Predictive value of intraoperative frozen section analysis of delphian and pretracheal lymph nodes for central lymph node metastasis and recurrence risk stratification in differentiated thyroid carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Yiran ¹ , ZHANG Yuxiao ² , TANG Zimei ¹ , YANG Rui ¹ ,  XIN Yue ¹ ,  MING Jie ¹

1. Department of Thyroid and Breast Surgery, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan 430050, P. R. China;
2. Department of Thyroid and Breast Surgery, Jingzhou Maternity and Child Health Care Hospital, Jingzhou, Hubei 434020, P. R. China;

Corresponding author：

XIN Yue, Email: xinyue_whuh@163.com; MING Jie, Email: mingjiewh@126.com

Keywords：

differentiated thyroid carcinoma; delphian lymph node; pretracheal lymph node; intraoperative frozen section pathology; central lymph node metastasis

DOI：

10.7507/1007-9424.202505100

Video：

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Objective To evaluate the predictive value of intraoperative frozen section analysis of the Delphian lymph node (DLN) and pretracheal lymph node (PLN) for central lymph node metastasis (LNM) and recurrence risk stratification in patients with differentiated thyroid carcinoma (DTC). Methods This retrospective study included 133 DTC patients who underwent initial surgery with intraoperative frozen section evaluation of the DLN and PLN at the Department of Thyroid and Breast Surgery, Union Hospital, Wuhan, between January 2023 and December 2024. Receiver operating characteristic (ROC) curves were used to assess the predictive value of DLN/PLN metastasis count and ratio for central LNM and recurrence risk stratification. The concordance between intraoperative frozen pathology and final postoperative pathology was also evaluated. Results Multivariate analysis identified age (<20 or >50 years) as protective factor (OR=0.332, P=0.012) and capsular invasion as risk factors for DLN/PLN metastasis (OR=2.823, P=0.017). DLN/PLN metastasis number and ratio showed strong predictive performance for central LNM >5 nodes, with AUC of 0.913 [95%CI (0.841, 0.986), P<0.001] and 0.910 [95%CI (0.837, 0.983), P<0.001], and optimal cut-off values of 1.5 nodes and 45.00%, respectively. For predicting intermediate-to-high recurrence risk, AUCs were 0.818 [95%CI (0.740, 0.895), P<0.001] and 0.800 [95%CI (0.720, 0.880), P<0.001], with cut-offs of 0.5 nodes and 26.79%, respectively. Intraoperative frozen pathology demonstrated a sensitivity of 88.00% (66/75), specificity of 100.00% (58/58), positive predictive value of 100.00% (66/66), and negative predictive value of 86.57% (58/67). Concordance with postoperative pathology was high, with a Kappa value of 0.849 [95%CI (0.761, 0.937), P<0.001] and an intraclass correlation coefficient of 0.917 [95%CI (0.885, 0.940), P<0.001]. Conclusions Intraoperative frozen section analysis of the DLN and PLN demonstrates reliable predictive value for central LNM and recurrence risk stratification in DTC. This method may help identify patients who could benefit from an extended surgical approach and is recommended as a valuable adjunct to intraoperative decision-making.

