Horm Metab Res 2017; 49(03): 201-207
DOI: 10.1055/s-0043-101917
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Independent Risk Factors Predicting Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma

Xiaolong Yu*
1   Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
1   Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
,
Xuejia Song*
2   Department of Endocrinology, First People’s Hospital of Qingdao Economic and Technological Development Zone, Qingdao, China
,
Wenhai Sun*
3   Department of Thyroid Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
,
Shihua Zhao
4   Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China
,
Jiajun Zhao
1   Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
,
Yan-Gang Wang
4   Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China
› Author Affiliations
Further Information

Publication History

received 15 July 2016

accepted 12 January 2017

Publication Date:
28 March 2017 (online)

Abstract

The incidence of papillary thyroid microcarcinoma (PTMC) has risen rapidly in recent years, and PTMC patients with central lymph node metastasis (CLNM) usually have poor prognosis. Independent risk factors predicting CLNM in PTMC have not been well understood. The aim of our study was to identify useful clinicopathological risk factors predicting CLNM in PTMC patients. This was a retrospective study of 917 patients with PTMC treated with surgery from January 2014 to December 2015 in our hospital. The relationship between clinicopathological factors and CLNM was analyzed to identify those factors predicting CLNM in PTMC. Univariate and multivariate logistic regression analyses were further performed. Of 917 PTMC patients, 344 (37.5%) were found to have CLNM confirmed by intraoperative frozen-section examination. Multivariate logistic regression analyses further found several independent factors predicting CLNM in PTMC patients, including male gender (OR=1.75, 95% CI 1.17–2.61; p=0.006), younger age (<45 years) (OR=1.69, 95%CI 1.20–2.38; p=0.002), positive CLNM on ultrasonography (OR=10.20, 95% CI 5.51–18.88; p<0.001), multifocality (OR=1.69, 95% CI 1.00–2.85; p=0.04), and larger tumor size (>5 mm) (OR=2.80, 95% CI 2.01–3.91; p<0.001). The findings of our study identified several useful and independent risk factors predicting CLNM in PTMC patients, such as male gender, younger age, multifocality, positive CLNM on ultrasonography, and larger tumor size. The CLNM is very common in PTMC patients, and routine prophylactic central neck dissection may be recommended in PTMC patients with those independent risk factors of CLNM.

