Thyroglobulin measurement on fine‐needle washout fluids: Influence of sample collection methods

Abstract

Thyroglobulin (Tg) measurement on fine-needle aspiration (FNA) specimens (Tg-FNA) is useful in the management of patients affected by differentiated thyroid carcinoma. However, the preanalytical procedure for FNA-Tg measurement is not standardized. We evaluated the accuracy of FNA-Tg measurement by using different tubes for needle washout fluids collection.Ultrasound-guided FNA was performed on a combined 156 lesions from 108 patients. Following cytology sampling, the needles were rinsed by normal saline and aliquots collected into three different tubes (plain serum tube, serum separator tube, and lithium-heparin tube, respectively). The Tg-FNA was measured by an immunoradiometric assay.The cytological examination was nondiagnostic in six cases, false-positive in one, and false-negative in two cases. The Tg-FNA was higher in plain serum tubes as compared with serum separator and lithium-heparin ones. FNA-Tg measurement on plain serum and serum separator tubes showed a 100% sensitivity while two false-negative results occurred by lithium-heparin tubes (sensitivity 98%).The diagnostic performance of FNA-Tg compared favorably with cytology. However, biases in FNA-Tg measurement may be introduced by different collection tubes. A collection of standardized washout fluids volume into plain serum tubes is highly recommended. Serum separator tubes and lithium-heparin tubes may lower measured FNA-Tg concentration. Diagn. Cytopathol. 2009;37:42-44. ' 2008 Wiley-Liss, Inc.Key Words: thyroglobulin; fine-needle aspiration; cytology; thyroid carcinoma; lymph nodesThe thyroglobulin (Tg) is a large glycoprotein stored in the follicular colloid of the thyroid gland acting as a prohormone in the intra-thyroid synthesis of thyroid hormones. It is produced only by normal thyrocytes or well differentiated thyroid cancer cells, and its tissue-specific origin predicates the clinical value of Tg testing. Serum Tg detection after thyroid ablation indicates the presence of residual healthy thyroid tissue or metastatic disease. Thus, important clinical decisions such as whether patients should undergo diagnostic or therapeutic procedures are based on the measurement of the serum Tg concentration in individual patients. 1 Typically measured with immunometric assays, Tg concentration can be falsely lowered due to interference from anti-Tg antibodies (Tg-Ab) or hook-effect while results can be spuriously high due to interference from heterophile antibodies. 2 Additionally, several preanalytical effects (e.g. freezing or repeated freezing and thawing of sera, hemolysis or lipemia, preanalytical use of different serum separating tubes) could affect the Tg measurement in serum. 3 Recently, the Tg measurement on fine-needle aspiration (FNA) washout fluids (FNA-Tg) showed to be useful in the management of patients affected by differentiated thyroid carcinoma (DTC). 4,5 Cunha et al. 6 evaluated 83 enlarged cervical lymph-nodes from 67 patients affected by DTC: the FNATg showed a sensitivity of 100% while cytology alone missed 9 of 20 DTC metast...

Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids

“…In the first studies, the threshold values were reported from 0.9 to 50 μg/L [5,27]. Also, the metastatic cases diagnosed in presence of thyroid gland and those detected in athyreotic patients were analyzed; substantial overlap of results was found, and FNA-Tg levels up to 88.8 μg/L were recorded in benign lymph nodes from DTC patients still awaiting thyroidectomy [16,20,21,[27][28][29][30]. Accordingly, different FNA-Tg cutoff was proposed in the presence (36 μg/L) or absence (1.7 μg/L) of thyroid [31].…”

“…The latter is the most used option because easily accessible and inexpensive (Tables 4-7) [17,19,75]. As regards FNA-Tg, the important but still poorly assessed issues of dilution volumes and washing solutions were evaluated at Oncology Institute of Southern Switzerland [20]. In that study, the needles were washed by 1 mL of normal saline solution, and wash aliquots were randomly collected into three different tubes: plain tube, serum separator tube, and lithium-heparin tube.…”

“…Even if FNA-Tg of the three groups were strongly correlated, the values were significantly higher in plain tubes as compared to the other two; furthermore, plain tubes and serum separator tubes provided 100% sensitivity, whereas false-negatives occurred in lithium-heparin tubes (98% sensitivity). Thus, the pre-analytical phase might introduce significant variability in FNA-Tg, which should be reduced by using a fixed dilution fluids volume and a plain tube (Table 7) [20].…”

Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges

“…However, some of these studies are based on TgAb measurements in the patient's serum or by inappropriate analytical methods for TgAb, such as agglutination methods. The analytically relevant question is whether there are TgAb in the sample being analyzed and whether these interfere in the immunoassay [30]. Measurement of TgAb themselves in washout fluid may equally be problematic, but attempts should be made to determine/validate the assays before use [26].…”

Measurement of human epidermal growth factor receptor type-2 extracellular domain and cancer antigen 15–3 levels in needle washout fluid: a potential adjunct to the cytological diagnosis of breast cancer

“…However, previous reports have indicated that the measurement of biomarkers in the needle washout fluid may provide information regarding the extracellular substances. For example, thyroglobulin detection in fine needle aspiration cytology (FNAC) washout fluid from cervical lymph nodes in which metastatic papillary carcinoma is suspected strengthens the cytological interpretation [1][2][3][4][5][6][7][8][9][10][11][12][13]. Another example is assaying for calcitonin in FNAC washout fluid from a mass suggestive of medullary carcinoma of the thyroid [14][15][16].…”