1.	Pizzato M, Li M, Vignat J, et al. The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020. Lancet Diabetes Endocrinol, 2022, 10(4): 264-272.
2.	Jung CK, Bychkov A, Kakudo K. Update from the 2022 World Health Organization classification of thyroid tumors: a standardized diagnostic approach. Endocrinol Metab (Seoul), 2022, 37(5): 703-718.
3.	殷德涛, 赵乾. 全球及中国甲状腺癌的发病特征及趋势. 中国普外基础与临床杂志, 2025, 32(6): 687-693.
4.	Boucai L, Zafereo M, Cabanillas ME. Thyroid cancer: a review. JAMA, 2024, 331(5): 425-435.
5.	DiMarco AN, Wong MS, Jayasekara J, et al. Risk of needing completion thyroidectomy for low-risk papillary thyroid cancers treated by lobectomy. BJS Open, 2019, 3(3): 299-304.
6.	Anda Apiñániz E, Zafon C, Ruiz Rey I, et al. The extent of surgery for low-risk 1-4 cm papillary thyroid carcinoma: a catch-22 situation. A retrospective analysis of 497 patients based on the 2015 ATA guidelines recommendation 35. Endocrine, 2020, 70(3): 538-543.
7.	Kluijfhout WP, Pasternak JD, Lim J, et al. Frequency of high-risk characteristics requiring total thyroidectomy for 1-4 cm well-differentiated thyroid cancer. Thyroid, 2016, 26(6): 820-824.
8.	中华医学会内分泌学分会, 中华医学会外科学分会甲状腺及代谢外科学组, 中国抗癌协会头颈肿瘤专业委员会, 等. 甲状腺结节和分化型甲状腺癌诊治指南 (第二版) . 国际内分泌代谢杂志. 2023, 43(2): 149-194.
9.	李思齐, 李燕, 张毅, 等. 甲状腺乳头状癌术中喉前及气管前淋巴结联合冷冻病理检测的临床价值. 中国普通外科杂志, 2018, 27(11): 1387-1392.
10.	Shaha AR, Tuttle RM. Delphian node-a sentinel node in thyroid cancer?. J Surg Oncol, 2021, 123(7): 1529-1530.
11.	Chen Q, Wei T, Wang XL, et al. The total number of prelaryngeal and pretracheal lymph node metastases: is it a reliable predictor of contralateral central lymph node metastasis in papillary thyroid carcinoma? J Surg Res, 2017, 214: 162-167.
12.	Houten PV, Netea-Maier RT, Smit JW. Differentiated thyroid carcinoma: an update. Best Pract Res Clin Endocrinol Metab, 2023, 37(1): 101687. doi: 10.1016/j.beem.2022.101687.
13.	Nabhan F, Dedhia PH, Ringel MD. Thyroid cancer, recent advances in diagnosis and therapy. Int J Cancer, 2021, 149(5): 984-992.
14.	Grani G, Sponziello M, Filetti S, et al. Thyroid nodules: diagnosis and management. Nat Rev Endocrinol, 2024, 20(12): 715-728.
15.	Luster M, Weber T, Verburg FA. Differentiated thyroid cancer-personalized therapies to prevent overtreatment. Nat Rev Endocrinol, 2014, 10(9): 563-574.
16.	Guo H, Wang Z, Yin K, et al. Sciellin promotes the development and progression of thyroid cancer through the JAK2/STAT3 signaling pathway. Mol Carcinog, 2024, 63(4): 701-713.
17.	Haugen BR, Alexander EK, Bible KC, 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, 2016, 26(1): 1-133.
18.	Ullmann TM, Papaleontiou M, Sosa JA. Current controversies in low-risk differentiated thyroid cancer: reducing overtreatment in an era of overdiagnosis. J Clin Endocrinol Metab, 2023, 108(2): 271-280.
19.	Georgiades C. Slow growth, excellent prognosis: the treatment and overtreatment of papillary thyroid cancer. Radiology, 2024, 311(1): e240207. doi: 10.1148/radiol.240207.
20.	Haugen BR. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: what is new and what has changed?. Cancer, 2017, 123(3): 372-381.
21.	Brito JP, Hay ID, Morris JC. Low risk papillary thyroid cancer. BMJ, 2014, 348: g3045. doi: 10.1136/bmj.g3045.
22.	Wang TS, Sosa JA. Thyroid surgery for differentiated thyroid cancer-recent advances and future directions. Nat Rev Endocrinol, 2018, 14(11): 670-683.
23.	Menegaux F, Lifante JC. Controversy: For or against thyroid lobectomy in>1cm differentiated thyroid cancer?. Ann Endocrinol (Paris), 2021, 82(2): 78-82.
24.	Fackelmayer OJ, Inabnet WB. Lobectomy or total thyroidectomy-where is the pendulum now for differentiated thyroid cancer?. Surg Oncol Clin N Am, 2023, 32(2): 373-381.
25.	Pak SJ, Kwon D, Kim BC, et al. Contralateral low-to-intermediate suspicion nodule is not a contraindication for lobectomy in patients with papillary thyroid carcinoma. Thyroid, 2023, 33(11): 1339-1348.
26.	Wang R, Tang Z, Wu Z, et al. Construction and validation of nomograms to reduce completion thyroidectomy by predicting lymph node metastasis in low-risk papillary thyroid carcinoma. Eur J Surg Oncol, 2023, 49(8): 1395-1404.
27.	Du J, Yang Q, Sun Y, et al. Risk factors for central lymph node metastasis in patients with papillary thyroid carcinoma: a retrospective study. Front Endocrinol (Lausanne), 2023, 14: 1288527. doi: 10.3389/fendo.2023.1288527.
28.	Yu K, Wu X, Dai L, et al. Risk factors associated with lymph node metastasis in papillary thyroid cancer: a retrospective analysis based on 2 428 cases. Front Oncol, 2024, 14: 1473858. doi: 10.3389/fonc.2024.1473858.
29.	Shao L, Wang Z, Dong W, et al. Risk factors associated with preferential lateral lymph node metastasis in papillary thyroid carcinoma. Cancer Med, 2023, 12(22): 20670-20676.
30.	Zhu J, Huang R, Yu P, et al. Clinical implications of Delphian lymph node metastasis in papillary thyroid carcinoma. Gland Surg, 2021, 10(1): 73-82.
31.	Yan Y, Wang Y, Liu N, et al. Predictive value of the delphian lymph node in cervical lymph node metastasis of papillary thyroid carcinoma. Eur J Surg Oncol, 2021, 47(7): 1727-1733.
32.	Huang J, Sun W, Zhang H, et al. Use of delphian lymph node metastasis to predict central and lateral involvement in papillary thyroid carcinoma: A systematic review and meta-analysis. Clin Endocrinol (Oxf), 2019, 91(1): 170-178.
33.	He JL, Yan YZ, Zhang Y, et al. A machine learning model utilizing delphian lymph node characteristics to predict contralateral central lymph node metastasis in papillary thyroid carcinoma: a prospective multicenter study. Int J Surg, 2025, 111(1): 360-370.
34.	Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin, 2017, 67(2): 93-99.
35.	Zhou L, Li H, Liang W, et al. Pretracheal-laryngeal lymph nodes in frozen section predicting contralateral paratracheal lymph nodes metastasis. Eur J Surg Oncol, 2020, 46(10 Pt A): 1829-1834.
36.	江桂英, 刘婉, 李水仁, 等. 术中快速冷冻病理检查对预测甲状腺乳头状癌淋巴结转移的临床价值. 黑龙江医药. 2023, 36(2): 434-436.