* These authors contributed equally to the study


 
  • References

  • 1 Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet 2016; 388: 2783-2795
  • 2 Pazaitou-Panayiotou K, Capezzone M, Pacini F. Clinical features and therapeutic implication of papillary thyroid microcarcinoma. Thyroid 2007; 17: 1085-1092
  • 3 Gschwandtner E, Klatte T, Swietek N, Bures C, Kober F, Ott J, Schultheis A, Neuhold N, Hermann M. Increase of papillary thyroid microcarcinoma and a plea for restrictive treatment: A retrospective study of 1,391 prospective documented patients. Surgery 2016; 159: 503-511
  • 4 Pellegriti G, Scollo C, Lumera G, Regalbuto C, Vigneri R, Belfiore A. Clinical behavior and outcome of papillary thyroid cancers smaller than 1.5 cm in diameter: study of 299 cases. J Clin Endocrinol Metab 2004; 89: 3713-3720
  • 5 Lee J, Song Y, Soh EY. Central lymph node metastasis is an important prognostic factor in patients with papillary thyroid microcarcinoma. J Korean Med Sci 2014; 29: 48-52
  • 6 Choi SY, Cho JK, Moon JH, Son YI. Metastatic lymph node ratio of central neck compartment has predictive values for locoregional recurrence in papillary thyroid microcarcinoma. Clin Exp Otorhinolaryngol 2016; 9: 75-79
  • 7 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. 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
  • 8 Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Miyauchi A. Preoperative ultrasonographic examination for lymph node metastasis: usefulness when designing lymph node dissection for papillary microcarcinoma of the thyroid. World J Surg 2004; 28: 498-501
  • 9 Choi YJ, Yun JS, Kook SH, Jung EC, Park YL. Clinical and imaging assessment of cervical lymph node metastasis in papillary thyroid carcinomas. World J Surg 2010; 34: 1494-1499
  • 10 Chinese Society of Endocrinology Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Chinese Journal of Endocrinology and Metabolism 2012; 28: 779-797
  • 11 Mitchell AL, Gandhi A, Scott-Coombes D, Perros P. Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol 2016; 130: S150-S160
  • 12 Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard BaG, Gilbert J, Harrison B, Johnson SJ, Giles TE, Moss L, Lewington V, Newbold K, Taylor J, Thakker RV, Watkinson J, Williams GR. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf) 2014; 81 (Suppl. 01) 1-122
  • 13 Zeng RC, Zhang W, Gao EL, Cheng P, Huang GL, Zhang XH, Li Q. Number of central lymph node metastasis for predicting lateral lymph node metastasis in papillary thyroid microcarcinoma. Head Neck 2014; 36: 101-106
  • 14 Kim SK, Park I, Woo JW, Lee JH, Choe JH, Kim JH, Kim JS. Predictive factors for lymph node metastasis in papillary thyroid microcarcinoma. Ann Surg Oncol 2016; 23: 2866-2873
  • 15 Zhang L, Yang J, Sun Q, Liu Y, Liang F, Liu Z, Chen G, Chen S, Shang Z, Li Y, Li X. Risk factors for lymph node metastasis in papillary thyroid microcarcinoma: Older patients with fewer lymph node metastases. Eur J Surg Oncol 2016; 42: 1478-1482
  • 16 Kent WD, Hall SF, Isotalo PA, Houlden RL, George RL, Groome PA. Increased incidence of differentiated thyroid carcinoma and detection of subclinical disease. CMAJ 2007; 177: 1357-1361
  • 17 Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 2006; 295: 2164-2167
  • 18 Ciampolillo A, Bellacicco M, Natalicchio A, Pezzolla A, Trerotoli P, Grammatica L, Achille G, Giorgino F. Clinical aggressiveness of incidental and non-incidental thyroid cancer. J Endocrinol Invest 2011; 34: 599-603
  • 19 Li D, Gao M, Li X, Xing M. Molecular aberrance in papillary thyroid microcarcinoma bearing high aggressiveness: identifying a “tibetan mastiff dog” from puppies. J Cell Biochem 2016; 117: 1491-1496
  • 20 Chen Y, Sadow PM, Suh H, Lee KE, Choi JY, Suh YJ, Wang TS, Lubitz CC. BRAF(V600E) Is correlated with recurrence of papillary thyroid microcarcinoma: a systematic review, multi-institutional primary data analysis, and meta-analysis. Thyroid 2016; 26: 248-255
  • 21 Bastos AU, Oler G, Nozima BH, Moyses RA, Cerutti JM. BRAF V600E and decreased NIS and TPO expression are associated with aggressiveness of a subgroup of papillary thyroid microcarcinoma. Eur J Endocrinol 2015; 173: 525-540
  • 22 Crescenzi A, Guidobaldi L, Nasrollah N, Taccogna S, Cicciarella Modica DD, Turrini L, Nigri G, Romanelli F, Valabrega S, Giovanella L, Onetti Muda A, Trimboli P. Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers. Horm Metab Res 2014; 46: 370-374
  • 23 Crescenzi A, Trimboli P, Modica DC, Taffon C, Guidobaldi L, Taccogna S, Rainer A, Trombetta M, Papini E, Zelano G. Preoperative assessment of tert promoter mutation on thyroid core needle biopsies supports diagnosis of malignancy and addresses surgical strategy. Horm Metab Res 2016; 48: 157-162
