Diagnostic Algorithm for Metastatic Lymph Nodes of Differentiated Thyroid Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Study Population
2.2. Optimal FNA-Tg Cutoff Values
2.3. Comparison of the Diagnostic Performance of FNAC, FNA-Tg, and Combined FNAC and FNA-Tg
2.4. Malignancy Rates of LNs Based on Sonographic Features, FNAC, and FNA-Tg
3. Discussion
4. Materials and Methods
4.1. Patient Selection
4.2. US and US-FNA
4.3. Measurement of Tg
4.4. Reference Standard
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Grani, G.; Fumarola, A. Thyroglobulin in lymph node fine-needle aspiration washout: A systematic review and meta-analysis of diagnostic accuracy. J. Clin. Endocrinol. Metab. 2014, 99, 1970–1982. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Lei, J.; Liu, Y.; Fan, Y.; Wang, X.; Lu, X. Preoperative predictors of lateral neck lymph node metastasis in papillary thyroid microcarcinoma. Medicine 2017, 96, e6240. [Google Scholar] [CrossRef] [PubMed]
- Watkinson, J.C.; Franklyn, J.A.; Olliff, J.F. Detection and surgical treatment of cervical lymph nodes in differentiated thyroid cancer. Thyroid 2006, 16, 187–194. [Google Scholar] [CrossRef]
- Orija, I.B.; Hamrahian, A.H.; Reddy, S.S. Management of nondiagnostic thyroid fine-needle aspiration biopsy: Survey of endocrinologists. Endocr. Pract. 2004, 10, 317–323. [Google Scholar] [CrossRef]
- Florentine, B.D.; Staymates, B.; Rabadi, M.; Barstis, J.; Black, A. The reliability of fine-needle aspiration biopsy as the initial diagnostic procedure for palpable masses: A 4-year experience of 730 patients from a community hospital-based outpatient aspiration biopsy clinic. Cancer 2006, 107, 406–416. [Google Scholar] [CrossRef] [PubMed]
- Hall, T.L.; Layfield, L.J.; Philippe, A.; Rosenthal, D.L. Sources of diagnostic error in fine needle aspiration of the thyroid. Cancer 1989, 63, 718–725. [Google Scholar] [CrossRef]
- Pacini, F.; Fugazzola, L.; Lippi, F.; Ceccarelli, C.; Centoni, R.; Miccoli, P.; Elisei, R.; Pinchera, A. Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: A clue to the diagnosis of metastatic differentiated thyroid cancer. J. Clin. Endocrinol. Metab. 1992, 74, 1401–1404. [Google Scholar]
- Shin, J.H.; Baek, H.J.; Chung, J.; Ha, J.E.; Kim, H.J.; Lee, H.Y.; LIm, H.K.; Moon, W.-J.; Na, D.G.; Park, J.S.; et al. Ultrasonography Diagnosis and Imaging-Based Management of Thyroid Nodules: Revised Korean Society of Thyroid Radiology Consensus Statement and Recommendations. Korean J. Radiol. 2016, 17, 370–395. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haugen, B.R.; Alexander, E.K.; Bible, K.C.; Doherty, G.M.; Mandel, S.J.; Nikiforov, Y.E.; Pacini, F.; Randolph, G.W.; Sawka, A.M.; Schlumberger, M.; et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. Off. J. Am. Thyroid. Assoc. 2016, 26, 1–133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Russ, G.; Bonnema, S.J.; Erdogan, M.F.; Durante, C.; Ngu, R.; Leenhardt, L. European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults: The EU-TIRADS. Eur. Thyroid. J. 2017, 6, 225–237. [Google Scholar] [CrossRef] [Green Version]