1. Pizzato M, Li M, Vignat J, et al. The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020. Lancet Diabetes Endocrinol, 2022, 10(4): 264-272.
2. Jung CK, Bychkov A, Kakudo K. Update from the 2022 World Health Organization classification of thyroid tumors: a standardized diagnostic approach. Endocrinol Metab (Seoul), 2022, 37(5): 703-718.
3. 殷德涛, 赵乾. 全球及中国甲状腺癌的发病特征及趋势. 中国普外基础与临床杂志, 2025, 32(6): 687-693.
4. Boucai L, Zafereo M, Cabanillas ME. Thyroid cancer: a review. JAMA, 2024, 331(5): 425-435.
5. DiMarco AN, Wong MS, Jayasekara J, et al. Risk of needing completion thyroidectomy for low-risk papillary thyroid cancers treated by lobectomy. BJS Open, 2019, 3(3): 299-304.
6. Anda Apiñániz E, Zafon C, Ruiz Rey I, et al. The extent of surgery for low-risk 1-4 cm papillary thyroid carcinoma: a catch-22 situation. A retrospective analysis of 497 patients based on the 2015 ATA guidelines recommendation 35. Endocrine, 2020, 70(3): 538-543.
7. Kluijfhout WP, Pasternak JD, Lim J, et al. Frequency of high-risk characteristics requiring total thyroidectomy for 1-4 cm well-differentiated thyroid cancer. Thyroid, 2016, 26(6): 820-824.
8. 中华医学会内分泌学分会, 中华医学会外科学分会甲状腺及代谢外科学组, 中国抗癌协会头颈肿瘤专业委员会, 等. 甲状腺结节和分化型甲状腺癌诊治指南 (第二版) . 国际内分泌代谢杂志. 2023, 43(2): 149-194.
9. 李思齐, 李燕, 张毅, 等. 甲状腺乳头状癌术中喉前及气管前淋巴结联合冷冻病理检测的临床价值. 中国普通外科杂志, 2018, 27(11): 1387-1392.
10. Shaha AR, Tuttle RM. Delphian node-a sentinel node in thyroid cancer?. J Surg Oncol, 2021, 123(7): 1529-1530.
11. Chen Q, Wei T, Wang XL, et al. The total number of prelaryngeal and pretracheal lymph node metastases: is it a reliable predictor of contralateral central lymph node metastasis in papillary thyroid carcinoma? J Surg Res, 2017, 214: 162-167.
12. Houten PV, Netea-Maier RT, Smit JW. Differentiated thyroid carcinoma: an update. Best Pract Res Clin Endocrinol Metab, 2023, 37(1): 101687. doi: 10.1016/j.beem.2022.101687.
13. Nabhan F, Dedhia PH, Ringel MD. Thyroid cancer, recent advances in diagnosis and therapy. Int J Cancer, 2021, 149(5): 984-992.
14. Grani G, Sponziello M, Filetti S, et al. Thyroid nodules: diagnosis and management. Nat Rev Endocrinol, 2024, 20(12): 715-728.
15. Luster M, Weber T, Verburg FA. Differentiated thyroid cancer-personalized therapies to prevent overtreatment. Nat Rev Endocrinol, 2014, 10(9): 563-574.
16. Guo H, Wang Z, Yin K, et al. Sciellin promotes the development and progression of thyroid cancer through the JAK2/STAT3 signaling pathway. Mol Carcinog, 2024, 63(4): 701-713.
17. Haugen BR, Alexander EK, Bible KC, 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, 2016, 26(1): 1-133.
18. Ullmann TM, Papaleontiou M, Sosa JA. Current controversies in low-risk differentiated thyroid cancer: reducing overtreatment in an era of overdiagnosis. J Clin Endocrinol Metab, 2023, 108(2): 271-280.
19. Georgiades C. Slow growth, excellent prognosis: the treatment and overtreatment of papillary thyroid cancer. Radiology, 2024, 311(1): e240207. doi: 10.1148/radiol.240207.
20. Haugen BR. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: what is new and what has changed?. Cancer, 2017, 123(3): 372-381.
