Thyroglobulin Measurement In Fine-needle Aspirates Research Articles

Thyroglobulin measurement in fine-needle aspirates of lymph nodes in patients with differentiated thyroid cancer

Background: The high incidence of cervical lymph nodes metastasis in highly differentiated thyroid carcinoma (DTC) and insufficient of existing diagnostic methods determines the urgency of finding reliable and more effective tests.
 Aims: The aim of our study is to determine the prognostic significance of the thyroglobulin measurement in washout fluid from fine-needle aspiration biopsy (FNA-Tg) and the cut-off value in the diagnosis of DTC lymph nodes metastasis.
 Materials and methods: 245 patients evaluated for suspicious cervical lymph nodes were retrospectively reviewed. All patients underwent FNA-Tg, serum thyroglobulin (sTg) levels, thyroglobulin antibodies (Tg-Ab), thyroid-stimulating hormone (TSH) were measured. 125 patients with malignant changes according to FNA and/or high FNA-Tgvalues underwent surgical treatment. Patients were divided into 2 groups with reactive (n = 23) and metastatic (n = 102) changes. FNA-TG was assayed on automated system Cobas 601 (Roche, France).
 Results: All patients were comparable by sex, age and levels of TSH, sTG, Tg-Ab. The FNA-Tg median in metastatic group was 537.0 [0.1; 1000], and in benign group – 17.9 [0.5; 158.0], p = 0.003. The sensitivity of isolated FNA was 85%, specificity 57%, AUC = 0.618, 95% CI 0.516–0.713. The sensitivity and specificity of FNA-Tg was 73% and 100%, respectively, AUC = 0.865, 95% CI 0.78–0.92. The optimal cut-off point for malignancy was >9.2 ng/ml (sensitivity 75%, specificity 100%), Youden Index 0.73.
 Conclusions: Additional FNA-Tg may increase the sensitivity of isolated FNA in evaluation of DTC lymph node metastasis. The optimized cut-off value >9.2 ng/ml can be proposed as a diagnostic threshold for the definition of malignancy.

Fine-needle aspiration for the diagnosis of lymph node metastasis in papillary thyroid carcinoma

Objective: To investigate the diagnostic performance of fine-needle aspiration (FNA) cytology for the detection of lateral lymph node metastases in patients with papillary thyroid carcinoma (PTC). Methods: A total of 109 lateral lymph nodes with suspicious metastases from 85 patients were retrospectively subjected to FNAC, fine-needle aspiration thyroglobulin measurement (FNATg), and FNATg/SerumTg measurement. Lymph node pathological results after surgery were taken as the gold standard. Using Mann-Whitney U test, Pearson linear model and ROC curve were used for data analysis. Results: The sensitivity, specificity and accuracy of FNATg for the diagnosis of lateral neck lymph node metastasis were respectively 93.7%, 90.0% and 93.3% and those of FNATg/SerumTg were respectively 89.9%, 90.0% and 93.2% respectively, the threshold values for FNATg and FNATg/SerumTg were 0.925 ng/ml and 1.007, respectively. The sensitivity, specificity and accuracy of FNATg combined with FNAC were respectively 91.0%,93.5% and 94.4%. The existence of thyroid tissue and the expression of serum Tg did not affect the expression of lymph node FNATg. The FNATg cutoff value of 0.925 ng/ml showed the best diagnostic performance in patients with a thyroid gland, while the FNATg/SerumTg cutoff ratio of 14.95 showed the best diagnostic performance in patients without a thyroid gland. The serum TgAb significantly interfered with the expression of FNATg in the lateral neck metastatic lymph nodes (P=0.049). Conclusions: FNATg alone or the combination of FNATg with FNAC are highly reliable in the diagnosis of lateral neck lymph node metastases in patients with PTC. The expression of TgAb may interfere with the accuracy of the diagnostic performance of FNATg.

