytological diagnosis was classified as ' benign , ' ' suspicious for a malignancy , ' ' malignant , ' ' indeterminate ' or ' inadequate . ' ' benign ' included a normal thyroid , nodular hyperplasia , lymphocytic thyroiditis or other benign conditions . '
suspicious for a malignancy ' included specimens showing clusters of atypical follicular cells with some nuclear grooves . '
malignant ' included specimens showing clusters of abnormal follicular cells with discrete nuclear grooves , intranuclear pseudoinclusions or a papillary projection . '
indeterminate ' referred to specimens showing follicular cell proliferative lesions that were indeterminate for a differential diagnosis of nodular hyperplasia , follicular neoplasm or a follicular variant of a ptc . in this study ,
an adequate specimen was defined as having more than six clusters of follicular thyroid cells and showing the presence of an identifiable colloid in each preparation ( 5 ) ; conversely , a specimen with less than six clusters of follicular thyroid cells in each slide was considered as ' inadequate . ' for each primary small malignancy , capsular invasion with tumor invasion into the thyroid capsule , a perithyroidal lymph node metastasis with tumor invasion into lymph nodes in the central neck , multifocality with an intraglandular metastasis in the ipsilateral lobe and bilaterality with an intraglandular metastatic lesion in the contralateral lobe were examined .
of 201 small nodules in 180 patients , 118 small nodules in 110 patients were not removed surgically and these nodules were excluded from the determination of diagnostic indices . of 83 nodules in 75 patients , lesions with ' benign ' cytology were regarded as having a negative cytology classification for a malignancy and lesions with ' suspicious for a malignancy ' or ' malignant ' cytology were regarded as having as a positive cytology classification for a malignancy .
lesions with an ' indeterminate ' ( n = 7 ) and ' inadequate ' ( n = 14 ) cytology as determined after the first us - fnab were excluded in the determination of the sensitivity , specificity , predictive value , accuracy , false positive rate and false negative rate . ultimately , of 62 nodules in 58 patients , the sensitivity , specificity , positive predictive value , negative predictive value , accuracy , false positive rate and false negative rate for the first us - fnab were examined .
of 201 small thyroid nodules ( maximum diameter range , 1.0 to 5.0 mm ; mean diameter , 3.4 mm ) in 180 patients ( female : male = 152:28 ; mean age , 48.0 years ; age range , 18 to 75 years ) , the incidence of adequate specimens was 162 ( 81% ) after the first us - fnab . of 201 biopsies ,
the cytology was classified as ' benign ' for 107 lesions ( 53% ) , ' suspicious for a malignancy ' for 22 lesions ( 11% ) , ' malignant ' for 16 lesions ( 8% ) , ' indeterminate ' for 17 lesions ( 9% ) and ' inadequate ' for 39 lesions ( 19% ) ( table 1 ) .
of the 75 patients , 41 patients underwent a total thyroidectomy , 21 patients underwent a lobectomy , 12 patients underwent a subtotal thyroidectomy and one patient underwent an isthmectomy .
fifty small malignant thyroid nodules in 49 patients ( female : male = 44:5 ; mean age , 44.2 years ; mean maximum diameter , 3.3 mm ; maximum diameter range , 1.0 to 5.0 mm ) were identified as ptmcs based on a pathological examination and were classified as 23 ( 46% ) primary and 27 ( 54% ) satellite ( smaller - sized ptcs that are distinguished from the largest ptc ) malignancy .
thirty - three small thyroid nodules with ' benign ' cytology in 33 patients showed 28 nodular hyperplasias and five ptmcs on the pathology after thyroid surgery . of the 23 pathologically confirmed primary malignancies , after the first us - fnab two lesions ( 9% ) were classified as ' benign , ' eight lesions ( 35% ) were classified as ' suspicious for a malignancy , ' 10 lesions ( 44% ) were classified as ' malignant , ' two lesions ( 9% ) were classified as ' indeterminate ' and one lesion ( 4% ) was classified as ' inadequate ' based on the cytology .
of five ( two benign , tow indeterminate , and one inadequate ) pathologically confirmed primary malignant nodules with negative cytology results after the first biopsy , four lesions were classified as ' suspicious for a malignancy ' after a second biopsy and one lesion was classified as ' benign ' after a second biopsy .
although one pathologically confirmed malignant nodule demonstrated negative cytology results even after two consecutive us - fnabs , the patient underwent thyroid surgery because of the high likelihood of a malignancy as found on diagnostic us .
of the 27 pathologically confirmed satellite malignancies after the first us - fnab , three lesions ( 11% ) were classified as ' benign , ' 10 lesions ( 37% ) were classified as ' suspicious for a malignancy , ' six lesions ( 22% ) were classified as ' malignant , ' two lesions ( 7% ) were classified as ' indeterminate ' and six lesions ( 22% ) were classified as ' inadequate ' based on the cytology .