  • 24 Jeon MJ, Kim WG, Choi YM, Kwon H, Lee YM, Sung TY, Yoon JH, Chung KW, Hong SJ, Kim TY, Shong YK, Song DE, Kim WB. Features predictive of distant metastasis in papillary thyroid microcarcinomas. Thyroid 2016; 26: 161-168
  • 25 Shi X, Liu R, Basolo F, Giannini R, Shen X, Teng D, Guan H, Shan Z, Teng W, Musholt TJ, Al-Kuraya K, Fugazzola L, Colombo C, Kebebew E, Jarzab B, Czarniecka A, Bendlova B, Sykorova V, Sobrinho-Simoes M, Soares P, Shong YK, Kim TY, Cheng S, Asa SL, Viola D, Elisei R, Yip L, Mian C, Vianello F, Wang Y, Zhao S, Oler G, Cerutti JM, Puxeddu E, Qu S, Wei Q, Xu H, O’Neill CJ, Sywak MS, Clifton-Bligh R, Lam AK, Riesco-Eizaguirre G, Santisteban P, Yu H, Tallini G, Holt EH, Vasko V, Xing M. Differential clinicopathological risk and prognosis of major papillary thyroid cancer variants. J Clin Endocrinol Metab 2016; 101: 264-274
  • 26 Liu FH, Kuo SF, Hsueh C, Chao TC, Lin JD. Postoperative recurrence of papillary thyroid carcinoma with lymph node metastasis. J Surg Oncol 2015; 112: 149-154
  • 27 Wang TS, Cheung K, Farrokhyar F, Roman SA, Sosa JA. A meta-analysis of the effect of prophylactic central compartment neck dissection on locoregional recurrence rates in patients with papillary thyroid cancer. Ann Surg Oncol 2013; 20: 3477-3483
  • 28 Gambardella C, Tartaglia E, Nunziata A, Izzo G, Siciliano G, Cavallo F, Mauriello C, Napolitano S, Thomas G, Testa D, Rossetti G, Sanguinetti A, Avenia N, Conzo G. Clinical significance of prophylactic central compartment neck dissection in the treatment of clinically node-negative papillary thyroid cancer patients. World J Surg Oncol 2016; 14: 247
  • 29 Nabhan F, Ringel MD. Thyroid nodules and cancer management guidelines: comparisons and controversies. Endocr Relat Cancer 2016;
  • 30 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
  • 31 Clark OH. Thyroid cancer and lymph node metastases. J Surg Oncol 2011; 103: 615-618
  • 32 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
  • 33 Soares P, Celestino R, Gaspar da Rocha A, Sobrinho-Simoes M. Papillary thyroid microcarcinoma: how to diagnose and manage this epidemic?. Int J Surg Pathol 2014; 22: 113-119
  • 34 Trimboli P, Treglia G, Giovanella L. Preoperative measurement of serum thyroglobulin to predict malignancy in thyroid nodules: a systematic review. Horm Metab Res 2015; 47: 247-252
  • 35 Siddiqui S, White MG, Antic T, Grogan RH, Angelos P, Kaplan EL, Cipriani NA. Clinical and pathologic predictors of lymph node metastasis and recurrence in papillary thyroid microcarcinoma. Thyroid 2016; 26: 807-815
  • 36 Kim SK, Park I, Woo JW, Lee JH, Choe JH, Kim JH, Kim JS. Predictive factors for lymph node metastasis in papillary thyroid microcarcinoma. Ann Surg Oncol 2016; 23: 2866-2873
  • 37 Wada N, Duh QY, Sugino K, Iwasaki H, Kameyama K, Mimura T, Ito K, Takami H, Takanashi Y. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg 2003; 237: 399-407
  • 38 Roh JL, Kim JM, Park CI. Central cervical nodal metastasis from papillary thyroid microcarcinoma: pattern and factors predictive of nodal metastasis. Ann Surg Oncol 2008; 15: 2482-2486
  • 39 Mulla M, Schulte KM. Central cervical lymph node metastases in papillary thyroid cancer: a systematic review of imaging-guided and prophylactic removal of the central compartment. Clin Endocrinol (Oxf) 2012; 76: 131-136
  • 40 Noureldine SI, Najafian A, Aragon Han P, Olson MT, Genther DJ, Schneider EB, Prescott JD, Agrawal N, Mathur A, Zeiger MA, Tufano RP. Evaluation of the effect of diagnostic molecular testing on the surgical decision-making process for patients with thyroid nodules. JAMA Otolaryngol Head Neck Surg 2016; 23: 676-682
  • 41 Ahn D, Sohn JH, Jeon JH, Jeong JY. Clinical impact of microscopic extrathyroidal extension in patients with papillary thyroid microcarcinoma treated with hemithyroidectomy. J Endocrinol Invest 2014; 37: 167-173
  • 42 Bircan HY, Koc B, Akarsu C, Demiralay E, Demirag A, Adas M, Alis H, Kemik O. Is Hashimoto’s thyroiditis a prognostic factor for thyroid papillary microcarcinoma?. Eur Rev Med Pharmacol Sci 2014; 18: 1910-1915
  • 43 Cupisti K, Lehwald N, Anlauf M, Riemer J, Werner TA, Krieg A, Witte J, Chanab A, Baldus SE, Krausch M, Raffel A, Herdter C, Schott M, Knoefel WT. Encapsulation status of papillary thyroid microcarcinomas is associated with the risk of lymph node metastases and tumor multifocality. Horm Metab Res 2014; 46: 138-144
  • 44 Park JP, Roh JL, Lee JH, Baek JH, Gong G, Cho KJ, Choi SH, Nam SY, Kim SY. Risk factors for central neck lymph node metastasis of clinically noninvasive, node-negative papillary thyroid microcarcinoma. Am J Surg 2014; 208: 412-418
  • 45 Yang Y, Chen C, Chen Z, Jiang J, Chen Y, Jin L, Guo G, Zhang X, Ye T. Prediction of central compartment lymph node metastasis in papillary thyroid microcarcinoma. Clin Endocrinol (Oxf) 2014; 81: 282-288