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Impact of thyroid carcinoma invasion of recurrent laryngeal nerve on cervical lymph node metastasis

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Abstract

Purpose

Papillary thyroid carcinoma (PTC) has a favorable prognosis. However, involvement of the recurrent laryngeal nerve (RLN) significantly increases the risk of recurrence. RLN invasion was an important factor in determining the extent of thyroid surgery. The purpose of this study was to compare clinicopathologic features and characterize risk factors of central and lateral lymph node metastasis (LLNM) of RLN invasion in patients with PTC.

Methods

A retrospective review was conducted of 130 patients with PTCs who had exclusive tumor involvement of the RLN at our institution between January 2014 and February 2019. All patients underwent total thyroidectomy and high-dose radioactive iodine (RAI) therapy. The clinicopathologic factors and prognostic outcomes of the patients with solitary and multiple RLN involvements were compared. Kaplan–Meier method was performed to compare the outcomes of tumor recurrence. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with LLNM.

Results

The invasion of the RLN was similar on both sides, with 58.5% on the right, 40.0% on the left, and 1.5% on both sides. Significant differences were observed in tumor size (p < 0.001), lymph node metastasis classification (p = 0.002), RLN resection (p < 0.001), and thyroglobulin (p = 0.010) in the solitary and multiple groups. During the median follow-up of 67 months, 9 (6.9%) patients developed recurrence. There were no statistical differences in recurrence for age, tumor size, gender, multifocality, lymph node metastasis (LNM), and RLN resection. According to receiver operating characteristic (ROC) curve analyses, a cut-off of tumor size > 1.7 cm was identified as the most sensitive and specific predictor of RLN with multiple involvements or LNM invasion. Univariate and multivariate analyses revealed that central lymph node metastasis (CLNM) and RLN invasion by LNM can serve as independent risk factors for LLNM (p = 0.006 and p < 0.001, respectively).

Conclusion

Our results indicate that recurrence was comparable in patients with solitary and multiple RLN involvements. Multiple RLN involvement was associated with pathological features such as larger tumors, RLN resection, and LLNM. The presence of LNM invading RLN and multiple nerve involvement increases the risk of intraoperative RLN resection. A higher risk of multiple invasion or LNM invasion should be considered when tumor size > 1.7 cm. The presence of CLNM and RLN invaded by LNM were independent predictors for LLNM, which could aid surgeons in deciding on lateral lymph node dissection.

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Abbreviations

PTC:

papillary thyroid carcinoma

RLN:

recurrent laryngeal nerve

LLNM:

lateral lymph node metastasis

CLNM:

central lymph node metastasis

LNM:

lymph node metastasis

RFS:

recurrence-free survival

RAI:

radioactive iodine

ROC:

receiver operating characteristic

AJCC:

American Joint Committee on Cancer classification

ATA:

American Thyroid Association

IONM:

intraoperative nerve monitoring

HR:

hazard ratio

TG:

thyroglobulin

TPOAb:

thyroidperoxidase antibodies

TSH:

thyroid stimulating hormone

References

  1. K.D. Miller, L. Nogueira, T. Devasia, A.B. Mariotto, K.R. Yabroff, A. Jemal et al. Cancer Treatment and Survivorship Statistics, 2022. CA Cancer J. Clin. 72, 409–436 (2022). https://doi.org/10.3322/caac.21731

    Article  PubMed  Google Scholar 

  2. A. Metere, V. Aceti, L. Giacomelli, The Surgical Management of Locally Advanced Well-Differentiated Thyroid Carcinoma: Changes over the Years According to the Ajcc 8th Edition Cancer Staging Manual. Thyroid Res 12, 10 (2019). https://doi.org/10.1186/s13044-019-0071-3

    Article  PubMed  PubMed Central  Google Scholar 

  3. M.L. Shindo, S.M. Caruana, E. Kandil, J.C. McCaffrey, L.A. Orloff, J.R. Porterfield et al. Management of Invasive Well-Differentiated Thyroid Cancer: An American Head and Neck Society Consensus Statement. Ahns Consensus Statement. Head. Neck 36, 1379–1390 (2014). https://doi.org/10.1002/hed.23619

    Article  PubMed  Google Scholar 

  4. J.C. McCaffrey, Aerodigestive Tract Invasion by Well-Differentiated Thyroid Carcinoma: Diagnosis, Management, Prognosis, and Biology. Laryngoscope 116, 1–11 (2006). https://doi.org/10.1097/01.MLG.0000200428.26975.86

    Article  PubMed  Google Scholar 

  5. T.Y. Farrag, R.A. Samlan, F.R. Lin, R.P. Tufano, The Utility of Evaluating True Vocal Fold Motion before Thyroid Surgery. Laryngoscope 116, 235–238 (2006). https://doi.org/10.1097/01.mlg.0000191472.02720.1f

    Article  PubMed  Google Scholar 

  6. T.V. McCaffrey, E.J. Bergstralh, I.D. Hay, Locally Invasive Papillary Thyroid Carcinoma: 1940–1990. Head. Neck 16, 165–172 (1994). https://doi.org/10.1002/hed.2880160211