eleven satellite malignant nodules that showed a negative cytology after the first biopsy were surgically removed without an additional biopsy as they showed a combined primary thyroid malignancy on simultaneous us - fnabs . for the first us - fnab of 62 nodules
, there were 34 ( 55% ) true positives , 0 ( 0% ) false positives , 23 ( 37% ) true negatives and five ( 8% ) false negatives . the sensitivity ( 87% ) ,
specificity ( 100% ) , positive predictive value ( 100% ) , negative predictive value ( 82% ) , accuracy ( 92% ) , false positive rate ( 0% ) and false negative rate ( 8% ) after an us - fnab for nodules smaller than 5 mm in the maximum diameter were determined ( table 2 ) .
twenty - three patients with a primary ptmc smaller than 5 mm in the maximum diameter underwent thyroid surgery .
capsular extension ( 9% , 2 of 23 ) , a perithyroidal lymph node metastasis ( 30% , 7 of 23 ) , multifocality ( 9% , 2 of 23 ) and bilaterality ( 4% , 1 of 23 ) were identified .
thyroid surgery for these patients included a total thyroidectomy ( n = 7 ) , a subtotal thyroidectomy ( n = 4 ) and a lobectomy ( n = 12 ) .
twenty - one patients ( 12% , 21 of 180 ) experienced mild pain that persisted for several minutes during or after the biopsy , but the pain subsided spontaneously without medication .
us - fnab is the least invasive , most simple and most accurate method to evaluate a thyroid nodular lesion .
however , the size criterion is still controversial for thyroid nodules evaluated on an us - fnab .
the american thyroid association ( ata ) guidelines suggest that , in general , only nodules larger than 10 mm in diameter should be evaluated as the nodules have the potential to represent a clinically significant cancer ( 6 ) . occasionally , there may also be nodules less than 10 mm in the maximum diameter that require evaluation due to suspicious us findings and/or a patient history of thyroid cancer ( 7 ) .
the society of radiologists in ultrasound consensus statement suggests performing us - fnab on thyroid nodules 10 mm or greater in the maximum diameter when the nodules exhibit microcalcifications or other us features associated with thyroid cancer , as an early diagnosis of thyroid cancer does not guarantee a decrease in recurrence or the mortality rate ( 8) .
burman ( 9 ) also mentioned that irrespective of which suggested minimum measurement or guideline is used , the most critical requirement is to monitor these patients with periodic clinical and us examinations .
however , many authorities suggest that it is important to diagnose thyroid cancer at an early stage to reduce the risk of recurrence or mortality ( 10 , 11 ) .
there are a few reports that have evaluated the use of an us - fnab of thyroid nodules less than 5 mm in the maximum diameter .
( 4 ) found a 64% adequate sampling rate for 25 small thyroid nodules less than 5 mm in diameter , but the study did not indicate whether the maximum or minimum diameter of the nodules had been measured .
( 12 ) retrospectively analyzed 243 patients with pathologically confirmed ptmcs , but the investigators did not comment on the adequacy or efficacy of us - fnabs for the thyroid nodules . in this study , the sensitivity and negative predictive value of performing an us - fnab for the diagnosis of small thyroid nodules equal to or less than 5 mm in the maximum diameter were relatively low as compared with values obtained for other diagnostic indices ; however , the specificity and positive predictive value were high . to the best of our knowledge ,
these are the highest rates among previously published reports , although the sensitivity and negative predictive value of an us - fnab for small - diameter thyroid nodules were 87% and 82% , respectively .
however , five ' benign ' nodules identified after the first us - fnab were later confirmed as ptmcs after thyroid surgery and were determined as false negative cytologies ( 8% ) , but false positive cytology was not detected .
this false negative rate for an us - fnab of small thyroid nodules less than 5 mm in the maximum diameter is relatively high ; however , this rate may be subject to change if non - operated nodules are surgically confirmed .
the size of the five ptmcs with false negative cytology as determined after the first us - fnab was less than 3 mm in the maximum diameter as determined on diagnostic us .
therefore , we assumed that the relatively high false negative rate was due to sampling of primarily normal tissue rather than the ptmc during the ' to - and - fro ' cell acquisition . in the present study , the incidence of capsular invasion of a ptmc smaller than 5 mm in the maximum diameter was 9% ( 2 of 23 ) , which was relatively low as compared to the studies of roti et al .
( 12 ) reported that two patients ( 2% , 2 of 86 ) with thyroid cancers less than 5 mm had regional lymph node metastases , but in the present study , 23 primary ptmcs equal to or less than 5 mm in the maximum diameter showed a perithyroidal lymph node metastasis ( 30% , 7 of 23 ) .
we presume that the high rate of a perithyroidal lymph node metastasis in the present study might be associated with the relatively high incidence of the subcapsular location of ptmcs . regarding the multifocality of a ptmc , roti et al .