- Whitley, R.J.; Ain, K.B. Thyroglobulin: A specific serum marker for the management of thyroid carcinoma. Clin. Lab Med. 2004, 24, 29–47. [Google Scholar] [CrossRef] [PubMed]
- Moon, J.H.; Kim, Y.I.; Lim, J.A.; Choi, H.S.; Cho, S.W.; Kim, K.W.; Park, H.J.; Paeng, J.C.; Park, Y.J.; Yi, K.H.; et al. Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: Large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results. J. Clin. Endocrinol. Metab. 2013, 98, 1061–1068. [Google Scholar] [CrossRef]
- Jung, J.Y.; Shin, J.H.; Han, B.K.; Ko, E.Y. Optimized cutoff value and indication for washout thyroglobulin level according to ultrasound findings in patients with well-differentiated thyroid cancer. AJNR Am. J. Neuroradiol. 2013, 34, 2349–2353. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chung, J.; Kim, E.K.; Lim, H.; Son, E.J.; Yoon, J.H.; Youk, J.H.; Kim, J.-A.; Moon, H.J.; Kwak, J.Y. Optimal indication of thyroglobulin measurement in fine-needle aspiration for detecting lateral metastatic lymph nodes in patients with papillary thyroid carcinoma. Head Neck 2014, 36, 795–801. [Google Scholar] [CrossRef]
- Giovanella, L.; Bongiovanni, M.; Trimboli, P. Diagnostic value of thyroglobulin assay in cervical lymph node fine-needle aspirations for metastatic differentiated thyroid cancer. Curr. Opin. Oncol. 2013, 25, 6–13. [Google Scholar] [CrossRef] [PubMed]
- Pak, K.; Suh, S.; Hong, H.; Cheon, G.J.; Hahn, S.K.; Kang, K.W.; Kim, E.E.; Lee, D.S.; Chung, J.-K. Diagnostic values of thyroglobulin measurement in fine-needle aspiration of lymph nodes in patients with thyroid cancer. Endocrine 2015, 49, 70–77. [Google Scholar] [CrossRef]
- Kim, D.W.; Jeon, S.J.; Kim, C.G. Usefulness of thyroglobulin measurement in needle washouts of fine-needle aspiration biopsy for the diagnosis of cervical lymph node metastases from papillary thyroid cancer before thyroidectomy. Endocrine 2012, 42, 399–403. [Google Scholar] [CrossRef]
- Kim, M.J.; Kim, E.K.; Kim, B.M.; Kwak, J.Y.; Lee, E.J.; Park, C.S.; Cheong, W.Y.; Nam, K.H. Thyroglobulin measurement in fine-needle aspirate washouts: The criteria for neck node dissection for patients with thyroid cancer. Clin. Endocrinol. Oxf. 2009, 70, 145–151. [Google Scholar] [CrossRef] [PubMed]
- Cunha, N.; Rodrigues, F.; Curado, F.; Ilhéu, O.; Cruz, C.; Naidenov, P.; Rascão, M.J.; Ganho, J.; Gomes, I.; Pereira, H.; et al. Thyroglobulin detection in fine-needle aspirates of cervical lymph nodes: A technique for the diagnosis of metastatic differentiated thyroid cancer. Eur. J. Endocrinol. 2007, 157, 101–107. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Snozek, C.L.; Chambers, E.P.; Reading, C.C.; Sebo, T.J.; Sistrunk, J.W.; Singh, R.J.; Grebe, S.K. Serum thyroglobulin, high-resolution ultrasound, and lymph node thyroglobulin in diagnosis of differentiated thyroid carcinoma nodal metastases. J. Clin. Endocrinol. Metab. 2007, 92, 4278–4281. [Google Scholar] [CrossRef] [Green Version]
