Skip to main content
SpringerLink
Log in

The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis

  • Review Article
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Although there have been many studies identifying clinical and pathologic factors that may predict central lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) patients without clinically cervical lymph node metastasis (cN0), the results were inconsistent. And whether prophylactic central lymph node dissection (pCLND) should be performed in cN0 PTMC remains controversial. The EMBASE, PubMed, MEDLINE and the Cochrane Library were searched until Oct 2015 to identify relevant studies. Primary outcomes were clinical and pathologic factors for CLNM. Secondary outcomes included CLNM rate, surgical complications of hypocalcaemia and recurrent laryngeal nerve(RLN) injury and neck recurrences. Statistical analysis was performed using Stata 12.0. Fourteen eligible studies enrolling 4573 patients were included in this meta-analysis. The overall incidence of CLNM was 33 % (95 % CI 29–37). An elevated risk of CLNM was significantly associated with male gender (OR 2.33, 95 % CI 1.71–3.17), age <45 years (OR 1.27, 95 % CI 1.08–1.48), tumor size >5 mm (OR 2.16, 95 % CI 1.87–2.50), multifocality (OR 1.73, 95 % CI 1.45–2.05), extrathyroidal extension (OR 1.99, 95 % CI 1.66–2.37) and lymphovascular invasion (OR 3.87, 95 % CI 1.64–9.10), but not with thyroid bilaterality (OR 1.41, 95 % CI 0.89–2.22) and chronic lymphocytic thyroiditis (OR 0.98, 95 % CI 0.66–1.47). The pooled frequency of permanent hypocalcaemia, permanent RLN injury and neck recurrences was 1.1, 0.5 and 2.8 %, respectively. cN0 PTMC patients have a considerable CLNM rate and have a low pooled incident of surgical complications and neck recurrences with pCLND. Six unfavorable clinical and pathologic factors, which were significantly associated with CLNM, were identified. These findings may help guide the application of pCLND or subsequent treatment in cN0 PTMC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Usluogullari CA, Onal ED, Ozdemir E, Ucler R, Kiyak G, Ersoy PE, Yalcin S, Guler G, Ersoy R, Caki B (2015) A retrospective analysis of prognostic factors predictive of lymph-node metastasis and recurrence in thyroid papillary microcarcinoma. Minerva Endocrinol 40(1):15–22

    CAS  PubMed  Google Scholar 

  2. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Kuma S, Kuma K, Miyauchi A (2003) An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 13(4):381–387. doi:10.1089/105072503321669875

    Article  PubMed  Google Scholar 

  3. Lombardi CP, Bellantone R, De Crea C, Paladino NC, Fadda G, Salvatori M, Raffaelli M (2010) Papillary thyroid microcarcinoma: extrathyroidal extension, lymph node metastases, and risk factors for recurrence in a high prevalence of goiter area. World J Surg 34(6):1214–1221. doi:10.1007/s00268-009-0375-x

    Article  PubMed  Google Scholar 

  4. Zeng RC, Li Q, Lin KL, Zhang W, Gao EL, Huang GL, Zhang XH, Zheng MH (2012) Predicting the factors of lateral lymph node metastasis in papillary microcarcinoma of the thyroid in eastern China. Clin Transl Oncol 14(11):842–847. doi:10.1007/s12094-012-0875-2

    Article  PubMed  Google Scholar 

  5. Hay ID, Grant CS, van Heerden JA, Goellner JR, Ebersold JR, Bergstralh EJ (1992) Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery 112 (6):1139–1146 (discussion 1146–1137)

  6. Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A (2014) Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid 24(1):27–34. doi:10.1089/thy.2013.0367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH (2003) Papillary microcarcinoma of the thyroid-prognostic significance of lymph node metastasis and multifocality. Cancer 98(1):31–40. doi:10.1002/cncr.11442

    Article  PubMed  Google Scholar 

  8. Roti E, degli Uberti EC, Bondanelli M, Braverman LE (2008) Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol 159(6):659–673. doi:10.1530/EJE-07-0896

    Article  CAS  PubMed  Google Scholar 

  9. Hay ID, Hutchinson ME, Gonzalez-Losada T, McIver B, Reinalda ME, Grant CS, Thompson GB, Sebo TJ, Goellner JR (2008) Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 144 (6):980–987. doi:10.1016/j.surg.2008.08.035 (discussion 987–988)

  10. Wada N, Duh QY, Sugino K, Iwasaki H, Kameyama K, Mimura T, Ito K, Takami H, Takanashi Y (2003) Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg 237(3):399–407. doi:10.1097/01.SLA.0000055273.58908.19

