Abstract
Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070–7.933), distant metastasis (HR = 3.860, 95 % CI 1.507–9.884), and cancer death (HR = 7.252, 95 % 2.189–24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185–4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300–19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-4533-5/MediaObjects/13277_2015_4533_Fig1_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-4533-5/MediaObjects/13277_2015_4533_Fig2_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-4533-5/MediaObjects/13277_2015_4533_Fig3_HTML.gif)
Similar content being viewed by others
References
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.
Hung W, Sarlis NJ. Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review. Thyroid. 2002;12:683–702.
Sherman SI. Thyroid carcinoma. Lancet. 2003;361:501–11.
Eustatia-Rutten CF, Corssmit EP, Biermasz NR, Pereira AM, Romijn JA, Smit JW. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2006;91:313–9.
Jovanovic L, Delahunt B, McIver B, Eberhardt NL, Bhattacharya A, Lea R, et al. Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma. Pathology. 2010;42:524–33.
Zhang L, Wei WJ, Ji QH, Zhu YX, Wang ZY, Wang Y, et al. Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients. J Clin Endocrinol Metab. 2012;97:1250–7.
Dinse GE, Lagakos SW. Nonparametric estimation of lifetime and disease onset distributions from incomplete observations. Biometrics. 1982;38:921–32.
Gill RD. Multistate life-tables and regression models. Math Popul Stud. 1992;3:259–76.
Koo BS, Lim HS, Lim YC, Yoon YH, Kim YM, Park YH, et al. Occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma. Ann Surg Oncol. 2010;17:1101–5.
Lee YS, Lim YS, Lee JC, Wang SG, Kim IJ, Lee BJ. Clinical implication of the number of central lymph node metastasis in papillary thyroid carcinoma: preliminary report. World J Surg. 2010;34:2558–63.
DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab. 1990;71:414–24.
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;37:376–84.
Pasieka JL, Thompson NW, McLeod MK, Burney RE, Macha M. The incidence of bilateral well-differentiated thyroid cancer found at completion thyroidectomy. World J Surg. 1992;16:711–6. discussion 716–717.
Pacini F, Elisei R, Capezzone M, Miccoli P, Molinaro E, Basolo F, et al. Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in low- and high-risk patients. Thyroid. 2001;11:877–81.
Park SY, Park YJ, Lee YJ, Lee HS, Choi SH, Choe G, et al. Analysis of differential braf(v600e) mutational status in multifocal papillary thyroid carcinoma: evidence of independent clonal origin in distinct tumor foci. Cancer. 2006;107:1831–8.
Lin JD, Chao TC, Hsueh C, Kuo SF. High recurrent rate of multicentric papillary thyroid carcinoma. Ann Surg Oncol. 2009;16:2609–16.
Passler C, Prager G, Scheuba C, Kaserer K, Zettinig G, Niederle B. Application of staging systems for differentiated thyroid carcinoma in an endemic goiter region with iodine substitution. Ann Surg. 2003;237:227–34.
Ito Y, Fukushima M, Tomoda C, Inoue H, Kihara M, Higashiyama T, et al. Prognosis of patients with papillary thyroid carcinoma having clinically apparent metastasis to the lateral compartment. Endocr J. 2009;56:759–66.
Ito Y, Miyauchi A, Jikuzono T, Higashiyama T, Takamura Y, Miya A, et al. Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grou**. World J Surg. 2007;31:838–48.
Yamashita H, Noguchi S, Murakami N, Toda M, Uchino S, Watanabe S, et al. Extracapsular invasion of lymph node metastasis. A good indicator of disease recurrence and poor prognosis in patients with thyroid microcarcinoma. Cancer. 1999;86:842–9.
Hotomi M, Sugitani I, Toda K, Kawabata K, Fujimoto Y. A novel definition of extrathyroidal invasion for patients with papillary thyroid carcinoma for predicting prognosis. World J Surg. 2012;36:1231–40.
Carcangiu ML. Diagnosis and prognostic factors in papillary carcinoma of the thyroid. Pathologica. 2003;95:271–3.
Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97:418–28.
Kuo SF, Lin SF, Chao TC, Hsueh C, Lin KJ, Lin JD. Prognosis of multifocal papillary thyroid carcinoma. Int J Endocrinol. 2013;2013:809382.
Grigsby PW, Reddy RM, Moley JF, Hall BL. Contralateral papillary thyroid cancer at completion thyroidectomy has no impact on recurrence or survival after radioiodine treatment. Surgery. 2006;140:1043–7. discussion 1047–1049.
Zhao Q, Ming J, Liu C, Shi L, Xu X, Nie X, et al. Multifocality and total tumor diameter predict central neck lymph node metastases in papillary thyroid microcarcinoma. Ann Surg Oncol. 2013;20:746–52.
Zhou YL, Gao EL, Zhang W, Yang H, Guo GL, Zhang XH, et al. Factors predictive of papillary thyroid micro-carcinoma with bilateral involvement and central lymph node metastasis: a retrospective study. World J Surg Oncol. 2012;10:67.
Kim HJ, Park HK, Byun DW, Suh K, Yoo MH, Min YK, Kim SW, Chung JH: Number of tumor foci as predictor of lateral lymph node metastasis in papillary thyroid carcinoma. Head Neck 2014.
Shepet K, Alhefdhi A, Lai N, Mazeh H, Sippel R, Chen H. Hereditary medullary thyroid cancer: age-appropriate thyroidectomy improves disease-free survival. Ann Surg Oncol. 2013;20:1451–5.
Sugg SL, Ezzat S, Rosen IB, Freeman JL, Asa SL. Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab. 1998;83:4116–22.
Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, et al. Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab. 2004;89:5583–91.
Lee SH, Lee SS, ** SM, Kim JH, Rho YS. Predictive factors for central compartment lymph node metastasis in thyroid papillary microcarcinoma. Laryngoscope. 2008;118:659–62.
Moo TA, Umunna B, Kato M, Butriago D, Kundel A, Lee JA, et al. Ipsilateral versus bilateral central neck lymph node dissection in papillary thyroid carcinoma. Ann Surg. 2009;250:403–8.
Koo BS, Choi EC, Yoon YH, Kim DH, Kim EH, Lim YC. Predictive factors for ipsilateral or contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma. Ann Surg. 2009;249:840–4.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Source(s) of funding
This research is supported by grants from the National Natural Science Foundation of China (81272934) and the Natural Science Foundation of Shanghai (12ZR1406800).
Conflicts of interest
None
Additional information
Ning Qu, Ling Zhang and Wei-li Wu contributed equally to this work.
Rights and permissions
About this article
Cite this article
Qu, N., Zhang, L., Wu, Wl. et al. Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer. Tumor Biol. 37, 8783–8789 (2016). https://doi.org/10.1007/s13277-015-4533-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-4533-5