- Zhao, H.; Wang, Y.; Wang, M.-J.; Zhang, Z.-H.; Wang, H.-R.; Zhang, B.; Guo, H.-Q. Influence of presence/absence of thyroid gland on the cutoff value for thyroglobulin in lymph-node aspiration to detect metastatic papillary thyroid carcinoma. BMC Cancer 2017, 17, 296. [Google Scholar] [CrossRef] [PubMed]
- Boi, F.; Baghino, G.; Atzeni, F.; Lai, M.L.; Faa, G.; Mariotti, S. The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg antibodies. J. Clin. Endocrinol. Metab. 2006, 91, 1364–1369. [Google Scholar] [CrossRef] [Green Version]
- Kim, H.; Kim, Y.N.; Kim, H.I.; Park, S.Y.; Choe, J.H.; Kim, J.H.; Kim, J.S.; Chung, J.H.; Kim, T.H.; Kim, S.W. Preoperative serum thyroglobulin predicts initial distant metastasis in patients with differentiated thyroid cancer. Sci. Rep. 2017, 7, 16955. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bachelot, A.; Cailleux, A.F.; Klain, M.; Baudin, E.; Ricard, M.; Bellon, N.; Caillou, B.; Travagli, J.P.; Schlumberger, M. Relationship between tumor burden and serum thyroglobulin level in patients with papillary and follicular thyroid carcinoma. Thyroid 2002, 12, 707–711. [Google Scholar] [CrossRef]
- Frasoldati, A.; Toschi, E.; Zini, M.; Flora, M.; Caroggio, A.; Dotti, C.; Valcavi, R. Role of thyroglobulin measurement in fine-needle aspiration biopsies of cervical lymph nodes in patients with differentiated thyroid cancer. Thyroid 1999, 9, 105–111. [Google Scholar] [CrossRef] [PubMed]
- Cignarelli, M.; Ambrosi, A.; Marino, A.; Lamacchia, O.; Campo, M.; Picca, G.; Giorgino, F. Diagnostic Utility of Thyroglobulin Detection in Fine-Needle Aspiration of Cervical Cystic Metastatic Lymph Nodes from Papillary Thyroid Cancer with Negative Cytology. Thyroid 2003, 13, 1163–1167. [Google Scholar] [CrossRef]
- Suh, Y.J.; Son, E.J.; Moon, H.J.; Kim, E.K.; Han, K.H.; Kwak, J.Y. Utility of thyroglobulin measurements in fine-needle aspirates of space occupying lesions in the thyroid bed after thyroid cancer operations. Thyroid 2013, 23, 280–288. [Google Scholar] [CrossRef] [PubMed]
Characteristic | Benign | Metastatic | p-Value |
---|---|---|---|
No. of patients | 418 | 755 | |
Age (years) | 50.8 ± 13.2 | 49.4 ± 14.7 | 0.003 |
Sex Male Female | 107 (25.6%) 311 (74.4%) | 266 (35.2%) 489 (64.8%) | 0.0004 |
No. of nodules | 528 | 1015 | |
Preoperative evaluation Lobectomy Total thyroidectomy | 261 (49.4%) 18 (3.4%) 249 (47.2%) | 604 (59.5%) 45 (4.4%) 366 (36.1%) | 0.0001 |
Sonographic diagnosis Benign Indeterminate Suspicious | 78 (14.8%) 371 (70.2%) 79 (15.0%) | 2 (0.2%) 143 (14.1%) 870 (85.7%) | <0.0001 |
Size Short axis diameter Longest diameter | 0.5 ± 0.2 1.1 ± 0.5 | 0.6 ± 0.5 1.1 ± 0.7 | <0.0001 0.242 |
FNA cytology Benign Malignant Indeterminate | 472 (89.4%) 1 (0.2%) 55 (10.4%) | 92 (9.1%) 804 (79.2%) 119 (11.7%) | <0.0001 |
FNA-Tg, ng/mL | 21.3 ± 465.7 | 45,266.8 ± 191,378.6 | <0.0001 |
Serum Tg, ng/mL | 9.2 ± 34.8 | 37.9 ± 201.0 | 0.001 |
Variables | Suspicious LN with Cystic Changes | Suspicious LN without Cystic Changes | Indeterminate Lymph Nodes | ||||||
---|---|---|---|---|---|---|---|---|---|
FNAC | FNA-Tg | Combined | FNAC | FNA-Tg | Combined | FNAC | FNA-Tg | Combined | |