Thyroglobulin Measurement in Fine-Needle Aspiration Improves the Diagnosis of Cervical Lymph Node Metastases in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is frequently associated with cervical lymph node metastases. Guidelines recommend performing ultrasound-guided fine-needle aspiration cytology (FNAC) for suspicious nodes to guide management. No specific recommendations are available for the use of FNA thyroglobulin assay (FNA-Tg). This study investigated the diagnostic value of performing FNAC and FNA-Tg. Patient demographics, preoperative investigations, surgery, and lymph node pathology were collected for patients with PTC who underwent lateral neck lymphadenectomy and central compartment reexploration from January 2000 to July 2015. Sensitivities and accuracies were obtained. Patients with both diagnostic studies performed were compared using McNemar's test of paired proportion. Patient, imaging, and lymph node characteristics were correlated with test accuracy. The 480 patients in this study underwent 706 lateral neck dissections or central compartment reexploration. All the patients underwent preoperative neck ultrasound. Among these patients, FNAC alone was performed before 426 operations (60%), FNAC with FNA-Tg before 105 operations (15%), and surgery without biopsy for 175 patients (25%). The sensitivity, positive predictive value, and accuracy were respectively 96, 95, 100% for FNAC, 99, 97, and 97% for FNA-Tg, and 95, 92, and 97% for FNAC in combination with FNA-Tg. In the subgroup of patients who had both tests performed, the sensitivity of FNA-Tg was superior to that of FNAC (95 vs 87%; p=0.04). The addition of FNA-Tg to FNAC increased the detection of metastatic PTC by 13%. For diagnosing cervical lymph node metastases in PTC, FNA-Tg is a valuable adjunct to FNAC. Its use should be considered to avoid missing metastatic disease in patients who may benefit from lymphadenectomy.

The value of thyroglobulin measurement in fine-needle aspiration for diagnosis of suspicious lymph nodes in patients with thyroid carcinoma after thyroidectomy

To investigate the value of thyroglobulin measurement in ultrasound guided fine-needle aspiration(FNA-Tg)for detecting neck node metastasis in patients with papillary thyroid carcinoma(PTC)after thyroidectomy. A total of 128 suspicious metastatic lymph nodes in 112 patients were retrospectively analyzed. Postoperative pathologic results were taken as the gold standard. The values of FNA and FNA-Tg combined FNA in the diagnosis of metastatic lymph nodes were compared with different ultrasonic features. The sensitivity, specificity and accuracy of single FNA for the diagnosis of neck node metastasis were 67.5%, 98.0% and 79.7% respectively, and those of FNA-Tg combined FNA were 87.0%, 100.0% and 92.2% respectively. Compared with single FNA, the sensitivity and accuracy of FNA-Tg combined FNA were increased significantly(χ(2)=8.319, P=0.004; χ(2)=8.275, P=0.004). When the ultrasonographic characteristics met any one of five indicators for neck node metastasis, the sensitivity, specificity and accuracy of single FNA for the diagnosis of neck node metastasis were 38.1%, 95.7% and 68.2% respectively, and those of FNA-Tg combined FNA were 71.0%, 100.0% and 86.4% respectively. Compared with single FNA, the sensitivity and accuracy of FNA-Tg combined FNA were increased significantly(χ(2)=4.709, P=0.030; χ(2)=4.141, P=0.042). When the ultrasonographic characteristics met any two of five indicators for neck node metastasis, the sensitivity, specificity and accuracy of single FNA for the diagnosis of neck node metastasis were 55.0%, 100.0% and 73.5% respectively, and those of FNA-Tg combined FNA were 90.0%, 100.0% and 94.1% respectively. Compared with single FNA, the sensitivity and accuracy of FNA-Tg combined FNA were increased significantly(χ(2)=6.140, P=0.013; χ(2)=5.314, P=0.021). The ultrasonographic characteristics met any three, four or five of five indicators or did not meet any of the indicators, there was no significant difference in the value of the diagnosis of metastatic lymph nodes between single FNA and FNA-Tg combined FNA(P>0.05). The combination of FNA with FNA-Tg could be helpful in diagnosis of lymph node metastasis. When the suspicious lymph nodes had one or two ultrasound characteristics for neck node metastasis, FNA-Tg could raise the sensitivity and accuracy of FNA, and FNA-Tg could not significantly improve in the diagnosis of FNA when presenting with no or with more than 2 ultrasonographic features.

Diagnostic values of thyroglobulin measurement in fine-needle aspiration of lymph nodes in patients with thyroid cancer.

We aimed to evaluate the diagnostic performance of measuring the concentration of thyroglobulin (Tg) in the washout fluid of the needle aspiration (FNA-Tg). We performed a systematic search of MEDLINE (inception to October 2013) and EMBASE (inception to October 2013) for English publications using keywords "thyroid", "aspiration", "washout", and "thyroglobulin". All searches were limited to human studies. We included studies of FNA-Tg measurement in the washout fluid rinsed with 1 ml of normal saline. Eight studies including 843 lymph nodes (LNs) were eligible for this study. The pooled sensitivity and specificity of preoperative studies are 0.89 [95 % CI 0.82-0.95], 0.60 [0.49-0.70], and those of postoperative studies are 1.0 [0.83-1.0], 1.0 [0.92-1.0]. To determine best cutoffs from each preoperative and postoperative study, the distance between the point (0, 1) and each observed cutoff values (1-specificity, sensitivity) was calculated, and the distance is minimal when the cutoff value of 32.04 for preoperative studies and of 0.9 for postoperative one are selected. FNA-Tg can be used for both preoperative and postoperative evaluation of LN metastasis. Although the cutoff values for the FNA-Tg has not been standardized, preoperative values of 32.04 ng/ml and postoperative values of 0.9 ng/ml are recommended for identifying neck LN metastasis.