( 13 ) reported that 32% ( 78 of 243 ) and 31% ( 63 of 203 ) of patients were indentified with multifocal lesions , respectively , but the investigators in both studies did not describe ptmcs less than 5 mm in the maximum diameter .
( 12 ) found that the incidence rate of bilaterality of a ptmc was 19% ( 45 of 243 ) , but the investigators did not separately mention the bilaterality rate of a ptmc less than 5 mm in the maximum diameter . in the present study , multifocality ( 9% , 2 of 23 ) and bilaterality ( 4% , 1 of 23 ) were identified .
to the best of our knowledge , no large - scale study has examined the incidence of regional lymph node metastases , multifocality and bilaterality of a ptmc less than 5 mm in the maximum diameter . in our study , significant complications related to performing an us - fnab were not detected in any of the patients .
several factors have been associated with a low incidence of complications with the use of the us - fnab procedure , including one sampling with one puncture , shortening of the procedure time , accurate targeting and watching the needle tip during the biopsy . in particular ,
continuous watching of the needle tip on the us monitor during the entire procedure is important in order to prevent arterial injury to the carotid or vertebral artery .
second , thyroid surgery for the thyroid malignancies included total , subtotal and a lobectomy and regional lymph node resection was not performed for all of the ptcs .
third , we did not consider if the presence of underlying diffuse thyroid disease influenced the outcome of the us - fnabs .
( 14 ) have suggested that in cases of underlying diffuse thyroid disease , such as thyroiditis or diffuse goiter , the outcome of an us - fnab for small thyroid nodules might have resulted in an negative influence .
finally , our technique of performing an us - fnab of thyroid nodules is not a standard technique .
the importance of early diagnosis of thyroid cancer in patients at low risk remains uncertain as thyroid cancers are typically slow growing and are associated with a low morbidity and mortality ( 6 , 8 , 15 ) .
however , we believe that early diagnosis of thyroid malignancies less than 5 mm in the maximum diameter by the use of diagnostic us and an us - fnab is helpful to improve patient morbidity rates for poorly differentiated thyroid malignancies . in addition , in our study , the diagnosis of 27 satellite small ptmcs after an us - fnab influenced the decision regarding the type of thyroid surgery ( e.g. , a lobectomy or total thyroidectomy ) . in conclusion ,
an us - fnab of thyroid nodules smaller than 5 mm in the maximum diameter is an effective diagnostic method if performed by an experienced radiologist . in the present study ,
primary ptmcs smaller than 5 mm in the maximum diameter had a low incidence of capsular invasion , multifocality and bilaterality , but a relatively high incidence of perithyroidal lymph node metastases .
 objectivethe aim of this study was to determine the efficacy of the use of an ultrasound - guided fine - needle aspiration biopsy ( us - fnab ) to diagnose thyroid nodules smaller than 5 mm in the maximum diameter and to evaluate pathological findings of small thyroid malignancies.materials and methodsfrom may 2007 to april 2008 , we evaluated the findings of us - fnabs of small thyroid nodules less than 5 mm in the maximum diameter . 
 the cytopathological findings were retrospectively reviewed and the diagnostic performance of the use of an us - fnab was examined in all patients.resultsof 201 small thyroid nodules in 180 patients , there were 162 adequate specimens ( 81% ) . among 180 patients , 
 75 patients underwent thyroid surgery and 50 malignant and 33 benign nodules were identified based on a pathological examination . 
 all small malignant thyroid nodules were identified as papillary thyroid microcarcinomas ( ptmcs ) . 
 there were 34 ( 55% ) true positive , 0 ( 0% ) false positive , 23 ( 37% ) true negative and five ( 8% ) false negative results for malignancy after performing a first us - fnab in 62 surgically confirmed nodules . the sensitivity ( 87% ) , 
 specificity ( 100% ) , positive predictive value ( 100% ) , negative predictive value ( 82% ) , accuracy ( 92% ) , false positive rate ( 0% ) and false negative rate ( 8% ) for an us - fnab were determined . in 23 patients with a primary ptmc , capsular invasion ( 9% , 2 of 23 ) , a perithyroidal lymph node metastasis ( 30% , 7 of 23 ) , the rate of multifocality ( 9% , 2 of 23 ) and bilaterality ( 4% , 1 of 23 ) were also determined.conclusionan us 
 - fnab of thyroid nodules smaller than 5 mm in the maximum diameter is an effective diagnostic procedure . 
MATERIALS AND METHODS
Patient Selection
Fine Needle Aspiration Biopsy Technique
Cytopathological Examinations
Diagnostic Performance
RESULTS
DISCUSSION