    PubMed  PubMed Central  Google Scholar 

  11. Zhang LY, Liu ZW, Liu YW, Gao WS, Zheng CJ (2015) Risk factors for nodal metastasis in cN0 papillary thyroid microcarcinoma. Asian Pac J Cancer Prevent APJCP 16(8):3361–3363

    Article  Google Scholar 

  12. Lan X, Sun W, Zhang H, Dong W, Wang Z, Zhang T (2015) A meta-analysis of central lymph node metastasis for predicting lateral involvement in papillary thyroid carcinoma. Otolaryngol Head Neck Surg Off J Am Acad Otolaryngol Head Neck Surg. doi:10.1177/0194599815601412

  13. Xiang D, Xie L, Xu Y, Li Z, Hong Y, Wang P (2015) Papillary thyroid microcarcinomas located at the middle part of the middle third of the thyroid gland correlates with the presence of neck metastasis. Surgery 157(3):526–533. doi:10.1016/j.surg.2014.10.020

    Article  PubMed  Google Scholar 

  14. Lee CR, Son H, Lee S, Kang SW, Jeong JJ, Nam KH, Chung WY, Park CS (2014) Lobectomy and prophylactic central neck dissection for papillary thyroid microcarcinoma: do involved lymph nodes mandate completion thyroidectomy? World J Surg 38(4):872–877. doi:10.1007/s00268-013-2348-3

    Article  PubMed  Google Scholar 

  15. So YK, Son YI, Hong SD, Seo MY, Baek CH, Jeong HS, Chung MK (2010) Subclinical lymph node metastasis in papillary thyroid microcarcinoma: a study of 551 resections. Surgery 148(3):526–531. doi:10.1016/j.surg.2010.01.003

    Article  PubMed  Google Scholar 

  16. Liu Z, Wang L, Yi P, Wang CY, Huang T (2014) Risk factors for central lymph node metastasis of patients with papillary thyroid microcarcinoma: a meta-analysis. Int J Clin Exp Pathol 7(3):932–937

    PubMed  PubMed Central  Google Scholar 

  17. Qu N, Zhang L, Ji QH, Chen JY, Zhu YX, Cao YM, Shen Q (2015) Risk factors for central compartment lymph node metastasis in papillary thyroid microcarcinoma: a meta-analysis. World J Surg 39(10):2459–2470. doi:10.1007/s00268-015-3108-3

    Article  PubMed  Google Scholar 

  18. Qu H, Sun GR, Liu Y, He QS (2015) Clinical risk factors for central lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 83(1):124–132. doi:10.1111/cen.12583

    Article  Google Scholar 

  19. Sun W, Lan X, Zhang H, Dong W, Wang Z, He L, Zhang T, Liu S (2015) Risk factors for central lymph node metastasis in cn0 papillary thyroid carcinoma: a systematic review and meta-analysis. PLoS One 10(10):e0139021. doi:10.1371/journal.pone.0139021

    Article  PubMed  PubMed Central  Google Scholar 

  20. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62 (10):1006–1012. doi:10.1016/j.jclinepi.2009.06.005

  21. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P (2012) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute web site. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

  22. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi:10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  23. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ahn BH, Kim JR, Jeong HC, Lee JS, Chang ES, Kim YH (2015) Predictive factors of central lymph node metastasis in papillary thyroid carcinoma. Ann Surg Treat Res 88(2):63–68. doi:10.4174/astr.2015.88.2.63

    Article  PubMed  PubMed Central  Google Scholar 

  25. Caliskan M, Park JH, Jeong JS, Lee CR, Park SK, Kang SW, Jeong JJ, Chung WY, Park CS (2012) Role of prophylactic ipsilateral central compartment lymph node dissection in papillary thyroid microcarcinoma. Endocr J 59(4):305–311

    Article  PubMed  Google Scholar 

  26. Ji YB, Yoo HS, Song CM, Park CW, Lee CB, Tae K (2015) Predictive factors and pattern of central lymph node metastasis in unilateral papillary thyroid carcinoma. Auris Nasus Larynx. doi:10.1016/j.anl.2015.09.005

    Google Scholar 

  27. Jiang LH, Chen C, Tan Z, Lu XX, Hu SS, Wang QL, Hou XX, Cao J, Ge MH (2014) Clinical characteristics related to central lymph node Metastasis in cN0 papillary thyroid carcinoma: a retrospective study of 916 patients. Int J Endocrinol 2014:385787. doi:10.1155/2014/385787