Thyroglobulin Measurement in Fine Needle Aspirates (Tg-FNA) of Cystic Neck Masses for Detection of Papillary Thyroid Carcinoma (PTC)

Introduction: Nuclear pseudoinclusions are one of the most specific pathologic features in diagnosing papillary thyroid carcinoma (PTC). However, the biologic nature of these pseudo-inclusions is largely unknown. Beta-catenin is an oncoprotein involved in Wnt signaling pathway which is activated in several malignancies including PTC. Using immunohistochemistry, we studied the expression of beta-catenin in PTC and hyalinizing trabecular adenoma (HTA), with particular focus on its expression in pseudoinclusions, both on histologic sections and on cytologic specimens. Materials and Methods: A cohort of 13 cases, including 8 cases of PTC and 5 cases of HTA, was applied in this study. Beta-catenin immunohistochemitry was performed on histology block recuts and cytology slides of each case. The beta-catenin labeling index of pseudoinclusions was counted in 15 high power fields and calculated in comparison with those counted on immediate next H&E stained histologic slides. Cytology slides were digitally scanned before destaining and restaining with beta-catenin. The number of beta-catenin-labeled pseudo-inclusions was compared with those digitally scanned slides. Results: On histologic sections, neoplastic cells from both PTC and HTA show much stronger membranous staining pattern of beta-catenin, compared to adjacent normal follicles or colloid nodules. However, labeling index of beta-catenin for nuclear pseudo-inclusions is significantly different between PTC and HTA. Strong intranuclear staining of beta-catenin was seen in 93.5% (range of 72-100%) of the pseudoinclusions in PTC, while only 6.4% (range of 0-13%) of pseudo-inclusions in HTA showed positive staining pattern (p<0.001). For cytologic slides, although it demonstrated similarly strong membranous staining pattern for beta-catenin in PTC cells, none of the nuclear pseudo-inclusions in both PTC and HTA was labeled with beta-catenin antibody on cytologic smears. Conclusions: Overexpression of the beta-catenin oncoprotein was seen in majority of the nuclear pseudo-inclusions in PTC, but only rarely seen in HTA. This differential expression suggests that activation of the betacatenin is likely involved in the formation of “malignant peudoinclusions” in PTC, but not in “benign peudoinclusions” in HTA. The failure of betacatenin labeling of pseudoinclusions on cytologic slides may be in part attributed to inability of the antibody to penetrate into nucleus through the intact cell membranes in cytologic preparations.

Optimal indication of thyroglobulin measurement in fine-needle aspiration for detecting lateral metastatic lymph nodes in patients with papillary thyroid carcinoma

The purpose of this study was to evaluate optimal indication of thyroglobulin (Tg) measurement in fine-needle aspiration (FNA) for detecting lateral metastatic lymph nodes in patients with papillary thyroid carcinoma (PTC). We performed a retrospective study of 241 lymph nodes of 220 patients who underwent ultrasound-guided FNA with Tg in FNA (FNA-Tg) washout fluid measurements for suspicious lymph nodes. On multivariate analysis, hyperechogenicity, cystic change, presence of calcifications, and peripheral vascularity were independent factors predictive of lymph node metastasis. After adding FNA-Tg, sensitivity and accuracy were significantly increased when the lymph node had 1 or 2 suspicious ultrasound features. However, sensitivity and accuracy were not significantly increased when the lymph node had multiple suspicious ultrasound features. Additional FNA-Tg can help diagnose a metastatic lymph node with 1 or 2 suspicious ultrasound features. However, additional FNA-Tg is not beneficial in lymph nodes with highly suspicious ultrasound features, in which FNA alone is sufficient for diagnosis of predictive of lymph node.

