Taking Tg measurements from FNAB washout fluid was proposed by Pacini, et al.16
for the early detection of cervical lymph node metastases in DPTC, and they reported that its use in combination with FNAC had better diagnostic performance than FNAC alone.5-14,16,17
Many studies have reported an increased sensitivity of FNAB-Tg.5-14,16,17
FNAB-Tg could contribute especially to the diagnosis of poor cellular material obtained from cystic metastasis.12
However, various threshold values have been suggested,2,3,6-14,16,17
partly because the indeterminate Tg ranged cases (0.2-100 ng/mL) showed a prevalence too low to provide statistically significant results. Tg also can be detected in FNAB washout fluid from even nonmetastatic lymph nodes in the presence of a thyroid gland and Tg can have a wide range in nonmetastatic and metastatic lymph nodes. Moreover, various techniques of FNAB-Tg assay were used with different analytical and functional sensitivities.3,8-11,14,17
Although one study3
included the largest numbers of patients among the published literature, there were only 22 cases (13.1% of 168 cases) with indeterminate Tg values, which may be covered between nonmetastatic and metastatic lymph nodes to verify the statistical significance of diagnostic potential. In the published studies, it is difficult to estimate the exact number of cases with an indeterminate range of Tg values in each study. However, the current study included more than four times the number of cases with an indeterminate Tg range than the prior study3
with the largest population among all those published on this subject.3,8
In most prior studies of the wide range of FNAB-Tg, the mean+2 standard deviation,3,10,12,14,16
the mean+standard deviation,11
and more than serum Tg2,3,7,8
have been reported as threshold values that differentiate nonmetastatic from metastatic lymph nodes. Only one study reported 1 ng/mL as a threshold value,6
and another designated it as 0.9 ng/mL.13
However, these studies covered a wide range of FNAB-Tg including over 100 ng/mL.3,6-8,10-14,17
The cutoff values suggested were determined by the extreme end of the wide spectrum of FNAB-Tg values rather than the indeterminate values.
In Kim, et al's.3
report, the Tg threshold value was suggested as 10 ng/mL to differentiate nonmetastatic and metastatic lymph nodes. With a large series of indeterminate ranges, 5 ng/mL showed the highest AUC (0.76; 95% CI, 0.6731-0.8476) and there was no significant difference from 10 ng/mL; however, three levels including 0.7, 1.0, and 50.0 ng/mL were not recommended due to low AUC and sensitivity. In the present study, the overall AUC of FNAB-Tg was 0.799. This result was not so high compared to the AUC (0.955-0.999) of the previous studies.3,6
This is because the Tg measurements of the present study only included an overlapped range between nonmetastatic and metastatic lymph nodes. However, a Tg value with less than 0.2 ng/mL and more than 100 ng/mL can be straightforwardly classified as nonmetastatic and metastatic lymph nodes, respectively. Therefore, if the aforementioned ranges (<0.2 ng/mL and >100 ng/mL) were included, the AUC would be much higher than in the previous studies.3,6
There were limitations to this study: first, there was no evaluation of diagnostic accuracy when the prespecified threshold values were combined with FNAC or directly compared with FNAC. We did not include the combination with FNAC because it can affect the diagnostic accuracy of FNAB-Tg. According to published reports,2,3,5-8,10-14,16
when FNAC was combined with FNAB-Tg, its sensitivity was increased to 96-100%. However, we would like to focus on assessing the complementary role and appropriate cutoff value for FNAB-Tg itself. Second, we did not compare the metastatic lymph nodes with higher FNAB-Tg and those with intermediate or lower FNAB-Tg. Further study of the details of the histology or prognosis of the metastatic lymph nodes at this level of FNAB-Tg value will be necessary to overcome this limitation. Third, even though we used 1 mL rinsed washout with normal saline, there may be a difference in the delicate diluted concentration of the washout. A more accurate quantitative analytic method should be developed to compensate for this limitation. Fourth, even though a recent study17
using measurements of FNAB albumin reported interference by the serum Tg can be negligible to FNAB-Tg results. However, this report17
showed much higher levels of FNAB-Tg measurements than did the present study. The negligibility of interference by the serum Tg in the low or intermediate FNAB-Tg measurements in this study must be solved by further investigation. Lastly, our study was retrospective, and we recruited cases with histologic confirmation, so we could not evaluate changes in surgical strategy based on FNAB-Tg results and also did not correlate or compare FNAB-Tg with corresponding serum Tg levels. Further study will be necessary to clarify these limitations.
In conclusion, we ascertained that 5 ng/mL had the most excellent diagnostic performance among FNAB-Tg levels in the present setting with a large series with an indeterminate range (0.2-100 ng/mL) of FNAB-Tg values. However, these results also need additional confirmation under different laboratory conditions, because there were no significant differences between the results for 5 and 10 ng/mL. Neck node dissection should be considered when FNAB-Tg is higher than this threshold value, regardless of FNAC results, to improve sensitivity and maintain specificity of FNAC. Additionally, US features predicting lymph node metastasis also deserve consideration in the appropriate interpretation of lymph node metastasis.