Measurement of calcitonin and cea in the needle washout fluid from thyroid nodule for the diagnosis of medullary thyroid carcinoma

Background. medullary thyroid carcinoma (mtc) produces serum markers including calcitonin (ct) and carcinoembryonic antigen (cea). The measurement of ct in fine-needle aspirate washout fluid (FNA-CT) improves the cytological diagnosis of mtc. However, no data are available about cut-off values for FNA-CT using currently immunoassay. The measurement of cea in the needle washout fluid (FNa-cea) in mtc has not been studied.

Objective: to assess the diagnostic value and propose cut-off values for FNA-CT and FNacea in the thyroid nodule to diagnose mtc.

Material and Methods. We conducted a retrospective analysis of 164 samples of fine-needle aspirate washout fluid collected from 92 patients with thyroid nodules, who underwent FNa followed by cytological examination and measurement of FNA-CT. seventeen cases with mtc and 41 with non-mtc nodules were histologically verified. one hundred and six nodules identified as non-mtc by cytology were not operated on. FNa-cea was additionally studied in 29 samples. The cut-off value was determined by Roc analysis.

Results. The FNA-CT level was >2000 pg/ml in all mtc nodules, except for one, in which the FNA-CT level was 638 pg/ml. In non-mtc nodules, the FNA-CT levels were <10 pg/ml and <100 pg/ml in 81 % and 90 %, respectively, however, it was >500 pg/ml in 5 %, and >1000 pg/ml in 2 %. At a cut-off value of 590 pg/ml, the sensitivity and specificity of FNA-CT were 100 % and 96 %, and at a cut-off of 1721 pg/ml, the corresponding values were 94 % and 99 %. The false positive FNA-CT values were 3.7 % and 1.2 % at the cut-off values of 590 pg/ml and 1721 pg/ml, respectively. The median levels of FNa-cea in mtc and non-mtc nodules were 59.3 ng/ml and 1.5 ng/ml, respectively. At a cut-off value of 7.5 ng/ml, the sensitivity of FNa-cea was 86 % and specificity was 100 %. Additional measurement of FNa-cea prevented all false-positive results of FNA-CT, but did not detect 2 mtcs with low FNa-cea levels (false-negative rate of 6.9 %). Among samples with FNA-CT value of >590 pg/ml and negative cytology (n=9), FNa-cea differentiated mtc with 100 % sensitivity and specificity.

Conclusion. The maximum sensitivity of FNA-CT in the thyroid nodule was at a cut-off value of 590 pg/ml (100 %), the maximum specificity was at a cut-off value of 1721 pg/ml (99 %). Risk of false positive result is the major challenge of FNA-CT. to reduce false-positive results, we recommend to measure FNa-cea in the nodules with negative cytology and high level of FNA-CT. At a cut-off value of 7.5 ng/ml, FNa-cea allows the false-positive FNA-CT to be excluded. 

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