21. Brito JP, Hay ID, Morris JC. Low risk papillary thyroid cancer. BMJ, 2014, 348: g3045. doi: 10.1136/bmj.g3045.
22. Wang TS, Sosa JA. Thyroid surgery for differentiated thyroid cancer-recent advances and future directions. Nat Rev Endocrinol, 2018, 14(11): 670-683.
23. Menegaux F, Lifante JC. Controversy: For or against thyroid lobectomy in>1cm differentiated thyroid cancer?. Ann Endocrinol (Paris), 2021, 82(2): 78-82.
24. Fackelmayer OJ, Inabnet WB. Lobectomy or total thyroidectomy-where is the pendulum now for differentiated thyroid cancer?. Surg Oncol Clin N Am, 2023, 32(2): 373-381.
25. Pak SJ, Kwon D, Kim BC, et al. Contralateral low-to-intermediate suspicion nodule is not a contraindication for lobectomy in patients with papillary thyroid carcinoma. Thyroid, 2023, 33(11): 1339-1348.
26. Wang R, Tang Z, Wu Z, et al. Construction and validation of nomograms to reduce completion thyroidectomy by predicting lymph node metastasis in low-risk papillary thyroid carcinoma. Eur J Surg Oncol, 2023, 49(8): 1395-1404.
27. Du J, Yang Q, Sun Y, et al. Risk factors for central lymph node metastasis in patients with papillary thyroid carcinoma: a retrospective study. Front Endocrinol (Lausanne), 2023, 14: 1288527. doi: 10.3389/fendo.2023.1288527.
28. Yu K, Wu X, Dai L, et al. Risk factors associated with lymph node metastasis in papillary thyroid cancer: a retrospective analysis based on 2 428 cases. Front Oncol, 2024, 14: 1473858. doi: 10.3389/fonc.2024.1473858.
29. Shao L, Wang Z, Dong W, et al. Risk factors associated with preferential lateral lymph node metastasis in papillary thyroid carcinoma. Cancer Med, 2023, 12(22): 20670-20676.
30. Zhu J, Huang R, Yu P, et al. Clinical implications of Delphian lymph node metastasis in papillary thyroid carcinoma. Gland Surg, 2021, 10(1): 73-82.
31. Yan Y, Wang Y, Liu N, et al. Predictive value of the delphian lymph node in cervical lymph node metastasis of papillary thyroid carcinoma. Eur J Surg Oncol, 2021, 47(7): 1727-1733.
32. Huang J, Sun W, Zhang H, et al. Use of delphian lymph node metastasis to predict central and lateral involvement in papillary thyroid carcinoma: A systematic review and meta-analysis. Clin Endocrinol (Oxf), 2019, 91(1): 170-178.
33. He JL, Yan YZ, Zhang Y, et al. A machine learning model utilizing delphian lymph node characteristics to predict contralateral central lymph node metastasis in papillary thyroid carcinoma: a prospective multicenter study. Int J Surg, 2025, 111(1): 360-370.
34. Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin, 2017, 67(2): 93-99.
35. Zhou L, Li H, Liang W, et al. Pretracheal-laryngeal lymph nodes in frozen section predicting contralateral paratracheal lymph nodes metastasis. Eur J Surg Oncol, 2020, 46(10 Pt A): 1829-1834.
36. 江桂英, 刘婉, 李水仁, 等. 术中快速冷冻病理检查对预测甲状腺乳头状癌淋巴结转移的临床价值. 黑龙江医药. 2023, 36(2): 434-436.

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Latest ArticlesPredictive value of intraoperative frozen section analysis of delphian and pretracheal lymph nodes for central lymph node metastasis and recurrence risk stratification in differentiated thyroid carcinoma

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