Usefulness of Thyroglobulin Measurement in Fine-needle Aspirates of Lymph Nodes for the Diagnosis of Lymph Node Metastasis of Papillary Thyroid Cancer

This article is available from http://www.labmedonline.org 2011, Laboratory Medicine Online This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Previous studies have shown that thyroglobulin (Tg) measurement in fine-needle aspirates (FNA) of lymph nodes can assist in evaluating cervical lymph node metastasis. In this study, we evaluated the diagnostic performances of FNA-Tg, serum-Tg, and FNA-Tg/serum-Tg in detecting lymph node metastasis. Methods: We retrospectively analyzed the diagnostic performances of FNA-Tg and serum-Tg in 641 cases (518 patients) with papillary thyroid cancer that underwent ultrasonography-guided fine-needle aspiration of cervical lymph nodes between March 2009 and February 2010. Results: The number of lymph nodes and median FNA-Tg level of the positive lymph node cytology group were 99 and 1,300 ng/mL (range, 0.25,000), respectively, whereas corresponding values in the negative cytology group were 359 and 4.7 ng/mL (range, 0.1-1,173). The AUCs of FNATg, serum-Tg, and FNA-Tg/serum-Tg ratio were 0.93 (95% CI, 0.90-0.97), 0.64 (95% CI, 0.57-0.70), and 0.83 (95% CI, 0.78-0.88), respectively. The sensitivity and specificity of FNA-Tg were 90.9% and 98.3%, respectively, and the percentage agreement with the cytology results was 96.7%. Conclusions: The agreement of FNA-Tg with the cytology results was good at the cutoff value of 35.9 ng/mL. The measurement of FNA-Tg in cases with uninterpretable cytology results can be useful in evaluating lymph node metastasis of papillary thyroid cancer.

Thyroglobulin measurement in fine-needle aspirates of lymph nodes in patients with differentiated thyroid cancer: a simple definition of the threshold value, with emphasis on potential pitfalls of the method

Thyroglobulin measurements in fine-needle aspirate (FNA-Tg) is an accurate method for the diagnosis of lymph node metastasis in differentiated thyroid carcinoma. The goal of this study is to determine the most appropriate diagnostic threshold value for FNA-Tg. Ultrasound-guided fine-needle aspiration-cytology (FNA-C) and FNA-Tg were performed on suspicious lymph nodes in 114 consecutive patients with thyroid cancer prior to thyroidectomy (n=13) or during follow-up (n=93), and in 16 control subjects. Functional sensitivity of the thyroglobulin assay was 0.7 ng/mL. Sensitivity and specificity of FNA-Tg and FNA-C were determined for different cut-off values within a range of 0.69-1.34 nanogram/punction (ng/p) using receiver operating characteristic curve analysis. The FNA-Tg cut-off value of 0.93 ng/p offers the best diagnostic performances: 94.2% sensitivity, 97.8% specificity. FNA-C showed 100% specificity in diagnostic samples, but low sensitivity of 71% due primarily to inadequate samples. Combining FNA-C and FNA-Tg resulted in 98% sensitivity and 100% specificity. A unique threshold of 0.93 ng/p gives high sensitivity and specificity, even in non-thyroidectomized patients. However, since false negative results may be observed in poorly differentiated thyroid cancer, FNA-C should remain combined to FNA-Tg.

Diagnostic Benefit of Thyroglobulin Measurement in Fine-Needle Aspiration for Diagnosing Metastatic Cervical Lymph Nodes from Papillary Thyroid Cancer: Correlations with US Features

ObjectiveOur goals were to determine the added value of fine-needle aspiration biopsy (FNAB)-thyroglobulin (Tg) measurements over FNAB-cytology alone for diagnosing metastatic nodes, and to determine whether the ultrasound features of lymph nodes can be used to identify lymph nodes that may benefit from FNAB-Tg measurement in patients with papillary thyroid cancer.Materials and MethodsWe retrospectively evaluated 76 surgically proven cervical lymph nodes. Twenty-nine patients were awaiting surgery and 18 patients had undergone thyroid surgery for papillary thyroid cancer. Ultrasound-guided FNAB and Tg measurements were performed and the ultrasound features were evaluated.ResultsThe accuracies, sensitivities, and specificities of FNAB-cytology, FNAB-Tg, and combined FNAB-Tg/cytology were 90%, 80%, and 100%; 92%, 95%, and 90%; and 93%, 96%, and 90%, respectively. The diagnostic sensitivity of FNAB-Tg for metastatic nodes was significantly higher than that of FNAB-cytology (p = 0.011). Furthermore, combined FNAB-Tg/cytology significantly increased sensitivity (p = 0.002) and accuracy (p = 0.03) as compared with FNAB-cytology.ConclusionCombined FNAB-Tg/cytology is significantly more sensitive and accurate at detecting metastatic nodes than FNAB-cytology alone. FNAB-Tg was better at diagnosing metastases in small lymph nodes.