    Article  CAS  PubMed  Google Scholar 

  7. L.P. Kowalski, J.G. Filho, Results of the Treatment of Locally Invasive Thyroid Carcinoma. Head. Neck 24, 340–344 (2002). https://doi.org/10.1002/hed.10058

    Article  PubMed  Google Scholar 

  8. T. Nishida, K. Nakao, M. Hamaji, W. Kamiike, K. Kurozumi, H. Matsuda. Preservation of Recurrent Laryngeal Nerve Invaded by Differentiated Thyroid Cancer. Ann. Surg. 226, 85–91 (1997). https://doi.org/10.1097/00000658-199707000-00012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. W. Chen, J. Lei, J. You, Y. Lei, Z. Li, R. Gong et al. Predictive Factors and Prognosis for Recurrent Laryngeal Nerve Invasion in Papillary Thyroid Carcinoma. Onco Targets Ther. 10, 4485–4491 (2017). https://doi.org/10.2147/OTT.S142799

    Article  PubMed  PubMed Central  Google Scholar 

  10. B.H. Lang, C.Y. Lo, K.P. Wong, K.Y. Wan, Should an Involved but Functioning Recurrent Laryngeal Nerve Be Shaved or Resected in a Locally Advanced Papillary Thyroid Carcinoma. Ann. Surg. Oncol. 20, 2951–2957 (2013). https://doi.org/10.1245/s10434-013-2984-8

    Article  PubMed  Google Scholar 

  11. H.S. Lee, S.W. Kim, T. Park, G.Y. Nam, J.C. Hong, K.D. Lee, Papillary Thyroid Carcinoma with Exclusive Involvement of a Functioning Recurrent Laryngeal Nerve May Be Treated with Shaving Technique. World J. Surg. 39, 969–974 (2015). https://doi.org/10.1007/s00268-014-2906-3

    Article  PubMed  Google Scholar 

  12. J. Boucek, M. Zabrodsky, M. Kuchar, O. Fanta, J. Skrivan, J. Betka, A New Strategy for the Surgical Management of Rln Infiltrated by Well-Differentiated Thyroid Carcinoma. Biomed. Res Int 2014, 616521 (2014). https://doi.org/10.1155/2014/616521

    Article  PubMed  PubMed Central  Google Scholar 

  13. H.S. Na, H.K. Kwon, S.C. Shin, Y.I. Cheon, M. Seo, J.C. Lee et al. Clinical Outcomes of T4a Papillary Thyroid Cancer with Recurrent Laryngeal Nerve Involvement: A Retrospective Analysis. Sci. Rep. 11, 6707 (2021). https://doi.org/10.1038/s41598-021-86226-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. G. Sapuppo, F. Palermo, M. Russo, M. Tavarelli, R. Masucci, S. Squatrito et al. Latero-Cervical Lymph Node Metastases (N1b) Represent an Additional Risk Factor for Papillary Thyroid Cancer Outcome. J. Endocrinol. Invest 40, 1355–1363 (2017). https://doi.org/10.1007/s40618-017-0714-y

    Article  CAS  PubMed  Google Scholar 

  15. I.J. Nixon, A.R. Shaha, Management of Regional Nodes in Thyroid Cancer. Oral. Oncol. 49, 671–675 (2013). https://doi.org/10.1016/j.oraloncology.2013.03.441

    Article  PubMed  Google Scholar 

  16. M. **ng, Molecular Pathogenesis and Mechanisms of Thyroid Cancer. Nat. Rev. Cancer 13, 184–199 (2013). https://doi.org/10.1038/nrc3431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. R.M. Tuttle, D.W. Ball, D. Byrd, R.A. Dilawari, G.M. Doherty, Q.Y. Duh et al. Thyroid Carcinoma. J. Natl Compr. Canc Netw. 8, 1228–1274 (2010). https://doi.org/10.6004/jnccn.2010.0093

    Article  PubMed  Google Scholar 

  18. R. Roka, Surgical Treatment of Locally Advanced Thyroid Cancer. Innov. Surg. Sci. 5, 27–34 (2020). https://doi.org/10.1515/iss-2020-0012

    Article  PubMed  PubMed Central  Google Scholar 

  19. B.R. Haugen, 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: What Is New and What Has Changed. Cancer 123, 372–381 (2017). https://doi.org/10.1002/cncr.30360

    Article  PubMed  Google Scholar 

  20. S. Miyamaru, D. Murakami, K. Nishimoto, N. Kodama, J. Tashiro, Y. Miyamoto, et al. Optimal Management of the Unilateral Recurrent Laryngeal Nerve Involvement in Patients with Thyroid Cancer. Cancers (Basel). 13. (2021) https://doi.org/10.3390/cancers13092129

  21. C.W. Wu, G. Dionigi, M. Barczynski, F.Y. Chiang, H. Dralle, R. Schneider et al. International Neuromonitoring Study Group Guidelines 2018: Part Ii: Optimal Recurrent Laryngeal Nerve Management for Invasive Thyroid Cancer-Incorporation of Surgical, Laryngeal, and Neural Electrophysiologic Data. Laryngoscope 128(Suppl 3), S18–S27 (2018). https://doi.org/10.1002/lary.27360