    PubMed  PubMed Central  Google Scholar 

  28. Kim BY, Jung CH, Kim JW, Lee SW, Kim CH, Kang SK, Mok JO (2012) Impact of clinicopathologic factors on subclinical central lymph node metastasis in papillary thyroid microcarcinoma. Yonsei Med J 53(5):924–930. doi:10.3349/ymj.2012.53.5.924

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lim YC, Choi EC, Yoon YH, Kim EH, Koo BS (2009) Central lymph node metastases in unilateral papillary thyroid microcarcinoma. Br J Surg 96(3):253–257. doi:10.1002/bjs.6484

    Article  CAS  PubMed  Google Scholar 

  30. Mao LN, Wang P, Li ZY, Wang Y, Song ZY (2015) Risk factor analysis for central nodal metastasis in papillary thyroid carcinoma. Oncol Lett 9(1):103–107. doi:10.3892/ol.2014.2667

    PubMed  Google Scholar 

  31. Park JP, Roh JL, Lee JH, Baek JH, Gong G, Cho KJ, Choi SH, Nam SY, Kim SY (2014) Risk factors for central neck lymph node metastasis of clinically noninvasive, node-negative papillary thyroid microcarcinoma. Am J Surg 208(3):412–418. doi:10.1016/j.amjsurg.2013.10.032

    Article  PubMed  Google Scholar 

  32. Wang W, Gu J, Shang J, Wang K (2013) Correlation analysis on central lymph node metastasis in 276 patients with cN0 papillary thyroid carcinoma. Int J Clin Exp Pathol 6(3):510–515

    PubMed  PubMed Central  Google Scholar 

  33. Xu D, Lv X, Wang S, Dai W (2014) Risk factors for predicting central lymph node metastasis in papillary thyroid microcarcinoma. Int J Clin Exp Pathol 7(9):6199–6205

    PubMed  PubMed Central  Google Scholar 

  34. Zhou YL, Gao EL, Zhang W, Yang H, Guo GL, Zhang XH, Wang OC (2012) Factors predictive of papillary thyroid micro-carcinoma with bilateral involvement and central lymph node metastasis: a retrospective study. World J Surg Oncol 10:67. doi:10.1186/1477-7819-10-67

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bircan HY, Koc B, Akarsu C, Demiralay E, Demirag A, Adas M, Alis H, Kemik O (2014) Is Hashimoto’s thyroiditis a prognostic factor for thyroid papillary microcarcinoma? Eur Rev Med Pharmacol Sci 18(13):1910–1915

    CAS  PubMed  Google Scholar 

  36. Varshney R, Pakdaman MN, Sands N, Hier MP, Rochon L, Black MJ, Payne RJ (2014) Lymph node metastasis in thyroid papillary microcarcinoma: a study of 170 patients. J Laryngol Otol 128(10):922–925. doi:10.1017/S0022215114001704

    Article  CAS  PubMed  Google Scholar 

  37. Guo Y, Liu Z, Yu P, Liu C, Ming J, Zhang N, Yusufu M, Chen C, Huang T (2015) Using foci number to predict central lymph node metastases of papillary thyroid microcarcinomas with multifocality. Int J Clin Exp Med 8(6):9925–9930

    PubMed  PubMed Central  Google Scholar 

  38. Kim TY, Hong SJ, Kim JM, Kim WG, Gong G, Ryu JS, Kim WB, Yun SC, Shong YK (2008) Prognostic parameters for recurrence of papillary thyroid microcarcinoma. BMC Cancer 8:296. doi:10.1186/1471-2407-8-296

    Article  PubMed  PubMed Central  Google Scholar 

  39. Zhao Q, Ming J, Liu C, Shi L, Xu X, Nie X, Huang T (2013) Multifocality and total tumor diameter predict central neck lymph node metastases in papillary thyroid microcarcinoma. Ann Surg Oncol 20(3):746–752. doi:10.1245/s10434-012-2654-2

    Article  PubMed  Google Scholar 

  40. Hyun SM, Song HY, Kim SY, Nam SY, Roh JL, Han MW, Choi SH (2012) Impact of combined prophylactic unilateral central neck dissection and hemithyroidectomy in patients with papillary thyroid microcarcinoma. Ann Surg Oncol 19(2):591–596. doi:10.1245/s10434-011-1995-6