Sensitivity | 70.9 (161/227) [64.6–76.7] | 99.6 * (226/227) [97.6–9.99] | 99.6 † (226/227) [97.6–9.99) | 86.6 (557/643) [83.8–89.2] | 91.0 * (585/643) [88.5–93.1] | 96.1 † (618/643) [94.3–97.5] | 60.1 (86/143) [51.6–68.2] | 81.8 * (117/143) [74.5–87.8] | 88.1 † (126/143) [81.7–92.9] |
Specificity | 100 (1/1) [2.5–100] | 100 (1/1) [2.5–100] | 100 (1/1) [2.5–100] | 98.7 (77/78) [93.1–100] | 92.3 (72/78) [84.0–97.1] | 91.0 (71/78) [82.4–96.3] | 100 (371/371) [99.0–100] | 99.2 (368/371) [97.7–99.8] | 99.1 (368/371) [97.7–99.8] |
PPV | 100 (161/161) [100–100] | 100 (226/226) [100–100] | 100 (226/226) [100–100] | 99.8 (557/558) [98.8–100] | 99.0 (585/591) [97.8–99.5] | 98.9 (618/625) [97.8–99.4] | 100 (86/86) [100–100] | 97.5 (117/120) [92.7–99.2] | 97.7 (126/129) [93.1–99.2] |
NPV | 1.5 (1/67) [1.2–1.8] | 50 (1/2) [12.4–87.6] | 50 (1/2) [12.4–87.6] | 47.2 (77/163) [42.3–52.2] | 55.4 (72/130) [49.1–61.5] | 74.0 (71/96) [65.8–80.8] | 86.7 (371/428) [84.2–88.8] | 93.4 (368/394) [90.9–95.3] | 95.6 (368/385) [93.3–97.1] |
Diagnostic accuracy | 71.1 (162/228) [64.7–96.9] | 99.6 * (227/228) [97.6–100] | 99.6 † (227/228) [97.6–100] | 87.9 (634/721) [85.3–90.2] | 91.1 (657/721) [88.8–93.1] | 95.6 † (689/721) [93.8–96.9] | 88.9 (457/514) [85.9–91.5] | 94.4 * (485/514) [92.0–96.2] | 96.1 † (494/514) [94.1–97.6] |
False-positive | 0 (0/161) | 0 (0/226) | 0 (0/226) | 0.2% (1/558) | 1% (6/591) | 1.1% (7/625) | 0 (0/86) | 2.5% (3/120) | 2.3% (3/129) |
False-negative | 1.5% (1/67) | 50% (1/2) | 50% (1/2) | 52.8% (86/163) | 44.6% (58/130) | 26% (25/96) | 13.3% (57/428) | 6.6% (26/394) | 4.4% (17/385) |
FNA Result | Sonographic Feature of LN | Malignancy Rate | ||
---|---|---|---|---|
Total | FNA-Tg > Cutoff | FNA-Tg < Cutoff | ||
Malignant | Suspicious Indeterminate | 99.9% (718/719) 100% (86/86) | 100% (685/685) 100% (77/77) | 97.1% (33/34) 100% (9/9) |
Benign | Suspicious Indeterminate | 45.7% (59/129) 9.1% (33/363) | 87.0% (40/46) 87.0% (20/23) | 22.9% (19/83) 3.8% (13/340) |
Indeterminate | Suspicious Indeterminate | 92.1% (93/101) 36.9% (24/65) | 100% (86/86) 100% (20/20) | 46.7% (7/15) 8.9% (4/45) |
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Chung, S.R.; Baek, J.H.; Choi, Y.J.; Sung, T.-Y.; Song, D.E.; Kim, T.Y.; Lee, J.H. Diagnostic Algorithm for Metastatic Lymph Nodes of Differentiated Thyroid Carcinoma. Cancers 2021, 13, 1338. https://doi.org/10.3390/cancers13061338
Chung SR, Baek JH, Choi YJ, Sung T-Y, Song DE, Kim TY, Lee JH. Diagnostic Algorithm for Metastatic Lymph Nodes of Differentiated Thyroid Carcinoma. Cancers. 2021; 13(6):1338. https://doi.org/10.3390/cancers13061338
Chicago/Turabian StyleChung, Sae Rom, Jung Hwan Baek, Young Jun Choi, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, and Jeong Hyun Lee. 2021. "Diagnostic Algorithm for Metastatic Lymph Nodes of Differentiated Thyroid Carcinoma" Cancers 13, no. 6: 1338. https://doi.org/10.3390/cancers13061338
APA StyleChung, S. R., Baek, J. H., Choi, Y. J., Sung, T.-Y., Song, D. E., Kim, T. Y., & Lee, J. H. (2021). Diagnostic Algorithm for Metastatic Lymph Nodes of Differentiated Thyroid Carcinoma. Cancers, 13(6), 1338. https://doi.org/10.3390/cancers13061338