    Article  PubMed  Google Scholar 

  22. S. Moritani, Impact of Lymph Node Metastases with Recurrent Laryngeal Nerve Invasion on Patients with Papillary Thyroid Carcinoma. Thyroid 25, 107–111 (2015). https://doi.org/10.1089/thy.2014.0152

    Article  PubMed  Google Scholar 

  23. J.A. Brooks, A.H. Abdelhamid Ahmed, Z. Al-Qurayshi, D. Kamani, N. Kyriazidis, R.J. Hammon et al. Recurrent Laryngeal Nerve Invasion by Thyroid Cancer: Laryngeal Function and Survival Outcomes. Laryngoscope 132, 2285–2292 (2022). https://doi.org/10.1002/lary.30115

    Article  PubMed  Google Scholar 

  24. F. Yang, J. Wang, Y. Rao, Y. Feng, L. Meng, J. Fang. Predictive Factors and Risk Analysis of Recurrent Laryngeal Nerve Invasion in Papillary Thyroid Carcinoma </= 1 Cm. Arch Endocrinol Metab.(2023) https://doi.org/10.20945/2359-3997000000537

  25. N. Agrawal, M.R. Evasovich, E. Kandil, S.I. Noureldine, E.A. Felger, R.P. Tufano et al. Indications and Extent of Central Neck Dissection for Papillary Thyroid Cancer: An American Head and Neck Society Consensus Statement. Head. Neck 39, 1269–1279 (2017). https://doi.org/10.1002/hed.24715

    Article  PubMed  Google Scholar 

  26. R.P. Tufano, J. Bishop, G. Wu, Reoperative Central Compartment Dissection for Patients with Recurrent/Persistent Papillary Thyroid Cancer: Efficacy, Safety, and the Association of the Braf Mutation. Laryngoscope 122, 1634–1640 (2012). https://doi.org/10.1002/lary.23371

    Article  CAS  PubMed  Google Scholar 

  27. B. Wojtczak, K. Kaliszewski, K. Sutkowski, M. Bolanowski, M. Barczynski, A Functional Assessment of Anatomical Variants of the Recurrent Laryngeal Nerve During Thyroidectomies Using Neuromonitoring. Endocrine 59, 82–89 (2018). https://doi.org/10.1007/s12020-017-1466-3

    Article  CAS  PubMed  Google Scholar 

  28. H. Masuoka, A. Miyauchi, Intraoperative Management of the Recurrent Laryngeal Nerve Transected or Invaded by Thyroid Cancer. Front Endocrinol. (Lausanne) 13, 884866 (2022). https://doi.org/10.3389/fendo.2022.884866

    Article  PubMed  Google Scholar 

  29. H.S. Lee, S.W. Kim, J.C. Hong, K.D. Lee, Papillary Thyroid Carcinoma with Exclusive Involvement of a Functioning Recurrent Laryngeal Nerve May Be Treated Using a Shaving Technique: Reply. World J. Surg. 39, 1853–1854 (2015). https://doi.org/10.1007/s00268-015-3027-3

    Article  PubMed  Google Scholar 

  30. Y.K. So, M.J. Kim, S. Kim, Y.I. Son, Lateral Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis for Prevalence, Risk Factors, and Location. Int J. Surg. 50, 94–103 (2018). https://doi.org/10.1016/j.ijsu.2017.12.029

    Article  PubMed  Google Scholar 

  31. B.C. Stack Jr., R.L. Ferris, D. Goldenberg, M. Haymart, A. Shaha, S. Sheth et al. American Thyroid Association Consensus Review and Statement Regarding the Anatomy, Terminology, and Rationale for Lateral Neck Dissection in Differentiated Thyroid Cancer. Thyroid 22, 501–508 (2012). https://doi.org/10.1089/thy.2011.0312

    Article  PubMed  Google Scholar 

  32. M. Song, Z. Huang, S. Wang, J. Huang, H. Shi, Y. Liu et al. Predictive Factors of Lateral Lymph Node Metastasis in Conventional Papillary Thyroid Carcinoma. Gland Surg. 9, 1000–1007 (2020). https://doi.org/10.21037/gs-20-482

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. The Department of Thyroid Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Feng Zhu, YiBin Shen, Li**an Zhu, LinHui Chen, FuQiang Li, **aoJun **e & YiJun Wu

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Contributions

F.Z. and J.W. conceived the study and designed the research. Q.L. and B.S. collected data and followed up with patients. X.Z. and H.C. carried out statistical analysis. F.Z. and J.X. wrote the manuscript and interpretation of data. All authors read and approved the final article.

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Correspondence to YiJun Wu.

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The authors declare no competing interests.

Ethical approval

The Clinical Research Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University authorized this retrospective study and waived the need to obtain informed consent (No. 0426 of 2023).

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Zhu, F., Shen, Y., Zhu, L. et al. Impact of thyroid carcinoma invasion of recurrent laryngeal nerve on cervical lymph node metastasis. Endocrine (2024). https://doi.org/10.1007/s12020-024-03879-0

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