    Article  PubMed  Google Scholar 

  41. Kim JY, Jung EJ, Park T, Jeong SH, Jeong CY, Ju YT, Lee YJ, Hong SC, Choi SK, Ha WS (2015) Impact of tumor size on subclinical central lymph node metastasis in papillary thyroid microcarcinoma depends on age. World J Surg Oncol 13:88. doi:10.1186/s12957-015-0478-9

    Article  PubMed  PubMed Central  Google Scholar 

  42. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19(11):1167–1214. doi:10.1089/thy.2009.0110

    Article  PubMed  Google Scholar 

  43. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L (2016) 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 26(1):1–133. doi:10.1089/thy.2015.0020

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yang Y, Chen C, Chen Z, Jiang J, Chen Y, Jin L, Guo G, Zhang X, Ye T (2014) Prediction of central compartment lymph node metastasis in papillary thyroid microcarcinoma. Clin Endocrinol (Oxf) 81(2):282–288. doi:10.1111/cen.12417

    Article  CAS  Google Scholar 

  45. Kim KE, Kim EK, Yoon JH, Han KH, Moon HJ, Kwak JY (2013) Preoperative prediction of central lymph node metastasis in thyroid papillary microcarcinoma using clinicopathologic and sonographic features. World J Surg 37(2):385–391. doi:10.1007/s00268-012-1826-3

    Article  PubMed  Google Scholar 

  46. Pisanu A, Saba A, Podda M, Reccia I, Uccheddu A (2015) Nodal metastasis and recurrence in papillary thyroid microcarcinoma. Endocrine 48(2):575–581. doi:10.1007/s12020-014-0350-7

    Article  CAS  PubMed  Google Scholar 

  47. Jung CK, Kang YG, Bae JS, Lim DJ, Choi YJ, Lee KY (2010) Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma. Mod Pathol 23(9):1201–1208. doi:10.1038/modpathol.2010.116

    Article  PubMed  Google Scholar 

  48. Sugg SL, Ezzat S, Rosen IB, Freeman JL, Asa SL (1998) Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab 83(11):4116–4122. doi:10.1210/jcem.83.11.5271

    CAS  PubMed  Google Scholar 

  49. Shattuck TM, Westra WH, Ladenson PW, Arnold A (2005) Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med 352(23):2406–2412. doi:10.1056/NEJMoa044190

    Article  CAS  PubMed  Google Scholar 

  50. Jovanovic L, Delahunt B, McIver B, Eberhardt NL, Grebe SK (2008) Most multifocal papillary thyroid carcinomas acquire genetic and morphotype diversity through subclonal evolution following the intra-glandular spread of the initial neoplastic clone. J Pathol 215(2):145–154. doi:10.1002/path.2342

    Article  CAS  PubMed  Google Scholar 

  51. Katoh R, Sasaki J, Kurihara H, Suzuki K, Iida Y, Kawaoi A (1992) Multiple thyroid involvement (intraglandular metastasis) in papillary thyroid carcinoma. A clinicopathologic study of 105 consecutive patients. Cancer 70(6):1585–1590

    Article  CAS  PubMed  Google Scholar 

  52. Lee JH, Kim Y, Choi JW, Kim YS (2013) The association between papillary thyroid carcinoma and histologically proven Hashimoto’s thyroiditis: a meta-analysis. Eur J Endocrinol 168(3):343–349. doi:10.1530/EJE-12-0903

    Article  CAS  PubMed  Google Scholar 

  53. Lang BH, Ng SH, Lau LL, Cowling BJ, Wong KP, Wan KY (2013) A systematic review and meta-analysis of prophylactic central neck dissection on short-term locoregional recurrence in papillary thyroid carcinoma after total thyroidectomy. Thyroid 23(9):1087–1098. doi:10.1089/thy.2012.0608

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China

    Liang-Sen Liu, Jun-Hong Li, Xue Liu & Zhi-Xiao Wei

  2. School of Basic Medicine, Guangxi Medical University, Nanning, Guangxi, China

    Jia Liang

  3. Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

    Li Jiang

  4. School of Public Health, Guangxi Medical University, Nanning, Guangxi, China

    Jian-Xiong Long & Yue-Ming Jiang

Authors
  1. Liang-Sen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jia Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun-Hong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xue Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian-Xiong Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yue-Ming Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhi-Xiao Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhi-Xiao Wei.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

No ethics approval was required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, LS., Liang, J., Li, JH. et al. The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis. Eur Arch Otorhinolaryngol 274, 1327–1338 (2017). https://doi.org/10.1007/s00405-016-4302-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-016-4302-0

Keywords

Search

Navigation