J Endocr Surg.  2017 Jun;17(2):63-72. 10.16956/jes.2017.17.2.63.

Bilateral Papillary Thyroid Cancer Increases the Risk of Lymph Node Metastasis Compared with Unilateral Multifocal Papillary Thyroid Cancer

• Han JR
• Jung JH
• Kim WW
• Lee J
• Park HY
• Kim HJ
• Park JY

• KMID: 2383823
• DOI: http://doi.org/10.16956/jes.2017.17.2.63

Abstract

PURPOSE
Papillary thyroid cancer (PTC) has a strong propensity for lymph node metastasis, which is related with local recurrence, and disease-specific survival in the elderly. We evaluated the association between lymph node metastasis and disease multifocality, bilaterality, and other clinicopathological variables to identify risk factors and aid surgical decision-making. The relationship between the number of foci and metastasis to cervical lymph node was also evaluated.
METHODS
Patients with PTC (n=819) undergoing thyroidectomy at our institution were included. The study population was segregated into 4 groups based on PTC multifocality and bilaterality.
RESULTS
Cervical lymph node metastasis, tumor size, and tumor extent were significantly different between the study groups. The frequency of central and lateral cervical lymph node metastasis was the highest in the bilateral multifocal disease group, followed by the bilateral solitary group, unilateral multifocal group, and the unilateral solitary group. One PTC focus per thyroid lobe was associated with increased metastasis (53.8%). Moreover, lymph node positivity doubled with 5-7 foci (71.4%), and tripled with ≥8 foci (100.0%). Bilateral solitary and bilateral multifocal PTC were identified as independent predictors of cervical lymph node metastasis.
CONCLUSION
Bilateral PTC was associated with lymph node positivity, which increased proportionally with the number of PTC foci. Bilateral solitary or multifocal PTC were associated with more aggressive features such as larger primary tumor size, more frequent extrathyroidal extensions, and regional lymph node metastasis. The presence of multiple bilateral foci or more than 3 foci are independent risk factors of lymph node metastases.

Keyword

Papillary thyroid cancer; Multifocal; Bilateral; Lymph node metastasis

MeSH Terms

Aged
Humans
Lymph Nodes*
Neoplasm Metastasis*
Recurrence
Risk Factors
Thyroid Gland*
Thyroid Neoplasms*
Thyroidectomy

Reference

1. Ministry of Health and Welfare (KR). Korea Central Cancer Registry. National Cancer Center (KR). Annual Report of Cancer Statistics in Korea in 2013. Cheongju: Ministry of Health and Welfare;2015.

2. Kuo SF, Lin SF, Chao TC, Hsueh C, Lin KJ, Lin JD. Prognosis of multifocal papillary thyroid carcinoma. Int J Endocrinol. 2013; 2013:809382.

3. Khanafshar E, Lloyd RV. The spectrum of papillary thyroid carcinoma variants. Adv Anat Pathol. 2011; 18:90–97.

4. Podnos YD, Smith D, Wagman LD, Ellenhorn JD. The implication of lymph node metastasis on survival in patients with well-differentiated thyroid cancer. Am Surg. 2005; 71:731–734.

5. Zaydfudim V, Feurer ID, Griffin MR, Phay JE. The impact of lymph node involvement on survival in patients with papillary and follicular thyroid carcinoma. Surgery. 2008; 144:1070–1077.

6. Lundgren CI, Hall P, Dickman PW, Zedenius J. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006; 106:524–531.

7. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 2003; 13:381–387.

8. Hay ID, Grant CS, van Heerden JA, Goellner JR, Ebersold JR, Bergstralh EJ. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992; 112:1139–1146.

9. Hughes DT, White ML, Miller BS, Gauger PG, Burney RE, Doherty GM. Influence of prophylactic central lymph node dissection on postoperative thyroglobulin levels and radioiodine treatment in papillary thyroid cancer. Surgery. 2010; 148:1100–1106.

10. Randolph GW, Duh QY, Heller KS. The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension. Thyroid. 2012; 22:1144–1152.

11. Hartl DM, Leboulleux S, Al Ghuzlan A, Baudin E, Chami L, Schlumberger M, et al. Optimization of staging of the neck with prophylactic central and lateral neck dissection for papillary thyroid carcinoma. Ann Surg. 2012; 255:777–783.

12. Popadich A, Levin O, Lee JC, Smooke-Praw S, Ro K, Fazel M, et al. A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer. Surgery. 2011; 150:1048–1057.

13. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, 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; 26:1–133.

14. Sancho JJ, Lennard TW, Paunovic I, Triponez F, Sitges-Serra A. Prophylactic central neck disection in papillary thyroid cancer: a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg. 2014; 399:155–163.

15. Sywak M, Cornford L, Roach P, Stalberg P, Sidhu S, Delbridge L. Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery. 2006; 140:1000–1005.

16. Kuhn E, Teller L, Piana S, Rosai J, Merino MJ. Different clonal origin of bilateral papillary thyroid carcinoma, with a review of the literature. Endocr Pathol. 2012; 23:101–107.

17. Mazeh H, Samet Y, Hochstein D, Mizrahi I, Ariel I, Eid A, et al. Multifocality in well-differentiated thyroid carcinomas calls for total thyroidectomy. Am J Surg. 2011; 201:770–775.

18. Pitt SC, Sippel RS, Chen H. Contralateral papillary thyroid cancer: does size matter? Am J Surg. 2009; 197:342–347.

19. Shattuck TM, Westra WH, Ladenson PW, Arnold A. Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med. 2005; 352:2406–2412.

20. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC Cancer Staging Manual and the future of TNM. Ann Surg Oncol. 2010; 17:1471–1474.

21. Wang W, Zhao W, Wang H, Teng X, Wang H, Chen X, et al. Poorer prognosis and higher prevalence of BRAF (V600E) mutation in synchronous bilateral papillary thyroid carcinoma. Ann Surg Oncol. 2012; 19:31–36.

22. Qu N, Zhang L, Wu WL, Ji QH, Lu ZW, Zhu YX, et al. Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer. Tumour Biol. 2016; 37:8783–8789.

23. Kim HJ, Sohn SY, Jang HW, Kim SW, Chung JH. Multifocality, but not bilaterality, is a predictor of disease recurrence/persistence of papillary thyroid carcinoma. World J Surg. 2013; 37:376–384.

24. Al Afif A, Williams BA, Rigby MH, Bullock MJ, Taylor SM, Trites J, et al. Multifocal papillary thyroid cancer increases the risk of central lymph node metastasis. Thyroid. 2015; 25:1008–1012.

25. Yang Y, Chen C, Chen Z, Jiang J, Chen Y, Jin L, et al. Prediction of central compartment lymph node metastasis in papillary thyroid microcarcinoma. Clin Endocrinol (Oxf). 2014; 81:282–288.

26. Kim KE, Kim EK, Yoon JH, Han KH, Moon HJ, Kwak JY. Preoperative prediction of central lymph node metastasis in thyroid papillary microcarcinoma using clinicopathologic and sonographic features. World J Surg. 2013; 37:385–391.